Stereoselectivity in the rhodium-catalysed reductions of nonconjugated dienes

Article abstract of DOI:10.1002/adsc.200900013

The stereochemical course of rhodium-catalysed addition of hydrogen and catecholborane to bicyclo[2.2.1]heptadiene, and of hydrogen to a range of cyclic dienes has been analysed. For hydroboration, the overall catalytic reaction possesses exo-selectivity, but the initial step is endo-selective. For hydrogenation (deuteration), the first step may occur with either exo- or endo- selectivity, depending on the structure of the diene. This enables a distinction to be made between pathways involving prior dissociation of the diene, and direct addition to the complexed diene without full dissociation. The relative ease of hydrogenation of the first and second doublebonds varies markedly with reactant structure, and also depends on the choice of catalyst ligands. For dicyclopentadiene, hydrogenation of the cyclopentene double bond is accompanied by rapid alkene isomerisation, as revealed by deuterium addition. The asymmetric hydrogenation of acyclic skipped mesodienes is reported, demonstrating control of relative rates of the two sequential steps, with ees of up to 53% after the first reduction.

Full text of DOI:10.1002/adsc.200900013

FULL PAPERS
DOI: 10.1002/adsc.200900013
Stereoselectivity in the Rhodium-Catalysed Reductions of Non-
Conjugated Dienes
Bao Nguyena and John M. Browna,*
a
Chemistry Research Laboratory, Oxford University, Mansfield Rd., Oxford OX1 3TA, UK
Fax : (+44)-1865-285-002; e-mail: john.brown@chem.ox.ac.uk
Received: January 10, 2009; Published online: April 16, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900013.
Abstract: The stereochemical course of rhodium-cat- bonds varies markedly with reactant structure, and
alysed addition of hydrogen and catecholborane to also depends on the choice of catalyst ligands. For di-
bicycloACHTUNGTRENNUNG[2.2.1]heptadiene, and of hydrogen to a range cyclopentadiene, hydrogenation of the cyclopentene
of cyclic dienes has been analysed. For hydrobora- double bond is accompanied by rapid alkene isomer-
tion, the overall catalytic reaction possesses exo-se- isation, as revealed by deuterium addition. The
lectivity, but the initial step is endo-selective. For hy- asymmetric hydrogenation of acyclic skipped meso-
drogenation (deuteration), the first step may occur dienes is reported, demonstrating control of relative
with either exo- or endo- selectivity, depending on rates of the two sequential steps, with ees of up to
the structure of the diene. This enables a distinction 53% after the first reduction.
to be made between pathways involving prior disso-
ciation of the diene, and direct addition to the com-
plexed diene without full dissociation. The relative Keywords: dienes; hydroboration; hydrogenation;
ease of hydrogenation of the first and second double rhodium; stereoselectivity
Introduction
bornene (NBE).[2] The first case to be studied was the
Rh complex-catalysed hydroformylation of NBE,
Depending on the structure of the reactant, product where exo-selectivity prevailed.[3] This was endorsed
and catalyst, hydrogenation and other catalysed reac- and extended to Pt complex-catalysed hydroformyla-
tions of an alkene may exhibit diastereo-, regio- or tion, and NBD was also shown to hydroformylate pre-
enantioselectivity. For a dialkene, the chemoselectivi- dominantly but not exclusively at the exo-face. It was
ty of the first step requires additional consideration. also demonstrated that cis-addition of D2/CO to NBE
In many cases, the desired selectivity is obtained by occurred.[4] An efficient exo-specific Rh-catalysed
involvement of a neighbouring directing group that asymmetric hydroformylation of NBE has been dem-
engages the metal in chelate binding.[1] In the present onstrated.[5] These results contrast with chelation-pro-
context, our interest lay in the hydrogenation of non- moted Rh complex-catalysed hydroacylation of al-
conjugated dienes, where there is the potential to kenes with salicylaldehyde. endo-Hydroacylation of
employ one double bond as directing group, exerting NBD occurs, whereas exo-addition occurs to NBE,
stereochemical control of reagent addition to the both with high selectivity.[6] In an extensive search for
other. This paper presents exploratory work in cyclic an enantioselective variant, Bolm and co-workers
systems, examining the course of addition as a func- found wide variability in the stereochemical course of
tion of diene structure. A preliminary investigation the hydroacylation of NBD, with Rh phosphoramidite
into the asymmetric hydrogenation of acyclic meso-al- complexes endo-selective but diphosphine complexes
kenes is reported.
