Asymmetric synthesis of 1-alkynylcyclopropane-1-carboxylates

Article abstract of DOI:10.1016/S0040-4039(00)01453-2

Dirhodium tetrakis(S-(N-dodecylbenzenesulfonyl)prolinate) (Rh₂S-DOSP₄) catalyzed decomposition of methyl alkynyldiazoacetates in the presence of alkenes results in highly diastereoselective and enantioselective cyclopropanations. (C) 2000 Published by Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01453-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8189–8192
Asymmetric synthesis of
1-alkynylcyclopropane-1-carboxylates
Huw M. L. Davies* and Timothy A. Boebel
Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260–3000, USA
Received 13 August 2000; revised 29 August 2000; accepted 1 September 2000
Abstract
Dirhodium tetrakis(S-(N-dodecylbenzenesulfonyl)prolinate) (Rh2S–DOSP4) catalyzed decomposition of
methyl alkynyldiazoacetates in the presence of alkenes results in highly diastereoselective and enantioselec-
tive cyclopropanations. © 2000 Published by Elsevier Science Ltd.
The metal catalyzed decomposition of a-diazocarbonyls in the presence of alkenes is a powerful
method for the synthesis of highly functionalized cyclopropanes.1 By far the most commonly used
a-diazocarbonyls have been the diazoacetates 1. Diastereoselective cyclopropanations, however,
with this system have been challenging.1,2 In recent years cyclopropanations by vinyldiazoacetates
(2)3 and phenyldiazoacetates (3)4 have been extensively studied because these cyclopropanations
are highly diastereoselective. Furthermore, these carbenoids display much greater chemoselectivity
than the carbenoids derived from simple diazoacetates.5 We have rationalized that carbenoids
containing both electron-withdrawing (EWG) and electron-donating (EDG) groups undergo highly
diastereoselective cyclopropanations because the trajectory of alkene approach to these carbenoids
is very demanding, occurring side-on over the electron withdrawing group, as illustrated in
transition-state model 5.3b On the basis of this hypothesis, we predicted that alkynyldiazoacetates
(4) would similarly undergo highly stereoselective and chemoselective cyclopropanations. The
synthesis of alkynyldiazoacetates and their subsequent cyclopropanation chemistry is the basis of
this paper.
* Corresponding author.
0040-4039/00/$ - see front matter © 2000 Published by Elsevier Science Ltd.
PII: S0040-4039(00)01453-2

8190
In order to explore the chemistry of alkynyldiazoacetates, three representative examples
were prepared as shown in reaction 1. The 3-alkyn-1-ols 6 were prepared by conventional
procedures and were readily oxidized to the acid and then converted to the 3-alkynoates 7. A
diazo transfer reaction on 7 with p-(acetamido)benzenesulfonyl azide (p-ABSA)6 and DBU as
base gave the alkynyldiazoacetates 8. Even though the yield for the formation of 8 was
moderately low (17–46% yield), these compounds exhibit reasonable stability and can be
stored in solution at 0°C for extended periods.
(1)
A further advantage of the aryl- and vinyldiazoacetate derived carbenoids is that highly
enantioselective transformations can be achieved by using dirhodium tetraprolinates such as
Rh2(S-DOSP)4 as catalyst.7 These catalysts are especially well suited for aryl- and vinyl-
diazoacetates, while only low asymmetric induction is obtained with these catalysts in cyclo-
propanation by ethyl diazoacetate.3b Therefore, the test reactions of alkynyldiazoactetates
were carried out using Rh2(S-DOSP)4 as the catalyst so that both the diastereoselectivity and
the enantioselectivity of the cyclopropanation could be studied. It has been previously shown
that Rh2(S-DOSP)4 catalyzed cyclopropanation of methyl phenyldiazoacetate (3, R=Me,
R%=H) occurs with very high enantioselectivity (97% ee).4c The parallel reaction with the
alkynyldiazoacetates 8a–c (Eq. (2)) also resulted in highly enantioselective cyclopropanations
(87–93% ee). The catalyst is sufficiently active that these reactions could be carried out at −78°C
(Table 1).
(2)
Table 1
R
Yield (%)
ee (%)
a
b
c
Ph
Et
TMS
68
42
83
93
91
87

