Asymmetric cyclopropanations by rhodium(II) N-(arylsulfonyl)prolinate catalyzed decomposition of vinyldiazomethanes in the presence of alkenes. Practical enantioselective synthesis of the four stereoisomers of 2-phenylcyclopropan-1-amino acid

Article abstract of DOI:10.1021/ja9604931

The rhodium N-(arylsulfonyl)prolinate catalyzed decomposition of vinyldiazomethanes in the presence of alkenes leads to a very general method for the synthesis of functionalized cyclopropanes in a highly diastereoselective and enantioselective mode. A det

Full text of DOI:10.1021/ja9604931

J. Am. Chem. Soc. 1996, 118, 6897-6907
6897
Asymmetric Cyclopropanations by Rhodium(II)
N-(Arylsulfonyl)prolinate Catalyzed Decomposition of
Vinyldiazomethanes in the Presence of Alkenes. Practical
Enantioselective Synthesis of the Four Stereoisomers of
2-Phenylcyclopropan-1-amino Acid
Huw M. L. Davies,*,† Paul R. Bruzinski,† Debra H. Lake,‡ Norman Kong,† and
Michael J. Fall‡
Contribution from the Department of Chemistry, State UniVersity of New York at Buffalo,
Buffalo, New York 14260-3000, and Department of Chemistry, Wake Forest UniVersity,
Box 7486, Winston-Salem, North Carolina 27109
ReceiVed February 15, 1996X
Abstract: The rhodium N-(arylsulfonyl)prolinate catalyzed decomposition of vinyldiazomethanes in the presence of
alkenes leads to a very general method for the synthesis of functionalized cyclopropanes in a highly diastereoselective
and enantioselective mode. A detailed study was undertaken to determine the key factors that control the
enantioselectivity of this process. The highest levels of enantioselectivity were obtained using cyclic N-(arylsulfonyl)-
amino acids as ligands for the dirhodium catalyst, and the optimized catalyst was tetrakis[N-[(4-dodecylphenyl)-
sulfonyl]-(L)-prolinato]dirhodium. The carbenoid structure has a critical effect on the degree of asymmetric induction,
and the combination of a small electron-withdrawing group such as a methyl ester and an electron-donating group
such as vinyl or phenyl resulted in the highest levels of enantioselectivity. The use of electron neutral alkenes and
pentane as solvent also enhanced the enantioselectivity of the process. The synthetic utility of this chemistry was
illustrated by its application to the synthesis of all four stereoisomers of 2-phenylcyclopropan-1-amino acid. The
occurrence of the highly stereoselective cyclopropanations was rationalized by a model in which the ligands were
considered to adopt a D2 symmetric arrangement.
The cyclopropane ring has drawn great synthetic interest1
because it is present in a number of useful natural2 and unnatural
products,3 and can be employed in several stereoselective
synthetic processes.4 In recent years, a number of enantiose-
lective methods have been developed for the construction of
the cyclopropane ring.5-7 A particularly powerful method is
the metal-catalyzed decomposition of diazo compounds in the
presence of alkenes.8-10 A new variation of this method is the
basis of this paper using vinyldiazomethanes as substrates and
chiral rhodium(II) carboxylates as catalysts. This approach leads
to the synthesis of highly functionalized vinylcyclopropanes with
excellent control of both diastereo- and enantioselectivity (eq
1).11 The synthetic utility of this chemistry has been illustrated
by its application to the synthesis of all four stereoisomers of
2-phenylcyclopropan-1-amino acid (1).7
(II) amide complexes of overall C2 symmetry9a-h have been
developed. The standard reaction that has been used to evaluate
these catalysts has been the asymmetric cyclopropanation of
(3) (a) English, M. L.; Stammer, C. H. Biochem. Biophys. Res. Commun.
1978, 85, 780. (b) Chipkin, R. E.; Stewart, J. M.; Stammer, C. H. Biochem.
Biophys. Res. Commun. 1979, 87, 890. (c) Shimohigashi, Y.; Stammer, C.
H.; Costa, T. Synthetic Peptides in Biotechnology; A. R. Liss, Inc.: New
York, 1988; p 203. (d) Edwards, H. V.; Dailey, O. D., Jr.; Bland, J. M.;
Cutler, H. G. ACS Symp. Ser. 1988, 380. (e) Tsang, J. W.; Schmeid, M.;
Nyfelter, R.; Goodman, M. J. J. Med. Chem. 1984, 27, 1663. (f) Mapelli,
C.; Stammer, C. H.; Lok, S.; Mierke, D. F.; Goodman, M. Int. J. Pept.
Protein Res. 1988, 32, 484. (g) Zhu, Y. F.; Yamazaki, T.; Tsang, J. W.;
Lok, S.; Goodman, M. J. Org. Chem. 1992, 57, 1074. (h) Kimura, H.;
Stammer, C. H.; Shimohigashi, Y.; Cui, R. L.; Stewart, J. Biochem. Biophys.
Res. Commun. 1983, 115, 112. (i) Shimohigashi, Y.; Stammer, C. H.; Costa,
T.; Vonvoigtlander, P. F. Int. J. Pept. Protein Res. 1983, 22, 489. (j) Mapelli,
C.; Kimura, H.; Stammer, C. H. Int. J. Pept. Protein Res. 1986, 28, 347.
(k) Malin, D. H.; Payza, K.; Lake, J. R.; Corriere, L. S.; Benson, T. M.;
Smith, D. A.; Baugher, R. K.; Ho, K.-K.; Burgess, K. Peptides 1993, 14,
47. (l) Burgess, K.; Ho, K.-K.; Pettitt, B. M. J. Am. Chem. Soc. 1994, 116,
799. (m) Shimhigashi, Y.; Costa, T.; Nitz, T. J.; Chen, H. C.; Stammer, C.
H. Biochem. Biophys. Res. Commun. 1984, 121, 966. (n) Shimhigashi, Y.;
Costa, T.; Pfeiffer, A.; Herz, A.; Kimura, H.; Stammer, C. H. FEBS Lett.
1987, 222, 71. (o) Malin, D. H.; Lake, J. R.; Ho, K.-K.; Corrier, L. S.;
Garber, T. M.; Waller, M.; Benson, T.; Smith, D. A.; Luu, T.-A.; Burgess,
K. Peptides 1993, 14, 731. (p) Campbell, M. M.; Horwell, D. C.; Mahon,
M. F.; Prithcard, M. C.; Walford, S. P. Bioorg. Med. Chem. Lett. 1993, 3,
667.
Even though the metal-catalyzed asymmetric cyclopropana-
tion of alkenes by diazo compounds has been greatly optimized
in recent years through the development of new chiral catalysts,
the process still has certain deficiencies. Over the last decade
a series of highly effective copper8 and ruthenium10 catalysts
containing chiral ligands of C2 symmetry and dimeric rhodium-
† State University of New York at Buffalo.