giving both exo- and endo-diastereoisomers. Related
Metal-catalysed additions to both bicyclo- reactions with NBE were exo-selective.[7] Hydroami-
ACHTUNGTRENNUNG
[14]
agents invariably add from the exo-direction to nor- plexes,[13] C H addition of terminal alkynes,
and
À
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Bao Nguyen[a] and John M. Brown
FULL PAPERS
Figure 1. Stereochemical course of catalytic addition reactions to norbornadiene 1 and norbornene 2.
catalysed alkyne cycloaddition,[15] and catalytic annu- Hydrogenation versus Hydroboration of
lation,[16] of NBE are all exo-selective. Several of Bicyclo
these reactions give exo-specific addition with norbor-
ACHTUNGTREN[NUNG 2.2.1]heptadienes
nadiene as well.[10,11,16] The main product reported Hydrogenation of NBD
during Rh complex-catalysed asymmetric hydrobora-
tion/oxidation of NBD is the exo-exo-2,6-diol. exo- Norbornadiene 1 (NBD) and cycloocta-1,5-diene
Addition to norbornadiene occurs in hydroallylation (COD) feature almost equally as stabilising ligands in
with allyl formate,[17] some Pauson–Khand reac- precatalysts for rhodium asymmetric hydrogenations.
tions,[18] Ru-catalysed cycloadditions,[19] and terminal For this reason considerable attention has been given
alkyne additions.[20] Aside from the hydroacylations to the reaction step that liberates the active catalyst,
and hydrogenation described above, only the Pauson– normally a diphosphine-rhodium solvate.[26] Since the
Khand reaction with enynes is endo-selective.[21] reduction of norbornadiene is normally much the
Hence all catalysed additions to norbornene are exo- faster of the two, claims and counterclaims have been
selective, and a clear majority of additions to norbor- made about their relative efficiency as precursor li-
nadiene are likewise. These results are summarised in gands in hydrogenation. On a laboratory scale with
Figure 1.
comparatively low catalyst/substrate ratios, hydroge-
The general consistency of results obtained with nation of the stabilising ligand is competitive with the
NBE 2 is in accord with the preferred exo-complexa- desired process, particularly when COD is em-
tion of the alkene that is observed in structurally char- ployed.[27] On a larger scale with commensurately
acterised complexes.[22] These include at least one ex- higher ratios, this is less so.[28]
ample for which the bridging methylene group pro-
Given these precedents,[29] NBD has provided a
À
vides an agostic C H interaction with the metal benchmark for study of diene reductions; reactive in-
centre,[23] and one with an agostic Pt H C1 arrange- termediates in the addition of H2 to NBDRh-
À À
ment.[24] The variable behaviour of NDB 1 is more in-
(PPh3)2BF4 in CH2Cl2 have been studied.[30] In our
ACHTUNGTRENNUNG
triguing. Preferred bidentate endo-coordination of own monitoring of the uptake of hydrogen by NBD,
NBD in transition metal complexes is well estab- it was observed that catalysis by complex 3 showed
lished, and exemplified in the common precatalysts successive fast and slow phases for the two stages. By
for rhodium asymmetric hydrogenation. In rarer ex- contrast, the first phase in catalysis by complex 4 was
amples where NBD is singly h2-coordinated to Ag, Cu slower than the second phase. Hydrogenation of
or Mn, bonding invariably occurs to the exo-face.[25] NBD with various P2Rh
ACTHNUTRGNE(UNG NBD) complexes has been
This implies that the stereochemical course of addi- studied by Heller et al., and variability of the rates of
tion to NBD reveals whether one or both double hydrogenation of the first and second double bonds
bonds are coordinated during the transfer process.
Results and Discussion
In the following sections a comparison of the addition
of hydrogen and secondary boron hydrides to norbor-
nadiene 1 is discussed first, followed by a survey of
the course of hydrogenation of non-conjugated cyclic
dienes. The final section concerns the asymmetric hy-
drogenation of an acyclic skipped diene.
