Regioselective Asymmetric Allylic Alkylation Reaction of α -Cyanoacetates Catalyzed by a Heterobimetallic Platina-/Palladacycle

Article abstract of DOI:10.1002/ejoc.201501290

Allylic substitution reactions provide a valuable tool for the functionalization of CH acidic pronucleophiles. Often, control over the stereocenter generated at the nucleophilic reactant is still a challenge. The majority of studies that address this issue employ metal complexes with a low metal oxidation state (e.g. Pd⁰) to form allyl complexes through oxidative addition. In this article we describe the use of heterobimetallic Pt^II/Pd^II complexes, which probably activate the olefinic substrates through an S_N2′ pathway. The reaction of α-cyanoacetates delivers linear allylation products with exclusive regioselectivity and high E/Z-selectivity for the new C=C double bond. Although the enantioselectivities attained are moderate, they are significantly higher than with related mono-Pd^II or -Pt^II catalysts or the corresponding bis-Pd^II complex, which indicates cooperation of the different metals. Control experiments suggest simultaneous activation of both reaction partners.

Full text of DOI:10.1002/ejoc.201501290

DOI: 10.1002/ejoc.201501290
Full Paper
Bimetallic Catalysis
Regioselective Asymmetric Allylic Alkylation Reaction of
α-Cyanoacetates Catalyzed by a Heterobimetallic
Platina-/Palladacycle
Marcel Weiss,[a] Julia Holz,[a] and René Peters*[a]
Abstract: Allylic substitution reactions provide a valuable tool through an SN2′ pathway. The reaction of α-cyanoacetates de-
for the functionalization of CH acidic pronucleophiles. Often, livers linear allylation products with exclusive regioselectivity
control over the stereocenter generated at the nucleophilic re- and high E/Z-selectivity for the new C=C double bond. Al-
actant is still a challenge. The majority of studies that address though the enantioselectivities attained are moderate, they are
this issue employ metal complexes with a low metal oxidation significantly higher than with related mono-PdII or -PtII catalysts
state (e.g. Pd0) to form allyl complexes through oxidative addi- or the corresponding bis-PdII complex, which indicates coopera-
tion. In this article we describe the use of heterobimetallic PtII/ tion of the different metals. Control experiments suggest simul-
PdII complexes, which probably activate the olefinic substrates taneous activation of both reaction partners.
Introduction
driven by the idea to simultaneously activate the nucleophile
and electrophile by intramolecular cooperation of both metal
centers. In contrast to traditional Pd0 catalysts, the investigated
catalysts contained palladacycle and platinacycle moieties with
the oxidation states of PdII and PtII, respectively, at the catalyti-
cally active centers. These soft Lewis acids were anticipated to
trigger the enolization of the pronucleophile and simultane-
ously enhance the electrophilicity of the allylic substrate by
generating an electrophilic η2-olefin complex. We envisioned
that the regioselectivity might thus be controlled by the posi-
tion of the allylic leaving group through an SN2′-like pathway.
Consequently, Pd0/II-based redox chemistry that involves the
generation of π-allyl complexes, in which two different allylic
termini would have to be differentiated by an incoming nucleo-
phile, would be avoided.
The densely functionalized chiral α-allylated α-cyanoacetate
products represent attractive synthetic building blocks, because
α-cyanoacetates have previously been shown to be very useful
precursors to biologically interesting quaternary α- and ꢀ-
amino acids.[7] Nonetheless, only a few studies about AAA reac-
tions of α-cyanoacetates have been reported. In 1996, Ito et
al. reported a bimetallic catalytic system for allylic substitution
reactions that consists of two distinct Rh and Pd complexes,
which separately activate the nucleophile and the electrophile,
respectively.[8] In 2011, Trost et al. described an elegant molyb-
denum-catalyzed regio-, enantio- and diastereoselective ap-
proach towards branched allylation products.[9]
Catalytic asymmetric allylic alkylation (AAA) reactions belong to
the most important reaction types in synthetic organic chemis-
try because a large variety of different nucleophile types may
be applied and the C=C double bond of the products offers
many options for further functionalization.[1] AAA reactions
have reached a very high level of efficiency in several aspects
such as reactivity, tolerance to functional groups, regioselectiv-
ity and stereocontrol at the allylic reaction partner.[2] Palladium
complexes belong to the most versatile catalysts for AAA reac-
tions.[1] Usually, these reactions proceed through oxidative ad-
dition of an allylic acetate/carbonate to a Pd0 catalyst to form
an electrophilic cationic π-allyl-Pd complex, which suffers outer-
sphere attack by a soft nucleophile resulting in a Pd0-olefin
complex as intermediate. The catalytic cycle is completed by
decomplexation of the product.
Despite the progress achieved in the last years for Pd-cata-
lyzed AAAs, stereocontrol by prochiral C-based nucleophiles is
still a challenging task.[3] A consequence of the nucleophilic
outer-sphere attack at the η3-bound allyl fragment remote to
the chiral information of an enantiopure ligand at Pd is often
poor control of the spatial arrangement of prochiral nucleo-
philes in the corresponding C–C bond-forming transition
state.[4] To address this issue, simultaneous control over both
reaction partners by cooperative catalysts[5] has been employed
as a strategy to accomplish enhanced stereocontrol in these
demanding cases.[6]
Herein, we report a study on an AAA reaction of racemic α-
cyanoacetate substrates with bimetallic catalysts. This work was
Results and Discussion
[a] Universität Stuttgart, Institut für Organische Chemie,
Pfaffenwaldring 55, 70569 Stuttgart, Germany
E-mail: rene.peters@oc.uni-stuttgart.de
Initial Studies with the Parent Allyl Acetate
As a model reaction we initially chose the AAA of α-phenyl
methyl ester 1a-Me with the parent allyl acetate 2a (Table 1).
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201501290.
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In previous investigations our research group has already
Trifluoroethanol was chosen as solvent because in previous
shown that metallocene-derived bis-palladacycles are capable projects that used ferrocene imidazoline platinacycle catalysts,
of activating α-cyanoacetates for enantioselective 1,4-addition the best results were achieved in this reaction medium.[12,10c]
reactions.[7a,10] In addition we have reported electrophilic olefin NaOAc was then added as a stoichiometric base to increase
activations with these bis-palladacycles[11] and related platinum the reactivity of the nucleophilic reaction partner. Under
catalysts,[12] which includes allylic imidate rearrangement reac- these conditions 3aa-Me was formed in a useful yield with an
tions.[13,14] Because we have previously found that a heterobi- enantiomeric excess (ee) of 62 % (Table 1, Entry 2). By perform-
metallic pallada-/platinacycle could sometimes outperform the ing the reaction at room temperature the ee was slightly lower
corresponding homobimetallic bis-palladacycle in the latter re- (Table 1, Entry 3). In the absence of catalyst, there was no prod-
action,[13] we also investigated both catalyst types in the model uct formation at all after 72 h at 50 °C (Table 1, Entry 4).
reaction.
By use of homobimetallic bis-palladacycle [FBIP-Cl]2 under
the conditions of Table 1, Entry 2, the product was formed with
improved yield, but as a racemate (Table 1, Entry 5). This differ-
ent outcome of the bis-palladacycle and the mixed pallada-/
platinacycle seems to stress a particular role of the Pt-center
with regard to stereocontrol. Due to an expected impact of the
anionic ligand X– used, a number of different silver salts were
subsequently investigated for catalyst activation. Although to-
sylate (Table 1, Entry 6) and nitrate (Table 1, Entry 7) ligands
did not improve enantioselectivity, with less Lewis-basic per-
chlorate (Table 1, Entry 8) the stereochemical outcome was
slightly improved. Screens of various solvents (Table 1, En-
tries 9–12) and alternative bases (Table 1, Entries 13–18) did not
result in higher ee values.
Table 1. Reaction development with allyl acetate (2a) as model substrate.
Use of Substituted Allylic Substrates
Substituted allylic substrates were then examined. At the outset
we were hoping that the postulated SN2′ pathway would allow
regioselective access to linear and branched allylation products
depending on the position of the leaving group in the allylic
substrate. Branched allylic acetates were thus expected to pro-
vide linear allylation products, whereas linear allylic acetates
should give branched products. In the latter case an additional
stereocenter would be formed to allow for double stereodiffer-
entiation, which was expected to result in improved enantio-
selectivities.
However, the investigation of different allylic hexenylacetate
isomers provided exclusively linear allylation products (Table 2).
For a sufficient reactivity an increased temperature of 70 °C was
required. With linear allylic acetate 2b and 5 mol-% of precata-
lyst, racemic product was formed in low yield (Table 2, Entry 1).
The reaction outcome with internal double bond isomers also
depended on the double bond geometry and with the (Z)-con-
figured isomer (Z)-2b the reactivity was further reduced, but a
slight excess of the (R)-enantiomer was noticed (Table 2,
Entry 2). Significantly better reactivity and slightly improved en-
antioselectivity were found with branched allylic acetate 2c
(Table 2, Entry 3). A similar outcome was also noticed with
Entry
M
X
Base
–
Solvent
T
[°C]
t
Yield ee
[h] [%][a] [%][b]
1
2
3
4
5
6
7
8
Pt
Pt
Pt
O2CC3F7
O2CC3F7 NaOAc
F3CCH2OH 50
F3CCH2OH 50
F3CCH2OH 22
F3CCH2OH 50
F3CCH2OH 50
F3CCH2OH 50
F3CCH2OH 50
F3CCH2OH 50
24
24 66
72 52
2
n.d.[c]
62
56
–
O2CC3F7 NaOAc
[d]
[d]
–
–
NaOAc
72
0
Pd
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
Pt
O2CC3F7 NaOAc
OTs
24 79
24 53
24 57
24 63
24 91
24 55
24 91
24 52
24 77
24 66
24 35
24 78
24 86
24 55
0
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
KOAc
54
55
68
10
25
8
NO3
ClO4
ClO4
ClO4
ClO4
ClO4
ClO4
ClO4
ClO4
ClO4
ClO4
ClO4
9
EtOH
CH2Cl2
THF
50
50
50
50
10
11
12
13
14
15
16
17
18
MeCN
8
F3CCH2OH 50
F3CCH2OH 50
F3CCH2OH 50
F3CCH2OH 50
F3CCH2OH 50
F3CCH2OH 50
24
40
–18[e]
28
39
–7[e]
LiOAc
NaOPh
NaOEt
Na2CO3
iPr2NEt
[a] Determined by 1H NMR spectroscopy with an internal standard. [b] Deter-
mined by GC. [c] n.d.: not determined. [d] In the absence of catalyst. [e] A
minus sign indicates preference for the other enantiomer.
For catalytic activity the chloride-bridged dimeric ferro- branched oct-1-en-3-yl acetate 2d (Table 2, Entry 4). Better en-
[16,17]
cene[15] bisimidazoline bis-palladacycle [FBIP-Cl]2
corresponding pallada-/platinacycle [FBIPP-Cl]2
and the antioselectivity was attained with a reduced amount of NaOAc
commonly (0.2 equiv.; Table 2, Entry 5). It is worth noting that full regio-
[13]
require removal of the inert chloride bridges to facilitate the selectivity was achieved for all five experiments and the C=C
substrate coordination in a monomeric catalyst species.[10,11,13] double bond in the product was formed with (E)-geometry
However, in the model reaction activation of [FBIPP-Cl]2 with nearly exclusively in all cases. The (Z)-product was either not
silver heptafluorobutyrate resulted in almost no product forma- detected or present in trace quantities. Unfortunately, no re-
tion if the reaction was run at 50 °C for 24 h in trifluoroethanol activity was observed with disubstituted substrate 2e (Table 2,
in the absence of a base (Table 1, Entry 1).
Entry 6).
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Table 2. Investigation of allylic acetate types with different double-bond sub-
stitution patterns and configurations.
presented in Table 2 and that 1,3-disubstituted substrate 2e
provided no product suggests that a terminal allylic double
bond is required for sufficient reactivity in the assumed SN2′-
pathway.
Scheme 1. Allylic acetate rearrangements catalyzed by the bismetallacycle.
In subsequent experiments we focused on the application of
terminal allylic substrates. The nature of the allylic leaving
group was investigated because it might influence the reactiv-
ity and olefin coordination behavior (Table 3). In these experi-
ments, AgOTs was used for catalyst activation. With oct-1-en-3-
yl acetate (2d) similar data was found as with AgClO4 (Table 2,
Entry 5 relative to Table 3, Entry 1).
Table 3. Investigation of different leaving groups.
[a] Determined by 1H NMR spectroscopy with an internal standard. [b] Deter-
mined by HPLC. [c] NaOAc (0.2 equiv.) was used.
At first glance the results presented in Table 2 might suggest
that the mixed pallada-/platinacycle does not promote an SN2′
pathway. It could be that – like with traditional Pd0 catalysts –
a π-allyl-Pd intermediate is generated, which is then attacked
at the sterically better accessible terminal allylic carbon. Such a
scenario would require a formal PdIV or PtIV oxidation state by
oxidative addition of the allylic acetate. It would then be ex-
pected that allylic acetate isomers like 2b, (Z)-2b, and 2c allow
for similar enantioselectivity, as in all cases the same type of π-
allyl-Pd intermediate could be expected to deliver the prod-
uct.[18]
Entry LG[a]
Allylic
substrate
Base
Yield
[%][b]
ee
[%][c]
1
2
3
4
5
6
7
8
9
OAc
O2CCF3
O2CtBu
O2CtBu
OAc
O2CPh
O2C-3-pyridyl
OC(=O)OCH2CF3
OP(=O)(OEt)2
2d
4
5
5
2d
6
7
8
9
NaOAc
NaOAc
NaOAc
NaO2CtBu
NaO2CtBu
NaOAc
NaOAc
NaOAc
66
3
54
24
5
11
22
32
–
58
58
30
36
0
38
12
20
6
NaOAc
[a] LG = leaving group. [b] Determined by 1H NMR spectroscopy with an
internal standard. [c] Determined by HPLC.
Alternatively, the allylic acetates might undergo a metalla-
cycle promoted [3,3]-rearrangement, similar to the allylic imi-
date rearrangements reported with this catalyst type,[13] and
By changing to the significantly less basic trifluoroacetate
such isomerization has been observed (Scheme 1). By using leaving group only traces of allylation product were formed
branched allylic acetate 2d in the absence of α-cyanoacetate, (Table 3, Entry 2). With a sterically demanding pivaloate leaving
an 84:16 mixture of branched and linear isomer was obtained group reactivity was regained, but the product was nearly race-
(2.5 mol-% of precatalyst) and some decomposition. By starting mic (Table 3, Entry 3). The replacement of NaOAc by sodium
from linear 2f and with the same catalyst loading, the pivaloate as base had almost no impact on the results using
branched/linear ratio was 10:90 and more decomposition was the pivaloate leaving group (Table 3, Entry 4). In contrast, a
noticed than with 2d. In that case the (R)-configured branched combination of acetate leaving group and NaOPiv base nega-
acetate was formed in slight excess (36 % ee). Although the tively affected both the yield and enantioselectivity (Table 3,
thermodynamic equilibrium was not reached after 24 h, isomer- Entry 5). Other leaving groups, such as benzoate, nicotinate,
ization might explain the formation of linear allylation product trifluoroethylcarbonate, and diethylphosphate, used in combi-
formed from internal olefins like 2b and (Z)-2b. The fact that nation with NaOAc did not provide any advantages (Table 3,
no branched allylation product was formed in the experiments Entries 6–9). Generally, it seems that an increase in the bulk of
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the leaving group is counterproductive to the enantioselectiv-
ity.
Table 5. Investigation of different substrate combinations.
To increase the enantioselectivity, a screening of various sil-
ver salts was performed for catalyst activation (Table 4).
Table 4. Investigation of different silver salts for catalyst activation.
Entry 3-R
R
R1
R2
Yield
[%][a]
ee
[%][b]
1
2
3
4
5
6
7
8
3aa-Me
Me
Bn
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
H
H
H
88
92
95
75
40
56
76
71
66
32
56
75
58
61
45
75
33
32
16
61[c]
42
67
66
55
61
57
59
66
61
54
39
52
60
69
63
48
48
46
3aa-Bn
3aa-nBu
3aa-iBu
3aa-Allyl
3ad-Me
3ad-Bn
3ad-nBu
3ad-iBu
3ad-tBu
3bd-Me
3cd-Me
3dd-Me
3ed-Me
3fd-Me
3ac-Me
3ag-Me
3ah-Me
3ai-Me
nBu
iBu
Allyl
Me
Bn
nBu
iBu
tBu
Me
Me
Me
Me
Me
Me
Me
Me
Me
Entry
X
Yield
[%][a]
ee
[%][b]
H
Pent
Pent
Pent
Pent
Pent
Pent
Pent
Pent
Pent
Pent
nPr
Cy
1
2
3
4
5
6
7
8
9
OTs
66
59
53
52
18
66
4
54
44
46
33
30
24
10
26
61
ClO4
O2CC3F7
OMs
OTf
SbF6
BF4
9
Ph
Ph
10
11
12
13
14
15
16
17
18
19
4-Br-C6H4
3-F-C6H4
3-MeO-C6H4
2-naphthyl
3-Me-C6H4
Ph
Ph
Ph
Ph
N(Tf)2
9
70
[c]
–
[a] Determined by 1H NMR spectroscopy with an internal standard. [b] Deter-
mined by HPLC. [c] [FBIPP-Cl]2 was not activated by a silver salt.
iBu
iPr
Entries 1 and 2 show again the results obtained with a cata-
lyst activated by silver tosylate and silver perchlorate, respec-
tively, which were the best results so far. With silver hepta-
fluorobutyrate the reaction outcome was similar (Table 4, En-
try 3). Other sulfonates, such as mesylate or triflate, did not
offer any advantages (Table 4, Entries 4 and 5). Surprisingly,
with weakly-/non-coordinating anions, the results strongly de-
pended on the anion used (Table 4, Entries 2 and 5–8).
Even more surprising was the observation that catalyst acti-
vation is not necessary for the title reaction. For other reaction
types, which we had previously reported with chloride-bridged
bis-pallada- or mixed pallada-/platinacycles, almost no catalytic
activity was noticed. The present reaction is thus the first
example in which non-activated bimetallic catalysts compete
well and provided the best combination of product yield and
enantioselectivity (Table 4, Entry 9).[19] The operational simplic-
ity is substantially improved without the need for activation by
a silver salt.
[a] Yield of isolated products after column chromatography. [b] Determined
by HPLC if not indicated otherwise. [c] Determined by GC.
Entry 5). This is supported by the fact that allylation products
were also obtained in the absence of allylic acetate 2 with 1a-
Allyl.