‡ Wake Forest University.
X Abstract published in AdVance ACS Abstracts, July 1, 1996.
(1) (a) Burgess, K.; Ho, K.; Moye-Sherman, D. Synlett 1994, 575. (b)
Stammer, C. H. Tetrahedron 1990, 46, 2231.
(2) For examples of naturally occurring cyclopropanamino acids, see:
(a) Sakamura, S.; Ichehara, A.; Shiraishi, K.; Sato, K.; Nishiyama, K.; Sakai,
R.; Furusaki, A.; Matsumoto, T. J. Am. Chem. Soc. 1977, 99, 636. (b)
Mitchell, R. E. Phytochemistry 1985, 24, 1485. (c) Hoffman, N. E.; Yang,
S. F.; Ichihara, A.; Sakamura, S. Plant Physiol. 1982, 70, 195. (d)
Wakamiya, T.; Nakamoto, H.; Shiba, T. Tetrahedron Lett. 1984, 25, 4411.
(e) Wakamiya, T.; Oda, Y.; Fujita, H.; Shiba, T. Tetrahedron Lett. 1986,
27, 2143.
S0002-7863(96)00493-3 CCC: $12.00 © 1996 American Chemical Society

6898 J. Am. Chem. Soc., Vol. 118, No. 29, 1996
DaVies et al.
alkenes by diazoacetate derivatives, and many of the catalysts
exhibit enantioselectivity of 98% ee or greater (eq 2). In
compounds. Indeed, the most widely used catalysts for car-
benoid transformations are the rhodium(II) carboxylates,13 but
attempts at developing chiral carboxylate catalysts for asym-
metric cyclopropanation have met with limited success.9i,j
In contrast to diazoacetates, the rhodium(II) carboxylate
catalyzed cyclopropanations of vinyldiazomethanes occur with
excellent diastereoselectivity.14 In many instances there is no
trace of the second isomer in the 1H NMR spectra of the crude
reaction mixtures, and only in the case of alkyl-substituted
alkenes and dienes does the diastereoselectivity degrade below
10:1. As the products from these reactions are geminally
substituted cyclopropanes that can be further manipulated for
the stereoselective construction of other ring systems,15 we
considered that the asymmetric version of this process would
be a powerful synthetic transformation. We have previously
reported an effective method to achieve asymmetric cyclopro-
panations with vinyldiazomethanes, but the process required
using a stoichiometric amount of a chiral auxiliary on the
vinyldiazomethane.16 In contrast, attempts at chiral catalysis
using the traditional chiral catalysts such as Masamune’s copper
(2) and Doyle’s rhodium(II) amide (3) complexes were unsuc-
cessful because the catalysts were not effective at decomposing
vinyldiazomethanes to vinylcarbenoids (eq 3).16 Consequently,
we have explored the possibility of developing chiral rhodium-
(II) carboxylates as effective catalysts for asymmetric cyclo-
propanations by vinyldiazomethanes.
general, however, intermolecular cyclopropanations by diazo-
acetates using rhodium and copper catalysts are not particularly
diastereoselective unless extremely bulky ester groups are
used,8e,12 although significant improvements in diastereoselec-
tivity have been recently found using ruthenium catalysis.10
Furthermore, the chiral catalysts do not have general applicabil-
ity for asymmetric transformations using other types of diazo
(4) (a) Reissig, H.-U. Top. Curr. Chem. 1988, 144, 73. (b) Reissig, H.-
U. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley:
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Soc. Res. 1988, 17, 229. (d) Pegg, G. G.; Meehan, G. V. Aust. J. Chem.
1990, 43, 1009. (e) Reissig, H.-U.; Wienand, A. Chem. Ber. 1991, 124,
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1989, 89, 165.
(5) (a) Williams, R. M. Aldrichim. Acta 1992, 25, 11. (b) Alami, A.;
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Bergmeier, S. C.; Frick, J. A.; Bathe, A.; Rapoport, H. J. Org. Chem. 1994,
59, 5336. (d) Groth, U.; Habrodt, W.; Schollkopf, U. Leibigs Ann. Chem.
1992, 22, 1149. (e) Aitken, D. J.; Royer, J.; Husson, H. Tetrahedron Lett.
1988, 29, 3315. (f) Aitken, D. J.; Royer, J.; Husson, H. J. Org. Chem. 1990,
55, 2814. (g) Alcaraz, C.; Herreo, A.; Marco, J. L.; Fernandez-Alverez, E.;
Bernabe, M. Tetrahedron Lett. 1992, 33, 5605. (h) Alami, A.; Calmes, M.;
Daunis, J.; Escale, F. Tetrahedron: Asymmetry 1991, 3, 175. (i) Charette,
A. B.; Cote, B. J. Am. Chem. Soc. 1995, 117, 12721. (j) Zhao, Y.; Yang,
T.-E.; Lee, M.; Chun, B. K.; Du, J.; Schinazi, R. F.; Lee, D.; Newton, M.
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de-Villigas, M. D.; Jimenez, A. I.; Lahoz, F. Tetrahedron Lett. 1994, 35,
617. (l) Chincilla, R.; Najera, C. Tetrahedron Lett. 1993, 34, 5799.
(6) (a) Burgess, K.; Ho, K.-K. J. Org. Chem. 1992, 57, 5931. (b) Burgess,
K.; Ho, K.-K.; Ke, C.-Y. J. Org. Chem. 1993, 58, 3767. (c) Burgess, K.;
Wen, L. Tetrahedron Lett. 1995, 36, 2725.
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8796. (b) Williams, R. M.; Fegley, G. J. J. Org. Chem. 1993, 58, 6933. (c)
Fernandez, M. D.; Frutos, M. P. D.; Marco, J. L.; Fernandez-Alverez, E.;
Bernabe, M. Tetrahedron Lett. 1989, 30, 3101. (d) Kimura, H.; Stammer,
C. H. J. Org. Chem. 1983, 48, 2440.
(8) (a) Nozaki, H.; Moriuti, S.; Takaya, H.; Noyori, R. Tetrahedron Lett.
1966, 5239. (b) Aratani, T.; Yoneyoshi, Y.; Nagase, T. Tetrahedron Lett.
1982, 23, 685. (c) Fritschi, H.; Leutenegger, U.; Pfaltz, A. HelV. Chim.
Acta 1988, 71, 1553. (d) Lowenthal, R. E.; Abiko, A.; Masamune, S.
Tetrahedron Lett. 1990, 31, 6005. (e) Evans, D. A.; Woerpel, K. A.; Hinman,
M. M.; Faul, M. M. J. Am. Chem. Soc. 1991, 113, 726. (f) Leutenegger,
U.; Umbricht, G.; Fahrni, C.; von Matt, P.; Pfalz, A. Tetrahedron 1992,
48, 2143. (g) Ito, K.; Katsuki, T. Tetrahedron Lett. 1993, 34, 2661. (h)
Gant, T. G.; Noe, M. C.; Corey, E. J. Tetrahedron Lett. 1995, 36, 8745.