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Stereoselectivity in the Rhodium-Catalysed Reductions of Non-Conjugated Dienes
FULL PAPERS
was observed and interpreted in their work.[31] The
postulated course of deuterium addition to NBD,[32]
catalysed by complexes 3 or 4, was re-examined and
2
confirmed in the present work. The H NMR of the
fully reduced norbornane (NBA) shows equal
amounts of exo- and endo-deuteration at the 2,3,5,6-
positions. As also previously indicated,[20] the first
step occurs to produce endo-d2-norbornene. The ini-
tial endo-hydride addition product is related to an in-
termediate that has been characterised.[33] Hence the
first deuteration occurs from the endo-direction and
the second is exo-specific, now specifically confirmed
1
2
by H, 13C and H NMR spectroscopy. After the first
addition step, dissociation/recoordination occurs se-
lectively to the exo-face of the monoene, to which
H2/D2 is preferentially delivered.
A different result was obtained when Crabtreeꢁs iri-
dium catalyst 5 was used to catalyse deuterium addi-
tion, albeit in the non-coordinating solvent CH2Cl2. In
this case the 2,3-exo-dideuterated isomer of 2 predo-
minated by 5:1. This implies a requirement for disso-
ciation of NBD prior to addition. Since accumulated
evidence demonstrates a stronger tendency for dihy-
drogen coordination to iridium compared to rhodi-
um,[34] the reacting diene must dissociate and reassoci-
ate subsequent to priming of the metal centre with
hydrogen. Mononuclear Ir polyhydrides are known,
and can function as reactive intermediates.[35] This
points to a radically different mechanism for hydroge-
nation with Crabtree-type catalysts, compared to their
cationic rhodium diphosphine counterparts. Polyhy-
dridic intermediates have been indicated in Ir com-
plex-catalysed directed hydrogenation,[36] and postu-
lated as intermediates in Ir complex-catalysed asym-
metric hydrogenation.[37]
Figure 2. Hydrogen uptake in MeOH, 218C, 1.4 atm initial
H2; (a) 0.34M 1, 0.0016M 3; (b) as (a) with 0.0016M 4; (c)
0.48M 6, 0.0053M 3, complete reduction in 6ꢂ104 secs; (d)
as (c) with 0.0053M 4, complete reduction in 2.5ꢂ104 secs.
The data are not corrected for pre-hydrogenation in the
warm-up period, patricularly affecting trace (c).
diene and the second slower addition occurs to the
exo-face. In the deuterated product the signals for
endo-H2,H3, and exo-H5,H6,[40] were absent save for
a trace of the latter (for full details of NMR spectra
Hydrogenation of 7-tert-Butoxynorbornadiene
Homogeneous hydrogenation of 7-tert-butoxynorbor- see the Supporting Information).
nadiene 6 had not been carried out previously; in het-
erogeneous catalysis, both Pd-C catalysed and Pt-cata-
lysed hydrogenation are specific for the anti-double Hydroboration
bond.[38] In structurally characterised complexes, the
tert-butoxy group is not innocent, and frequently pro- The asymmetric hydroboration of NBD had been pre-
vides an additional coordination site in an exo-alkene viously reported as part of H. C. Brownꢁs classic
chelate.[39] In the present work, the reactivity of the work.[9] Later refinement of the original work provid-
two double bonds in diene 6 is dramatically different ed a 62% yield of exo-norborn-2-en-5-ol 6 in 80% ee
with both catalysts 3 and 4, and the syn-alkene is rap- In their original demonstration of catalytic asymmet-
idly reduced. Reduction of the remaining double ric hydroboration, Burgess and Ohlmeyer reported
bond is much slower, as indicated by the comparison that the double hydroboration/oxidation of NBD
with NBD shown in Figure 2. Using complex 3 as cat- using DIOP as ligand and an exess of catecholborane
alyst and stopping the reaction at ca. 60% completion gave exo-2,6-diol as the major product in 76% ee[11]
provides exclusive formation of that the anti-product These results indicate that catalytic hydroboration of
7 in the first step. Carrying out the reduction with D2 NBD is exo-selective in both steps, unlike hydrogena-
gave product 8 anticipated from NBD addition; the tion. The present set of experiments, where catechol-
rapid first addition occurs to the endo-face of the borane is not in large excess, show that the exo-endo
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Table 1. Stereochemical course of hydroboration of NBD
1.[a]
Hydrogenation of Cyclic Non-Conjugated Dienes
Cyclopentadiene Dimer
endo-Dicyclopentadiene 10 provides an interesting
case. Hydrogenation proceeds smoothly in a two-