Also for the reaction with allylic acetate 2d equipped with
R2 = n-pentyl a number of different ester groups on cyano-
acetates 1-R were examined (Table 5, Entries 6–10). As a general
trend the reactivity decreased with increasing steric demand of
the ester moiety. Substrates equipped with methyl, benzyl, and
n-butyl ester groups formed the product in good yield (Table 5,
Entries 6–8). A tert-butyl ester moiety resulted in a lower prod-
uct yield (Table 5, Entry 10). In general, the enantioselectivity is
not much influenced by the ester type employed.[20]
In addition, the α-phenyl substituent was formally replaced
by alternative aryl residues (Table 5, Entries 11–15). With a 4-
Br-phenyl substituent on the α-cyanoacetate both yield and en-
antioselectivity decreased relative to when a phenyl residue
was used (Table 5, Entries 6 and 11). With a 3-F-phenyl group
the reactivity was slightly enhanced, but enantioselectivity was
negatively affected (Table 5, Entry 12). In contrast, with 3-MeO-
phenyl and 2-naphthyl residues similar enantioselectivities were
found (Table 5, Entries 13 and 14) as with phenyl. The best
enantioselectivity in this series was noticed for 3-Me-phenyl-
substituted α-cyanoacetate (Table 5, Entry 15).
Investigation of Substrate Scope and Limitations
The optimized conditions with the non-activated catalyst were
then utilized to investigate different combinations of α-cyano-
acetates and allylic acetates as reaction partners (Table 5). The
reaction conditions optimized for oct-1-en-3-yl acetate (2d)
were also applied to the parent allyl acetate (Table 5, Entries 1–
5).
Unfortunately, insufficient reactivity was found for α-alkyl-
substituted α-cyanoacetates (not shown). This lack of reactivity
might be ascribed to a less efficient enolization of the pro-
nucleophile in the absence of an acidifying α-aryl substituent
because almost no conversion was noticed in these cases.
In addition, the influence of various alkyl residues R2 at the
The ester residues of the α-cyanoacetate were varied and –
with the exception of the allyl ester – good to very high product
yields were obtained. The best result in terms of reactivity and
enantioselectivity was obtained with the n-butyl ester moiety
(Table 5, Entry 3). The moderate yield with the allyl ester is not
surprising because the allyl ester moiety is likely to compete
with the allyl acetate substrate as allyl transfer reagent (Table 5, allylic position of 2 was investigated (Table 5, Entries 16–19).
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With the linear n-propyl substituent the data were slightly bet- 3ad-Me in improved yield although in almost racemic form
ter (Table 5, Entry 16) relative to the n-pentyl substituent (Table 6, Entries 2 and 5), whereas the corresponding mixed
(Table 5, Entry 6). Branching within R2 either at the α- or ꢀ- pallada-/platinacycles formed the product with moderate but
position is not well tolerated though, as the reactivity strongly significant ee values (Table 6, Entries 1 and 4). A different out-
decreased (Table 5, Entries 17–19).
come was found for both non-activated catalysts. Although
heterobimetallic [FBIPP-Cl]2 formed 3ad-Me in good yield and
with improved enantioselectivity (Table 6, Entry 8), the use of
homobimetallic [FBIP-Cl]2 gave the product with low ee and in
poor yield (Table 6, Entry 9). In addition, monometallacycles
showed inferior performance relative to heterobimetallic
[FBIPP-Cl]2.[21] Monoplatinacycle 10 provided 3ad-Me in poor
Moreover, aryl substituents R2 were not well accommodated
and the corresponding substrates resulted in poor yields (0–
21 %) and low enantioselectivity (e.g. for Ph: ≈ 30 % ee). Our
catalyst thus seems to be complementary to the catalyst system
reported by Trost, for which aryl-substituted allylic substrates
were preferred, whereas the use of alkyl substituents was not
reported.[9]
yield as a racemate (Table 6, Entry 3), and monopalladacycle
[22]
[FIP-Cl]2
showed good reactivity but enantioselectivity was
poor (Table 6, Entry 7). Obviously, only the heterobimetallic PdII/
PtII combination was capable of generating allylated product
3ad-Me with ee values higher than 10 %. Although the enantio-
selectivity is not particularly high yet for this latter catalyst, the
significantly better enantioselectivity might point to coopera-
tion between both metal centers. Unfortunately, attempts to
prepare the corresponding ferrocene-based bisplatinacycle for
analysis were unsuccessful.
Mechanistic Considerations
(a) Investigation of Different Catalyst Types
As already shown (Table 1, Entry 5), it was found that ferrocene
bisimidazoline bis-palladacycle [FBIP-Cl]2 activated by silver
heptafluorobutyrate generated the allylation product in good
yield, yet as a racemate from parent allyl acetate 2a. Similar
results were also obtained during control reactions with oct-1-
en-3-yl acetate (2d) as a branched allylic substrate (Table 6).
Activation of [FBIP-Cl]2 by either a sterically very demanding
silver sulfonate salt or by silver perchlorate provided product
(b) Kinetic Monitoring of the Reaction Progress
The reaction progress of the allylation of 1a-Me by 2d catalyzed
by the mixed pallada-/platinacycle activated by AgOTs was ana-
lyzed over 48 h at 70 °C (Figure 1). For that purpose, small
samples were taken from the reaction mixture and filtered
through silica gel (petroleum ether/ethyl acetate, 10:1) to re-
Table 6. Investigation of different catalysts.
Entry
Precatalyst
X
Y
Yield
[%][a]
ee
[%][b]
1
2
3
[FBIPP-Cl]2
[FBIP-Cl]2
10
[FBIPP-Cl]2
[FBIP-Cl]2
[FBIPP-Cl]2
[FIP-Cl]2
O3S-2,4,6-Me3-C6H2
O3S-2,4,6-Me3-C6H2
O3S-2,4,6-Me3-C6H2
ClO4
ClO4
OTs
20
20
10
20
20
20
10
0
50
68
10
54
69
66
70
70
16
43
1
1
36
5
54
9
4[c]
5[c]
6
7
8
9
OTs
[d]
[FBIPP-Cl]2
[FBIP-Cl]2
–
61
17
[d]
–
0
[a] Determined by 1H NMR spectroscopy with an internal standard. [b] Deter-
mined by HPLC. [c] NaOAc (1 equiv.) was used. [d] No silver salt was used for
catalyst activation.
Figure 1. Progress of the allylation reaction: time dependence of conversion
and ee.
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move the dark red colored catalyst, which adhered to the top ther complicated by the isomerization reaction of the branched
of the filter. After solvent removal the filtrates were analyzed by allylic acetate (shown in Scheme 1), which provides the (S)-en-
1H NMR spectroscopy and chiral stationary phase HPLC.
After nearly linear product increase up to about 30 % conver-
sion within the first two hours, the rate of reaction started to
show a dependence on the decreasing substrate amount. After
antiomer in slight excess (ee = 4 %). These data suggest that
the (S)-enantiomer underwent the AAA reaction slightly more
rapidly than the (R)-enantiomer.
This effect is supported by the investigation of enantiopure
one day, conversion was not complete (84 %) and reached 91 % allylic acetate substrates 2d. Whereas with racemic substrate 2d
after 48 hours. During the first two hours of the reaction the (2 equiv.) product 3ad-Me was isolated in 56 % yield and with
enantioselectivity was a bit lower than at the end of the reac- 61 % ee (Table 5, Entry 6), the use of enantiopure (S)-2d fur-
tion. The final ee value is nearly reached after a reaction time nished 3ad-Me in 62 % yield and with 73 % ee. In contrast, (R)-
of 6 hours.
2d furnished 3ad-Me in a yield of 48 % and with just 31 % ee.
The time dependence of the enantioselectivity might indi-
The optimized reaction conditions utilized for the experi-
cate that more than one mechanism is operative. For example, ments presented in Table 5 were also applied to linear allylic
competition between the mono- and bimetallic pathways can substrate 2f (structural formula depicted in Scheme 1). The
be envisaged. Both of these mechanisms should have different product was formed in a poor 9 % yield and with an ee of 37 %.
kinetic rate laws that result in different concentration depend- As already shown in Scheme 1, 2f is also partly and slowly
encies of both mechanisms. A competing monometallic mecha- rearranged into branched allylic substrate 2d (which finally
nism is likely because the monopalladacycle [FIP-Cl]2 was also should undergo the allylation reaction) by the heterobimetallic
capable of forming the allylation product in good yields catalyst FBIPP that favors formation of the (R)-configured enan-
(Table 6, Entry 7).
tiomer of 2d. Because (R)-2d provided 3ad-Me with lower enan-
tioselectivity, this can at least partly explain why linear sub-
strates react less enantioselectively than branched substrates.
(c) Study of a Control Pronucleophile
To study if just the activation of the allyl acetate (which is other-
wise a poor electrophile) by the catalyst is necessary for the
reaction to proceed, a control experiment was performed. In
this control reaction the α-cyanoacetate was replaced by ꢀ-keto
ester 11, which, for comparability, was also equipped with a
phenyl substituent at the α-position. The enolization tendency
should be inherently larger for ꢀ-keto esters relative to α-cyano-
acetate pronucleophiles.[23] If enolization of the α-cyanoacetate
is not triggered by the catalyst, an allylation reaction of ꢀ-keto
ester 11 could thus also be expected. However, under opti-
mized conditions with 11 no allylation product 12 was found
(Scheme 2). Coordination of the hard Lewis basic functionalities
of 11 to the soft Lewis acidic catalyst centers is probably not
favorable enough under the reaction conditions. The most likely
mechanistic scenario should thus involve a catalyst species in
which the cyano moiety of the substrate is coordinated to a
metal center to induce enolization in the catalyst sphere.
(e) Possible Mechanistic Scenario
A possible explanation for a preferred reaction of the (S)-config-
ured allylic acetate could, for instance, involve chelate-type co-
ordination of the allylic acetate, in which the olefin moiety
adopts (in close analogy to the mechanistic models of other
reported activations of olefin substrates by metallocene imid-
azoline pallada-/platinacycle catalysts)[7a,10–13] a position trans
to the imidazoline donor. In such a coordination mode the bulk
of the substrate would be expected to point away from the
ferrocene core to minimize steric repulsion. In that case, for the
(S)-enantiomer of allylic acetate 2d residue R2 could adopt a
pseudo-equatorial position (Scheme 3), whereas for (R)-2d, it
would be pseudo-axially oriented (not shown). Different prod-
uct enantiomers could then be the consequence of different
reactive conformations of the coordinated cyanoacetate
(Scheme 3).
Scheme 2. Control experiment with ꢀ-keto ester substrate 11.
(d) Analysis of the Remaining Allylic Acetate and Use of
Enantiopure Allylic Acetates
For useful yields an excess of the racemic allylic acetate was
usually employed (2 equiv.). The reaction in Table 4, Entry 1 was
repeated with only one equivalent of allylic acetate 2d to ana-
lyze the enantiomer composition of the remaining starting ma-
Scheme 3. Working model.
Because the heterobimetallic FBIPP-catalyst is clearly supe-
terial. It was found that unreacted 2d (yield: 44 % as deter- rior to the mono-palladacycle and -platinacycle catalysts
1
mined by H NMR spectroscopic analysis of the crude product (Table 6), and because the control experiment shown in
with an internal standard) was somewhat enriched with the (R)- Scheme 2 indicates that the cyanoacetate is also activated by
enantiomer (ee = 26 %, determined by GC). The situation is fur- the catalyst, an intramolecular bimetallic mechanism appears
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215
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reasonable.[24,25] In addition, it seems likely that the corre-
sponding enolate of the cyanoacetate undergoes C–C bond for-
mation, because no reaction was observed in the absence of
base. However, the moderate enantioselectivity suggests that
the reactive conformation of the cyanoacetate might not be
tightly controlled, thus allowing pathways via the Si- and Re-
enolate faces, with the former being favored. It is also likely
that monometallic pathways do compete with such a bimetallic
pathway, because the monopalladacycle also provided large
rial. For thin layer chromatography (TLC), silica-gel plates from
Merck (silica gel 60 F254) were used. Visualization occurred by
fluorescence quenching under UV light and/or by staining with
KMnO4/NaOH followed by heating (230 °C). Purification by flash-
chromatography was performed with silica gel 0.040–0.063 mm
provided by Merck with a forced flow of eluent at 0.2–0.4 bar pres-
sure. NMR spectra were recorded at 21 °C with spectrometers that
operated at 500, 300, or 250 MHz for 1H nuclei; at 125, 75, or 63 MHz
for 13C nuclei; and at 235 MHz for 19F nuclei. Deuterated solvents
were used as received. Abbreviations for multiplicities are as follows:
product amounts, yet in nearly racemic form. The observation s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br.
(broad signal). IR spectra were recorded by the IR service of the
University of Stuttgart, Germany, with a spectrometer with an ATR
unit. The aggregation state of the sample is stated in parentheses.
Optical rotation was measured with a polarimeter that operates at
the sodium D line with a 100 mm path cell length. Melting points
were measured in open glass capillaries. Mass spectra were ob-
tained from the MS service of the University of Stuttgart, Germany.
The ionization method is stated in parentheses. Enantiomeric ex-
cesses (ee values) were determined by high performance liquid
chromatography (HPLC) or gas chromatography (GC). GC spectra
were recorded by the GC service of the University of Stuttgart, Ger-
many. The applied method is given in the description of the respec-
tive product.
that the bis-palladacycles are much less enantioselective could
mean that in that case a monometallic pathway might be pre-
ferred.
Conclusions
We have reported a study of a heterobimetallic PtII/PdII catalyst
in the enantio-, diastereo- and regioselective allylation reaction
of α-cyanoacetate pronucleophiles. In this planar chiral ferro-
cene-based system palladacycle and platinacycle moieties are
likely to cooperate in the activation of both substrates as con-
trol experiments suggest. Even though enantioselectivities are
moderate, they are significantly higher relative to the corre-
sponding bis-palladacycle. This stresses a special role of plati-
num(II) in this process, which is not understood yet. Although
platinum is often regarded as a slower analogue of palladium,
our studies indicate that by cooperation with a second metal
in a heterobimetallic system platinum instead of palladium has
a positive impact on the reaction outcome.[13] These insights
might also be useful for catalyst design in other reactions trig-
gered by soft bimetallic catalysts.
General Procedures (GPs)
General Procedure for the Synthesis of α-Cyanoacetates
(GP1):[10a] nBuLi (1.6
M in hexane, 2.30 equiv.) was added to a solu-
tion of diisopropylamine (2.35 equiv.) in tetrahydrofuran (THF;
2.3 mL/mmol nitrile) at –78 °C. The reaction mixture was warmed
to room temperature, stirred for 5 min and cooled to –78 °C again.
Then a solution of nitrile (1.00 equiv.) in THF (0.9 mL/mmol nitrile)
was added dropwise. The reaction mixture was warmed to room
temperature, stirred for 10 min and cooled to –78 °C again. Then a
solution of methyl chloroformate (1.05 equiv.) in THF (0.6 mL/mmol
nitrile) was added and the reaction mixture was stirred for 4.5 h at
–78 °C. The reaction was stopped by addition of saturated aqueous
ammonium chloride solution (2.5 mL/g). Following the addition of
Et2O (18.8 mL/g) and H2O (5.0 mL/g) the phases were separated.
Experimental Section
General Methods: All reactions were performed in oven-dried
(150 °C) glassware under a positive pressure of nitrogen (about
0.2 bar). Liquids and solutions were added by syringe and septa for
all reactions. For catalytic reactions, all glassware (also for catalyst
activation and preparation of stock solutions) was washed thor-
oughly with demineralized water to remove traces of chloride. N,N-
Dimethylformamide was stored in crown-capped bottles under ar-
gon over 4 Å molecular sieves. Acetonitrile and dichloromethane
were purified by distillation and subsequently by a solvent purifica-
tion system. 2,2,2-Trifluoroethanol was dried and degassed prior to
use. n-Hexane (HPLC grade) and isopropanol (HPLC grade) were
used as received. For work-up procedures and column chromatog-
raphy technical-grade solvents (petroleum ether and ethyl acetate)
were purified by distillation prior to use. Solvents were mostly re-
moved at a heating bath temperature of 40 °C and 600–10 mbar
pressure by rotary evaporation. Non-volatile compounds were dried
The organic phase was washed with HCl (1
M; 3 × 7.5 mL/g), H2O
(7.5 mL/g), and saturated aqueous NaCl solution (7.5 mL/g), and
dried with Na2SO4. After the removal of the solvent the crude prod-
uct was purified by distillation or column chromatography.
General Procedure for the Synthesis of Racemic Addition Pro-
ducts (GP2). Option A: Sodium hydride (55 % in mineral oil,
1.10 equiv.) was suspended in THF (2 mL/mmol α-cyanoacetate)
and cooled to 0 °C. Now a solution of corresponding α-cyanoacet-
ate (1.00 equiv.) in THF (2 mL/mmol α-cyanoacetate) was added.
The reaction mixture was warmed to room temperature and stirred
for 30 min. Then allyl bromide (3.00 equiv.) was added dropwise
and the reaction mixture was stirred for another 3 h at room tem-
perature. Subsequently, H2O was added. The phases were separated
and the aqueous phase was extracted with diethyl ether
(3 × 8.0 mL/mmol α-cyanoacetate). The combined organic phases
were washed with HCl (1 M), H2O, and saturated aqueous NaCl solu-
[13]
in vacuo at 0.1 mbar. [FBIP-Cl]2[16] and [FBIPP-Cl]2 were prepared
tion, dried with MgSO4, and the solvent was removed under re-
duced pressure. Column chromatography (silica gel, petroleum
ether/ethyl acetate, 10:1) gave the product as a colorless liquid. The
reaction conditions were not optimized.
Option B:[26] (E)-2-Octen-1-ol (3.00 equiv.) was dissolved in THF
[0.8 mL/mmol (E)-2-octen-1-ol] and cooled to –78 °C. Next, nBuLi
in accordance with literature procedures. Benzyl 2-cyano-2-phenyl-
acetate (1a-Bn), butyl 2-cyano-2-phenylacetate (1a-nBu), isobutyl 2-
cyano-2-phenylacetate (1a-iBu), and tert-butyl 2-cyano-2-phenyl-
acetate (1a-tBu) were prepared in accordance with literature[10a]
procedures. All other laboratory chemicals were purchased from
commercial suppliers and were used without purification unless
otherwise indicated, yields refer to chromatographically purified (1.6
compounds and are calculated in mol-% of the used starting mate-
M in n-hexane, 3.15 equiv.) was added and the reaction mixture
was stirred for 2 min at –78 °C. Then methanesulfonyl chloride
216 © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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(3.30 equiv.) and LiBr (9.00 equiv.) were added successively. The
reaction mixture was warmed to 0 °C, stirred for 1 h at this tempera-
ture, and subsequently transferred to a solution of corresponding
sodium salt [from the corresponding α-cyanoacetate (1.00 equiv.)
and sodium hydride (55 % in mineral oil, 1.01 equiv.)] in THF
[C(O)OCH2CH=CH2]}, 4.69–4.62 (m, 2 H, CH2CH=CH2) ppm. 13C NMR
(75 MHz, CDCl3): δ = 164.7, 130.6, 129.9, 129.34, 129.25, 127.9, 119.4,
115.6, 67.3, 43.6 ppm. IR (in CDCl3): ν = 3034, 2947, 2254, 1743,
˜
1649, 1600, 1496, 1455, 1424, 1363, 1307, 1230, 1194, 1154, 1079,
1020, 983, 939, 842, 732, 696, 617, 555 cm–1. MS (ESI): m/z (%) =
(2.4 mL/mmol α-cyanoacetate) in THF. The resulting reaction mix- 224.07 (100 %) [M + Na]+. HRMS (ESI): m/z calcd. for C12H11NNaO2
ture was stirred for 3 h at room temperature. Subsequently, H2O
was added. The phases were separated and the aqueous phase was
extracted with diethyl ether (3 × 2.0 mL/mmol α-cyanoacetate). The
[M + Na]+ 224.0682; found 224.0678.
