Rhodium-Catalyzed Asymmetric [5+2] Cycloaddition of Alkyne- Vinylcyclopropanes

Article abstract of DOI:10.1002/chem.200901463

The development of such an asymmetric catalysis by the use of a rhodium complex coordinated with chiral phosphoramidite ligand, achieving very high enantiomeric excesses has been reported. Transition-metal-catalyzed cycloaddition of vinylcyclopropanes wit

Full text of DOI:10.1002/chem.200901463

DOI: 10.1002/chem.200901463
Rhodium-Catalyzed Asymmetric [5+2] Cycloaddition of Alkyne–
Vinylcyclopropanes
Ryo Shintani,* Hiroki Nakatsu, Keishi Takatsu, and Tamio Hayashi*[a]
Table 1. Ligand effect in the rhodium-catalyzed asymmetric [5+2] cyclo-
addition of 1a.
Transition-metal-catalyzed [5+2] cycloaddition of vinylcy-
À
clopropanes with carbon carbon unsaturated bonds is an ef-
ficient way of constructing seven-membered carbocycles.
Several transition metals such as rhodium,[1] ruthenium,[2]
nickel,[3] and iron[4] can catalyze these reactions with alkynes
as the reaction partner, and alkenes[1c,5] and allenes[6] can
also be employed under rhodium catalysis.[7,8] Unfortunately,
however, the development of asymmetric variants of this
useful transformation has not met much success so far. In
fact, to the best of our knowledge, only a recent report by
Wender addressed this issue, achieving high enantioselectivi-
ty for several alkene-tethered vinylcyclopropanes using a
cationic Rh/(R)-binap catalyst.[9] For cycloaddition of
alkyne–vinylcyclopropanes, in contrast, there is no effective
catalytic asymmetric method available to date.[10] Herein we
describe the development of such an asymmetric catalysis
by the use of a rhodium complex coordinated with chiral
phosphoramidite ligand, achieving very high enantiomeric
excesses (up to >99.5% ee).
Entry
Ligand (equiv to Rh)
Yield [%][a]
ee [%][b]
1
2
3
4
5
(R)-binap (1.1)
(R)-segphos (1.1)
(R)-H8-binap (1.1)
37
29
18
64 (S)
46 (S)
55 (S)
75 (R)
99 (R)
T
31
A
88[c]
[a] Determined by 1H NMR against an internal standard (MeNO2).
[b] Determined by chiral HPLC on a Chiralcel OD-H column with
hexane/2-propanol 95:5. [c] Isolated yield.
Initially, we employed alkyne–vinylcyclopropane 1a as a
model substrate and attempted a cycloaddition reaction in
the presence of 5 mol% of a cationic Rh/(R)-binap[11] com-
plex in dichloromethane at 308C (Table 1, entry 1). Under
these conditions, 37% yield of cycloadduct 2a was obtained
after 5 h with moderate ee value of 64%. The use of other
axially chiral bisphosphine ligands such as (R)-segphos[12]
and (R)-H8-binap[13] resulted in lower yields and enantiose-
lectivity under otherwise the same conditions (18–29%
yield, 46–55% ee; entries 2 and 3). In contrast, chiral phos-
phoramidite ligand (S,S,S)-3[14] (1.5 equiv to Rh) induced
somewhat better enantioselectivity (75% ee; entry 4) and its
diastereomeric ligand (S,R,R)-3[14,15] dramatically improved
both reactivity and stereoselectivity, giving product 2a in
88% yield with as high as 99% ee (entry 5). The absolute
configuration of 2a thus obtained was determined to be (R)
by X-ray crystallographic analysis as shown in Figure 1.[16]
The scope of the present catalysis using ligand (S,R,R)-3
is illustrated in Table 2. Not only aryl groups (1a–c) but also
alkyl groups (1d and 1e) are well tolerated as the substitu-
ent on the alkyne, leading to the corresponding cycloadducts
2 with uniformly high yield and excellent enantioselectivity
(87–90% yield, ꢀ94% ee; entries 1–6), and the amount of
ligand (S,R,R)-3 can be reduced to 6 mol% (1.2 equiv to
Rh) as shown in entry 2. High enantioselectivity is also ach-
ieved with substrate 1 f having a terminal alkyne, although
[a] Dr. R. Shintani, H. Nakatsu, K. Takatsu, Prof. Dr. T. Hayashi
Department of Chemistry, Graduate School of Science
Kyoto University, Sakyo, Kyoto 606-8502 (Japan)
Fax : (+81)75-753-3988
E-mail: shintani@kuchem.kyoto-u.ac.jp
thayashi@kuchem.kyoto-u.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200901463.
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Chem. Eur. J. 2009, 15, 8692 – 8694

