Dirhodium(II) tetra(N-(dodecylbenzenesulfonyl)prolinate) catalyzed enantioselective cyclopropenation of alkynes

Article abstract of DOI:10.1021/ol049928c

Dirhodium tetrakis((S)-N-(dodecylbenzenesulfonyl)prolinate) (Rh ₂(S-DOSP)₄) is an effective chiral catalyst for the enantioselective cyclopropenation of alkynes by methyl aryldiazoacetates.

Full text of DOI:10.1021/ol049928c

ORGANIC
LETTERS
2004
Vol. 6, No. 8
1233-1236
Dirhodium(II)
Tetra(N-(dodecylbenzenesulfonyl)prolinate)
Catalyzed Enantioselective
Cyclopropenation of Alkynes
Huw M. L. Davies* and Gene H. Lee
Department of Chemistry, UniVersity at Buffalo, The State UniVersity of New York,
Buffalo, New York 14260-3000
hdaVies@acsu.buffalo.edu
Received January 12, 2004
ABSTRACT
Dirhodium tetrakis((S)-N-(dodecylbenzenesulfonyl)prolinate) (Rh2(S-DOSP)4) is an effective chiral catalyst for the enantioselective cyclopropenation
of alkynes by methyl aryldiazoacetates.
Strained ring systems such as cyclopropanes, aziridines, and
epoxides are very versatile intermediates for organic syn-
thesis.1 The even more highly strained cyclopropene ring also
undergoes a number of useful transformations, especially
addition reactions across the strained double bond.2 Cycload-
dition reactions of various types are also highly favored, as
well as free-radical-induced additions2l,m and transition-metal-
catalyzed hydrogenation, hydrosilation,2j hydrostannation,2j
and hydroboration.2k Addition reactions not commonly
observed with electron-neutral double bonds such as reactions
with Grignard reagents2e,n and organozinc,2n,r and organo-
cupurate,2p,q and organolithium2o reagents are also very
efficient.
propenone as chiral building blocks.3 More recently, effective
catalytic methods for the desymmetrization of cyclopropenes
have been developed such as hydrosilation,2j hydrostannation,2j
and hydroboration.2k
An alternative strategy for the use of cyclopropenes in
asymmetric synthesis would be to develop a practical method
for the enantioselective synthesis of the cyclopropene build-
(2) Reviews: (a) Halton, B.; Banwell, M. G. In The Chemistry of the
Cyclopropyl Group; Patai, S., Rappoport, Z., Eds.; Wiley: Chichester, 1987;
p 1224. (b) Baird, M. S. Top. Curr. Chem. 1988, 144, 139. (c) Baird, M.
S.; Schmidt, T. In Carbocyclic Three-Membered Ring Compounds; de
Meijere, Ed.; Georg Thieme Verlag: Stuttgart, 1996; p 114. (d) Baird, M.
S. Cyclopropenes: Transformations: Addition Reactions. In Houben-Weyl;