Methyl 2-(4-Bromophenyl)-2-cyanoacetate (1b-Me): In accord-
ance with GP1 (4-bromophenyl)acetonitrile (500.0 mg, 2.55 mmol,
1.00 equiv.) was treated with methyl chloroformate (207.4 μL,
253.1 mg, 2.68 mmol, 1.05 equiv.). Column chromatography (silica
gel, petroleum ether/ethyl acetate = 5:1) afforded the product as a
pale yellow liquid (565.5 mg, 2.23 mmol, 87 %). C10H8BrNO2, MW:
254.08 g/mol. 1H NMR (300 MHz, CDCl3): δ = 7.60–7.53 [m, 2 H,
phenyl C(3/5)H], 7.37–7.31 [m, 2 H, phenyl C(2/6)H], 4.70 {s, 1 H, Ar-
CH(CN)[C(O)OCH3]}, 3.81 [s, 3 H, C(O)OCH3] ppm. The analytical data
obtained agree with that reported in the literature.[28]
combined organic phases were washed with HCl (1
M), H2O, and
saturated aqueous NaCl solution, dried with MgSO4, and the solvent
was removed under reduced pressure. Column chromatography (sil-
ica gel, petroleum ether/ethyl acetate, 20:1) gave the product as a
colorless liquid. The reaction conditions were not optimized.
Option C:[27] [Pd(allyl)Cl]2 (0.5 mol-%) and triphenylphosphine
(2.2 mol-%) were dissolved in THF (1 mL/mmol α-cyanoacetate) and
stirred for 15 min at room temperature. The solution was then trans-
ferred to a mixture of α-cyanoacetate (1.00 equiv.), sodium acetate
(0.03 equiv.), N,O-bis(trimethylsilyl)acetamide (1.00 equiv.), and the
corresponding allylic acetate (1.00 equiv.). The resulting reaction
mixture was stirred for 14 h at room temperature, before being
suspended in petroleum ether/ethyl acetate (10:1) and filtered (sil-
ica gel). Column chromatography (silica gel, petroleum ether/ethyl
acetate, 20:1) gave the product as a colorless liquid. The reaction
conditions were not optimized.
Methyl 2-Cyano-2-(3-fluorophenyl)acetate (1c-Me): In accord-
ance with GP1 (3-fluorophenyl)acetonitrile (500.0 mg, 3.70 mmol,
1.00 equiv.) was treated with methyl chloroformate (300.9 μL,
367.1 mg, 3.89 mmol, 1.05 equiv.). Column chromatography (silica
gel, petroleum ether/ethyl acetate = 10:1) afforded the product as
a pale yellow liquid (649.9 mg, 3.36 mmol, 91 %). C10H8FNO2, MW:
193.18 g/mol. 1H NMR (500 MHz, CD2Cl2): δ = 7.46–7.40 [m, 1 H,
phenyl C(5)H], 7.29–7.25 [m, 1 H, phenyl C(6)H], 7.23–7.18 [m, 1 H,
phenyl C(2)H], 7.16–7.11 [m, 1 H, phenyl C(4)H], 4.82 {s, 1 H, Ar-
CH(CN)[C(O)OCH3]}, 3.80 [s, 3 H, C(O)OCH3] ppm. 13C NMR (125 MHz,
CD2Cl2): δ = 165.5, 163.3, 132.6, 131.4, 124.3, 116.7, 115.7, 115.6,
54.6, 43.5 ppm. 19F NMR (235 MHz, CDCl3): δ = –110.77 ppm. IR
General Procedure for the Catalytic Asymmetric Synthesis of
Addition Products (GP3): A solution of catalyst [FBIPP-Cl]2 (5 mol-
%) in 2,2,2-trifluoroethanol (c = 10 mmol/L) was added to a mixture
of α-cyanoacetate (1.00 equiv.), allylic acetate (2.00 equiv.), and so-
dium acetate (0.20 equiv.) under a N2 atmosphere. The reaction
vessel was sealed and the reaction mixture was stirred for 24 h at
the indicated temperature. The reaction mixture was subsequently
suspended in petroleum ether/ethyl acetate (10:1) and purified by
filtration (silica gel).
(in CDCl ): ν = 1747, 1615, 15994, 1489, 1450, 1436, 1319, 1225,
˜
3
1165, 1138, 1007, 923, 874, 783, 749, 684, 522 cm–1. MS (ESI): m/z
(%) = 192.05 (100 %) [M – H]–, 133.03 (77 %) [M – C2H3O2 – H]–.
HRMS (ESI): m/z calcd. for C12H7FNO2 [M – H]– 192.0466; found
192.0467.
General Procedure for the Activation of Catalyst (GP4): For cata-
lyst activation [FBIPP-Cl]2 (5 mol-%) and the corresponding silver
salt (20 mol-%) were dissolved in acetonitrile (1 mL/8 mg [FBIPP-
Cl]2). The mixture was stirred at room temperature overnight and
then filtered through a short pad of Celite, which was washed with
acetonitrile. The solvent was removed by a steady flow of nitrogen,
followed by high vacuum and a catalyst stem solution in 2,2,2-tri-
fluoroethanol was then prepared (c = 10 mmol/L based on [FBIPP-
Cl]2).
Methyl 2-Cyano-2-(3-methoxyphenyl)acetate (1d-Me): In accord-
ance with GP1 (3-methoxyphenyl)acetonitrile (500.0 mg, 3.40 mmol,
1.00 equiv.) was treated with methyl chloroformate (276.3 μL,
337.1 mg, 3.57 mmol, 1.05 equiv.). Column chromatography (silica
gel, petroleum ether/ethyl acetate = 5:1) afforded the product as a
pale yellow liquid (392.4 mg, 1.91 mmol, 56 %). C11H11NO3, MW:
205.21 g/mol. 1H NMR (300 MHz, CDCl3): δ = 7.36–7.28 [m, 1 H,
phenyl C(5)H], 7.06–7.00 [m, 1 H, phenyl C(6)H], 7.00–6.95 [m, 1 H,
phenyl C(2)H], 6.95–6.88 [m, 1 H, phenyl C(4)H], 4.71 {s, 1 H, Ar-
CH(CN)[C(O)OCH3]}, 3.81 (s,
3 H, Ar-OCH3), 3.79 [s, 3 H,
Synthesis of α-Cyanoacetates
C(O)OCH3] ppm. The analytical data obtained agree with that re-
Methyl 2-Cyano-2-phenylacetate (1a-Me): In accordance with
GP1 2-phenylacetonitrile (500.0 mg, 4.27 mmol, 1.00 equiv.) was
treated with methyl chloroformate (377.8 μL, 423.5 mg, 4.48 mmol,
1.05 equiv.). Distillation (143 °C, 13 mbar) afforded the product as
a colorless liquid (484.7 mg, 2.77 mmol, 65 %). C10H9NO2, MW:
175.19 g/mol. 1H NMR (300 MHz, CDCl3): δ = 7.51–7.36 (m, 5 H,
phenyl CH), 4.75 {s, 1 H, Ph-CH(CN)[C(O)OCH3]}, 3.80 [s, 3 H,
C(O)OCH3] ppm. The analytical data obtained agree with that re-
ported in the literature.[10a]
ported in the literature.[28]
Methyl 2-Cyano-2-(2-naphthalen-2-yl)acetate (1e-Me): In accord-
ance with GP1 2-naphthylacetonitrile (500.0 mg, 2.99 mmol,
1.00 equiv.) was treated with methyl chloroformate (243.2 μL,
296.7 mg, 3.14 mmol, 1.05 equiv.). The light yellow solid (524.6 mg,
2.33 mmol, 78 %) was obtained after recrystallization from ethyl
acetate/ petroleum ether. C14H11NO2, MW: 225.25 g/mol. 1H NMR
(300 MHz, CDCl3): δ = 7.99–7.94 [m, 1 H, naphthyl C(8)H], 7.94–7.82
[m, 3 H, naphthyl C(1/4/5)H], 7.59–7.49 [m, 3 H, naphthyl C(3/6/7)H],
4.91 {s, 1 H, Ar-CH(CN)[C(O)OCH3]}, 3.81 [s, 3 H, C(O)OCH3] ppm. The
analytical data obtained agree with that reported in the litera-
ture.[28]
Allyl 2-Cyano-2-phenylacetate (1a-Allyl): In accordance with GP1
2-phenylacetonitrile (2.0 g, 17.07 mmol, 1.00 equiv.) was treated
with allyl chloroformate (1.9 mL, 2.2 g, 17.93 mmol, 1.05 equiv.).
Column chromatography (silica gel, petroleum ether/ethyl acetate =
10:1) afforded the product as a colorless liquid (1.4 g, 7.14 mmol, Methyl 2-Cyano-2-(2-m-tolyl)acetate (1f-Me): In accordance with
42 %). C12H11NO2, MW: 201.23 g/mol. 1H NMR (300 MHz, CDCl3): δ = GP1 m-tolylacetonitrile (500.0 mg, 3.81 mmol, 1.00 equiv.) was
7.51–7.35 (m, 5 H, phenyl CH), 5.93–5.77 (m, 1 H, CH2-CH=CH2),
5.33–5.20 (m, H, CH2-CH=CH2), 4.78 {s, H, Ph-CH(CN)-
treated with methyl chloroformate (310.0 μL, 378.2 mg, 4.00 mmol,
1.05 equiv.). Column chromatography (silica gel, petroleum ether/
2
1
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ethyl acetate = 7:1) afforded the product as a pale yellow liquid 2.40 mmol, 47 %). C9H18O, MW: 142.24 g/mol. 1H NMR (300 MHz,
(438.4 mg, 2.32 mmol, 61 %). C11H11NO2, MW: 189.21 g/mol. 1H
NMR (300 MHz, CDCl3): δ = 7.35–7.19 (m, 5 H, phenyl CH), 4.74 {s,
1 H, Ar-CH(CN)[C(O)OCH3]}, 3.78 [s, 3 H, C(O)OCH3], 2.38 (s, 3 H, Ar-
CH3) ppm. The analytical data obtained agree with that reported in
the literature.[28]
CDCl3): δ = 5.70–5.56 (m, 1 H, olefinic H), 5.52–5.39 (m, 1 H, olefinic
H), 4.12–4.00 (m, 1 H, CHOH), 2.07–1.94 (m, 2 H, CH=CH-CH2), 1.63–
1.24 (m, 6 H, CH3-CH2-CH2-CHOH, CH=CH-CH2-CH2-CH3), 0.98–0.83
(m, 6 H, 2 × CH3) ppm. (E)-Non-5-en-4-ol (341.4 mg, 2.40 mmol,
1.00 equiv.) and acetic anhydride (11.3 mL, 12.3 g, 120.01 mmol,
50.00 equiv.) were dissolved in pyridine (45.6 mL) and stirred for
3 h at room temperature. Then methanol (22.7 mL) was added. The
reaction mixture was stirred for 1 h at room temperature before
H2O (45.4 mL) was added. The reaction mixture was extracted with
diethyl ether (3 ×). The combined organic phases were washed with
Synthesis of the Allylic Substrates
(Z)-Hex-2-en-1-yl Acetate [(Z)-2b]:[29] (Z)-Hex-2-en-1-ol (200.0 mg,
2.00 mmol, 1.00 equiv.) and acetic anhydride (9.4 mL, 10.2 g,
99.84 mmol, 50.00 equiv.) were dissolved in pyridine (37.8 mL) and
stirred for 3 h at room temperature. Next, methanol (18.9 mL) was
added. The reaction mixture was stirred for 1 h at room temperature
before H2O (37.8 mL) was added. The reaction mixture was ex-
tracted with diethyl ether (3 ×). The combined organic phases were
HCl (1
M) and H2O. The organic phase was dried with MgSO4 and
the solvent was removed under reduced pressure. Column chroma-
tography (silica gel, petroleum ether/ethyl acetate = 20:1) afforded
the product as a colorless liquid (365.8 mg, 1.99 mmol, 83 %).
1
washed with HCl (1 M) and H2O. The organic phase was dried with
C
11H20O2, MW: 184.28 g/mol. H NMR (300 MHz, CDCl3): δ = 5.74–
MgSO4 and the solvent was removed under reduced pressure. Col-
umn chromatography (silica gel, petroleum ether/ethyl acetate =
20:1) afforded the product as a colorless liquid (281.1 mg,
2.00 mmol, 99 %). C8H14O2, MW: 142.20 g/mol. 1H NMR (300 MHz,
CDCl3): δ = 5.71–5.49 (m, 2 H, AcOCH2-CH=CH-CH2), 4.66–4.59 (m,
2 H, AcOCH2-CH=CH-CH2), 2.13–2.03 [m, 5 H, OC(O)CH3, CH=CH-
CH2], 1.48–1.33 (m, 2 H, CH2-CH2-CH3), 0.91 (t, J = 7.3 Hz, 3 H, CH2-
CH3) ppm. The analytical data obtained agree with that reported in
the literature.[30]
5.64 (m, 1 H, olefinic H), 5.42–5.32 (m, 1 H, olefinic H), 5.25–5.15 (m,
1 H, CHOAc), 2.06–1.95 [m, 5 H, OC(O)CH3, CH=CH-CH2], 1.69–1.23
(m, 6 H, CH3-CH2-CH2-CHOH, CH=CH-CH2-CH2-CH3), 0.97–0.83 (m, 6
H, 2 × CH2-CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 170.6, 134.3,
128.7, 75.0, 36.8, 34.4, 22.3, 21.6, 18.6, 14.0, 13.8 ppm. IR (in CDCl3):
ν = 2959, 2932, 2874, 1736, 1459, 1371, 1236, 1135, 1087, 1018, 968,
˜
943, 828, 744, 610, 516 cm–1. MS (ESI): m/z (%) = 207.14 (100 %)
[M + Na]+, 193.08 (100 %) [M – CH2 + Na]+. HRMS (ESI): m/z calcd.
for C11H20NaO2 [M + Na]+ 207.1356; found 207.1353.
Hex-1-en-3-yl Acetate (2c):[29] Hex-1-en-3-ol (239.8 μL, 200.0 mg,
2.00 mmol, 1.00 equiv.) and acetic anhydride (9.4 mL, 10.2 g,
99.84 mmol, 50.00 equiv.) were dissolved in pyridine (37.8 mL) and
stirred for 3 h at room temperature. Next, methanol (18.9 mL) was
added. The reaction mixture was stirred for 1 h at room temperature
before H2O (37.8 mL) was added. The reaction mixture was ex-
tracted with diethyl ether (3 ×). The combined organic phases were
(E)-Oct-2-en-1-yl Acetate (2f):[29] (E)-Oct-2-en-1-ol (302.2 mg,
2.36 mmol, 1.00 equiv.) and acetic anhydride (11.1 mL, 12.0 g,
117.85 mmol, 50.00 equiv.) were dissolved in pyridine (45.0 mL) and
stirred for 3 h at room temperature. Then methanol (22.4 mL) was
added. The reaction mixture was stirred for 1 h at room temperature
before H2O (45.0 mL) was added. The reaction mixture was ex-
tracted with diethyl ether (3 ×). The combined organic phases were
washed with HCl (1 M) and H2O. The organic phase was dried with
washed with HCl (1 M) and H2O. The organic phase was dried with
MgSO4 and the solvent was removed under reduced pressure. Col-
umn chromatography (silica gel, petroleum ether/ethyl acetate =
20:1) afforded the product as a colorless liquid (168.0 mg,
1.18 mmol, 59 %). C8H14O2, MW: 142.20 g/mol. 1H NMR (300 MHz,
CDCl3): δ = 5.85–5.70 [m, 1 H, CH2=CH-CH(O)(CH2)], 5.28–5.12 [m, 3
H, CH2=CH-CH(O)(CH2)], 2.06 [s, 3 H, OC(O)CH3], 1.71–1.48 [m, 2 H,
(CH)CH(O)-CH2-CH2-CH3], 1.42–1.27 [m, 2 H, (CH)CH(O)-CH2-CH2-
CH3], 0.92 (t, J = 7.2 Hz, 3 H, CH2-CH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 170.5, 136.8, 116.6, 74.8, 36.4, 21.4, 18.5, 14.0 ppm. IR
MgSO4 and the solvent was removed under reduced pressure. Col-
umn chromatography (silica gel, petroleum ether/ethyl acetate =
20:1) afforded the product as a colorless liquid (297.3 mg,
1
1.75 mmol, 74 %). C10H18O2, MW: 170.25 g/mol. H NMR (300 MHz,
CDCl3): δ = 5.83–5.71 (m, 1 H, AcOCH2-CH=CH-CH2), 5.62–5.49 (m,
1 H, AcOCH2-CH=CH-CH2), 4.54–4.47 (m, 2 H, AcOCH2-CH=CH-CH2),
2.12–1.98 [m, 5 H, OC(O)CH3, CH=CH-CH2], 1.45–1.20 [m, 6 H, CH2-
(CH2)3-CH3], 0.89 (t, J = 6.9 Hz, 3 H, CH2-CH3) ppm. The analytical
data obtained agree with that reported in the literature.[30]
(in CDCl3): ν = 2961, 2937, 2875, 1737, 1648, 1466, 1425, 1371, 1234,
˜
1119, 1088, 1019, 989, 968, 922, 828, 734, 609 cm–1. MS (EI): m/z
1-Cyclohexylallyl Acetate (2g):[31] Cyclohexanal (216.0 μL,
200.0 mg, 1.78 mmol, 1 equiv.) was added dropwise to a THF solu-
tion of vinylmagnesium bromide (3.0 mL, 1M, 397.9 mg, 3.03 mmol,
(%) = 142.1 (1 %) [M]+, 100.1 (35 %) [M – C2H3O]+, 43.0 (100 %)
[C2H3O]+. HRMS (EI): m/z calcd. for C8H14O2 [M]+ 142.0994; found
142.1005.