COMMUNICATION
ducted on a gram scale with a reduced catalyst loading
(2 mol% Rh), and simple recrystallization of the crude ma-
terial from CH2Cl2/hexane readily provides product 2a with-
out chromatographic purification in essentially enantiopure
form [87% yield, >99.5% ee; Eq. (1)].
Figure 1. X-ray crystal structure of (R)-2a.
Table 2. Scope of the rhodium-catalyzed asymmetric [5+2] cycloaddition
of alkyne–vinylcyclopropanes 1.
To gain some insight into the active catalyst species in the
present transformation, we conducted some control experi-
ments using 1a as the substrate and made the following ob-
servations. 1) By using 2.2 equiv, rather than 1.5 equiv, of
(S,R,R)-3 to Rh, 1a remained mostly unreacted, giving 2a
only in 4% yield. 2) Replacement of phenyl groups of
(S,R,R)-3 by methyl groups ((S)-4[14]) resulted in a dramatic
decrease of enantioselectivity [6% ee; Eq. (2)], whereas re-
placement of methyl groups of (S,R,R)-3 by phenyl groups
((S)-5) did not affect the enantioselectivity (99% ee). These
results indicate that catalytically active species of the pres-
ent asymmetric reaction is presumably a 1:1 complex of Rh/
phosphoramidite, and that the presence of phenyl groups in
the nitrogen substituent is necessary to induce significantly
high enantioselectivity.
Entry Substrate
Product
Yield
[%][a]
ee
[%][b]
1
1a (R=Ph)
1a (R=Ph)
1b (R=4-
2a
2a
2b
88
89
89
99
99
98
2[c]
3
MeOC6H4)
4
5
1c (R=4-ClC6H4)
1d (R=Me)
1e (R=iPr)
1 f (R=H)
2c
2d
2e
2 f
90
87
87
53
94
>99.5
99
6
7[d]
92
8
87
90
82
99
95
83
9[e]
With regard to the structure of a Rh/ACTHNUTRGNEUNG(S,R,R)-3 complex,
10
Mezzetti recently disclosed that (S,R,R)-3 can coordinate to
a cationic rhodium(I) as a P–(h2-arene) bidentate ligand
using its phenyl moiety of the nitrogen substituent.[17] Be-
cause phosphoramidite ligands with pendant phenyl groups
((S,S,S)-3, (S,R,R)-3, and (S)-5) display much higher enan-
tioselectivity than ligand (S)-4 in the present catalysis, h2 co-
ordination of the phenyl group seems to play an important
role for the stereocontrol of this process. On the basis of the
[a] Isolated yield. [b] Determined by chiral HPLC with hexane/2-propa-
nol. [c] 6 mol% of (S,R,R)-3 was used. [d] The reaction was conducted at
408C for 48 h at 0.01m. [e] The reaction was conducted for 24 h at 0.01m.
the yield becomes somewhat lower due to the decomposi-
tion of 1 f during the reaction (53% yield, 92% ee; entry 7).
Other alkyne–vinylcyclopropanes, such as 1g with methyl
group on the cyclopropane, 1h with an oxygen tether, and
1i with a carbon tether, can be effectively employed as well
under these reaction conditions (82–90% yield, 83–99% ee;
entries 8–10). Furthermore, the reaction of 1a can be con-
X-ray crystal structure of [{RhACHTUNTRGENN(UG nbd)AHCTUNGTRENN(UGN (R,S,S)-3)}SbF6] report-
ed by Mezzetti,[17] along with the studies by Yu, Wender,
and Houk on the reaction mechanism for [5+2] cycloaddi-
tions,[7,9] a proposed stereochemical pathway for the reaction
of 1a catalyzed by Rh/
ACHTUNGTRENN(UNG S,R,R)-3 is illustrated in Scheme 1.
Thus, h2 coordination of one of the phenyl groups in
Chem. Eur. J. 2009, 15, 8692 – 8694
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www.chemeurj.org
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T. Hayashi, R. Shintani et al.
ogy, Japan (the Global COE Program “Integrated Materials Science” on
Kyoto University).
Keywords: asymmetric
catalysis
·
cycloaddition
·
phosphoramidite · rhodium
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Scheme 1. Proposed stereochemical pathway for asymmetric [5+2] cyclo-
addition of 1a catalyzed by Rh/(S,R,R)-3.
AHCTUNGTRENNUNG
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(S,R,R)-3 would organize the conformation of its rhodium
complex in such a way that one of the naphthyl moieties of
(S,R,R)-3 effectively blocks the bottom right quadrant and
the top right quadrant becomes wide open. This organized
chiral environment around the rhodium would facilitate a
face-selective coordination of 1a in the form of A, rather
than A’, to minimize the steric repulsion of the cyclopropyl
moiety of 1a. Oxidative cyclization of vinylcyclopropane
from complex A, followed by insertion of alkyne, would
lead to intermediate B, reductive elimination of which gives
cycloadduct 2a with R configuration.
In summary, we have developed a highly efficient asym-
metric intramolecular [5+2] cycloaddition of alkyne–vinylcy-
clopropanes under rhodium catalysis. High enantioselectivi-
ties of up to >99.5% ee have been achieved by the use of a
chiral phosphoramidite ligand. The reaction can be easily
scaled up and the stereochemical model of the present catal-
ysis has also been proposed.
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[10] Only two examples of up to 56% ee were reported in reference [9a].
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[16] CCDC 725714 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
Experimental Section
General procedure for Table 2: A solution of [{RhClACTHNUGTRNE(UNG C2H4)2}2] (1.9 mg,
9.8 mmol Rh) and (S,R,R)-3 (7.9 mg, 15 mmol) in CH2Cl2 (1.0 mL) was
stirred for 20 min at room temperature. Substrate 1 (0.20 mmol) was
added to it with additional CH2Cl2 (0.5 mL), and then sodium tetrakis-
ACHTUNGTRENNUNG(3,5-bis(trifluoromethyl)phenyl)borate (11 mg, 12 mmol) was added to it
with additional CH2Cl2 (0.5 mL). The resulting solution was stirred for
5 h at 308C, and the reaction was quenched with water. After extraction
with CH2Cl2, the organic layer was dried over MgSO4, filtered, and con-
centrated under vacuum. The residue was purified by silica gel prepara-
tive TLC to afford cycloadduct 2.
Acknowledgements
[17] I. S. Mikhel, H. Rꢁegger, P. Butti, F. Camponovo, D. Huber, A.
Mezzetti, Organometallics 2008, 27, 2937.
Support has been provided in part by a Grant-in-Aid for Scientific Re-
search, the Ministry of Education, Culture, Sports, Science, and Technol-
Received: June 1, 2009
Published online: July 27, 2009
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Chem. Eur. J. 2009, 15, 8692 – 8694