(9) (a) Doyle, M. P.; Brandes, B. D.; Kazala, A. P.; Pieters, R. J.; Jarstfer,
M. B.; Watkins, L. M.; Eagle, C. T. Tetrahedron Lett. 1990, 31, 6613. (b)
Doyle, M. P.; Pieters, R. J.; Martin, S. F.; Austin, R. E.; Oalmann, C. J.;
Muller, P. J. Am. Chem. Soc. 1991, 113, 1423. (c) Protopopova, M. N.;
Doyle, M. P.; Muller, P.; Ene, D. J. Am. Chem. Soc. 1992, 114, 2755. (d)
Doyle, M. P.; Winchester, W. R.; Hoorn, J. A. A.; Lynch, V.; Simonsen,
S. H.; Ghosh, R. J. Am. Chem. Soc. 1993, 115, 9968. (e) Martin, S. F.;
Oalmann, C. J.; Lira, S. Tetrahedron 1993, 49, 3521. (f) Martin, S. F.;
Spaller, M. R.; Liras, S.; Hartmann, B. J. Am. Chem. Soc. 1994, 116, 4493.
(g) Doyle, M. P.; Protopova, M. N.; Brandes, B. D.; Davies, H. M. L.;
Huby, N. J. S.; Whitesell, J. K. Synlett 1993, 151. (h) Doyle, M. P; Austin,
R. E.; Bailey, A. S.; Dwyer, M. P.; Dyatkin, A. B.; Kalinin, A. V.; Kwan,
M. M. Y.; Lira, S.; Oalmann, C. J.; Pieters, R. J.; Protopova, N.; Raab, C.
E.; Roos, G. H. P.; Zhou, Q.-L.; Martin, S. F. J. Am. Chem. Soc. 1995,
117, 5763. (i) Kennedy, M.; McKervey, M. A.; Maguire, A. R.; Roos, G.
H. P. J. Chem. Soc., Chem. Commun. 1990, 361. (j) Brunner, H.;
Kluschanzoff, Wutz, K. Bull. Chem. Soc. Belg. 1989, 98, 63.
Even though previous attempts at asymmetric cyclopropa-
nation using chiral rhodium(II) carboxylates had not been
fruitful, sufficient literature precedence existed to indicate that
the rhodium(II) carboxylate scaffold could be employed for the
design of useful chiral catalysts.17,18 Two chiral rhodium(II)
carboxylate catalyst systems have shown promise in other
asymmetric carbenoid reactions. The prolinate-derived catalyst
417 and the phenylalanine-derived catalyst 518 resulted in
moderately high levels of asymmetric induction for intramo-
lecular C-H insertions as illustrated in eqs 4 and 5. Using
this precedence as a staring point, we have studied the utilization
of these and related catalysts in asymmetric transformations of
vinylcarbenoid intermediates. The details of this study are the
basis of this paper.
(13) (a) Ye, T.; McKervey, M. A. Chem. ReV. 1994, 94, 1091. (b) Davies,
H. M. L. In ComprehensiVe Organic Synthesis; Trost, B. M., Ed.; Pergamon
Press: Oxford, 1991; Vol. 4, pp 1031-1068. (c) Padwa, A.; Krumpe, K.
E. Tetrahedron 1992, 48, 5385. (d) Adams, J.; Spero, D. M. Tetrahedron
1991, 47, 1765.
(14) Davies, H. M. L.; Clark, T. J.; Church, L. A. Tetrahedron Lett.
1989, 30, 5057.
(15) Davies, H. M. L. Tetrahedron 1993, 49, 5203.
(16) Davies, H. M. L.; Huby, N. J. S.; Cantrell, W. R., Jr.; Olive, J. L.
J. Am. Chem. Soc. 1993, 115, 9468.
(17) McKervey, M. A.; Ye, T. J. Chem. Soc., Chem. Commun. 1992,
823.
(10) (a) Nishiyama, H.; Itoh, Y.; Matsumoto, H.; Park, S.-B.; Itoh, K. J.
Am. Chem. Soc. 1994, 116, 2223. (b) Nishiyama, H.; Itoh, Y.; Sugawara,
Y.; Matsumoto, H.; Aoki, K.; Itoh, K. Bull. Chem. Soc. Jpn. 1995, 68,
1247.
(11) For a preliminary account of portions of this work, see: (a) Davies,
H. M. L.; Hutcheson, D. K. Tetrahedron Lett. 1993, 34, 7243. (b) Davies,
H. M. L.; Bruzinski, P. R.; Fall, M. J. Tetrahedron Lett., in press.
(12) 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.
(18) (a) Hashimoto, S.; Watanabe, N.; Ikegami, S. Tetrahedron Lett.
1990, 31, 5173. (b) Hashimoto, S.; Watanabe, N.; Sato, T.; Shiro, M.;
Ikegami, S. Tetrahedron Lett. 1993, 34, 5109.
(19) Pirrung, M. C.; Zhang, J. Tetrahedron Lett. 1992, 33, 5987.

Decomposition of Vinyldiazomethanes
J. Am. Chem. Soc., Vol. 118, No. 29, 1996 6899
Table 1. Effect of Catalysts and Solvent on Asymmetric Induction
ee, %
ee, %
catalyst solvent (abs config) catalyst solvent (abs config)
4
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
pentane 90 (1S,2S)
CH2Cl2 79 (1S,2S)
pentane 92 (1S,2S)
74 (1S,2S)
76 (1S,2S)
83 (1S,2S)
74 (1S,2S)
6e
6f
6g
7
8
9
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
pentane 81 (1S,2S)
pentane 81 (1S,2S)
75 (1S,2S)
61 (1S,2S)
30 (1S,2S)
30 (1S,2S)
6 (1S,2S)
6a
6b
6c
6c
6d
6d
10
Results
Table 2. Effect of Ester Size on Asymmetric Induction
A series of catalysts were readily prepared by high-temper-
ature ligand exchange between the chiral carboxylic acid and
rhodium(II) acetate.19 The majority of these catalysts were
prolinate derivatives (6a-i) that contained different N-sulfonyl
functionalities. In order to determine how critical the presence
of the proline ring would be for high asymmetric induction,
the acyclic derivatives 7 and 8, the azetidinecarboxylate 9 and
the picolinate 10 were also prepared.
substrate
R
solvent
ee, % (abs config)
11a
11a
11b
11b
11c
11c
11d
11d
OMe
OMe
OEt
CH2Cl2
pentane
CH2Cl2
pentane
CH2Cl2
pentane
CH2Cl2
pentane
74 (1S,2S)
90 (1S,2S)
68 (1S,2S)
84 (1S,2S)
43 (1S,2S)
76 (1S,2S)
9 (1S,2S)
OEt
OiPr
OiPr
OtBu
OtBu
50 (1S,2S)
effect and high asymmetric induction was obtained with either
the 4-methoxyphenyl derivative 6a (76% ee) or the 4-nitrophenyl
derivative 6b (83% ee). The hydrophobic 4-tert-butylphenyl
(6c) and 4-dodecylphenyl (6d) catalysts were prepared in order
that the effect of using a hydrocarbon solvent could be explored.