1.70 equiv.) at 0 °C. The reaction mixture was stirred for 3 h at room
temperature, quenched with water (1.0 mL), and diluted with Et2O
(4.6 mL). The mixture was washed with HCl (10 %) and saturated
aqueous K2CO3 solution. After drying with MgSO4 and decantation,
4-(dimethylamino)pyridine (DMAP; 261.4 mg, 2.14 mmol, 1.2 equiv.)
was added, followed by the dropwise addition of acetic anhydride
(202.3 μL, 218.4 mg, 2.14 mmol, 1.2 equiv.). The reaction mixture
was stirred for 4 h and then washed with H2O, HCl (10 %), and
saturated aqueous NaHCO3 solution. The organic phase was dried
with Na2SO4 and the solvent was removed under reduced pressure.
Column chromatography (silica gel, petroleum ether/ethyl acetate =
20:1) afforded the product as a colorless liquid (145.6 mg,
[29]
(E)-Non-5-en-4-yl Acetate (2e):
Freshly ground magnesium
(154.9 mg, 6.37 mmol, 1.25 equiv.) was suspended in diethyl ether
(1.0 mL). To this suspension, 1-bromopropane (578.5 μL, 6.37 mmol,
1.25 equiv.) was added in portions. The reaction mixture was stirred
until the magnesium dissolved completely. Next, (E)-hex-2-enal
(500 mg, 5.09 mmol, 1.00 equiv.) was added dropwise. The reaction
mixture was warmed to 40 °C and stirred for 2 h. After cooling
to room temperature ice (637 mg) was added. Saturated aqueous
ammonium chloride solution was added until the precipitate dis-
solved completely. The phases were separated and the aqueous
phase was extracted twice with diethyl ether. The combined or-
ganic phases were washed with saturated aqueous NaHSO4 solu-
tion, saturated aqueous NaHCO3 solution, and water, dried with
Na2SO4, and the solvent was removed under reduced pressure. Col-
umn chromatography (silica gel, petroleum ether/ethyl acetate =
10:1) afforded the product as a colorless liquid (341.4 mg,
1
0.80 mmol, 45 %). C10H18O2, MW: 182.26 g/mol. H NMR (300 MHz,
CDCl3): δ = 5.83–5.67 [m, 1 H, CH2=CH-CH(O)(CH)], 5.27–5.14 [m, 2
H, CH2=CH-CH(O)(CH)], 5.10–4.99 [m, 1 H, CH2=CH-CH(O)(CH)], 2.07
[s, 3 H, OC(O)CH3], 1.83–1.60 (m, 5 H, cyclohexyl CH2), 1.59–1.46 [m,
1 H, H2C=CH-CH(O)-CH], 1.31–0.90 (m, 5 H, cyclohexyl CH2) ppm.
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The analytical data obtained agree with that reported in the litera- 1-octen-3-ol (261.9 μL, 220.0 mg, 1.72 mmol, 1.00 equiv.) in benzene
ture.[32]
(3.4 mL) were added. The reaction mixture was stirred for 1 h at
room temperature, filtered, and the filter cake was washed with
diethyl ether (17 mL). The combined organic phases were washed
with a saturated aqueous NaHCO3 solution (10 %) and H2O, dried
with Na2SO4, and the solvent was removed under reduced pressure.
Column chromatography (silica gel, petroleum ether/ethyl acetate =
30:1) afforded the product as a colorless liquid (89.6 mg, 0.42 mmol,
5-Methylhex-1-en-3-yl Acetate (2h):[31] 3-Methylbutyraldehyde
(622.7 μL, 500.0 mg, 5.81 mmol, 1 equiv.) was added dropwise to a
THF solution of vinylmagnesium bromide (9.9 mL, 1M, 1295.4 mg,
9.87 mmol, 1.70 equiv.) at 0 °C. The reaction mixture was stirred for
2 h at room temperature, quenched with water (2.5 mL), and diluted
with Et2O (5.9 mL). The mixture was washed with HCl (10 %) and
saturated aqueous K2CO3 solution. After drying with MgSO4 and
decantation, DMAP (851.1 mg, 6.97 mmol, 1.2 equiv.) was added,
followed by the dropwise addition of acetic anhydride (658.5 μL,
711.2 mg, 6.97 mmol, 1.2 equiv.). The reaction mixture was stirred
for 4 h and then washed with H2O, HCl (10 %), and saturated aque-
ous NaHCO3 solution. The organic phase was dried with Na2SO4
and the solvent was removed under reduced pressure. Column
chromatography (silica gel, pentane/diethyl ether = 50:1) afforded
1
25 %). C13H24O2, MW: 212.33 g/mol. H NMR (300 MHz, CDCl3): δ =
5.85–5.71 [m, 1 H, CH2=CH-CH(O)(CH2)], 5.25–5.09 [m, 3 H, CH2=CH-
CH(O)(CH2)], 1.69–1.50 [m, 2 H, (CH)CH(O)-CH2-CH2], 1.40–1.24 (m, 6
H, CH2-CH2-CH2-CH2-CH3), 1.21 [s, 9 H, OC(O)C(CH3)3], 0.88 (t, J =
6.7 Hz, 3 H, CH2-CH3) ppm. The analytical data obtained agree with
that reported in the literature.[37]
Oct-1-en-3-yl Benzoate (6):[36] Benzoyl chloride (241.2 mg,
1.72 mmol, 1.00 equiv.) was dissolved in benzene (3.4 mL). To this
mixture zinc (112.2 mg, 1.72 mmol, 1.00 equiv.) and a solution of
1-octen-3-ol (261.9 μL, 220.0 mg, 1.72 mmol, 1.00 equiv.) in benzene
(3.4 mL) were added. The reaction mixture was stirred for 1 h at
room temperature, filtered, and the filter cake was washed with
diethyl ether (17 mL). The combined organic phases were washed
with a saturated aqueous NaHCO3 solution (10 %) and H2O, dried
with Na2SO4, and the solvent was removed under reduced pressure.
Column chromatography (silica gel, petroleum ether/ethyl acetate =
30:1) afforded the product as a colorless liquid (193.4 mg,
the product as a colorless liquid (281.2 mg, 1.80 mmol, 31 %).
1
C10H18O2, MW: 152.26 g/mol. H NMR (300 MHz, CDCl3): δ = 5.83–
5.69 [m, 1 H, CH2=CH-CH(O)(CH)], 5.36–5.27 [m, 1 H, CH2=CH-
CH(O)(CH)], 5.27–4.11 [m, 2 H, CH2=CH-CH(O)(CH)], 2.05 [s, 3 H,
OC(O)CH3], 1.72–1.52 [m, 2 H, CH(O)-CH2-CH(CH3)2], 1.45–1.32 [m, 1
H, (CH)CH(O)-CH2-CH(CH3)2], 0.92 [d, J = 6.4 Hz, 3 H, CH(O)-CH2-
CH(CH3)2], 0.91 [d, J = 6.4 Hz, 3 H, CH(O)-CH2-CH(CH3)2] ppm. The
analytical data obtained agree with that reported in the litera-
ture.[33]
4-Methylprop-1-en-3-yl Acetate (2i):[31] Isobutyraldehyde
(632.9 μL, 500.0 mg, 6.93 mmol, 1 equiv.) was added dropwise to a
THF solution of vinylmagnesium bromide (11.8 mL, 1M, 1547.2 mg,
11.79 mmol, 1.70 equiv.) at 0 °C. The reaction mixture was stirred
for 2 h at room temperature, quenched with water (2.5 mL) and
diluted with Et2O (5.9 mL). The mixture was washed with HCl (10 %)
and saturated aqueous K2CO3 solution. After drying with MgSO4
and decantation, DMAP (1016.5 mg, 8.32 mmol, 1.2 equiv.) was
added, followed by the dropwise addition of acetic anhydride
(786.5 μL, 849.5 mg, 8.32 mmol, 1.2 equiv.). The reaction mixture
was stirred for 4 h and then washed with H2O, HCl (10 %), and
saturated aqueous NaHCO3 solution. The organic phase was dried
with Na2SO4 and the solvent was removed under reduced pressure.
Column chromatography (silica gel, pentane/diethyl ether = 50:1)
afforded the product as a colorless liquid (255.2 mg, 1.80 mmol,
1
0.91 mmol, 53 %). C15H20O2, MW: 232.32 g/mol. H NMR (300 MHz,
CDCl3): δ = 8.11–8.03 [m, 2 H, phenyl C(2/6)H], 7.60–7.51 [m, 1 H,
phenyl C(4)H], 7.49–7.40 [m, 2 H, phenyl C(3/5)H], 6.00–5.86 [m, 1
H, CH2=CH-CH(O)(CH2)], 5.54–5.44 [m, 1 H, CH2=CH-CH(O)(CH2)],
5.38–5.15 [m, 2 H, CH2=CH-CH(O)(CH2)], 1.88–1.64 [m, 2 H, CH(O)-
CH2-CH2], 1.49–1.23 (m, 6 H, CH2-CH2-CH2-CH2-CH3), 0.89 (t, J =
6.7 Hz, 3 H, CH2-CH3) ppm. The analytical data obtained agree with
that reported in the literature.[37]
Oct-1-en-3-yl Nicotinate (7):[38] Nicotinic acid (319.2 mg,
2.59 mmol, 1.10 equiv.) was dissolved in CH2Cl2 (4.8 mL) and cooled
to 0 °C. To this solution dicyclohexylcarbodiimide (632.2 mg,
3.06 mmol, 1.30 equiv.) and DMAP (144.0 mg, 1.18 mmol,
0.50 equiv.) were added. The resulting solution was stirred for
30 min at 0 °C. Then a solution of 1-octen-3-ol (359.8 μL, 302.2 mg,
2.36 mmol, 1.00 equiv.) in CH2Cl2 (4.8 mL) was added and the reac-
tion mixture was stirred for 2 h at 0 °C. Subsequently the reaction
mixture was diluted with diethyl ether, filtered through Celite, and
the solvent was removed under reduced pressure. Column chroma-
tography (silica gel, petroleum ether/ethyl acetate = 10:1) afforded
the product as a colorless liquid (380.2 mg, 1.63 mmol, 69 %).
C14H19NO2, MW: 233.31 g/mol. 1H NMR (300 MHz, CDCl3): δ = 9.28–
1
26 %). C10H18O2, MW: 142.20 g/mol. H NMR (300 MHz, CDCl3): δ =
5.83–5.68 [m, 1 H, CH2=CH-CH(O)(CH)], 5.27–5.16 [m, 2 H, CH2=CH-
CH(O)(CH)], 5.08–5.00 [m, 1 H, CH2=CH-CH(O)(CH)], 2.07 [s, 3 H,
OC(O)CH3], 1.94–1.78 [m, 1 H, CH(O)-CH(CH3)2], 0.91 [d, J = 6.8 Hz,
3 H, CH(O)-CH(CH3)2], 0.90 [d, J = 6.8 Hz, 3 H, CH(O)-CH(CH3)2] ppm.
The analytical data obtained agree with that reported in the litera-
ture.[31]
q
9.22 (m, 1 H, C=CH-N), 8.81–8.75 (m, 1 H, N=CH-CH), 8.36–8.28 (m,
1 H, qC-CH=CH), 7.44–7.36 (m, 1 H, CH-CH=CH), 5.98–5.82 [m, 1 H,
CH2=CH-CH(O)(CH2)], 5.56–5.46 [m, 1 H, CH2=CH-CH(O)(CH2)], 5.39–
5.19 [m, 2 H, CH2=CH-CH(O)(CH2)], 1.89–1.65 [m, 2 H, (CH)CH(O)-
CH2-CH2], 1.46–1.23 (m, 6 H, CH-CH2-CH2-CH2-CH2-CH3), 0.89 (t, J =
6.9 Hz, 3 H, CH2-CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 164.6,
153.4, 151.0, 137.1, 136.3, 126.5, 123.3, 117.2, 76.2, 34.3, 31.6, 24.8,
Oct-1-en-3-yl 2,2,2-Trifluoroacetate (4):[34] A mixture of 1-octen-
3-ol (595.2 μL, 500.0 mg, 3.90 mmol, 1.00 equiv.) and 2,2,2-trifluoro-
acetic anhydride (5.1 mL, 7.6 g, 36.18 mmol, 9.28 equiv.) was
warmed to 75 °C and stirred for 15 min. All volatiles were then
removed under reduced pressure. Distillation (20 mbar, 58 °C) af-
forded the product as a colorless liquid (661.3 mg, 2.95 mmol,
76 %). C10H15F3O2, MW: 224.22 g/mol. 1H NMR (300 MHz, CDCl3):
δ = 5.88–5.73 [m, 1 H, CH2=CH-CH(O)(CH2)], 5.42–5.24 [m, 3 H, CH2=
CH-CH(O)(CH2)], 1.86–1.60 [m, 2 H, (CH)CH(O)-CH2-CH2], 1.43–1.22
(m, 6 H, CH2-CH2-CH2-CH2-CH3), 0.89 (t, J = 6.7 Hz, 3 H, CH2-
CH3) ppm. The analytical data obtained agree with that reported in
the literature.[35]
22.6, 14.0 ppm. IR (in CDCl3): ν = 2931, 2860, 1720, 1647, 1590,
˜
1467, 1419, 1327, 1273, 1193, 1111, 1023, 987, 930, 893, 830, 740,
702, 680, 620 cm–1. MS (ESI): m/z (%) = 256.13 (100 %) [M + Na]+,
124.04 (54 %) [C6H6NO2]+. HRMS (ESI): m/z calcd. for C14H19NNaO2
[M + Na]+ 256.1308; found 256.1287.
Oct-1-en-3-yl (2,2,2-Trifluoroethyl)carbonate (8):[39] 1,1′-Carbon-
yldiimidazole (303.5 mg, 1.87 mmol, 1.20 equiv.) was dissolved in
Oct-1-en-3-yl Pivalate (5):[36] Pivaloyl chloride (206.9 mg,
1.72 mmol, 1.00 equiv.) was dissolved in benzene (3.4 mL). To this CH2Cl2 (1.9 mL). To this solution 1-octen-3-ol (238.1 μL, 200.0 mg,
mixture zinc (112.2 mg, 1.72 mmol, 1.00 equiv.) and a solution of 1.56 mmol, 1.00 equiv.) was added and the resulting solution was
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stirred for 3 h at room temperature. CH2Cl2 and H2O were added
to the resulting suspension. The phases were separated and the
organic phase was washed twice with H2O, dried with MgSO4 and
the solvent was removed under reduced pressure. The residue was
dissolved in CH2Cl2 (1.6 mL) and 2,2,2-trifluoroethanol (247.3 μL,
327.7 mg, 3.28 mmol, 2.10 equiv.) and 4-(dimethylamino)pyridine
(38.1 mg, 0.31 mmol, 0.20 equiv.) were added. The reaction mixture
was stirred for 12 h at room temperature. The solvent was then
removed under reduced pressure. Column chromatography (silica
gel, petroleum ether/CH2Cl2 = 100:1 – 10:1) afforded the product
as a colorless liquid (261.9 mg, 1.03 mmol, 66 %). C11H17F3O3, MW:
254.25 g/mol. 1H NMR (300 MHz, CDCl3): δ = 5.88–5.73 [m, 1 H,
CH2=CH-CH(O)(CH2)], 5.38–5.20 [m, 3 H, CH2=CH-CH(O)(CH2)], 5.13–
5.03 [m, 1 H, CH2=CH-CH(O)(CH2)], 4.57–4.43 (m, 2 H, OCH2CF3),
1.82–1.55 [m, 2 H, (CH)CH(O)-CH2-CH2], 1.45–1.20 (m, 6 H, CH-CH2-
CH2-CH2-CH2-CH3), 0.87 (t, J = 6.7 Hz, 3 H, CH2-CH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 153.6, 135.5, 122.8, 118.1, 81.0, 63.3, 34.1, 31.5,
24.6, 22.6, 14.0 ppm. 19F NMR (235 MHz, CDCl3): δ = 74.5 ppm. IR
the product as a white solid (2.1 g, 5.44 mmol, 77 %). C2AgF6NO4S2,
MW: 388.01 g/mol. 13C NMR (75 MHz, CD3CN): δ = 117.1 (CF3) ppm.
19F NMR (235 MHz, CD3CN): δ = –80.22 (CF3) ppm. The analytical
data obtained agree with that reported in the literature.[10a]
Synthesis of Racemic Addition Products
Methyl 2-Cyano-2-phenylpent-4-enoate (rac-3aa-Me): In accord-
ance with GP2, Option A, methyl 2-cyano-2-phenylacetate (1a-Me;
91.2 μL, 100.0 mg, 0.57 mmol, 1.00 equiv.) was treated with sodium
hydride (55 % in mineral oil, 25.2 mg, 0.58 mmol, 1.01 equiv.) and
allyl bromide (148.0 μL, 207.2 mg, 1.71 mmol, 3.00 equiv.) in THF
(2.3 mL). Column chromatography (silica gel, petroleum ether/ethyl
acetate = 10:1) afforded the product as a colorless liquid (105.6 mg,
0.49 mmol, 86 %).
Benzyl 2-Cyano-2-phenylpent-4-enoate (rac-3aa-Bn): In accord-
ance with GP2, Option A, benzyl 2-cyano-2-phenylacetate (1a-Bn;
101.7 mg, 0.41 mmol, 1.00 equiv.) was treated with sodium hydride
(55 % in mineral oil, 17.8 mg, 0.41 mmol, 1.01 equiv.) and allyl
bromide (104.9 μL, 146.9 mg, 1.21 mmol, 3.00 equiv.) in THF
(1.7 mL). Column chromatography (silica gel, petroleum ether/ethyl
acetate = 10:1) afforded the product as a colorless liquid (109.7 mg,
0.38 mmol, 93 %).
(in CDCl3): ν = 2935, 2864, 1758, 1414, 1296, 1243, 1166, 1130, 989,
˜
955, 909, 840, 785, 733, 641 cm–1. MS (ESI): m/z (%) = 277.10 (100 %)
[M + Na]+, 166.99 (64 %) [C3H3F3NaO3]+. HRMS (ESI): m/z calcd. for
C
11H17F3NaO3 [M + Na]+ 277.1022; found 277.1020.
Diethyl Oct-1-en-3-yl Phosphate (9):[40] 1-Octen-3-ol (238.1 μL,
200.0 mg, 1.56 mmol, 1.00 equiv.) was dissolved in pyridine (1.0 mL,
1.0 g, 12.39 mmol, 7.94 equiv.) and cooled to 0 °C. To the resulting
solution diethylchlorophosphate (270.5 μL, 323.0 mg, 1.87 mmol,
1.20 equiv.) and DMAP (19.1 mg, 0.16 mmol, 0.10 equiv.) were
added. The reaction mixture was warmed to room temperature and
stirred for 1 h. Subsequently, the reaction mixture was diluted with
ethyl acetate (6.5 mL) and H2O (1.6 mL) was added. The resulting
mixture was washed twice with saturated aqueous CuSO4 solution
(3.2 mL) and saturated aqueous NaCl solution, dried with MgSO4,
and the solvent was removed under reduced pressure. Filtration
over alumina oxide (diethyl ether) and subsequent removal of the
solvent under reduced pressure afforded the product as a colorless
liquid (200.7 mg, 0.76 mmol, 49 %). C12H25O4P, MW: 264.30 g/mol.