phase process with either catalyst 3 or 4, but the first
step giving monoene 12 is much faster than the
second in both cases. On deuterium addition the fa-
miliar pattern of endo-addition to the first double
bond was observed. The second double bond is also
hydrogenated cleanly and stereoselectively to the cy-
cloalkane 11, but interpretation of the results proved
1
to be challenging, since the NMR spectra, both for H
and 2H addition experiments, were more complex
than expected. Chemical shift separation in the
proton spectrum is small, and it required analysis at
700 MHz assisted by 13C J-correlation in order to
assign all the signals with confidence.[42] The addition
of deuterium to diene 10 catalysed by complex 3 gave
deuterated 11. The near complete lack of an H8-endo
signal at 1.23 ppm proved the key in assigning the
course of the first addition. It proved impossible to
analyse the deuterium distribution in the cyclopen-
tane moiety completely by 1H NMR. Clarification
Entry Catalyst (mol%) Borane Yield (%) endo:exo
1
2
3
4
5
6
7
8
9
10
A (0.6)
A (8.3)
A (11.8)
A (26.3)
A (0.6)
A (1)
B (1)
C (1)
B (1)
C (1)
I
I
I
I
I
II
I
I
II
II
85
82
78
85
75
80
73
77
72
75
1.0:21.7
1.0:19.4
1.0:14.0
1.0:3.9
1.0:16.3[b]
1.0:9.0
1.0:18.5
1.0:30.2
1.0:49.5
1.0:43.0
2
arose from analysis of the H-coupled 13C NMR spec-
[a]
Conditions: NBD 0.3 mmol, borane 1 equiv., THF
trum, which revealed all four separate product carbon
nuclei derived from the alkene double bonds because
of their characteristic a- and b-isotope shifts.[43] endo-
Dideuteration at the norbornene moiety is accompa-
nied by ca. 5% of monodeuteration, unlike the clean
addition seen in the bicycloACTHNUTRGNEUGN[2.2.1] series. (Figure 3).
For reduction of the cyclopentene double bond, at
least six isotopomers can be identified by analysis of
1.5 mL (all 0.2M in reactants), room temperature; cata-
lyst
A=[(S,S)-MeDuPhos]Rh
G
B=
[(NBD)RhCl]2, C=(NBD)2RhOTf; I=catecholborane,
2 h; II=pinacolborane, 12 h; endo:exo ratios were deter-
1
mined by integrating the respective H NMR signals at
6.44 and 6.16 ppm, see Supporting Information.
4 equiv. NBD relative to catecholborane were used.
[b]
product ratio for the first hydroboration step is C4 of the 13C NMR spectrum. The presence of 3,5-di-
strongly turnover dependent (see Table 1, entries 1– deuterated species (6%) as well as small quantities of
5). More endo-isomer is formed in the initial step both 2- and 3-monodeuterated species requires H-iso-
than later, consistent with differentiation between the merisation in an intermediate, as well as H/D ex-
initial stoichiometric (endo-rich) and subsequent cata- change with the reagent. In addition, the formation of
lytic (exo-rich) stages. Pinacolborane also reacts with a substantial amount of the 3,4,5-trideuterated species
predominant, but less pronounced exo-selectivity indicates that this reaction intermediate must be able
(entry 6). Although (S,S)-MeDuPhos was employed to exchange hydrogen isotope with external D2. This
as the ligand, the reactions were not significantly exchange process also accounts for the incursion of
enantioselective (<10% ee).
some monodeuterated species at C7. Concurrent anal-
In an effort to divert hydroboration to the endo- ysis of C3,C5 on the same sample reveals a small
face of NBD, ligand-free catalysts were employed (en- amount of dideuteration at C4, the signals of the rele-
tries 7–10). Under these conditions a labile rhodium vant isotopomers being starred in Figure 2 (B). This
boride intermediate is involved, and for styrene syn- observation requires that the initial addition to D3,4 in
À
À
Rh B addition followed by syn-Rh H elimination compound 10 is exo-stereoselective rather than ste-
leads to the corresponding b-vinylborane.[41] Since reospecific.
that outcome is not possible in a rigid cyclic system, a
Further proof of exo-selectivity in hydrogenation of
normal hydroboration route is anticipated and indeed the cyclopentene double bond is afforded by the slow
observed. The results are similar to those with ligated and incomplete hydrogenation of allylic ether 12. The
catalysts (entries 7 and 8). When pinacolborane is reaction effectively stops after reduction of the nor-
used, the stereoselectivity is lower with catalyst A bornene double bond, consistent with steric inhibition
(entry 6), but higher with catalysts B or C (entries 9 of coordination at the exo-face of the cyclopentene af-
and 10).
forded by the OMe group.