Thieme: Stuttgart, 1997; E17 d/2, p 2794. Recent examples: (e) Fox, J.
M.; Liao, L. J. Am. Chem. Soc. 2002, 124, 14322. (f) Delgado, A.; Castedo,
L.; Mascarenas, J. L. Org. Lett. 2002, 18, 3091. (g) Suito, K.; Ono, K.; Ito,
N.; Tada, N.; Ando, S. Heterocycles 2002, 2, 235. (h) Binger, P.; Wedemann,
P.; Brinke, U. H. Org. Synth. 2000, 77, 254. (i) Ferjancic, Z.; Cekovic, Z.;
Saicic, R. N. Tetrahedron Lett. 2000, 16, 2979. (j) Rubina, M.; Rubin, M.;
Gevorggyan, V. J. Am. Chem. Soc. 2002, 124, 11566. (k) Rubina, M.; Rubin,
M.; Gevorgyan, V. J. Am. Chem. Soc. 2003, 125, 7198. (l) Nakamura, E.;
Machii, D.; Imubushi, T. J. Am. Chem. Soc. 1989, 111, 6849. (m) Yamago,
S.; Ejiri, S.; Nakamura, E. Chem. Lett. 1994, 1889. (n) Nakamura, M.; Hirai,
A.; Nakamura, E. J. Am. Chem. Soc. 2000, 122, 978. (o) Kubota, K.; Mori,
S.; Nakamura, M.; Nakamura, E. J. Am. Chem. Soc. 1998, 120, 13334. (p)
Nakamura, E.; Isaka, M.; Matsuzawa, S. J. Am. Chem. Soc. 1988, 110,
1297. (q) Isaka, M.; Nakamura, E. J. Am. Chem. Soc. 1990, 112, 7428. (r)
Nakamura, M.; Arai, M.; Nakamura, E. J. Am. Chem. Soc. 1995, 117, 1179.
(s) Cho, S. H.; Liebeskind, L. S. J. Org. Chem. 1987, 52, 2631. (t)
Marchueta, I.; Verdaguer, X.; Moyano, A.; Pericas, M. A.; Riera, A. Org.
Lett. 2001, 20, 3193.
To enhance the synthetic potential of cyclopropenes
further, the development of methods for their utilization in
enantioselective reactions is highly desirable. A very effective
method has been the use of C2 symmetric ketals of cyclo-
(1) (a) Reissig, H.-U.; Zimmer, R.; Chem. ReV. 2003, 103, 1151. (b)
Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B. Chem. ReV. 2003,
103, 977. (c) Li, A.; Dai, L.; Aggarwal, V. K. Chem. ReV. 1997, 97, 2341.
(d) Binger, P.; Buch, H. M. Top. Curr. Chem. 1987, 135, 77. (e) Jennings,
P. W.; Johnson, L. L. Chem. ReV. 1994, 94, 2241. (f) Protopopova, M. N.;
Shapiro, E. A. Russ. Chem. ReV. 1989, 58, 667. (g) Maas, G. Top. Curr.
Chem. 1987, 137, 75. (h) Park, C. S.; Kim, M. S.; Sim, T. B.; Pyun, D. K.;
Lee, C. H.; Choi, D.; Lee, W. K.; Chang, J.-W.; Ha, H-J. J. Org. Chem.
2003, 68, 43. (i) Kim, B. M.; So, S. M.; Choi, H. J. Org. Lett. 2002, 4,
949. (j) Yan, Z.; Weaving, R.; Dauban, P.; Dodd, R. H. Tetrahedron Lett.
2002, 43, 7593. (k) Katsuki, T AdV. Synth. Catal. 2002, 344, 131.
(3) Nakamura, M.; Isobe, H.; Nakamura, E. Chem. ReV. 2003, 103, 1295.
10.1021/ol049928c CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/17/2004