1H NMR (300 MHz, CDCl3): δ = 5.91–5.76 [m, 1 H, CH2=CH-
CH(O)(CH2)], 5.36–5.16 [m, 2 H, CH2=CH-CH(O)(CH2)], 4.81–4.68 [m,
2 H, CH2=CH-CH(O)(CH2)], 4.19–4.01 [m, 4 H, OP(O)(OCH2CH3)2],
1.81–1.53 [m, 2 H, (CH)CH(O)-CH2-CH2], 1.44–1.21 [m, 12 H, CH2-
CH2-CH2-CH2-CH3, OP(O)(OCH2CH3)2], 0.88 (t, J = 6.7 Hz, 3 H, CH2-
CH3) ppm. The analytical data obtained agree with that reported in
the literature.[41]
Butyl 2-Cyano-2-phenylpent-4-enoate (rac-3aa-nBu): In accord-
ance with GP2, Option A, butyl 2-cyano-2-phenylacetate (1a-nBu;
97.9 μL, 98.7 mg, 0.45 mmol, 1.00 equiv.) was treated with sodium
hydride (55 % in mineral oil, 20.0 mg, 0.46 mmol, 1.01 equiv.) and
allyl bromide (117.8 μL, 164.9 mg, 1.36 mmol, 3.00 equiv.) in THF
(1.9 mL). Column chromatography (silica gel, petroleum ether/ethyl
acetate = 10:1) afforded the product as a colorless liquid (109.8 mg,
0.43 mmol, 94 %).
Isobutyl 2-Cyano-2-phenylpent-4-enoate (rac-3aa-iBu): In ac-
cordance with GP2, Option A, isobutyl 2-cyano-2-phenylacetate (1a-
iBu; 99.6 μL, 101.1 mg, 0.47 mmol, 1.00 equiv.) was treated with
sodium hydride (55 % in mineral oil, 20.5 mg, 0.47 mmol,
1.01 equiv.) and allyl bromide (120.6 μL, 168.9 mg, 1.40 mmol,
3.00 equiv.) in THF (1.9 mL). Column chromatography (silica gel,
petroleum ether/ethyl acetate = 10:1) afforded the product as a
colorless liquid (118.2 mg, 0.46 mmol, 99 %).
Allyl 2-Cyano-2-phenylpent-4-enoate (rac-3aa-Allyl): In accord-
ance with GP2, Option A, allyl 2-cyano-2-phenylacetate (1a-Allyl;
100.0 mg, 0.50 mmol, 1.00 equiv.) was treated with sodium hydride
(55 % in mineral oil, 21.9 mg, 0.50 mmol, 1.01 equiv.) and allyl
bromide (128.8 μL, 180.4 mg, 1.49 mmol, 3.00 equiv.) in THF
(1.7 mL). Column chromatography (silica gel, petroleum ether/ethyl
acetate = 10:1) afforded the product as a colorless liquid (97.1 mg,
0.40 mmol, 81 %).
Synthesis of Silver Salts
({1,1,1-Trifluoro-N-[(trifluoromethyl)sulfonyl]methyl}sulfon-
amido)silver [AgN(Tf)2]:[10a] Lithium bis[(trifluoromethyl)-
sulfonyl]amide (2.0 g, 7.11 mmol, 1.00 equiv.), was dissolved in de-
Methyl (E)-2-Cyano-2-phenyldec-4-enoate (rac-3ad-Me): In ac-
cordance with GP2, Option B, methyl 2-cyano-2-phenylacetate (1a-
Me; 93.6 μL, 102.6 mg, 0.59 mmol, 1.00 equiv.) was treated with
sodium hydride (55 % in mineral oil, 25.9 mg, 0.59 mmol,
1.01 equiv.) and a solution of (E)-2-octen-3-ol (267.3 μL, 225.3 mg,
mineralized water. Concentrated HCl (12
M) was added to afford a
polyhydrate of the protonated species. This was extracted with di-
ethyl ether and the solvent was removed under reduced pressure.
The obtained residue was taken up in diethyl ether, stirred for
5 min, and the solvent was removed by decantation. This process
was repeated three times. The residue was subsequently dissolved
in acetonitrile (35 mL) and silver carbonate (1.1 g, 3.91 mmol,
0.55 equiv.) was added. The reaction mixture was stirred for 2 h
at room temperature to generate a white precipitate. The reaction
mixture was filtered and the solvent was removed under reduced
pressure. The resulting colorless liquid was stirred for 1 h in diethyl
1.76 mmol, 3.00 equiv.), nBuLi (1.6
M
in n-hexane, 1.15 mL,
1.85 mmol, 3.15 equiv.), methanesulfonyl chloride (149.6 μL,
221.4 mg, 1.93 mmol, 3.3 equiv.), and LiBr (457.8 mg, 5.27 mmol,
9.00 equiv.) in THF (2.8 mL). Column chromatography (silica gel,
petroleum ether/ethyl acetate = 20:1) afforded the product as a
colorless liquid (103.9 mg, 0.36 mmol, 62 %).
ether (10 mL), the solvent was removed under reduced pressure Benzyl (E)-2-Cyano-2-phenyldec-4-enoate (rac-3ad-Bn): In ac-
and subsequently H2O (25 mL) was added and the mixture was
stirred for another hour. Solvent removal under reduced pressure
afforded a pale yellow solid. Recrystallization from CH2Cl2 afforded
cordance with GP2, Option B, benzyl 2-cyano-2-phenylacetate (1a-
Bn; 95.7 mg, 0.38 mmol, 1.00 equiv.) was treated with sodium
hydride (55 % in mineral oil, 16.8 mg, 0.39 mmol, 1.01 equiv.) and
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a solution of (E)-2-octen-3-ol (173.8 μL, 146.5 mg, 1.14 mmol,
3.00 equiv.), nBuLi (1.6 in n-hexane, 1.15 mL, 1.85 mmol,
3.15 equiv.), methanesulfonyl chloride (97.3 μL, 144.0 mg,
Methyl (E)-2-Cyano-2-(3-fluorophenyl)dec-4-enoate (rac-3cd-
Me): In accordance with GP2, Option C, methyl 2-cyano-2-(3-fluoro-
phenyl)acetate 1c-Me (42.9 mg, 0.22 mmol, 1.00 equiv.) was treated
M
1.26 mmol, 3.3 equiv.), and LiBr (297.7 mg, 3.43 mmol, 9.00 equiv.) with sodium acetate (0.5 mg, 6.66 μmol, 0.03 equiv.), bis(trimethyl-
in THF (1.8 mL). Column chromatography (silica gel, petroleum
ether/ethyl acetate = 20:1) afforded the product as a colorless liquid
(88.1 mg, 0.24 mmol, 64 %).
silyl)acetamide (54.3 μL, 45.2 mg, 0.22 mmol, 1.00 equiv.), [Pd-
(allyl)Cl]2 (0.4 mg, 1.11 μmol, 0.5 mol-%), triphenylphosphine
(1.3 mg, 4.89 μmol, 2.2 mol-%), and oct-1-en-3-yl acetate (2d;
43.1 μL, 37.8 mg, 0.22 mmol, 1.00 equiv.) in THF (222.1 μL). Column
chromatography (silica gel, petroleum ether/ethyl acetate = 20:1)
afforded the product as a colorless liquid (56.7 mg, 0.19 mmol,
84 %).
Butyl (E)-2-Cyano-2-phenyldec-4-enoate (rac-3ad-nBu): In ac-
cordance with GP2, Option B, butyl 2-cyano-2-phenylacetate (1a-
nBu; 102.3 μL, 103.1 mg, 0.48 mmol, 1.00 equiv.) was treated with
sodium hydride (55 % in mineral oil, 21.0 mg, 0.48 mmol,
1.01 equiv.) and a solution of (E)-2-octen-3-ol (216.5 μL, 182.5 mg, Methyl (E)-2-Cyano-2-(3-methoxyphenyl)dec-4-enoate (rac-3dd-
1.42 mmol, 3.00 equiv.), nBuLi (1.6 in n-hexane, 0.93 mL, Me): In accordance with GP2, Option C, methyl 2-cyano-2-(3-
M
1.50 mmol, 3.15 equiv.), methanesulfonyl chloride (121.2 μL,
179.4 mg, 1.57 mmol, 3.3 equiv.), and LiBr (370.9 mg, 4.27 mmol,
9.00 equiv.) in THF (2.3 mL). Column chromatography (silica gel,
petroleum ether/ethyl acetate = 20:1) afforded the product as a
colorless liquid (77.3 mg, 0.24 mmol, 50 %).
methoxyphenyl)acetate (1d-Me; 42.1 mg, 0.21 mmol, 1.00 equiv.)
was treated with sodium acetate (0.5 mg, 6.16 μmol, 0.03 equiv.),
bis(trimethylsilyl)acetamide (50.2 μL, 41.7 mg, 0.21 mmol,
1.00 equiv.), [Pd(allyl)Cl]2 (0.4 mg, 1.03 μmol, 0.5 mol-%), triphenyl-
phosphine (1.2 mg, 4.51 μmol, 2.2 mol-%), and oct-1-en-3-yl acetate
(2d; 39.8 μL, 34.9 mg, 0.21 mmol, 1.00 equiv.) in THF (205.2 μL).
Column chromatography (silica gel, petroleum ether/ethyl acetate =
20:1) afforded the product as a colorless liquid (39.9 mg, 0.13 mmol,
62 %).
Isobutyl (E)-2-Cyano-2-phenyldec-4-enoate (rac-3ad-iBu): In ac-
cordance with GP2, Option B, isobutyl 2-cyano-2-phenylacetate (1a-
iBu; 103.8 μL, 105.4 mg, 0.49 mmol, 1.00 equiv.) was treated with
sodium hydride (55 % in mineral oil, 21.4 mg, 0.49 mmol,
1.01 equiv.) and a solution of (E)-2-octen-3-ol (221.4 μL, 186.6 mg, Methyl (E)-2-Cyano-2-(2-naphthalen-2-yl)dec-4-enoate (rac-
1.46 mmol, 3.00 equiv.), nBuLi (1.6
M
in n-hexane, 0.96 mL,
3ed-Me): In accordance with GP2, Option C, methyl 2-cyano-2-(2-
naphthalen-2-yl)acetate (1e-Me; 100.0 mg, 0.44 mmol, 1.00 equiv.)
was treated with sodium acetate (1.1 mg, 13.32 μmol, 0.03 equiv.),
bis(trimethylsilyl)acetamide (108.5 μL, 90.3 mg, 0.44 mmol,
1.00 equiv.), [Pd(allyl)Cl]2 (0.8 mg, 2.22 μmol, 0.5 mol-%), triphenyl-
phosphine (2.6 mg, 9.77 μmol, 2.2 mol-%), and oct-1-en-3-yl acetate
(2d; 86.1 μL, 75.6 mg, 0.44 mmol, 1.00 equiv.) in THF (444.0 μL).
Column chromatography (silica gel, petroleum ether/ethyl acetate =
20:1) afforded the product as a colorless liquid (121.7 mg,
0.36 mmol, 82 %).
1.53 mmol, 3.15 equiv.), methanesulfonyl chloride (123.9 μL,
183.4 mg, 1.60 mmol, 3.3 equiv.), and LiBr (379.2 mg, 4.37 mmol,
9.00 equiv.) in THF (2.3 mL). Column chromatography (silica gel,
petroleum ether/ethyl acetate = 20:1) afforded the product as a
colorless liquid (75.2 mg, 0.23 mmol, 47 %).
tert-Butyl (E)-2-Cyano-2-phenyldec-4-enoate (rac-3ad-tBu): In
accordance with GP2, Option B, tert-butyl 2-cyano-2-phenylacetate
(1a-tBu; 96.2 mg, 0.44 mmol, 1.00 equiv.) was treated with sodium
hydride (55 % in mineral oil, 19.6 mg, 0.45 mmol, 1.01 equiv.) and
a solution of (E)-2-octen-3-ol (202.1 μL, 170.3 mg, 1.33 mmol,
Methyl (E)-2-Cyano-2-(2-m-tolyl)dec-4-enoate (rac-3fd-Me): In
3.00 equiv.), nBuLi (1.6
3.15 equiv.), methanesulfonyl chloride (113.1 μL, 167.4 mg,
1.46 mmol, 3.3 equiv.), and LiBr (346.1 mg, 3.99 mmol, 9.00 equiv.) acetate (0.6 mg, 7.01 μmol, 0.03 equiv.), bis(trimethylsilyl)acetamide
M
in n-hexane, 0.87 mL, 1.40 mmol, accordance with GP2, Option C, methyl 2-cyano-2-(2-m-tolyl)acetate
(1f-Me; 44.2 mg, 0.23 mmol, 1.00 equiv.) was treated with sodium
in THF (2.1 mL). Column chromatography (silica gel, petroleum
ether/ethyl acetate = 20:1) afforded the product as a colorless liquid
(96.3 mg, 0.29 mmol, 66 %).
(57.1 μL, 47.5 mg, 0.23 mmol, 1.00 equiv.), [Pd(allyl)Cl]2 (0.4 mg,
1.17 μmol, 0.5 mol-%), triphenylphosphine (1.4 mg, 5.14 μmol,
2.2 mol-%), and oct-1-en-3-yl acetate (2d; 45.3 μL, 39.8 mg,
0.23 mmol, 1.00 equiv.) in THF (233.6 μL). Column chromatography
(silica gel, petroleum ether/ethyl acetate = 20:1) afforded the prod-
uct as a colorless liquid (56.4 mg, 0.19 mmol, 81 %).
Methyl (E)-2-Cyano-2-phenyloct-4-enoate (rac-3ac-Me): In ac-
cordance with GP2, Option C, methyl 2-cyano-2-phenylacetate (1a-
Me; 9.1 μL, 10.0 mg, 0.06 mmol, 1.00 equiv.) was treated with
sodium acetate (0.1 mg, 0.17 μmol, 0.03 equiv.), bis(trimethylsilyl)- Methyl (E)-2-Cyano-5-cyclohexyl-2-phenylpent-4-enoate (rac-
acetamide (14.0 μL, 11.6 mg, 0.06 mmol, 1.00 equiv.), [Pd(allyl)Cl]2
(0.1 mg, 0.03 μmol, 0.5 mol-%), triphenylphosphine (0.3 mg,
3ag-Me): In accordance with GP2, Option C, methyl 2-cyano-2-
phenylacetate (1a-Me; 25.8 μL, 27.2 mg, 0.16 mmol, 1.00 equiv.)
0.13 μmol, 2.2 mol-%), and hex-1-en-3-yl acetate (2c; 8.1 mg, was treated with sodium acetate (0.4 mg, 4.65 μmol, 0.03 equiv.),
0.06 mmol, 1.00 equiv.) in THF (57.1 μL). Column chromatography bis(trimethylsilyl)acetamide (37.9 μL, 31.5 mg, 0.16 mmol,
(silica gel, petroleum ether/ethyl acetate = 20:1) afforded the prod- 1.00 equiv.), [Pd(allyl)Cl]2 (0.3 mg, 0.78 μmol, 0.5 mol-%), triphenyl-
uct as a colorless liquid (7.9 mg, 0.03 mmol, 54 %).
phosphine (0.9 mg, 3.41 μmol, 2.2 mol-%), and 1-cyclohexylallyl
acetate (2g; 28.3 mg, 0.16 mmol, 1.00 equiv.) in THF (155.0 μL). The
reaction mixture was stirred at 70 °C. Column chromatography (sil-
ica gel, petroleum ether/ethyl acetate = 20:1) afforded the product
as a colorless liquid (28.6 mg, 0.10 mmol, 62 %).
Methyl (E)-2-(4-Bromophenyl)-2-cyanodec-4-enoate (rac-3bd-
Me): In accordance with GP2, Option C, methyl 2-(4-bromophenyl)-
2-cyanoacetate (1b-Me; 48.5 mg, 0.19 mmol, 1.00 equiv.) was
treated with sodium acetate (0.5 mg, 5.73 μmol, 0.03 equiv.), bis(tri-
methylsilyl)acetamide (46.7 μL, 38.8 mg, 0.19 mmol, 1.00 equiv.), Methyl (E)-2-Cyano-7-methyl-2-phenylpent-4-enoate (rac-3ah-
[Pd(allyl)Cl]2 (0.4 mg, 0.95 μmol, 0.5 mol-%), triphenylphosphine Me): In accordance with GP2, Option C, methyl 2-cyano-2-phenyl-
(1.1 mg, 4.20 μmol, 2.2 mol-%), and oct-1-en-3-yl acetate (2d;
acetate (1a-Me; 56.3 μL, 59.2 mg, 0.34 mmol, 1.00 equiv.) was
37.0 μL, 32.5 mg, 0.19 mmol, 1.00 equiv.) in THF (190.9 μL). Column treated with sodium acetate (0.8 mg, 10.13 μmol, 0.03 equiv.),
chromatography (silica gel, petroleum ether/ethyl acetate = 20:1) bis(trimethylsilyl)acetamide (82.6 μL, 68.7 mg, 0.34 mmol,
afforded the product as a colorless liquid (36.5 mg, 0.10 mmol,
53 %).
1.00 equiv.), [Pd(allyl)Cl]2 (0.6 mg, 1.69 μmol, 0.5 mol-%), triphenyl-
phosphine (2.0 mg, 7.43 μmol, 2.2 mol-%), and 5-methylhex-1-en-
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3-yl acetate (2h; 52.8 mg, 0.34 mmol, 1.00 equiv.) in THF (337.6 μL). MS (ESI): m/z (%) = 314.11 (100) [M + Na]+. HRMS (ESI): m/z calcd.
The reaction mixture was stirred at 70 °C. Column chromatography for C19H17NNaO2 [M + Na]+ 314.1151; found 314.1139.
(silica gel, petroleum ether/ethyl acetate = 20:1) afforded the prod-
Butyl (R)-2-Cyano-2-phenylpent-4-enoate [(R)-3aa-nBu]: In ac-
uct as a colorless liquid (35.7 mg, 0.13 mmol, 39 %).
cordance with GP3 butyl 2-cyano-2-phenylacetate (1a-nBu; 9.1 μL,
9.1 mg, 0.04 mmol, 1.00 equiv.) was treated with allyl acetate (2a;
9.0 μL, 8.4 mg, 0.08 mmol, 2.00 equiv.), sodium acetate (0.7 mg,
0.01 mmol, 0.20 equiv.) and [FBIPP-Cl]2 (5.5 mg, 2.09 μmol, 5 mol-
%) in 2,2,2-trifluoroethanol (209.4 μL) at 50 °C. Column chromatog-
raphy (silica gel, petroleum ether/ethyl acetate = 20:1) afforded the
product as a colorless liquid (10.3 mg, 0.04 mmol, 95 %, ee = 67 %).