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FULL PAPERS
Figure 3. (A) Exchange pathways in D2 reduction of the cyclopentene double bond of compound 10; (B) isotopomer distri-
bution in the 13C NMR spectrum of the deuterated product 11, C4, C3,C5, C8,C9 shown. The starred peaks indicate dideuter-
ated C4 isotopomers.
endo-Dicyclopenta-4,8-dien-3-one
dominant species formed exhibits a characterisic
eight-line multiplet associated with two distinct coor-
When the corresponding dienone 13 was hydrogenat- dinated alkenes (dP =59.6 ppm, JP,Rh =146 Hz, JP, P
=
ed, both steps, and particularly the second to form the 20 Hz; dP =57.3 ppm, JP,Rh =138 Hz). If the observed
saturated ketone 14, were quite slow (Figure 4). A po- species is not the true catalytic intermediate and dis-
tential reason is made clear by analysis of the sociation of the alkene from this species is required
31P NMR spectrum of the Rh-DPPE solvate complex before hydrogenation, slow turnover can be ex-
in CD3OD with added 13. This shows that the pre- plained.
Figure 4. 31P NMR spectrum of Rh-coordinated dienone 13 in the presence of hydrogenated catalyst 3, CD3OD, 298 K; d=
59.6 ppm, JP, Rh 146 Hz; 57.3 ppm, JP, Rh 138 Hz, JP, P 19.5 Hz; P2Rh solvate is present at d=80.5 ppm.
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Bao Nguyen[a] and John M. Brown
FULL PAPERS
1
Full analysis of the H NMR spectrum of the first ed proton pairs, including the anomalous carbonyl-in-
named product 14 was carried out, in order to make duced deshielding of endo-H10, observed at 1.58 ppm
secure assignments in the corresponding D2 addition in CD3OD. The three remaining protons of the
experiment. On the basis of COSY, HMBC and CH2CH2 bridge resonate between 1.37 and 1.22 ppm.
HSQC spectra both the position and configuration of It proved important to distinguish between protons at
all hydrogens were established. There is considerable C6 (1.81 and 1.35 ppm) and C5 (1.90 and 1.75 ppm),
signal overlap, even at 500 MHz, but the exo- and and this was achieved through COSY and HMBC cor-
endo-hydrogens of 14 related to the alkene of 13 may relation spectra. Reaction of dienone 15 with D2 cata-
be identified. One anomaly is presented in compari- lysed by complex 3 resulted first in exo-addition to
the norbornene double bond, as had been observed
for the enone 14 described above. The second addi-
tion step also took place from the exo-direction re-
vealed by the loss of exo-H5, but with some (subse-
quent) scrambling of the deuterium at C4 adjacent to
the carbonyl group.
The stereochemical course of the first hydrogena-
tion for the a,b-unsaturated ketones 13 and 15 differs
from the three examples 1, 6 and 10 described earlier,
where reaction occurs overwhelmingly from the endo-
direction. This indicates that h2,h2-coordination is not
invariably advantageous during hydrogen addition to
dienes, since the electron-poor enones dissociate from
rhodium prior to transfer of H2 (or D2) to the norbor-
nene double bond.
Asymmetric Hydrogenation of a Skipped Diene
son with hydrocarbon 11. The two endo-hydrogens at
C8 and C9 are quite dispersed, being at 1.30 and The results obtained in the section “Hydrogenation of
1.63 ppm respectively (vs. 1.20 ppm in compound 11). Cyclic Non-Conjugated Dienes” provide a guide for
The deshielded member of the pair belongs to C9, reduction of acyclic dienes, and demonstrate the inde-
and the effect arises from the anisotropic field of the pendence of the two reaction steps. Hydrogenation of
C1 carbonyl group.[44] On addition of D2 to the dien- skipped dienes was the objective. To be useful in syn-
1
one 13 the ensuing H NMR spectrum is much sim- thesis, the reaction needs to be chemoselective, with
pler, but shows nine rather than the expected ten pro- the first double bond reacting faster than the second.
tons. The reason for this is seen to be a second keto- Dialkene chelation of the diene fragment during the
enol promoted deuteration a- to the carbonyl group first hydrogenation step is presumably responsible.