8191
In order to explore the diastereoselectivity of these cyclopropanations, a series of reactions of
8a–c was carried out with various mono-substituted alkenes. As summarized in Eq. (3), the
reaction of all three diazo compounds with styrene resulted in cyclopropanation with high-
diastereoselectivity (84–98% de) and enantioselectivity (56–89% ee).8 Extension of the reaction of
8a to other electron rich alkenes resulted in similarly high stereoselectivity (Table 2).
(3)
Table 2
Diazo
R1
R2
Product
Yield (%)
de (%)
ee (%)
8a
8b
8c
8a
8a
Ph
Et
TMS
Ph
Ph
Ph
Ph
Ph
OBu
OAc
10a
10b
10c
11
68
91
84
66
61
84
98
88
\94
\94
89
56
65
87
95
12
We have recently described the considerable difference in chemoselectivity between vinyl- and
aryldiazoacetates compared to simple diazoacetates.5 For example, for vinyldiazoacetates and
phenyldiazoacetates the chemoselectivity ratio for competing cyclopropanation between styrene
versus 1-hexene is about 50:1, while for ethyl diazoacetate it is only about 3:1. The chemoselec-
tivity of alkynyldiazoacetates appeared to be very high because 1-hexene was not effectively
cyclopropanated. Indeed, decomposition of 8a in the presence of styrene and 1-hexene led to
selective cyclopropanation of styrene by a ratio of >20:1 (Eq. (4)).
(4)
One of the most distinctive features of vinyldiazoacetate intermolecular cyclopropanations is
that no reaction occurs with trans alkenes.3b,9 In order to explore if a similar reactivity profile
is displayed by the alkynyldiazoacetates, 8a was decomposed in the presence of a 1:1 mixture of
methyl propenyl ether. This resulted in the formation of 14 as a single diastereomer in 45% ee
(Eq. (5)). This result demonstrates that 8a displays the same type of selectivity as the
vinyldiazoacetates.
(5)

8192
In summary, these studies demonstrate that alkynyldiazoacetates have a similar reactivity
profile to aryl- and vinyldiazoacetates. The resulting carbenoids have high chemoselectivity and
undergo highly stereoselective cyclopropanations. This reactivity appears to be a general feature
of rhodiumꢀcarbenoids that contain both electron donor and acceptor groups, and is pre-
sumably caused by the stabilizing influence of the donor group. It is considered that the high
stereoselectivity is due to a very demanding trajectory of approach of the alkene to the
carbenoid, with approach occurring over the acceptor group. As the trajectory is based on an
electronic argument, the same sense of enantioselectivity would be expected from the alkynyl-
diazoacetates. The observation of similar enantioselectivity and same sense of asymmetric
induction is good supporting evidence for the proposed mechanism because if steric factors
governed the approach of the alkene, attack over the linear alkynyl groups might have been
expected leading to the opposite sense of asymmetric induction.
Acknowledgements
Financial support of this work by the National Science Foundation (CHE 9726124) is
gratefully acknowledged. We also thank Pfizer, Inc. for a Pfizer Undergraduate Summer
Research Fellowship to T.A.B. Technical assistance by Mr. Douglas Stafford is also greatly
appreciated.
References
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2. For recent advances in stereoselectivity of diazoacetate cyclopropanations, see (a) Doyle, M. P.; Bagheri, V.;
Wandless, T. J.; Harn, N. K.; Brinker, D. A.; Eagle, C. T.; Loh, K. L. J. Am. Chem. Soc. 1990, 112, 1906. (b)
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8. The absolute stereochemistry of 10a was determined by catalytic hydrogenation of both 10a and (1S,2S)-methyl
2-phenyl-1-(2-(Z)-styryl)cyclopropane-1-carboxylate (see Ref. 3b) to (1S,2S)-methyl 2-phenyl-1-(2-
phenylethyl)cyclopropane-1-carboxylate. The absolute stereochemistry of the other products is drawn assuming a
similar trajectory of attack as was observed for the vinyldiazoacetates (see Ref. 3b).
9. Davies, H. M. L.; Hu, B. Heterocycles 1993, 35, 385.
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