The enantiomeric excess was determined by HPLC: Chiralcel
OD-H, n-hexane, 0.8 mL min–1, λ = 210 nm; 39.87 min Rf(major
enantiomer), 55.62 min Rf(minor enantiomer). C16H19NO2, MW:
257.33 g/mol. [α]D24 = –16.0 (c = 0.51 g/dL, CHCl3, sample with ee =
67 %). 1H NMR (300 MHz, CDCl3): δ = 7.58–7.51 [m, 2 H, phenyl
C(2/6)H], 7.46–7.33 [m, 3 H, phenyl C(3/4/5)H], 5.83–5.66 (m, 1 H,
Methyl (E)-2-Cyano-6-methyl-2-phenylpent-4-enoate (rac-3ai-
Me): In accordance with GP2, Option C, methyl 2-cyano-2-phenyl-
acetate (1a-Me; 67.3 μL, 70.8 mg, 0.40 mmol, 1.00 equiv.) was
treated with sodium acetate (1.0 mg, 12.12 μmol, 0.03 equiv.),
bis(trimethylsilyl)acetamide (98.7 μL, 82.2 mg, 0.40 mmol,
1.00 equiv.), [Pd(allyl)Cl]2 (0.7 mg, 2.02 μmol, 0.5 mol-%), triphenyl-
phosphine (2.3 mg, 8.88 μmol, 2.2 mol-%), and 4-methylprop-1-en-
3-yl acetate (2i; 57.4 mg, 0.40 mmol, 1.00 equiv.) in THF (403.9 μL).
The reaction mixture was stirred at 70 °C. Column chromatography
(silica gel, petroleum ether/ethyl acetate = 20:1) afforded the prod-
uct as a colorless liquid (30.5 mg, 0.12 mmol, 29 %).
q
qC-CH2-CH=CH2), 5.32–5.18 (m, 2 H, C-CH2-CH=CH2), 4.26–4.09 [m,
Synthesis of Enantiomerically Enriched Addition Products by
Asymmetric Catalysis
2 H, C(O)OCH2CH2CH2CH3], 3.17–3.06 (m, 1 H, qC-CH2-CH=CH2),
2.91–2.79 (m, 1 H, q C-CH2 -CH=CH2 ), 1.66–1.52 [m, 2 H,
C(O)OCH2CH2CH2CH3], 1.37–1.21 [m, 2 H, C(O)OCH2CH2CH2CH3],
0.87 [t, J = 7.3 Hz, 3 H, C(O)OCH2CH2CH2CH3] ppm. 13C NMR
(75 MHz, CDCl3): δ = 167.3, 134.3, 130.8, 129.3, 129.1, 126.3, 121.4,
Methyl (R)-2-Cyano-2-phenylpent-4-enoate [(R)-3aa-Me]: In ac-
cordance with GP3 methyl 2-cyano-2-phenylacetate (1a-Me; 7.5 μL,
8.2 mg, 0.05 mmol, 1.00 equiv.) was treated with allyl acetate (2a;
10.1 μL, 9.4 mg, 0.09 mmol, 2.00 equiv.), sodium acetate (0.8 mg,
0.01 mmol, 0.20 equiv.), and [FBIPP-Cl]2 (6.1 mg, 2.34 μmol, 5 mol-
%) in 2,2,2-trifluoroethanol (234.0 μL) at 50 °C. Column chromatog-
raphy (silica gel, petroleum ether/ethyl acetate = 10:1) afforded the
product as a colorless liquid (8.9 mg, 0.04 mmol, 88 %, ee = 61 %).
The enantiomeric excess was determined by GC: Bondex-UN-α+ꢀ,
[50 °C, 1 min, 2.5 °C/min → 100 °C, 80 min, 5 °C/min → 200 °C];
102.15 min Rf(major enantiomer), 104.10 min Rf(minor enantiomer).
C13H13NO2, MW: 215.25 g/mol. [α]D24 = –26.5 (c = 0.68 g/dL, CHCl3,
sample with ee = 65 %). 1H NMR (300 MHz, CDCl3): δ = 7.58–7.51
[m, 2 H, phenyl C(2/6)H], 7.46–7.34 [m, 3 H, phenyl C(3/4/5)H], 5.82–
5.65 (m, 1 H, qC-CH2CH=CH2), 5.31–5.19 (m, 2 H, qC-CH2CH=CH2),
3.79 [s, 3 H, C(O)OCH3], 3.18–3.06 (m, 1 H, qC-CH2-CH=CH2), 2.93–
2.80 (m, 1 H, qC-CH2-CH=CH2) ppm. 13C NMR (75 MHz, CDCl3): δ =
167.9, 134.0, 130.7, 129.3, 129.1, 126.3, 121.5, 118.0, 54.2, 54.1
118.1, 73.1, 54.3, 42.2, 27.8, 18.90, 18.87 ppm. IR (in CDCl ): ν =
˜
3
2960, 2924, 2853, 1744, 1643, 1495, 1450, 1381, 1220, 1146, 1067,
1034, 992, 928, 767, 729, 696, 507 cm–1. MS (ESI): m/z (%) = 280.13
(100) [M + Na]+. HRMS (ESI): m/z calcd. for C16H19NNaO2 [M + Na]+
280.1308; found 280.1306.
Isobutyl (R)-2-Cyano-2-phenylpent-4-enoate [(R)-3aa-iBu]: In ac-
cordance with GP3 isobutyl 2-cyano-2-phenylacetate (1a-iBu; 9.0 μL,
9.1 mg, 0.04 mmol, 1.00 equiv.) was treated with allyl acetate (2a;
9.0 μL, 8.4 mg, 0.08 mmol, 2.00 equiv.), sodium acetate (0.7 mg,
0.01 mmol, 0.20 equiv.) and [FBIPP-Cl]2 (5.5 mg, 2.09 μmol, 5 mol-
%) in 2,2,2-trifluoroethanol (209.4 μL) at 50 °C. Column chromatog-
raphy (silica gel, petroleum ether/ethyl acetate = 20:1) afforded the
product as a colorless liquid (8.1 mg, 0.03 mmol, 75 %, ee = 66 %).
The enantiomeric excess was determined by HPLC: Chiralcel
OD-H, n-hexane, 0.8 mL min–1, λ = 210 nm; 37.93 min Rf(major
enantiomer), 57.23 min Rf(minor enantiomer). C16H19NO2, MW:
257.33 g/mol. [α]D24 = –16.5 (c = 0.41 g/dL, CHCl3, sample with ee =
66 %). 1H NMR (300 MHz, CDCl3): δ = 7.59–7.52 [m, 2 H, phenyl
C(2/6)H], 7.45–7.33 [m, 3 H, phenyl C(3/4/5)H], 5.84–5.66 (m, 1 H,
[C(O)OCH ], 42.5 ppm. IR (in CDCl ): ν = 2957, 2921, 2851,
˜
3
3
1748, 1644, 1493, 1450, 1436, 1236, 1147, 933, 869 768, 732, 696,
501 cm–1. MS (EI): m/z (%) = 215.1 (35) [M]+, 174.1 (100) [M – C3H5]+,
156.1 (35) [M – CO2Me]+. HRMS (ESI): m/z calcd. for C13H13NNaO2
[M + Na]+ 238.0838; found 238.0829.
q
qC-CH2-CH=CH2), 5.32–5.18 (m, 2 H, C-CH2-CH=CH2), 4.04–3.87 [m,
Benzyl (R)-2-Cyano-2-phenylpent-4-enoate [(R)-3aa-Bn]: In ac-
cordance with GP3 benzyl 2-cyano-2-phenylacetate (1a-Bn;
10.0 mg, 0.04 mmol, 1.00 equiv.) was treated with allyl acetate (2a;
8.6 μL, 8.0 mg, 0.08 mmol, 2.00 equiv.), sodium acetate (0.7 mg,
0.01 mmol, 0.20 equiv.) and [FBIPP-Cl]2 (5.2 mg, 1.99 μmol, 5 mol-
%) in 2,2,2-trifluoroethanol (199.0 μL) at 50 °C. Column chromatog-
raphy (silica gel, petroleum ether/ethyl acetate = 10:1) afforded the
product as a colorless liquid (10.7 mg, 0.04 mmol, 92 %, ee = 42 %).
The enantiomeric excess was determined by HPLC: Chiralcel OD-H,
n-hexane/i-PrOH (99.5:0.5), 0.8 mL min–1, λ = 210 nm; 20.14 min
Rf(major enantiomer), 22.70 min Rf(minor enantiomer). C19H17NO2,
2 H, C(O)OCH2CH(CH3)2], 3.18–3.08 (m, 1 H, qC-CH2-CH=CH2), 2.92–
2 . 8 1 ( m , 1 H , q C - C H 2 - C H = C H 2 ) , 2 . 0 2 – 1 . 8 2 [ m , 1 H ,
C(O)OCH2 CH(CH3 )2 ], 0.86 [d, J = 6.8 Hz, 6 H, C(O)OCH2-
CH(CH3)2] ppm. 13C NMR (75 MHz, CDCl3): δ = 167.4, 134.3, 130.8,
129.3, 129.0, 126.3, 121.4, 118.1, 67.1, 54.3, 42.3, 30.4, 19.0,
13.7 ppm. IR (in CDCl ): ν = 3066, 2964, 2932, 2876, 1745, 1644,
˜
3
1599, 1496, 1470, 1450, 1394, 1372, 1265, 1225, 1146, 1069, 1034,
978, 929, 767, 730, 696, 643, 503 cm–1. MS (ESI): m/z (%) = 280.13
(100) [M + Na]+. HRMS (ESI): m/z calcd. for C16H19NNaO2 [M + Na]+
280.1308; found 280.1305.
MW: 291.35 g/mol. [α]D24 = –4.9 (c = 0.53 g/dL, CHCl3, sample with Allyl (R)-2-Cyano-2-phenylpent-4-enoate [(R)-3aa-Allyl]: In ac-
ee = 42 %). 1H NMR (300 MHz, CDCl3): δ = 7.54–7.48 [m, 2 H, phenyl cordance with GP3 allyl 2-cyano-2-phenylacetate (1a-Allyl; 9.3 mg,
C(2/6)H], 7.43–7.35 [m, 3 H, phenyl C(3/4/5)H], 7.34–7.28 [m, 2 H,
CH2-phenyl C(2/6)H], 7.25–7.21 [m, 3 H, CH2-phenyl C(3/4/5)H],
5.80–5.64 (m, 1 H, C-CH2-CH=CH2), 5.29–5.15 [m, 4 H, C-CH2-CH=
CH2, C(O)OCH2Ph], 3.17–3.07 (m, 1 H, qC-CH2-CH=CH2), 2.92–2.81
(m, 1 H, qC-CH2-CH=CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 167.1,
134.7, 133.9, 130.7, 129.3, 129.1, 128.72, 128.65, 128.0, 126.4, 121.5,
0.05 mmol, 1.00 equiv.) was treated with allyl acetate (2a; 10.0 μL,
9.3 mg, 0.09 mmol, 2.00 equiv.), sodium acetate (0.8 mg, 0.01 mmol,
0.20 equiv.) and [FBIPP-Cl]2 (6.0 mg, 2.31 μmol, 5 mol-%) in 2,2,2-
trifluoroethanol (231.1 μL) at 50 °C. Column chromatography (silica
gel, petroleum ether/ethyl acetate = 20:1) afforded the product as
a colorless liquid (4.3 mg, 0.02 mmol, 39 %, ee = 55 %). The enantio-
q
q
118.0, 68.6, 54.3, 42.3 ppm. IR (in CDCl ): ν = 3034, 1745, 1642, 1496, meric excess was determined by HPLC: Chiralcel OD-H, n-hexane/
˜
3
1450, 1374, 1263, 1216, 1028, 990, 929, 730, 695, 598, 514 cm–1
.
iPrOH (99.5:0.5), 0.8 mL min–1, λ = 210 nm; 13.14 min Rf(major enan-
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tiomer), 14.37 min Rf(minor enantiomer). C15H15NO2, MW: 241.29 g/
361.2 (2) [M]+, 251.1 (14) [PhCH(CN)(CO2Bn)]+, 91.1 (100) [Ph – CH2]+.
mol. [α]D23 = –12.2 (c = 0.41 g/dL, CHCl3, sample with ee = 55 %). 1H HRMS (EI) m/z calcd. for C24H27NO2 [M]+ 361.2042; found 361.2040.
NMR (300 MHz, CDCl3): δ = 7.60–7.53 [m, 2 H, phenyl C(2/6)H], 7.46–
Butyl (R,E)-2-Cyano-2-phenyldec-4-enoate [(R)-3ad-nBu]: In ac-
7.34 [m, 3 H, phenyl C(3/4/5)H], 5.91–5.67 (m, 2 H, 2 × CH2CH=CH2),
cordance with GP3 butyl 2-cyano-2-phenylacetate (1a-nBu; 9.0 μL,
5.32–5.18 (m, 4 H, 2 × CH2CH=CH2), 4.74–4.58 (m, 2 H, OCH2CH=
9.1 mg, 0.04 mmol, 1.00 equiv.) was treated with oct-1-en-3-yl ace-
CH2), 3.19–3.07 (m, 1 H, qC-CH2-CH=CH2), 2.93–2.81 (m, 1 H, qC-CH2-
tate (2d; 16.3 μL, 14.2 mg, 0.08 mmol, 2.00 equiv.), sodium acetate
CH=CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 166.9, 134.0, 130.7,
(0.7 mg, 0.01 mmol, 0.20 equiv.) and [FBIPP-Cl]2 (5.5 mg, 2.09 μmol,
129.3, 129.1, 126.3, 121.5, 119.2, 117.9, 67.4, 54.2, 42.3 ppm. IR
5 mol-%) in 2,2,2-trifluoroethanol (208.8 μL) at 70 °C. Column chro-
(in CDCl3): ν = 3084, 1743, 1645, 1598, 1494, 1450, 1360, 1267, 1214,
˜
matography (silica gel, petroleum ether/ethyl acetate = 20:1) af-
forded the product as a colorless liquid as an inseparable mixture
of (E)- and (Z)-isomers [9.7 mg, 0.03 mmol, 71 %, ee = 59 %; (E)/(Z) =
1144, 1034, 991, 927, 767, 729, 695, 641, 558, 507 cm–1. MS (ESI):
m/z (%) = 264.10 (100) [M + Na]+. HRMS (ESI): m/z calcd. for
C15H15NNaO2 [M + Na]+ 264.0995; found 264.0984.
18:1]. The enantiomeric excess was determined by HPLC: Chiralcel
OD-H, n-hexane, 0.8 mL min–1, λ = 210 nm; 38.63 min Rf(major
Methyl (R,E)-2-Cyano-2-phenyldec-4-enoate [(R)-3ad-Me]: In ac-
enantiomer), 79.20 min Rf(minor enantiomer). C21H29NO2, MW:
cordance with GP3 methyl 2-cyano-2-phenylacetate (1a-Me;
327.47 g/mol. [α]D23 = –13.0 (c = 0.51 g/dL, CHCl3, sample with ee =
10.0 μL, 10.5 mg, 0.06 mmol, 1.00 equiv.) was treated with oct-1-
59 %). 1H NMR (300 MHz, CDCl3): δ = 7.58–7.51 [m, 2 H, phenyl
C(2/6)H], 7.44–7.32 [m, 3 H, phenyl C(3/4/5)H], 5.72–5.58 (m, 1 H,
en-3-yl acetate (2d; 23.3 μL, 20.4 mg, 0.12 mmol, 2.00 equiv.), so-
dium acetate (1.0 mg, 0.01 mmol, 0.20 equiv.) and [FBIPP-Cl]2
(7.8 mg, 3.00 μmol, 5 mol-%) in 2,2,2-trifluoroethanol (300.0 μL) at
olefinic H), 5.42–5.29 (m, 1 H, olefinic H), 4.25–4.09 [m, 2 H,
C(O)OCH2CH2CH2CH3], 3.11–3.00 (m, 1 H, qC-CH2-CH=CH), 2.83–2.72
70 °C. Column chromatography (silica gel, petroleum ether/ethyl
q
(m, 1 H, C-CH2-CH=CH), 2.03–1.92 (m, 2 H, CH=CH-CH2), 1.66–1.52
acetate = 20:1) afforded the product as a colorless liquid as an
[m, 2 H, C(O)OCH2CH2CH2CH3], 1.38–1.14 [m, 8 H, CH2-CH2-CH2-CH3,
inseparable mixture of (E)- and (Z)-isomers [9.5 mg, 0.03 mmol,
C ( O ) O C H 2 C H 2 C H 2 C H 3 ] , 0 . 9 2 – 0 . 8 2 [ m , 6 H , C H 2 - C H 3 ,
56 %, ee = 61 %; (E)/(Z) = 18:1]. The enantiomeric excess was deter-
C(O)OCH2CH2CH2CH3] ppm. 13C NMR (125 MHz, CDCl3): δ = 167.6,
138.1, 134.5, 129.2, 128.9, 126.4, 122.0, 118.3, 67.0, 54.9, 41.5, 32.6,
mined by HPLC: Chiralcel OD-H, n-hexane, 0.8 mL min–1, λ = 210 nm;
55.80 min Rf(major enantiomer), 70.77 min Rf(minor enantiomer).
C18H23NO2, MW: 285.39 g/mol. [α]D23 = –20.0 (c = 0.59 g/dL, CHCl3,
sample with ee = 61 %). 1H NMR (300 MHz, CDCl3): δ = 7.58–7.50
[m, 2 H, phenyl C(2/6)H], 7.45–7.33 [m, 3 H, phenyl C(3/4/5)H], 5.72–
5.58 (m, 1 H, olefinic H), 5.41–5.28 (m, 1 H, olefinic H), 3.78 [s, 3 H,
C(O)OCH3], 3.11–3.00 (m, 1 H, qC-CH2-CH=CH), 2.83–2.72 (m, 1 H,
qC-CH2-CH=CH), 1.98 (q, J = 7.0 Hz, 2 H, CH=CH-CH2), 1.37–1.14 (m,
6 H, CH2-CH2-CH2-CH3), 0.87 (t, J = 7.0 Hz, 3 H, CH2-CH3) ppm. 13C
NMR (125 MHz, CDCl3): δ = 168.1, 138.2, 134.3, 129.2, 129.0, 126.4,
121.9, 118.3, 54.7, 54.0, 41.7, 32.6, 31.3, 28.9, 22.6, 14.2 ppm. IR
31.3, 30.4, 28.9, 22.6, 19.0, 14.2, 13.7 ppm. IR (in CDCl ): ν = 2959,
˜
3
2929, 2873, 2858, 1745, 1599, 1496, 1450, 1380, 1219, 1066, 1034,
972, 842, 762, 729, 696, 502 cm–1. MS (ESI): m/z (%) = 350.21 (100)
[M + Na]+. HRMS (ESI): m/z calcd. for C21H29NNaO2 [M + Na]+
350.2091; found 350.2075.