The 4-tert-butylphenyl catalyst 6c has rather low solubility in
pentane and does not dissolve fully under the catalysis reaction
conditions while the 4-dodecylphenyl catalyst 6d is very soluble
in pentane. The change of the reaction solvent from dichlo-
romethane to pentane resulted in a major improvement in
enantioselectivity, leading to the formation of 12a in 90-92%
ee. An N-arylsulfonyl functionality appears to be a structural
requirement for high asymmetric induction because the reaction
with the N-isopropylsulfonyl catalyst 6g resulted in the formation
of 12a in only 30% ee. The necessity of the ring system was
readily seen from the results with the acyclic derivatives 7 and
8 which also resulted in low levels of enantioselectivity (6-
30% ee). Even though a cyclic amino acid derivative is
required, certain flexibility in terms of ring size can be tolerated
since high levels of asymmetric induction were observed for
both the azetidinecarboxylate complex 9 (81% ee) and the
pipecolinate complex 10 (81% ee).
For all the chiral catalysts that have been developed for
asymmetric cyclopropanation using diazoacetate as substrate,
very large improvements in asymmetric induction have been
observed on increasing the size of the ester group.8-10 Con-
sequently, we examined the effect of changing the ester size
from methyl to tert-butyl with a series of vinyldiazomethane
derivatives 11a-d, and the results are summarized in Table 2.
In contrast to the previous studies on diazoacetate derivatives,
increasing the ester size of the vinyldiazomethanes caused a
drastic loss of enantioselectivity while the diastereoselectivity
was essentially unaltered. The reactions were carried out in
both dichloromethane and pentane as solvent, and in each
solvent system a steady drop in enantioselectivity was observed
The evaluation of these catalysts was carried out using the
cyclopropanation between methyl 2-diazo-4-phenylbutenoate
(11a)20 and styrene with 0.01 equiv of catalyst and dichlo-
romethane as solvent at 25 °C as the standard reaction (eq 6).
The results are summarized in Table 1. These initial studies
were carried out with either 5 or 20 equiv of styrene, but as
will be discussed later, either amount of styrene resulted in very
similar enantioselectivity and isolated yield of product. In all
cases, the diastereoselectivity of these reactions was excellent,
favoring the E-isomer 12a over the Z-isomer by a ratio of at
least 40:1 (typically from 43:1 to 70:1). All the reactions
proceeded in moderate to excellent yields ranging from 46% to
91%. Under the traditional conditions for carbenoid reactions
using dichloromethane as solvent, all of the N-arylsulfonyl
prolinate catalysts resulted in the formation of the cyclopropane
12a with good asymmetric induction (64-83% ee).21 The
absolute stereochemistry of the major isomer of 12a in all cases
was 1S,2S.22 Electronic changes on the aryl ring had a minimal
(20) (a) Davies, H. M. L.; Cantrell, W. R., Jr.; Romines, K. R.; Baum,
J. S. Org. Synth. 1991, 70, 93. (b) Baum, J. S.; Shook, D. A.; Davies, H.
M. L.; Smith, H. D. Synth. Commun. 1987, 17, 1709.
1
(21) Enantiomeric excesses (% ee) were determined by H NMR using
tris[3-[(heptafluoropropyl)hydroxymethylene]-(-)-camphorato]praseodymium-
(III) as a chiral shift reagent and intergration of the split methoxy signal,
or by HPLC using a Diacel Chiralcel OJ analytical column (see ref 29).
(22) The absolute configuration of 12a was determined by comparison
of the optical rotation of 12a with that of an authentic sample (see ref 16).
(23) The major enantiomer for 12b-d was assigned as (1S,2S) on the
basis of the ORD spectra of 12b-d similar to that of 12a.

6900 J. Am. Chem. Soc., Vol. 118, No. 29, 1996
DaVies et al.
Table 4. Effect of Alkene Structure on Asymmetric Induction
Table 3. Effect of Temperature and Equivalence of Catalyst on
Asymmetric Induction
temp,
°C
amt of
catalyst, equiv
amt of
additive, equiv
ee, %
(abs config)
temp,
°C
ee, %
yield,
%
catalyst
R
product (abs config)
25
98a
69b
35
-20
-78
25
25
25
25
25
0.01
0.01
0.01
0.01
0.01
0.01
0.001
0.0001
0.001
0.001
0.0001
0.0001
-
-
-
-
92 (1S,2S)
82 (1S,2S)
86 (1S,2S)
91 (1S,2S)
93 (1S,2S)
98 (1S,2S)
87 (1S,2S)
50 (1S,2S)
89 (1S,2S)
90 (1S,2S)
67 (1S,2S)
61 (1S,2S)
6c
6d
6c
6d
6c
6d
6c
6d
6c
6d
6c
6c
6c
25
-78
25
-78
25
-78
25
-78
25
C6H5
C6H5
12a
12a
13
13
14
14
15
15
16
16
17
18
19
90 (1S,2S)
98 (1S,2S)
89 (1S,2S)
>97 (1S,2S)
83 (1S,2S)
90 (1S,2S)
76
95
59
93
79
68
91
70
87
41
40
26
83
65
63
65
58
p-ClC6H4
p-ClC6H4
p-MeOC6H4
p-MeOC6H4
AcO
-
-
-
AcO
EtO
acetate (0.01)
prolinate (0.01)
acetate (0.01)
prolinate (0.01)
-78
25
25
EtO
nBu
>90
25
Et
>95
a Reaction carried out in refluxing heptane. b Reaction carried out
in refluxing hexane.
25
iPr
95
1.2 equiv, and this was achieved without resorting to syringe
pump techniques for vinyldiazomethane addition.
on increasing the size of the ester group from methyl to ethyl
to isopropyl to tert-butyl (from 74% to 9% ee in dichlo-
romethane and from 90% to 50% ee in pentane).21,23
A series of experiments using monosubstituted alkenes were
then carried out to determine the effect of the electronic nature
of the alkene on asymmetric induction, and these results are
summarized in Table 4. The initial series of experiments were
carried out at room temperature using 6c as catalyst. A steady
drop in enantioselectivity was observed with electron rich
alkenes as seen for the cyclopropanes 12a-16 (90-59% ee),
while simple alkyl-substituted alkenes resulted in the formation
of the cyclopropanes 17-19 with very high levels of enanti-
oselectivity (>90% ee).25,26 Even though the enantioselectivity
is exceptionally high in the case of simple alkenes, some
degradation in diastereoselectivity (from >40:1 to ∼15:1) is
observed. Further improvement in enantioselectivity was pos-
sible by carrying out these reactions at -78 °C using 6d as
catalyst. Under these conditions all the reactions proceeded in
>90% ee, although the isolated yields were slightly lower than
the reactions carried out at room temperature.