ing blocks, which then undergo reactions in a stereoselective
manner. The most notable method to date for the enantio-
selective synthesis of cyclopropenes has been the metal-
catalyzed cyclopropenation of alkynes by diazoacetates.4 A
number of chiral catalysts have been developed for this
transformation, the most notable being Doyle’s chiral
dirhodium carboxamidates.4a These enantioselective cyclo-
propenations can be conducted on a range of alkynes, but
the diazo compounds have been limited thus far to diazo-
acetates. In this paper, we describe procedures for the
enantioselective cyclopropenation using aryldiazoacetates,
which greatly expands the range of readily accessible chiral
cyclopropenes to those containing a quaternary carbon center.
Concurrently, Fox and co-workers have developed an
alternative method to similar types of cyclopropenes by
means of kinetic resolution strategies.5
were conducted using methyl phenyldiazoacetate as the
carbenoid precursor (Table 1). The optimum conditions were
Table 1. Rh2(S-DOSP)4-Catalyzed Enantioselective
Cylopropenation with Methyl Phenyldiazoacetatea
The metal-catalyzed decomposition of aryl diazoacetates
and vinyl diazoacetates generates a distinctive class of
transient-metal carbenoids, functionalized with both a donor
and acceptor group.6 The donor/acceptor-substituted car-
benoids are more stabilized than the conventional carbenoids
derived from diazoacetates. They are capable of remarkably
stereoselective reactions, such as cyclopropanation,7 [4 +
3] cycloaddition,8 [3 + 2] cycloaddition9 and intermolecular
C-H insertion.10 The most generally effective chiral catalyst
for the various transformations of these donor/acceptor-
substituted carbenoids has been the dirhodium(II) tetrapro-
linate Rh2(S-DOSP)4 (1).11 In this paper, we show that Rh2(S-
DOSP)4 is also an exceptional catalyst for enantioselective
cylopropenations.
a Reactions were performed by the addition of the diazo compound (1.0
mmol) in 5 mL of hexanes over a 5-h period to a solution of the alkyne
(10.0 mmol) and catalyst (0.01 mmol) in 10 mL of hexanes. See the
Supporting Information for details.
To explore the scope of alkynes that would be amenable
found to be slow addition of the diazo compound (over 5 h)
to a hexane solution of Rh2(S-DOSP)4 (1 mol %) and the
alkyne (10 equiv) at room temperature (23 °C). Under these
conditions, the reaction with phenylacetylene generated the
cyclopropene 2 in 62% yield and 90% ee (entry 1). Similar
reactions were observed with various aromatic acetylenes
(entries 2-5). An especially interesting substrate is the
p-ethylbenzene derivative (entry 5) because this shows that
cyclopropenation is favored over benzylic C-H insertion.
An effective cyclopropenation of an enyne is also possible
indicating selective cyclopropenation over cyclopropanation
of the trisubstituted alkene (entry 6). The cyclopropenation
to Rh2(S-DOSP)4-catalyzed cyclopropenations, test reactions
(4) (a) Doyle, M. P.; Protopopova, M. N.; Muller, P.; Shapiro, E. A. J.
Am. Chem. Soc. 1994, 116, 8492. (b) Doyle, M. P.; Protopopova, M. N.;
Muller, P.; Ene, D. J. Am. Chem. Soc. 1992, 114, 2755. (c) Doyle, M. P.;
Eene, D.; Peterson, C. S.; Lynch, V. Angew. Chem., Int. Ed. 1999, 38, 700.
(d) Mu¨ller, P.; Imoga¨ı, H. Tetrahedron: Asymmetry 1998, 9, 4419. (e)
Imoga¨ı, H.; Bernardinelli, G.; Gra¨nicher, C.; Moran, M.; Rossier, J.-C.;
Mu¨ller, P. HelV. Chim. Acta 1998, 81, 1754. (f) Petiniot, N.; Anciaux, A.
J.; Noels, A. F.; Hubert, A. J.; Teyssie´, P. Tetrahedron Lett. 1978, 14, 1239.
(5) Concurrent with the work being reported here, Fox and co-workers
have developed an alternative kinetic resolution strategy to cyclopropenes
containing quaternary stereocenters: Fox, J. personal communication.
(6) Davies, H. M. L. Curr. Org. Chem. 1998, 2, 463.
(7) (a) Davies, H. M. L.; Bruzinski, P.; Hutcheson, D. K.; Kong, N.;
Fall, M. J. J. Am. Chem. Soc. 1996, 118, 6897. (b) Davies, H. M. L.;
Antoulinakis, E. G. Org. React. 2001, 57, 1.
(8) Davies, H. M. L. In AdVances in Cycloaddition; Haramata, M. E.,
Eds.; JAI Press: Greenwich, CT, 1999; Vol. 5, pp 119-164.
(9) Davies, H. M. L.; Xiang, B.; Kong, N.; Stafford, D. G. J. Am. Chem.
Soc. 2001, 123, 7461.
(10) (a) Davies, H. M. L.; Beckwith, R. E. J. Chem. ReV. 2003, 103,
2861. (b) Davies, H. M. L. J. Mol. Catal. A: Chem. 2002, 189, 125.
(11) Davies, H. M. L. Eur. J. Org. Chem. 1999, 2459, 9.
1234
Org. Lett., Vol. 6, No. 8, 2004