2
at C4, and this is clear from the H NMR spectrum of When the central carbon is monosubstituted or un-
the product, where the signal at 41.6 ppm correspond- symmetrically disubstituted, the first reaction step in-
ing to C2 is a pentuplet. Surprisingly, analysis of the volves desymmetrisation; the product is chiral. Suc-
1
ensuing H NMR demonstrates that D2 addition to cessful “meso-trick” experiments are quite rare in
both alkenes occurs from the exo-direction, character- enantioselective hydrogenation,[46] although common
istic of a norbornene pathway for reduction of the elsewhere.[47] There are only a few structurally charac-
first double bond. The endo-protons at C5 and C9 terised 1,4-diene complexes, and the dialkene may co-
1
remain intact, and are clearly visible in the H NMR ordinate with Cs symmetry or with C2 symmetry.[48]
of deuterated product.
With a C2 symmetric ligand this gives rise to four dif-
ferent coordination modes as shown in Figure 5; the
locally chiral forms iii) and iv) are of particular inter-
est.
endo-Tricyclo[6.2.1.02,7]undeca-4,9-dien-3-one
Penta-1,4-dien-3-ol 17a is readily available and suit-
Hydrogenation of the homologous dienone 15 is even able for this purpose. In order to avoid the possible
slower than that of dienone 13, ultimately giving the involvement of competing hydroxy-directed hydroge-
saturated ketone 16.[45] Again, full assignment of the nation,[49] the related TBDMS ether 17b was first em-
1H and 13C NMR spectra of the final product was car- ployed as reactant (Figure 6). Hydrogenation oc-
ried out, with the necessary aid of COSY, NOESY, curred very rapidly in MeOH solution with a variety
HMBC and HSQC spectra. This sequence located of catalysts, as shown in Table 2. It is clear that the
and identified the six methylene carbons and associat- first double bond was hydrogenated more rapidly
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Stereoselectivity in the Rhodium-Catalysed Reductions of Non-Conjugated Dienes
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Figure 5. Hydrogen uptake in MeOH by 10, 13 and 15. 218; (i) catalyst 3; (a) cat 5.39 mM, 10 0.57M, H
cat 2.64 mM, 13 0.26M, H2A(init) 2.0 atm, (c) cat 3.69 mM, 15 0.33M, H2A
(init) 2.0 atm, complete reduction in 1.5ꢂ105 secs; (ii)
catalyst 4 (a) cat 5.22 mM, 10 0.59M, H2A(init) 1.4 atm, (b) cat 5.17 mM, 13 0.26M, H2A(init) 2.2 atm, (c) cat 3.69 mM, 15
0.36M, H2A
(init) 1.8 atm, >90% reduction in 8ꢂ104 secs.
2ACHTUNGTREN(NUGN init) 1.4 atm., (b)
C
CHTUNGTRENNUNG
C
CHTUNGTRENNUNG
CHTUNGTRENNUNG
Figure 6. A) The reaction pathway in hydrogenation of 1,4-dienes 17 by rhodium diphosphine complexes, B) possible h2,h2
modes of diene coordination in 17a; i), ii) Cs mode, iii) C2 Si, Si, iv) C2 Re, Re.
Table 2. Hydrogenation of dienol 17a and its silyl ethers.<W=3
Entry[a]
Ligand L2
Dppb
A
N
Reactant
Time [min]
17:18:19
ee [%] of 18
1
2
3
4
17b
17b
17b
17b
17b
17b
17c
17d
17a
10
5
10
10
8
20
15
–
0:100:0
0:100:0
0:52:48
12:68:20
12:87.5:0.5
0:50:50
13:62:25
No reaction
0:100:0
–
20
15
ND
50 (R)
ND
47 (R)
–
5
ACHTUNGTRENNUNG
N
N
6
7[b]
8
9
E
45
53 (R)
[a]
Conditions: 0.136 mmol 17, 1 mol% catalyst [RhL2NBD]OTf, 1 mL MeOH, initial H2 pressure 1.6 atm, 218C.
In dichloroethane.