Extension of the reaction to more substituted alkenes was
then examined. In the case of a 1,1-disubstituted alkene such
as 2-methylpropene, an exceptionally high level of enantiose-
lectivity (95% ee)26 in the formation of the cyclopropane 20
was observed. We have found that vinylcarbenoids typically
fail to react with trans-alkenes,27,28 and this was verified in the
rhodium(II) prolinate catalyzed reactions by using cis- and trans-
2-butenes as substrates. Rhodium(II) prolinate 6d catalyzed
decomposition of 11a in the presence of cis-2-butene resulted
in the formation of the meso compound 21 in 80% yield. In
contrast, a mixture of products was formed in the parallel
reaction of 11a with trans-2-butene, from which no cyclopro-
pane product was isolable. These results underscore the inability
of vinylcarbenoids to react with trans-alkenes. A further
example of the reaction with a cis-alkene was carried out at
-78 °C using 2,3-dihydrofuran as substrate, and this resulted
in the formation of the fused cyclopropane 23 in 86% ee and
84% yield.
The next series of experiments examined the effects of the
reaction temperature and the amount of catalyst on these
transformations (Table 3). The 4-dodecylphenylprolinate cata-
lyst 6d was used because it is the most soluble in hydrocarbon
solvents. As can be seen in entries 1-5, the temperature of
the reaction (+98 to -78 °C) had a significant effect on the
extent of asymmetric induction (82-98% ee). Particularly
impressive is the fact that 6d is still an effectice catalyst even
at -78 °C. All of the initial standard reactions were carried
out using 0.01 equiv of catalyst. In order to determine the
minimum amount of catalyst that would be required in this
chemistry, the reaction was examined using decreasing amounts
of catalyst. On using 0.001 equiv of 6d instead of the standard
0.01 equiv, a slight drop in enantioselectivity was observed
(from 92% to 87% ee) while on decreasing the amount of
catalyst to 0.0001 equiv, the enantioselectivity dropped to 50%
ee and the reaction stopped at 50% completion. One possible
cause of the drop of enantioselectivity could be dissociation of
the carboxylate ligand; therefore, further experiments were
carried out with carboxylate ligands as additives. Addition of
0.1 equiv of acetic acid or 0.1 equiv of N-[(4-dodecylphenyl)-
sulfonyl]proline had very little effect on the asymmetric
induction using either 0.001 or 0.0001 equiv of 6d. This result
would indicate that ligand exchange reactions are not the cause
of the drop in enantioselectivity when very small quantities of
chiral catalyst are used. Instead, general catalyst degradation
or poisoning is probably occurring.
Under the standard reaction conditions either 5 or 20 equiv
of styrene was used to trap the carbenoid intermediate. Excess
styrene was used because with most intermolecular carbenoid
reactions, ineffective capture of the carbenoid would occur
unless extremely slow rates of diazoalkane addition using
syringe pump techniques are employed.24 Even though the
excess styrene can be readily recovered, such an excess of
trapping agent would be unacceptable for expensive alkenes.
Consequently, the effect of alkene concentration on both the
yield and enantioselectivity of cyclopropanation product was
examined. Remarkably, both the yield (83-89%) and enanti-
oselectivity (90-92% ee) of the reaction remained virtually
unchanged on varying the amount of styrene used from 20 to
(25) The absolute configurations for 13 and 14 have been assigned on
the basis of the ORD spectra of these compounds similar to that of 12a.
(26) The absolute configurations assigned for 15-20 and 23 are tentative
and are based on the proposed transition state model for the asymmetric
induction.
(27) Davies, H. M. L.; Clark, T. J.; Smith, H. D. J. Org. Chem. 1991,
56, 3817.
(28) Davies, H. M. L.; Hu, B. J. Org. Chem. 1992, 57, 3186.
(29) Davies, H. M. L.; Peng, Z.-Q.; Houser, J. H. Tetrahedron Lett. 1994,
35, 8939.
(24) Doyle, M. P.; Van Leusen, D.; Tamblyn, W. H. Synthesis 1981,
787.

Decomposition of Vinyldiazomethanes
J. Am. Chem. Soc., Vol. 118, No. 29, 1996 6901
Scheme 1a
In principle, the asymmetric cyclopropanations between
vinylcarbenoids and alkenes offer numerous synthetic op-
portunities. We have already communicated how the reaction
between vinylcarbenoids and dienes can lead to a tandem
asymmetric cyclopropanation/Cope rearrangement, leading to
a general enantioselective synthesis of seven-membered rings.29
This study showed that the asymmetric cyclopropanation can
be carried out with a variety of diazovinylacetate derivatives
and is not limited to the 4-phenyl-2-diazobutenoate system.
Another application of this chemistry has recently been de-
scribed by Corey, leading to the enantioselective synthesis of
sertraline.30 The asymmetric vinylcarbenoid chemistry also
appears to offer a very practical approach for the asymmetric
construction of cyclopropanamino acids as illustrated for the
phenylcyclopropane 12a (eq 7). Either of the diastereomeric
cyclopropanamino acids 1a and 1c should be obtainable from
12a while the corresponding enantiomers 1b and 1d should be
obtainable from ent-12a.
t
a Conditions (a) RuCl3/NaIO4. (b) (1) NEt3, DPPA, BuOH; (2)
((CH3)3COCO)2O. (c) -OH. (d) 3 M HCl/EtOAc. (e) K2CO3, Me2SO4.
Figure 1.
in 27 was then readily achieved using NaOH in methanol34 to
give 28 in 75% yield after recrystallization. The acid 28 was
then converted to the Boc-protected amine 29 in 76% yield using
the Curtius rearrangement conditions32 described above. The
ester in 29 was then hydrolyzed with LiOH‚H2O in methanol
and water,7c and the crude material was directly converted to
the amine 1c as its hydrochloride salt in 83% overall yield with
3 N HCl in EtOAc.33 The other two stereoisomers of phenyl-
cyclopropanamino acid 1b and 1d were readily obtained using
the above procedures starting from ent-12a.