can also be conducted on 1-hexyne, but with slightly
diminished yield and enantioselectivity (entry 7).
Normally, the methyl styryldiazoacetate is an exceptional
source of a donor/acceptor carbenoid,7a but its reaction with
phenylacetylene failed to produce cyclopropene 14. The
failure of this reaction may be due to the instability of the
product rather than an inherent problem with the reaction
itself.
The cyclopropanation chemistry of donor/acceptor-sub-
stituted carbenoids is very distinctive because it is highly
chemoselective.7 A Hammett study on relative rates of
reactivity of methyl phenyldiazoacetate with different sty-
renes showed a very close correlation to the σ+ scale and
indicated that buildup of positive charge at the benzylic
carbon occurred in the transition state (F ) -1.0).13 To
determine if the cyclopropenation reaction displayed a similar
level of chemoselectivity, competition reactions were con-
ducted between different alkynes (Table 3). The electron-
The absolute configuration of 2 was determined to be (R)
by hydrogenation of 2 with diimide.4a Addition of hydrogen
to 2 gave a 1:1 mixture of diastereomers 9a and 9b, in which
the optical rotation for 9a ([R]25D -20.0, c 0.15, CHCl3, 90%
ee) confirmed it was the (1R,2R) cyclopropane (lit.7 [R]25
D
-28.5, c 1.1, CHCl3, 89% ee). The absolute configuration
of 3-8 is assigned as (R) by analogy to 2.
The cyclopropenation can be extended to a range of
aryldiazoacetates (Table 2). In most cases, the yields are in
Table 3. Relative Reactivity of Alkynes
Table 2. Rh2(S-DOSP)4-Catalyzed Enantioselective
Cylopropenation of Phenylacetylene with Various Aryl- and
Vinyldiazoacetates12
R
relative rate vs phenylacetylene
p-MeOC6H4
p-EtC6H4
p-ClC6H4
n-Bu
5.9
1.9
1.1
0.06
rich p-methoxyphenylacetylene was the most reactive while
1-hexyne was 18 times less reactive than phenylacetylene.
Thus, the electronic influence on cyclopropenation by the
donor/acceptor-substituted carbenoids is very similar to the
results observed for cyclopropanation.
A major mechanistic issue relating to the reactions of the
donor/acceptor-substituted carbenoids is the trajectory of
attack of the trapping species. In our earlier model for
cyclopropanation by the donor/acceptor-substituted car-
benoids, the alkene was considered to approach the rhodium
carbenoid in a side-on manner,7 but more recent kinetic
isotope and modeling studies indicated that an end-on
approach is more likely.14 The cyclopropenation chemistry
was considered to be a good test for the trajectory of
approach of the alkyne because cyclopropenation of 1,2-
disubstituted alkynes would appear to be impossible for a
reaction occurring by an end-on approach because the alkyne
substituent would collide with the catalyst surface, while the
side-on approach would still be feasible (Figure 1).
To test this issue, cyclopropenation of 1-phenyl-1-propyne
or 1,2-diphenylethyne was attempted. Neither substrate
a 2.5-10 equiv of alkyne was used. See the Supporting Information for
details. b 2 mol % catalyst was used.
(12) For the synthesis of diazo compounds, see: (a) Davies, H. M. L.;
Huby, N. J. S.; Cantrell, W. R., Jr.; Olive, J. L. J. Am. Chem. Soc. 1993,
115, 9468. (b) Davies, H. M. L.; Hansen, T.; Churchill, M. R. J. Am. Chem.
Soc. 2000, 122, 3063. (c) Davies, H. M. L.; Townsend, R. J. J. Org. Chem.
2001, 66, 6595.
(13) Davies, H. M. L.; Panaro, S. A. Tetrahedron 2000, 56, 4871.
(14) Nowlan, D. T.; Gregg, T. M.; Davies, H. M. L.; Singleton, D. A. J.
Am. Chem. Soc. 2003, 125, 15902.
the 50-65% range, but the p-methoxy derivative 11 was
formed in much lower yield (24%), presumably reflecting
the lower reactivity of the p-methoxyphenyl carbenoid.
Org. Lett., Vol. 6, No. 8, 2004
1235

acetate, which does react with 1-phenylpropene.4a,f The total
lack of reactivity of disubstituted alkynes is consistent with
a reaction mechanism involving end-on approach.
In summary, these studies demonstrate that the Rh2(S-
DOSP)4-catalyzed reactions of aryldiazoacetates with 1-sub-
stituted alkynes results in the enantioselective synthesis of
cyclopropenes containing quaternary centers. This work
expands the range of readily available chiral cyclopropenes,
which can be used as chiral building blocks for organic
synthesis.
Figure 1. Comparison of side-on7 and end-on14 approaches for
cyclopropenation.
Acknowledgment. Financial support of this work by the
National Science Foundation (CHE 0350536) is gratefully
acknowledged.
generated any cyclopropene product. These results are in
contrast to cyclopropenation reactions with ethyl diazo-
Supporting Information Available: Full experimental
data of all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL049928C
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