[b]
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Bao Nguyen[a] and John M. Brown
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Figure 7. Hydrogenation of 3-tert-butyldimethylsilyloxypenta-1,4-diene with the DipampRh+ complex, Table 2, entry 3. Re-
sults of curve fitting for reaction in a constant volume hydrogenator according to the data shown, simulated by Berkeley Ma-
donna (Kagi Software).
than the second in all cases, although the relative and ed was the alcohol 18a, however. It was demonstrated
absolute reactivities varied with the catalyst. The achi- in a control experiment that addition of the (S,S)-
ral DPPB complex gives complete reduction to the Chiraphos catalyst (5 mol%) to a solution of 17c in
1
monoene 18b without significant further reaction, as CD3OD and monitoring by H NMR led to desilyla-
does Chiraphos, (entries 1 and 2). Standard methods tion within 5 min. In ClCH2CH2Cl, this side reaction
for the determination of enantiomer excess did not did not occur and enantioselective hydrogenation of
work in this case. After TBAF-promoted desilylation, 17c was observed albeit with lower chemoselectivity
the 31P NMR method introduced by Feringa et al. (entry 7). The corresponding TIPS ether 17d proved
proved effective and was utilised in subsequent unreactive towards H2 (entry 8), presumably demon-
cases.[50] An ee of 20% was demonstrated this way for strating the severe steric bulk of the silane. Finally,
the reaction of entry 2. For entry 3, the reaction re- hydrogenation of the parent alcohol 17a was studied,
mains fast but less separation between the first and since the observed reduction of 17c, appeared to in-
second steps was evident. This is also apparent in the volve prior desilylation. This occurred smoothly, and
BINAP case (entry 4) since starting material is pres- effectively stopped after the first step, giving 18a in
ent at the same time as both part-reduced 18b and 53% ee (entry 9)!
fully reduced product 19b. Overall, the most promis-
Since the nature of the substituent has little effect
ing results were obtained in entry 5 with (S,S)-MeDu- on the ee, a directing effect is unlikely. The distinct
phos as catalyst, where an ee of 50% (R) was ob- chemoselectivity favouring the first step militates in
served accompanied by good chemoselectivity be- favour of a reactive intermediate in which both
tween the first and second steps.[51] This was followed double bonds remain coordinated. Four alternative
up with a more detailed analysis of the course of reac- conformations of the coordinated diene are accessible
tion (Figure 7). The experimental data were fitted ac- (Figure 6), and there is no evidence to indicate wheth-
cording to a kinetic model, taking into account sub- er the C2 or Cs forms are preferred. The accessibility
strate binding in both the first and second stages. The of C2-symmetric forms C and D provides the opportu-
initial slope of the fast sector was ca. 10 times greater nity for chiral discrimination on co-complexation with
than the initial slope of the subsequent slow sector. a C2-symmetric diphosphine ligand, and this would
With the more bulky (S,S)-i-PrBPE as ligand play a part in the overall selectivity observed.
(entry 6), less distinction between the first and second
steps was observed.
Changing the silyl group was less fruitful. With the Conclusions
corresponding dimethylphenylsilyl ether 17c, rapid
Rh-catalysed reduction was observed in MeOH, effec- Even the simplest hydrogenations can exhibit com-
tively stopping after the first step. The product isolat- plex pathways. The stereochemical course of reduc-
1340
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Adv. Synth. Catal. 2009, 351, 1333 – 1343

Stereoselectivity in the Rhodium-Catalysed Reductions of Non-Conjugated Dienes
FULL PAPERS
tion of the norbornene double bond in a series of
dienes is dependent on the environment of the second
double bond. For chelating dialkenes 1, 6 and 10, the
first reduction step occurs from the endo-direction
with rhodium (but not iridium) catalysts, in accord
with the Chelate type reactions shown in Figure 1.
Where the dialkene bears an electron-withdrawing
carbonyl group, reaction is far slower and in accord
with the Open type reactions of Figure 1. It was also
observed that the bridge substituent in dialkene 6
strongly affected the regioselectivity of the first reduc-
tion step. Deuterium addition revealed rapid H-shifts
that occurred during the second step of reduction of
dicyclopentadiene 10. In contrast, catalytic hydrobora-
tion of 1 occurs predominantly from the exo-direction,
but extrapolation of results at low turnover indicates
that the initial step is endo-selective. This indicates
that the reagent competes successfully with the for
the second coordination site of dialkene chelation.
The selectivity observed in reduction of chelating
cyclic dienes may be applied to hydrogenation of
meso-1,4-dienes. The results obtained demonstrate
good control of chemoselectivity, with the first step
occuring significantly faster. Modest ees are obtained,
indicating the benefit of further study.