The approach that was used to prepare the four phenylcy-
clopropanamino acids 1a-d is shown in Scheme 1. Either
enantiomer of the phenylcyclopropane 12a or ent-12a can be
obtained enantiomerically pure by decomposition of 11a in the
presence of styrene under the optimized reaction conditions
using the appropriate enantiomer of the catalyst 6d (92% ee,
83% yield), followed by a single recrystallization from 2-pro-
panol (70% recovery). The vinyl portion in the cyclopropane
Discussion
Considering that it has been previously suggested that the
rhodium carboxylate framework was far from ideal for the
development of chiral catalysts,35 the high levels of asymmetric
induction that we have obtained with the rhodium(II) prolinate/
vinyldiazomethane system deserve further comment. The basic
structure of the rhodium(II) carboxylate core has been well
established through a number of X-ray structure determina-
tions.18b,36 The rhodium complex is dimeric in nature with four
bridging carboxylate ligands as shown in Figure 1, and it is
generally assumed that the complex remains dimeric during the
catalytic process.13 The empty axial positions have been
postulated to be the site of catalytic activity, and as there are
two axial sites and all the carboxylate groups are pointing away
from these sites, it was considered that chiral carboxylates would
not lead to efficient chiral catalysts. Clearly, this is not the
case with the rhodium prolinate system, and the issue that needs
31
12a was oxidatively cleaved with RuCl3‚H2O/NaIO4 to give
the corresponding acid 24 in 70% yield. Treatment of the acid
24 with diphenylphosphoryl azide32 resulted in a Curtius
rearrangement, and the intermediate isocycanate was trapped
by tert-butyl alcohol. The crude product was treated with di-
tert-butyl dicarbonate to protect any free amine byproduct that
was formed, and this led to the formation of the Boc-protected
amine 25 in 68% overall yield after recrystallization. The
methyl ester was then hydrolyzed to give the acid 26 in 77%
yield, which was then readily converted to the amine 1a as its
hydrochloride salt by treatment in 3 N HCl in EtOAc33 in 83%
yield. The second diastereomer 1c was readily obtained by first
treatment of 24 with Me2SO4/K2CO3 to form the diester 27 (94%
yield). Selective hydrolysis of the ester trans to the phenyl ring
(30) Corey, E. J.; Gant, T. G. Tetrahedron Lett. 1994, 35, 5373.
(31) Carlsen, P. H. J.; Katsuki, T.; Martin, V. S.; Sharpless, K. B. J.
Org. Chem. 1981, 46, 3936.
(34) De Kimpe, N.; Boeykens, M.; Tehrani, K. A. J. Org. Chem. 1994,
59, 8215.
(32) Ninomiya, K.; Shiori, T.; Yamada, S. Tetrahedron 1974, 30, 2151.
(33) Stahl, G. L.; Walter, R.; Smith, C. W. J. Org. Chem. 1978, 43,
2285.
(35) Doyle, M. P. Recl. TraV. Chim. Pays-Bas 1991, 110, 305.
(36) Cotton, F. A.; DeBoer, B. G.; LaPrade, M. D.; Ripal, J. R.; Ucko,
D. A. Acta Crystallogr. 1971, B27, 1664.

6902 J. Am. Chem. Soc., Vol. 118, No. 29, 1996
DaVies et al.
Figure 2.
to be addressed is how the arrangement of the four prolinate
ligands around the dirhodium core can lead to a complex that
can induce such high enantioselectivity.
Figure 3.
state. The distinction between the electron-withdrawing group
(ester) and the electron-donating group (vinyl or phenyl) on the
carbenoid appears to be crucial and is supported by this work
and earlier studies,14 which showed a drop in diastereoselectivity
when the vinyl group contained a second electron-withdrawing
group. As the site of attack of the alkene on the vinylcarbenoid
is dependent on electronic factors (approach on the side of the
electron-withdrawing group instead of the electron-donating
group), the high diastereoselectivity is not noticeably affected
by steric factors either at the vinyl position or on the electron-
withdrawing group. Presumably, in carbenoid systems lacking
the combination of donor/acceptor functionality, the trajectory
for alkene approach is less rigorously defined, leading to lower
overall diastereoselectivity.
The direction of attack of the alkene to the rhodium/vinyl-
carbenoid complex will be critical in setting up the asymmetric
induction. It is generally accepted that the cyclopropanation
by rhodium-stabilized carbenoids occurs in a concerted non-
synchronous mode, and models of the approach of the alkene
have been postulated to explain the stereochemical preferences
in the reactions with diazoacetate derivatives.37 Rhodium/
carbenoid cyclopropanations occur with retention of alkene
configuration37a while buildup of charge during a nonsynchro-
nous cyclopropanation is consistent with the common occurrence
of side products due to the intermediacy of zwitterionic
intermediates when the carbenoid is very electron deficient and
the alkene is electron rich.37a,38
The two most striking features of vinylcarbenoid cyclopro-
panations are the excellent diastereoselectivity of the process
and the total lack of reactivity of vinylcarbenoids toward trans-
alkenes in intermolecular reaction. This second feature is
reminiscent of the epoxidation chemistry of metal oxo species
where preferred reaction with cis-alkenes has been the basis of
a proposal that the attack of the alkene occurs in a side-on
approach.39 In related studies, we have shown that the structure
of the carbenoid has a profound effect on the stereoselectivity
of the cyclopropanation.11b For example, in contrast to vinyl-
diazomethanes, cyclopropanation of styrene by ethyl diazo-
acetate using 6c as catalyst resulted in a 1.2:1 E/Z mixture of
cyclopropanes with the E- and Z-isomers formed in 6% and
30% ee, respectively. In the case of carbenoids containing both
an electron-withdrawing group (such as an ester) and an
electron-donating group (such as an alkene or phenyl), highly
stereoselective cyclopropanations are routinely observed.
The most reasonable mechanism that is consistent with all
these observations is shown in Figure 2. The alkene approaches
the vinylcarbenoid side-on in a nonsynchronous mode from the
side of the electron-withdrawing group with its bulky function-
ality pointing away from the face of the rhodium complex. A
trans-alkene is unreactive because it is unable to avoid having
a substituent pointing directly toward the rhodium surface. As
the reaction proceeds, the alkene would need to rotate outward
to form the cyclopropane ring, where R would end up on the
same side as the vinyl group, leading to the observed stereo-
chemistry. The nonsynchronous nature of the reaction appears
to be important for the diastereoselection because the highest
diastereoselectivity is observed when the alkene is electron rich,
a situation that would enhance charge buildup in the transition
The next issue that was considered was what the preferred
interaction between the rhodium complex and the carbenoid
would be. The answer to this question was approached by MM2
followed by extended Hu¨ckel calculations on the interaction
between rhodium(II) acetate and a vinylcarbene.40 The results
indicated that the carbene would preferentially line up staggered
to the oxygen ligands of the carboxylates rather than in an
eclipsed orientation (Figure 3). This would seem reasonable
on steric grounds, but also, a staggered arrangement is required
for stabilization of the carbenoid ligand by metal back-bonding
because at least in the rhodium(II) dimer, the dyz and dxz orbitals
are hybridized to from two new orbitals that lie in this staggered
position.41 The staggered arrangement of the carbenoid was
also proposed in Doyle’s model to explain the enantioselectivity
induced by the rhodium(II) carboxamide catalysts,31 although
the requirement of such an arrangement for the occurrence of
back-bonding was not considered.42
Even with a well-defined approach of the alkene to the
vinylcarbenoid complex and with the expectation that the
vinylcarbenoid would exist in a staggered arrangement to the
dirhodium core, further stereochemical issues must be involved
to explain the high enantioselectivity observed in these cyclo-
propanations. At this stage of the discussion there are eight
possible orientations for the bonding of the vinylcarbenoid to
the rhodium core. Further insight into the three-dimensional
structure of the rhodium(II) prolinate catalysts was obtained by
MM2 modeling studies using X-ray-determined bond lengths
and angles for the rhodium carboxylate core. Even though the
modeling failed to generate well-defined minima, it became clear
that the prolinate ligands caused certain steric constraints. In
particular, by using a cyclic amino acid ligand such as prolinate,
crowding occurs when the NSO2Ar group adopts a position at
(37) (a) Doyle, M. P. Chem. ReV. 1986, 86, 919. (b) O’Bannon, P. E.;