Isobutyl (R,E)-2-Cyano-2-phenyldec-4-enoate [(R)-3ad-iBu]: In
accordance with GP3 isobutyl 2-cyano-2-phenylacetate (1a-iBu;
9.0 μL, 9.1 mg, 0.04 mmol, 1.00 equiv.) was treated with oct-1-en-
3-yl acetate (2d; 16.4 μL, 14.3 mg, 0.08 mmol, 2.00 equiv.), sodium
acetate (0.7 mg, 0.01 mmol, 0.20 equiv.) and [FBIPP-Cl]2 (5.5 mg,
2.10 μmol, 5 mol-%) in 2,2,2-trifluoroethanol (210.2 μL) at 70 °C.
Column chromatography (silica gel, petroleum ether/ethyl acetate =
20:1) afforded the product as a colorless liquid as an inseparable
mixture of (E)- and (Z)-isomers [9.1 mg, 0.03 mmol, 66 %, ee = 66 %;
(E)/(Z) = 22:1]. The enantiomeric excess was determined by HPLC:
Chiralcel OD-H, n-hexane/iPrOH (99.8:0.2), 0.8 mL min–1, λ = 210 nm;
9.93 min Rf(major enantiomer), 11.25 min Rf(minor enantiomer).
C21H29NO2, MW: 327.47 g/mol. [α]D23 = –6.5 (c = 0.51 g/dL, CHCl3,
sample with ee = 66 %). 1H NMR (300 MHz, CDCl3): δ = 7.58–7.51
[m, 2 H, phenyl C(2/6)H], 7.45–7.34 [m, 3 H, phenyl C(3/4/5)H], 5.72–
5.58 (m, 1 H, olefinic H), 5.43–5.29 (m, 1 H, olefinic H), 4.03–3.86 [m,
2 H, C(O)OCH2CH(CH3)2], 3.12–3.01 (m, 1 H, qC-CH2-CH=CH), 2.83–
2.73 (m, 1 H, qC-CH2-CH=CH), 2.03–1.85 [m, 3 H, CH=CH-CH2,
C(O)OCH2CH(CH3)2], 1.37–1.14 (m, 6 H, CH2-CH2-CH2-CH3), 0.90–0.82
[m, 9 H, CH2-CH3, C(O)OCH2CH(CH3)2] ppm. 13C NMR (125 MHz,
CDCl3): δ = 167.5, 138.1, 134.5, 129.2, 128.9, 126.4, 122.0, 118.3, 72.9,
54.9, 41.4, 32.6, 31.3, 28.9, 27.8, 22.6, 18.91, 18.88, 14.2 ppm. IR
(in CDCl ): ν = 2956, 2927, 2856, 1748, 1599, 1495, 1450, 1435, 1378,
˜
3
1234, 1134, 973, 761, 730, 696, 505 cm–1. MS (ESI): m/z (%) = 308.16
(100) [M + Na]+. HRMS (ESI): m/z calcd. for C18H23NNaO2 [M + Na]+
308.1621; found 308.1615.
Benzyl (R,E)-2-Cyano-2-phenyldec-4-enoate [(R)-3ad-Bn]: In ac-
cordance with GP3 benzyl 2-cyano-2-phenylacetate (1a-Bn;
11.0 mg, 0.04 mmol, 1.00 equiv.) was treated with oct-1-en-3-yl
acetate (2d; 17.1 μL, 14.9 mg, 0.09 mmol, 2.00 equiv.), sodium
acetate (0.7 mg, 0.01 mmol, 0.20 equiv.) and [FBIPP-Cl]2 (5.7 mg,
2.19 μmol, 5 mol-%) in 2,2,2-trifluoroethanol (218.9 μL) at 70 °C.
Column chromatography (silica gel, petroleum ether/ethyl acetate =
20:1) afforded the product as a colorless liquid as an inseparable
mixture of (E)- and (Z)-isomers [12.0 mg, 0.03 mmol, 76 %, ee =
57 %; (E)/(Z) = 19:1]. The enantiomeric excess was determined by
HPLC: Chiralcel OD-H, n-hexane/iPrOH (99.5:0.5), 0.8 mL min–1, λ =
210 nm; 13.75 min Rf(major enantiomer), 15.53 min Rf(minor enanti-
omer). C24H27NO2, MW: 361.49 g/mol. [α]D23 = –7.6 (c = 0.6 g/dL,
CHCl3, sample with ee = 57 %). 1H NMR (300 MHz, CDCl3): δ = 7.54–
7.48 [m, 2 H, phenyl C(2/6)H], 7.42–7.34 [m, 3 H, phenyl C(3/4/5)H],
7.34–7.28 [m, 2 H, CH2-phenyl C(2/6)H], 7.26–7.21 [m, 3 H, CH2-
phenyl C(3/4/5)H], 5.69–5.56 (m, 1 H, olefinic H), 5.38–5.26 (m, 1 H,
olefinic H), 5.26–5.14 [m, 2 H, C(O)OCH2Ph], 3.12–3.01 (m, 1 H, qC-
(in CDCl3): ν = 2959, 2928, 2874, 2857, 1745, 1599, 1496, 1468, 1450,
˜
1394, 1372, 1222, 1034, 972, 942, 905, 729, 697, 650, 503 cm–1
.
MS (EI): m/z (%) = 327.2 (6) [M]+, 217.1 (34) [PhCH(CN)(CO2iBu)+],
161.0 (100) [PhCH(CN)(CO2H)]+. HRMS (EI): m/z calcd. for C21H29NO2
[M]+ 327.2198; found 327.2195.
q
CH2-CH=CH), 2.83–2.73 (m, 1 H, C-CH2-CH=CH), 2.00–1.89 (m, 2 H,
CH=CH-CH2), 1.35–1.12 (m, 6 H, CH2-CH2-CH2-CH3), 0.86 (t, J = tert-Butyl (R,E)-2-Cyano-2-phenyldec-4-enoate [(R)-3ad-tBu]: In
7.0 Hz, 3 H, CH2-CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 167.3,
accordance with GP3 tert-butyl 2-cyano-2-phenylacetate (1a-tBu;
138.2, 134.8, 134.2, 129.2, 129.0, 128.7, 128.6, 128.0, 126.4, 121.8, 9.0 mg, 0.04 mmol, 1.00 equiv.) was treated with oct-1-en-3-yl
118.2, 68.5, 54.9, 41.4, 32.6, 31.3, 28.8, 22.6, 14.2 ppm. IR (in CDCl3):
acetate (2d; 16.2 μL, 14.1 mg, 0.08 mmol, 2.00 equiv.), sodium ace-
ν = 3065, 3035, 2956, 2927, 2856, 1747, 1599, 1497, 1451, 1376,
tate (0.7 mg, 0.01 mmol, 0.20 equiv.) and [FBIPP-Cl]2 (5.4 mg,
˜
1252, 1215, 1029, 972, 911, 729, 696, 508 cm–1. MS (EI): m/z (%) = 2.07 μmol, 5 mol-%) in 2,2,2-trifluoroethanol (207.1 μL) at 70 °C.
Eur. J. Org. Chem. 2016, 210–227
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223
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Column chromatography (silica gel, petroleum ether/ethyl acetate = 6 H, CH2-CH2-CH2-CH3), 0.87 (t, J = 7.3 Hz, 3 H, CH2-CH3) ppm. 13C
20:1) afforded the product as a colorless liquid as an inseparable
NMR (125 MHz, CDCl3): δ = 167.7, 138.6, 133.3, 132.4, 128.2, 123.4,
mixture of (E)- and (Z)-isomers [4.4 mg, 0.01 mmol, 32 %, ee = 61 %; 121.4, 117.8, 54.3, 54.1, 41.6, 32.6, 31.3, 28.8, 22.6, 14.2 ppm. IR
(E)/(Z) = 8:1]. The enantiomeric excess was determined by HPLC:
Chiralcel OD-H, n-hexane, 0.8 mL min–1, λ = 210 nm; 25.17 min
Rf(major enantiomer), 36.51 min Rf(minor enantiomer). C21H29NO2,
(in CDCl3): ν = 2956, 2926, 2856, 1747, 1489, 1436, 1400, 1233, 1182,
˜
1077, 1011, 973, 824, 785, 747, 713, 511 cm–1. MS (EI): m/z (%) =
363.1 (5) [M]+, 253.0 (100) [ArCH(CN)(CO2Me)]+, 111.1 (93) [C8H15]+,
MW: 327.47 g/mol. [α]D23 = –6.2 (c = 0.41 g/dL, CHCl3, sample with 69.1 (95) [C5H8]+. HRMS (ESI): m/z calcd. for C18H22BrNNaO2
ee = 55 %). 1H NMR (300 MHz, CDCl3): δ = 7.56–7.50 [m, 2 H, phenyl [M + Na]+ 386.0726; found 386.0716.
C(2/6)H], 7.43–7.31 [m, 3 H, phenyl C(3/4/5)H], 5.71–5.58 (m, 1 H,
Methyl (R,E)-2-Cyano-2-(3-fluorophenyl)dec-4-enoate [(R)-3cd-
q
olefinic H), 5.43–5.31 (m, 1 H, olefinic H), 3.06–2.96 (m, 1 H, C-CH2-
Me]: In accordance with GP3 methyl 2-cyano-2-(3-fluorophenyl)-
CH=CH), 2.76–2.66 (m, 1 H, qC-CH2-CH=CH), 2.04–1.94 (m, 2 H, CH=
acetate (1c-Me; 18.1 mg, 0.09 mmol, 1.00 equiv.) was treated with
CH-CH2), 1.43 [s, 9 H, C(O)C(CH3)3], 1.37–1.16 (m, 6 H, CH2-CH2-CH2-
oct-1-en-3-yl acetate (2d; 36.3 μL, 31.9 mg, 0.19 mmol, 2.00 equiv.),
sodium acetate (1.5 mg, 0.02 mmol, 0.20 equiv.) and [FBIPP-Cl]2
(12.2 mg, 4.68 μmol, 5 mol-%) in 2,2,2-trifluoroethanol (468.5 μL) at
CH3), 0.87 (t, J = 6.9 Hz, 3 H, CH2-CH3) ppm. 13C NMR (125 MHz,
CDCl3): δ = 166.3, 137.8, 135.0, 129.1, 128.7, 126.3, 122.2, 118.7, 84.3,
55.4, 41.4, 32.6, 31.3, 28.9, 27.8, 27.7, 22.6, 14.2 ppm. IR (in CDCl3):
70 °C. Column chromatography (silica gel, petroleum ether/ethyl
ν = 2957, 2927, 2856, 1738, 1599, 1495, 1451, 1395, 1370, 1254,
˜
acetate = 20:1) afforded the product as a colorless liquid as an
inseparable mixture of (E)- and (Z)-isomers [21.3 mg, 0.07 mmol,
75 %, ee = 39 %; (E)/(Z) = 20:1]. The enantiomeric excess was deter-
mined by HPLC: Chiralcel OD-H, n-hexane, 0.8 mL min–1, λ = 210 nm;
38.30 min Rf(major enantiomer), 41.15 min Rf(minor enantiomer).
C18H22FNO2, MW: 303.38 g/mol. [α]D23 = –16.5 (c = 0.20 g/dL, CH2Cl2,
sample with ee = 39 %). 1H NMR (300 MHz, CDCl3): δ = 7.41–7.32
1153, 1072, 1034, 972, 840, 758, 738, 697, 505 cm–1. MS (ESI): m/z
(%) = 350.21 (100) [M + Na]+, 310.14 (60) [M – C4H8 + Na]+.
HRMS (ESI): m/z calcd. for C21H29NNaO2 [M + Na]+ 350.2091; found
350.2089.
Methyl (R,E)-2-Cyano-2-phenyloct-4-enoate [(R)-3ac-Me]: In ac-
cordance with GP3 methyl 2-cyano-2-phenylacetate (1a-Me; 7.5 μL,
8.2 mg, 0.05 mmol, 1.00 equiv.) was treated with hex-1-en-3-yl ace- [m, 2 H, phenyl C(5/6)H], 7.30–7.23 [m, 1 H, phenyl C(2)H], 7.11–7.00
tate (2c; 13.3 mg, 0.09 mmol, 2.00 equiv.), sodium acetate (0.8 mg, [m, 1 H, phenyl C(4)H], 5.69–5.60 (m, 1 H, olefinic H), 5.37–5.29 (m,
0.01 mmol, 0.20 equiv.) and [FBIPP-Cl]2 (6.1 mg, 2.34 μmol, 5 mol- 1 H, olefinic H), 3.78 [s, 3 H, C(O)OCH3], 3.07–3.00 (m, 1 H, qC-CH2-
q
%) in 2,2,2-trifluoroethanol (234.0 μL) at 70 °C. Column chromatog- CH=CH), 2.81–2.73 (m, 1 H, C-CH2-CH=CH), 1.98 (q, J = 7.2 Hz, 2 H,
raphy (silica gel, petroleum ether/ethyl acetate = 20:1) afforded the
product as a colorless liquid as an inseparable mixture of (E)- and
(Z)-isomers [9.0 mg, 0.03 mmol, 75 %, ee = 63 %; (E)/(Z) = 19:1]. The
enantiomeric excess was determined by HPLC: Chiralcel OD-H, n-
CH=CH-CH2), 1.35–1.16 (m, 6 H, CH2-CH2-CH2-CH3), 0.87 (t, J =
6.9 Hz, 3 H, CH2-CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 167.6,
163.0, 138.6, 136.6, 130.8, 122.2, 121.5, 117.8, 116.1, 113.9, 54.1, 41.7,
32.6, 31.3, 28.8, 22.6, 14.1 ppm. 19F NMR (235 MHz, CDCl3): δ =
hexane, 0.8 mL min–1, λ = 210 nm; 53.60 min Rf(major enantiomer), –73.64, –110.90 ppm. IR (in CDCl3): ν = 2957, 2927, 2857, 1748, 1613,
˜
72.73 min Rf(minor enantiomer). C16H19NO2, MW: 257.33 g/mol. 1592, 1489, 1436, 1232, 1182, 1153, 973, 880, 846, 785, 731, 689,
[α]D23 = –20.3 (c = 0.59 g/dL, CHCl3, sample with ee = 63 %). 1H NMR 526, 454 cm–1. MS (EI): m/z (%) = 303.2 (3) [M]+, 193.1 (100)
(300 MHz, CDCl3): δ = 7.58–7.51 [m, 2 H, phenyl C(2/6)H], 7.44–7.33
[m, 3 H, phenyl C(3/4/5)H], 5.71–5.59 (m, 1 H, olefinic H), 5.41–5.28
(m, 1 H, olefinic H), 3.78 [s, 3 H, C(O)OCH3], 3.12–3.01 (m, 1 H, qC-
[ArCH(CN)(CO2Me)]+, 111.1 (77) [C8H15]+, 69.1 (89) [C5H8]+.
HRMS (ESI): m/z calcd. for C18H22FNNaO2 [M + Na]+ 326.1527; found
326.1522.
q
CH2-CH=CH), 2.83–2.72 (m, 1 H, C-CH2-CH=CH), 1.97 (q, J = 7.0 Hz,
Methyl (R,E)-2-Cyano-2-(3-methoxyphenyl)dec-4-enoate [(R)-
3dd-Me]: In accordance with GP3 methyl 2-cyano-2-(3-methoxy-
phenyl)acetate (1d-Me; 18.0 mg, 0.09 mmol, 1.00 equiv.) was treated
with oct-1-en-3-yl acetate (2d; 34.0 μL, 29.9 mg, 0.18 mmol,
2.00 equiv.), sodium acetate (1.4 mg, 0.02 mmol, 0.20 equiv.) and
[FBIPP-Cl]2 (11.5 mg, 4.39 μmol, 5 mol-%) in 2,2,2-trifluoroethanol
(438.6 μL) at 70 °C. Column chromatography (silica gel, petroleum
ether/ethyl acetate = 20:1) afforded the product as a colorless liquid
as an inseparable mixture of (E)- and (Z)-isomers [16.0 mg,
0.05 mmol, 58 %, ee = 52 %; (E)/(Z) = 23:1]. The enantiomeric excess
2 H, CH=CH-CH2), 1.41–1.27 (m, 2 H, CH2-CH3), 0.84 (t, J = 7.3 Hz, 3
H, CH2-CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 168.0, 138.0, 134.3,
129.2, 129.0, 126.3, 122.1, 118.3, 54.7, 54.0, 41.7, 34.7, 22.4,
13.6 ppm. IR (in CDCl ): ν = 2958, 2929, 2872, 2246, 1747, 1599,
˜
3
1495, 1450, 1435, 1379, 1232, 1184, 1144, 1048, 971, 761, 730, 696,
651, 507 cm–1. MS (ESI): m/z (%) = 280.13 (100) [M + Na]+.
HRMS (ESI): m/z calcd. for C16H19NNaO2 [M + Na]+ 280.1308; found
280.1292.
Methyl (R,E)-2-(4-Bromophenyl)-2-cyanodec-4-enoate [(R)-3bd-
Me]: In accordance with GP3 methyl 2-(4-bromophenyl)-2-cyano-
acetate (1b-Me; 24.1 mg, 0.10 mmol, 1.00 equiv.) was treated with
oct-1-en-3-yl acetate (2d; 36.8 μL, 32.3 mg, 0.19 mmol, 2.00 equiv.),
was determined by HPLC: Chiralcel AS-H, n-hexane, 1.3 mL min–1
,
λ = 210 nm; 29.15 min Rf(major enantiomer), 42.78 min Rf(minor
enantiomer). C19H25NO3, MW: 315.41 g/mol. [α]D23 = –24.3 (c =
sodium acetate (1.6 mg, 0.02 mmol, 0.20 equiv.) and [FBIPP-Cl]2 0.10 g/dL, CH2Cl2, sample with ee = 52 %). 1H NMR (500 MHz,
(12.4 mg, 4.74 μmol, 5 mol-%) in 2,2,2-trifluoroethanol (474.3 μL) at
70 °C. Column chromatography (silica gel, petroleum ether/ethyl
CDCl3): δ = 7.31 [t, J = 8.2 Hz, 1 H, phenyl C(5)H], 7.15–7.05 [m, 2
H, phenyl C(2/6)H], 6.89 [dd, J = 1.2, 8.2 Hz, 3 H, phenyl C(4)H], 5.69–
acetate = 20:1) afforded the product as a colorless liquid as an 5.61 (m, 1 H, olefinic H), 5.39–5.30 (m, 1 H, olefinic H), 3.82 (s, 3 H,
inseparable mixture of (E)- and (Z)-isomers [19.3 mg, 0.05 mmol,
phenylOCH3), 3.78 [s, 3 H, C(O)OCH3], 3.07–3.00 (m, 1 H, qC-CH2-
q
56 %, ee = –54 %; (E)/(Z) = 15:1]. The enantiomeric excess was deter- CH=CH), 2.81–2.73 (m, 1 H, C-CH2-CH=CH), 1.99 (q, J = 6.9 Hz, 2 H,
mined by HPLC: Chiralcel OD-H, n-hexane, 1.3 mL min–1, λ = 210 nm;
29.55 min Rf(minor enantiomer), 33.68 min Rf(major enantiomer).