Experimental Section
General Hydrogenation Procedure
Hydrogenations were performed in a modified Schlenk tube
that had been fitted with an RS 286–670 differential pres-
sure transducer from RS Components. The pressure trans-
ducer signal output was connected to an ACD+16 data-
Figure 8. The experimental set-up for hydrogenation reac-
tions, conducted in constant volume apparatus.
logger from Pico Technology Ltd, which in turn was con-
nected to an IBM PC compatible computer running PicoLog
software from the same company, via an RS232 connector
(Figure 8). The pressure transducer measured the difference
between the pressure inside and outside the vessel in the
range of 0–30 psi, corresponding to output signal range of 0–
100 mV. It was calibrated prior to use against atmospheric
pressure and high vacuum. The ACD+16 data-logger deliv-
ers a Æ5 V power supply to the transducer and receives
readings from the sensor, logging these data to the IBM PC
computer every five seconds.
A modified Schlenk line was used with the hydrogenation
vessels. The normal vacuum/argon outlets were connected to
a three-way Swagelokꢃ valve which allowed switching con-
nection between vacuum/argon or hydrogen (steel line fitted
with pressure control gauge) and the vessel.
The reaction vessel was assembled and charged with hy-
drogen at 2.0 atm pressure. Insignificant voltage decrease in
reading from the pressure transducer after 24 h indicated
that the vessel was sufficiently sealed for experiments.
The general procedure for pressure-monitoring hydroge-
nation follows the procedures described below.
Reactants, catalyst and degassed solvent were transferred
to the vessel under argon and the vessel was fitted with the
pressure transducer. The reaction mixture was cooled to
À788C and evacuated under high vacuum with vigorous stir-
ring. Hydrogen was charged at a specified pressure, and
then evacuated under high vacuum. This process was repeat-
ed twelve times to ensure saturation of hydrogen in the so-
lution. Hydrogen was finally charged to the specified pres-
sure and the Youngꢁs tap was sealed. The reaction mixture
was allowed to warm up without stirring to room tempera-
ture using a water bath. Pressure within the vessel was al-
lowed to equilibrate. The computer monitored and recorded
the readings of the pressure, which were displayed in a volt-
age vs. time graph. The reaction mixture was stirred vigo-
rously at ambient temperature (21 8C) in the water bath
until completion, as indicated by on-screen monitoring. Re-
action was stopped by venting excess hydrogen. In many
cases, the reaction was performed in CD3OD and NMR
spectra of the crude mixtures were recorded directly without
any work-up. When other solvents were used, the reaction
mixture was filtered through a short pad of silica using di-
chloromethane as eluent before solvents were evaporated
under vacuum to give the products.
Adv. Synth. Catal. 2009, 351, 1333 – 1343
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1341

Bao Nguyen[a] and John M. Brown
FULL PAPERS
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Typical Procedure for Asymmetric Hydrogenation
(17b, entry 5, Table 1)
The starting material was prepared as previously de-
scribed.[52] The hydrogenation vessel (Figure 8) was charged
with diene 17b (0.027 g., 0.136 mmol) and complex {Rh-
ACHTUNGTRENNUNG[(S,S)-MeDuphos]NBD}OTf (0.65 mg, 0.01 equiv., from
stock solution in MeOH?) in MeOH (1.0 mL). After equili-
bration under H2 as described above, the reaction mixture
was stirred for 8 min. After standard work-up the product 3-
tert-butyldimethylsiloxy-1-pentene,[53] containing 12% of un-
reduced starting material, was dissolved in THF (2 mL.) and
added dropwise at 08C to a 1M solution of tetrabutylammo-
nium fluoride in THF (1.36 mL). The solution was stirred at
08C for 1 hour and allowed to warm up to room tempera-
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washed with brine solution (3ꢂ10 mL). The organic solution
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give 1-penten-3-ol as the main product, which was dissolved
in CDCl3 and used directly in the next step. To this solution
was added pyridine (11 mL, 0.134 mmol) and PCl3 (4 mL,
0.045 mmol) at room temperature. The reaction mixture was
stirred for 30 min. and the 31P NMR was taken directly (see
Supporting Information for full details of ee determination).
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Acknowledgements
We thank the Clarendon Fund (Oxford) and Balliol College
for Scholarships (to BN) as well as the Leverhulme Founda-
tion for a fellowship (to JMB). Johnson-Matthey kindly pro-
vided a loan of precious metal salts. We thank the CRL NMR
Facility and Dr. T. D. W. Claridge and Dr. B. Odell for their
help.
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[22] Examples are taken from the CSSR database, see
codons BAZJER, BCHPPF01, CUKVUF, EJAJEE,
EJAJOO, GELKAJ10, ISUDUC, IZUFAK, JIKTEC,
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ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1343