Dailey, W. P. J. Org. Chem. 1989, 54, 3096. (c) Brown, K. C.; Kodadek,
T. J. Am. Chem. Soc. 1992, 114, 8336.
(38) (a) Alonso, M. E.; Morales, A.; Chitty, A. W. J. Org. Chem. 1982,
47, 3747. (b) Alonso, M. E.; Jano, P.; Hernandez, M. I.; Greenberg, R. S.;
Wenkert, E. J. Org. Chem. 1983, 48, 3047. (c) Alonso, M. E.; Garcia, M.
C. J. Org. Chem. 1985, 50, 988. (d) Wenkert, E.; Alonso, M. E.; Buckwalter,
B. L.; Sanchez, E. L. J. Am. Chem. Soc. 1983, 105, 2021.
(40) Calculations were carried out on a CAChe STEREO Worksystem
using the standard software programs supplied by CAChe Scientific,
Beaverton, OR.
(41) (a) Cotton, F. A.; Walton, R. A. Multiple Bonds Between Metal
Atoms; Clarendon Press: Oxford, 1993; p 672. (b) Norman, J. G., Jr.; Kolari,
H. J. J. Am. Chem. Soc. 1978, 100, 791.
(39) Jacobsen, E. N. In Catalytic Asymmetric Synthesis; Ojima, I., Ed.;
VCH Publishers: New York, 1993; pp 159-202.
(42) Pirrung, M. C.; Morehead, A. T., Jr. J. Am. Chem. Soc. 1994, 116,
8991.

Decomposition of Vinyldiazomethanes
J. Am. Chem. Soc., Vol. 118, No. 29, 1996 6903
Figure 5.
Figure 5 where the thickened lines represent the steric influence
of the arylsulfonyl group. Due to the symmetry of the system
only one face of the catalyst needs to be considered. Assuming
once again that the alkene approaches side-on over the electron-
withdrawing group, then in the model shown in Figure 5, attack
from the back is inhibited by the effect of the arylsulfonyl group.
The effect of the arylsulfonyl group would be greatest when
the transition state requires close approach of the alkene to the
carbene, and this would be consistent with the observation that
electron rich alkenes result in lowered enantioselectivity as these
substrates would be expected to have earlier transition states.
Presumably, nonpolar solvents would favor less charge separa-
tion43 and a later transition state, and this is consistent with the
significantly enhanced enantioselectivity observed when hy-
drocarbons are used as solvent instead of dichloromethane.
Increasing the size of the ester group causes an unfavorable
steric effect between the ester group and the sulfonyl group,
and so, the ester is forced to bend away from the SO2, and this
would block the originally open face of the carbenoid. This
would explain why bulky ester groups result in significantly
lower enantioselectivity. The low enantioselectivity observed
with the other diazoacetate systems is presumably because they
lack the donor/acceptor functionality combination of the vinyl-
diazoacetate system. The overall effect of this would be to
increase greatly the flexibility on how the alkene can approach
the carbene.
In summary, the rhodium prolinate catalyzed decomposition
of vinyldiazomethanes in the presence of alkenes leads to a very
general method for the synthesis of functionalized cyclopropanes
in a highly diastereoselective and enantioselective mode. The
synthesis of all four stereoisomers of 2-phenylcyclopropanamino
acid underscores the potential of this chemistry for asymmetric
synthesis. In a recent review on the synthesis of cyclopropan-
amino acids, our earlier approach using a chiral auxiliary on
the vinylcarbenoid was considered to be “possibly the most
practical synthesis of 2R,3R-cyclo-Phe published to date”.1a The
new approach described herein using a chiral catalyst is much
more practical and general than our earlier strategy, and should
enable a wide range of cyclopropanamino acids to be readily
prepared with high enantioselectivity.
Figure 4.
the periphery of the rhodium carboxylate core. Consequently,
the NSO2Ar group preferentially adopts either an up (R) or a
down (â) arrangement. The effect of this is to place the
arylsulfonyl groups sufficiently close to influence the site of
carbenoid coordination such that a reasonable mechanism for
asymmetric induction is possible.
Consideration of this type of arrangement for the NSO2Ar
group for all four ligands would lead to four possible orienta-
tions, and these are illustrated in Figure 4. The R, R, R, R form
would have C4 symmetry, the R, R, â, â form would have C2
symmetry, the R, â, R, â form would have D2 symmetry, and
the R, R, R, â form would lack high symmetry. Two of these
forms are highly unlikely to cause the cyclopropanation to occur
with high enantioselectivity. The R, R, R, â form lacks any
simplifying symmetry elements, and thus cyclopropanation
through this form would be expected to have a large number of
possible transition states, leading to low overall enantioselec-
tivity. As the R, R, R, R form does not have a symmetry axis
of rotation perpendicular to the rhodium-rhodium bond, the
two rhodium faces are different; one face is shielded while the
other is open but unlikely to exhibit great asymmetric induction.
The most promising conformation is the R, â, R, â form. Due
to the symmetry of the system both faces of the catalyst would
give the same asymmetric induction, and only two distinct
staggered orientations are possible, and of these, one is very
crowded. The alternative R, R, â, â form is also reasonable as
both faces of the catalyst would give the same asymmetric
induction, but due to the lower symmetry compared to the R,
â, R, â form there are twice as many staggered orientations
possible for the carbenoid/rhodium complex.
A model has been presented to explain the highly stereose-
lective cyclopropanations that were observed. The most exciting
feature of this model is that it leads to the suggestion that a
new approach for designing chiral catalysts of high symmetry
would be by appropriate arrangement of fairly simple ligands
in a complex instead of by the traditional approach which entails
the use of elaborate ligands of defined symmetry. Further
studies are in progress to exploit other aspects of these
asymmetric cyclopropanations in organic synthesis. Also, we
are in the process of testing the working model for asymmetric
induction through the design and evaluation of new catalysts
Even though at this stage it is difficult to rule out all the
possible conformations available to the rhodium prolinate
catalyst, all the stereochemical results that we have obtained
so far can be rationalized by proposing that the catalysis occurs
through the D2 symmetric R, â, R, â conformation of the
complex.13 This can be represented in the diagram shown in
(43) (a) Davies, H. M. L.; Saikali, E.; Clark, T. J.; Chee, E. H.