CH=CH-CH2), 1.35–1.17 (m, 6 H, CH2-CH2-CH2-CH3), 0.87 (t, J =
6.9 Hz, 3 H, CH2-CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 167.9,
C18H22BrNO2, MW: 364.28 g/mol. [α]D23 = –25.0 (c = 0.10 g/dL, CH2Cl2, 160.2, 138.2, 135.7, 130.2, 121.9, 118.5, 118.2, 114.3, 112.4, 55.5, 54.7,
1
sample with ee = –54 %). H NMR (300 MHz, CDCl3): δ = 7.56–7.51
[m, 2 H, phenyl C(3/5)H], 7.45–7.39 [m, 3 H, phenyl C(2/6)H], 5.69–
5.59 (m, 1 H, olefinic H), 5.37–5.27 (m, 1 H, olefinic H), 3.79 [s, 3 H,
C(O)OCH3], 3.06–2.99 (m, 1 H, qC-CH2-CH=CH), 2.79–2.72 (m, 1 H,
54.0, 41.6, 32.6, 31.3, 28.9, 22.6, 14.2 ppm. IR (in CDCl ): ν = 2956,
˜
3
2927, 2856, 1748, 1602, 1586, 1491, 1453, 1435, 1294, 1233, 1177,
1157, 1047, 973, 876, 780, 729, 694, 568, 456 cm–1. MS (EI): m/z
(%) = 315.2 (6) [M]+, 205.1 (100) [ArCH(CN)(CO2Me)]+, 173.1 (42)
qC-CH2-CH=CH), 1.98 (q, J = 6.9 Hz, 2 H, CH=CH-CH2), 1.35–1.15 (m, [ArCH(CN)(CO2Me) – OMe]+, 111.1 (11) [C8H15]+, 69.1 (22) [C5H8]+.
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HRMS (ESI): m/z calcd. for C19H25NNaO3 [M + Na]+ 338.1727; found
338.1738.
(9.9 mg, 3.79 μmol, 5 mol-%) in 2,2,2-trifluoroethanol (378.6 μL) at
70 °C. Column chromatography (silica gel, petroleum ether/ethyl
acetate = 20:1) afforded the product as a colorless liquid as an
inseparable mixture of (E)- and (Z)-isomers [7.5 mg, 0.03 mmol,
33 %, ee = 48 %; (E)/(Z) = 18:1]. The enantiomeric excess was deter-
mined by HPLC: Chiralcel OD-H, n-hexane, 1.3 mL min–1, λ = 210 nm;
38.05 min Rf(major enantiomer), 96.07 min Rf(minor enantiomer).
Methyl (R,E)-2-Cyano-2-(2-naphthalen-2-yl)dec-4-enoate [(R)-
3ed-Me]: In accordance with GP3 methyl 2-cyano-2-(2-naphthalen-
2-yl)acetate (1e-Me; 18.5 mg, 0.08 mmol, 1.00 equiv.) was treated
with oct-1-en-3-yl acetate (2d; 31.8 μL, 27.9 mg, 0.16 mmol,
2.00 equiv.), sodium acetate (1.3 mg, 0.02 mmol, 0.20 equiv.) and
[FBIPP-Cl]2 (10.7 mg, 4.10 μmol, 5 mol-%) in 2,2,2-trifluoroethanol
(409.5 μL) at 70 °C. Column chromatography (silica gel, petroleum
ether/ethyl acetate = 20:1) afforded the product as a colorless liquid
as an inseparable mixture of (E)- and (Z)-isomers [16.8 mg,
0.05 mmol, 61 %, ee = –60 %; (E)/(Z) = 18:1]. The enantiomeric
excess was determined by HPLC: Chiralcel OD-H, n-hexane,
1.3 mL min–1, λ = 210 nm; 74.81 min Rf(minor enantiomer),
106.55 min Rf(major enantiomer). C22H25NO2, MW: 335.45 g/mol.
[α]D23 = –35.0 (c = 0.10 g/dL, CH2Cl2, sample with ee = –60 %). 1H
NMR (300 MHz, CDCl3): δ = 8.07–8.04 [m, 1 H, naphthyl C(8)H], 7.91–
7.82 [m, 3 H, naphthyl C(1/4/5)H], 7.62–7.51 [m, 3 H, naphthyl C(3/
6/7)H], 5.71–5.65 (m, 1 H, olefinic H), 5.42–5.33 (m, 1 H, olefinic H),
3.79 [s, 3 H, C(O)OCH3], 3.18–3.12 (m, 1 H, qC-CH2-CH=CH), 2.94–
2.87 (m, 1 H, qC-CH2-CH=CH), 1.97 (q, J = 7.0 Hz, 2 H, CH=CH-CH2),
1.33–1.13 (m, 6 H, CH2-CH2-CH2-CH3), 0.83 (t, J = 7.0 Hz, 3 H, CH2-
CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 168.1, 138.3, 133.21,
133.18, 131.5, 129.2, 128.5, 127.7, 127.2, 127.0, 126.2, 123.3, 121.9,
118.4, 54.8, 54.0, 41.5, 32.6, 31.3, 28.9, 22.6, 14.1 ppm. IR (in CDCl3):
C
19H23NO2, MW: 297.40 g/mol. [α]D23 = –21.7 (c = 0.06 g/dL, CH2Cl2,
sample with ee = 48 %). 1H NMR (500 MHz, CDCl3): δ = 7.58–7.50
[m, 2 H, phenyl C(2/6)H], 7.44–7.33 [m, 3 H, phenyl C(3/4/5)H], 5.62–
5.54 (m, 1 H, olefinic H), 5.37–5.26 (m, 1 H, olefinic H), 3.78 [s, 3 H,
C(O)OCH3], 3.08–2.99 (m, 1 H, qC-CH2-CH=CH), 2.80–2.72 (m, 1 H,
qC-CH2-CH=CH), 1.97–1.86 [m, 1 H, H2C=CH-CH(O)-CH], 1.73–1.57
(m, 5 H, cyclohexyl CH2), 1.34–0.90 (m, 5 H, cyclohexyl CH2) ppm.
13C NMR (125 MHz, CDCl3): δ = 168.1, 144.0, 134.3, 129.2, 129.0,
126.4, 119.5, 118.2, 54.8, 53.9, 41.7, 40.8, 32.9, 32.8, 26.2, 26.0 ppm.
IR (in CDCl ): ν = 2923, 2850, 1746, 1495, 1449, 1435, 1231, 1035,
˜
3
970, 843, 760, 730, 696, 505 cm–1. MS (EI): m/z (%) = 297.2 (2) [M]+,
175.0 (60) [PhCH(CN)(CO2Me)]+, 123.1 (100) [C9H15]+, 81.0 (60)
[C6H9]+, 67.0 (25) [C5H7]+. HRMS (ESI): m/z calcd. for C19H23NNaO2
[M + Na]+ 320.1621; found 320.1612.
Methyl (R,E)-2-Cyano-7-methyl-2-phenyloct-4-enoate [(R)-3ah-
Me]: In accordance with GP3 methyl 2-cyano-2-phenylacetate (1a-
Me; 17.7 μL, 18.6 mg, 0.11 mmol, 1.00 equiv.) was treated with 5-
methylhex-1-en-3-yl acetate (2h; 33.2 mg, 0.21 mmol, 2.00 equiv.),
sodium acetate (1.7 mg, 0.02 mmol, 0.20 equiv.) and [FBIPP-Cl]2
(13.9 mg, 5.31 μmol, 5 mol-%) in 2,2,2-trifluoroethanol (531.3 μL) at
70 °C. Column chromatography (silica gel, petroleum ether/ethyl
acetate = 20:1) afforded the product as a colorless liquid as an
inseparable mixture of (E)- and (Z)-isomers [9.2 mg, 0.03 mmol,
32 %, ee = 48 %; (E)/(Z) = 14:1]. The enantiomeric excess was deter-
mined by HPLC: Chiralcel OD-H, n-hexane, 1.3 mL min–1, λ = 210 nm;
31.74 min Rf(major enantiomer), 46.21 min Rf(minor enantiomer).
C17H21NO2, MW: 271.36 g/mol. [α]D23 = –19.0 (c = 0.20 g/dL, CH2Cl2,
sample with ee = 48 %). 1H NMR (500 MHz, CDCl3): δ = 7.58–7.51
[m, 2 H, phenyl C(2/6)H], 7.44–7.33 [m, 3 H, phenyl C(3/4/5)H], 5.69–
5.59 (m, 1 H, olefinic H), 5.39–5.29 (m, 1 H, olefinic H), 3.78 [s, 3 H,
C(O)OCH3], 3.11–3.04 (m, 1 H, qC-CH2-CH=CH), 2.84–2.76 (m, 1 H,
qC-CH2-CH=CH), 1.88 [t, J = 7.0 Hz, 2 H, CH2-CH(CH3)2], 1.59–1.51
[m, 1 H, CH2-CH(CH3)2], 0.83 [d, J = 7.0 Hz, 3 H, CH2-CH(CH3)2], 0.82
[d, J = 7.0 Hz, 3 H, CH2-CH(CH3)2] ppm. 13C NMR (125 MHz, CDCl3):
δ = 168.1, 136.9, 134.3, 129.2, 129.0, 126.3, 123.0, 118.3, 54.7, 54.0,
ν = 2955, 2926, 2855, 1747, 1599, 1509, 1435, 1364, 1232, 1183,
˜
1046, 972, 895, 858, 816, 750, 723, 477 cm–1. MS (EI): m/z (%) =
335.2 (6) [M]+, 225.1 (100) [ArCH(CN)(CO2Me)]+, 193.1 (17)
[ArCH(CN)(CO2Me) – OMe]+. HRMS (ESI): m/z calcd. for C22H25NNaO2
[M + Na]+ 358.1778; found 358.1787.
Methyl (R,E)-2-Cyano-2-(2-m-tolyl)dec-4-enoate [(R)-3fd-Me]: In
accordance with GP3 methyl 2-cyano-2-(2-m-tolyl)acetate (1f-Me;
19.0 mg, 0.10 mmol, 1.00 equiv.) was treated with oct-1-en-3-yl
acetate (2d; 38.9 μL, 34.2 mg, 0.20 mmol, 2.00 equiv.), sodium
acetate (1.6 mg, 0.02 mmol, 0.20 equiv.) and [FBIPP-Cl]2 (13.1 mg,
5.02 μmol, 5 mol-%) in 2,2,2-trifluoroethanol (502.1 μL) at 70 °C.
Column chromatography (silica gel, petroleum ether/ethyl acetate =
20:1) afforded the product as a colorless liquid as an inseparable
mixture of (E)- and (Z)-isomers [13.4 mg, 0.05 mmol, 45 %, ee =
69 %; (E)/(Z) = 36:1]. The enantiomeric excess was determined by
HPLC: Chiralcel OD-H, n-hexane, 1.3 mL min–1, λ = 210 nm;
32.74 min Rf(major enantiomer), 39.71 min Rf(minor enantiomer).
C19H25NO2, MW: 299.41 g/mol. [α]D23 = –12.0 (c = 0.10 g/dL, CH2Cl2,
sample with ee = 69 %). 1H NMR (300 MHz, CDCl3): δ = 7.36–7.26
[m, 3 H, phenyl C(2/5/6)H], 7.19–7.14 [m, 1 H, phenyl C(4)H], 5.70–
5.61 (m, 1 H, olefinic H), 5.39–5.30 (m, 1 H, olefinic H), 3.78 [s, 3 H,
C(O)OCH3], 3.08–3.00 (m, 1 H, qC-CH2-CH=CH), 2.80–2.71 (m, 1 H,
qC-CH2-CH=CH), 2.38 (s, 3 H, Ar-CH3) 1.99 (q, J = 7.2 Hz, 2 H, CH=
CH-CH2), 1.35–1.16 (m, 6 H, CH2-CH2-CH2-CH3), 0.87 (t, J = 7.3 Hz, 3
H, CH2-CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 168.1, 139.1, 138.1,
134.2, 129.8, 129.1, 127.0, 123.3, 122.0, 118.4, 54.6, 53.9, 41.6, 33.0,
41.9, 41.7, 28.3, 22.27, 22.26 ppm. IR (in CDCl3): ν = 2955, 2926,
˜
1747, 1495, 1450, 1385, 1367, 1233, 1184, 1035, 972, 759, 730, 697,
507 cm– 1 . MS (EI): m/z (%) = 271.2 (2) [M]+ , 175.0 (100)
[PhCH(CN)(CO2Me)]+, 143.0 (17) [C9H5NO]+, 97.1 (66) [C7H13]+, 55.1
(40) [C4H7]+. HRMS (ESI): m/z calcd. for C17H21NNaO2 [M + Na]+
294.1465; found 294.1466.
Methyl (R,E)-2-Cyano-6-methyl-2-phenylhept-4-enoate [(R)-3ai-
Me]: In accordance with GP3 methyl 2-cyano-2-phenylacetate (1a-
Me; 17.3 μL, 18.2 mg, 0.10 mmol, 1.00 equiv.) was treated with 4-
methylprop-1-en-3-yl acetate (2i; 29.5 mg, 0.21 mmol, 2.00 equiv.),
sodium acetate (1.7 mg, 0.02 mmol, 0.20 equiv.) and [FBIPP-Cl]2
(13.5 mg, 5.19 μmol, 5 mol-%) in 2,2,2-trifluoroethanol (518.6 μL) at
70 °C. Column chromatography (silica gel, petroleum ether/ethyl
acetate = 20:1) afforded the product as a colorless liquid as an
inseparable mixture of (E)- and (Z)-isomers [4.4 mg, 0.02 mmol,
16 %, ee = 46 %; (E)/(Z) = 17:1]. The enantiomeric excess was deter-
mined by HPLC: Chiralcel OD-H, n-hexane, 1.3 mL min–1, λ = 210 nm;
30.44 min Rf(major enantiomer), 66.23 min Rf(minor enantiomer).
C16H19NO2, MW: 257.33 g/mol. [α]D23 = –14.1 (c = 0.10 g/dL, CH2Cl2,
sample with ee = 46 %). 1H NMR (500 MHz, CDCl3): δ = 7.58–7.50
[m, 2 H, phenyl C(2/6)H], 7.44–7.33 [m, 3 H, phenyl C(3/4/5)H], 5.64–
31.3, 28.9, 22.6, 21.7, 14.2 ppm. IR (in CDCl3): ν = 2956, 2926, 2856,
˜
1747, 1607, 1489, 1435, 1379, 1230, 1180, 1045, 971, 784, 128, 697,
439 cm– 1 . MS (EI): m/z (%) = 299.2 (5) [M]+ , 189.1 (100)
[ArCH(CN)(CO2Me)]+, 157.1 (20) [ArCH(CN)(CO2Me) – OMe]+, 111.1
(18) [C8H15]+, 69.1 (20) [C5H8]+. HRMS (ESI): m/z calcd. for
C19H25NNaO2 [M + Na]+ 322.1778; found 322.1781.
Methyl (R,E)-2-Cyano-5-cyclohexyl-2-phenylpent-4-enoate [(R)-
3ag-Me]: In accordance with GP3 methyl 2-cyano-2-phenylacetate
(1a-Me; 12.6 μL, 13.3 mg, 0.08 mmol, 1.00 equiv.) was treated with
1-cyclohexylallyl acetate (2g; 27.6 mg, 0.15 mmol, 2.00 equiv.), so-
dium acetate (1.2 mg, 0.02 mmol, 0.20 equiv.) and [FBIPP-Cl]2
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5.55 (m, 1 H, olefinic H), 5.35–5.26 (m, 1 H, olefinic H), 3.78 [s, 3 H,
C(O)OCH3], 3.08–2.99 (m, 1 H, qC-CH2-CH=CH), 2.80–2.72 (m, 1 H,
qC-CH2-CH=CH), 2.30–2.18 [m, 1 H, CH(CH3)2], 0.93 [d, J = 7.0 Hz, 3
H, CH(CH3)2], 0.92 [d, J = 7.0 Hz, 3 H, CH(CH3)2] ppm. 13C NMR
(125 MHz, CDCl3): δ = 168.1, 145.2, 134.3, 129.2, 129.0, 126.4, 119.0,
[12]
[13]
[14]
118.2, 54.8, 53.9, 41.6, 31.3, 22.4, 22.3 ppm. IR (in CDCl3): ν = 2958,
˜
2928, 2870, 1748, 1495, 1450, 1435, 1246, 1034, 973, 762, 731, 670,
507 cm–1
. MS (EI): m/z (%) =
257.1 (3) [M]+, 175.0 (75)
[PhCH(CN)(CO2Me)]+, 143.0 (16) [C9H5NO]+, 83.1 (100) [C6H11]+.
HRMS (ESI): m/z calcd. for C16H19NNaO2 [M + Na]+ 280.1308; found
280.1305.
Acknowledgments
This work was financially supported by the Deutsche For-
schungsgemeinschaft (DFG) (PE 818/6-1). The Fonds der Chem-
ischen Industrie (FCI) and the Landesgraduiertenförderung
Baden-Württemberg, Germany are kindly acknowledged for
Ph. D. fellowships to M. W.
[15]
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After this finding, a number of additional acetate bases (0.2 equiv.) were
screened in combination with [FBIPP-Cl]2. None of them resulted in a
higher reactivity and the enantioselectivity could only slightly be im-
proved: Ca(OAc)2: 11 % yield/65 % ee; Mn(OAc)2: 15 % yield/63 % ee;
Zn(OAc)2: 46 % yield/57 % ee; and CsOAc: 64 % yield/53 % ee.
X-ray crystal structure analysis was not applicable as products 3 are oils.
The absolute configuration of compound 3ad-tBu (Table 5, Entry 10) was
determined as (R) by chemical correlation (see the Supporting Informa-
tion). The absolute configuration of other compounds 3 was assigned
by analogy.
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Keywords: Synthetic methods · Homogeneous catalysis ·
Sandwich complexes · Palladium · Platinum
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