Tetrahedron Lett. 1990, 31, 6299. (b) Davies, H. M. L.; Saikali, E.; Young,
W. B. J. Org. Chem. 1991, 56, 5696. (c) Padwa, A.; Austin, D. J.; Xu, S.
L. J. Org. Chem. 1992, 57, 1330.

6904 J. Am. Chem. Soc., Vol. 118, No. 29, 1996
DaVies et al.
1881.7361 (60, C91H143N4O16Rh2S4); 1867.7227 (88, C90H141N4O16-
that are conformationally constrained such that they are forced
to adopt a D2 symmetric arrangement.
Rh2S4); 1853.7089 (100, C89H139N4O16Rh2S4); 1839.6975 (84, C88H137
-
N4O16Rh2S4); 1825.6819 (50, C87H135N4O16Rh2S4).
Tetrakis[N-[[3,5-Bis(trifluoromethyl)phenyl]sulfonyl]-(L)-proli-
nato]dirhodium (6e): (1.55 g, 3.95 mmol), (0.35 g, 0.79 mmol), (50
mL), (40:60); yield 0.56 g of a green solid (mp 306-309 °C) (40%);
IR (CDCl3) 3154, 2984, 2900, 1819, 1684 cm-1; 1H NMR (200 MHz,
CDCl3) δ 8.23 (s, 8 H), 8.02 (s, 4 H), 4.25 (br d, 4 H, J ) 9.62 Hz),
3.65-3.51 (m, 4 H), 2.25-1.58 (m, 20 H). Anal. Calcd for C52H40F24-
N4O16Rh2S4: C, 35.35; H, 2.28; N, 3.17. Found: C, 35.36; H, 2.39;
N, 3.20.
Tetrakis[N-[(2,4,6-triisopropylphenyl)sulfonyl]-(L)-prolinato]-
dirhodium (6f): (0.5 g, 1.3 mmol), (0.058 g, 0.13 mmol), (30 mL),
(50:50); yield 0.21 g of a green solid (mp 177-181 °C) (93%); IR
(CDCl3) 3501, 2963, 1604, 1313 cm-1; 1H NMR (200 MHz, CDCl3) δ
7.12 (s, 8 H), 4.34 (br d, 4 H, J ) 8.2 Hz), 4.20-4.00 (m, 8 H), 3.48-
3.30 (m, 4 H), 3.05-2.85 (m, 8 H), 2.20-1.80 (m, 12 H), 1.75-1.60
(m, 4 H), 1.30-1.18 (3 s, 72 H); 13C NMR (50.3 MHz, CDCl3) δ 192.3,
152.5, 151.2, 132.1, 123.7, 61.3, 46.9, 37.1, 31.1, 29.4, 25.0, 24.8, 24.2,
23.5; HRMS (FAB) calcd for C80H121N4O16Rh2S4 (m + H), 1727.5771,
found (m + H) 1727.5792.
Experimental Section
General Procedures. 1H NMR spectra were run at 200, 300, 400,
or 500 MHz and 13C NMR spectra at either 50.3 or 75 MHz with the
sample solvent being CDCl3 unless otherwise noted. Mass spectral
determinations were carried out at 70 eV. THF, diethyl ether, and
hexanes were dried over and distilled from sodium metal with
benzophenone as the indicator. CH2Cl2 was dried over and distilled
from CaH2. Pentane was dried over activated molecular sieves (4 Å)
for 24 h prior to use. Column chromatography was carried out on
silica gel 60 (230-400 mesh). Commercially available reagents were
used without additional purification unless noted. Melting points are
uncorrected. Ligands for catalysts 6-10 were prepared by treatment
of the desired amino acid with the appropriate sulfonyl chloride
according to the published procedure.44 The diazo compounds methyl
2-diazo-4-phenyl-3-butenoate (11a), ethyl 2-diazo-4-phenyl-3-butenoate
(11b), isopropyl 2-diazo-4-phenyl-3-butenoate (11c), tert-butyl 2-diazo-
4-phenyl-3-butenoate (11d), and tetrakis[N-(phenylsulfonyl)-(L)-pro-
linato]dirhodium (4)19 were prepared according to literature procedures.
General Procedure for High-Temperature Ligand Exchange.19
A mixture of the carboxylate ligand (5-10 equiv) and dirhodium
tetraacetate (1 equiv) in chlorobenzene was refluxed through a Soxhlet
extractor filled with CaCO3 under an argon atmosphere for 6 days,
while the CaCO3 in the thimble was changed every 2 days. The mixture
was then concentrated in Vacuo, and the residue was dissolved in CH2-
Cl2. The mixture was then washed with saturated NaHCO3, dried (Na2-
SO4), and then concentrated in Vacuo. The residue was purified on
silica using ether/petroleum ether as the eluent in the ratio specified in
parentheses. The amounts of carboxylate ligand, rhodium acetate, and
solvent are presented in that order in abbreviated form.
Tetrakis[N-(isopropylsulfonyl)-(L)-prolinato]dirhodium (6g): (0.4
g, 1.8 mmol), (0.079 g, 0.18 mmol), (50 mL), (100:0); yield 0.116 g
of a green solid (mp 219-222 °C) (59%); IR (CDCl3) 3000, 2982,
1
1683, 1699 cm-1; H NMR (200 MHz, CDCl3) δ 4.35 (dd, 4 H, J )
9.06, 3.02 Hz), 4.15 (br s, 4 H), 3.59-3.30 (m, 8H), 3.22 (quin, 4 H,
J ) 6.8 Hz), 2.02-1.68 (m, 12 H), 1.34 (app t, 24 H); 13C NMR (50.3
MHz, CDCl3) δ 193.05, 61.94, 53.87, 48.02, 31.49, 25.13, 16.74, 16.35.
Anal. Calcd for C32H56N4O16Rh2S4: C, 35.36; H, 5.19; N, 5.15.
Found: C, 35.37; H, 5.37; N, 5.06.
Tetrakis[N-[(4-tert-butylphenyl)sulfonyl]-(L)-valinato]dirhodi-
um (7): (1.08 g, 3.38 mmol), (0.2954 g, 0.68 mmol), (30 mL), (60:
40); yield 0.723 g of a green solid (mp 235-238 °C dec) (72%); IR
Tetrakis[N-[(4-methoxyphenyl)sulfonyl]-(L)-prolinato]dirhodi-
um (6a): (0.531 g, 1.9 mmol), (0.08 g, 0.19 mmol), (40 mL), (1:0);
yield 0.212 g of a green solid (mp 202-205 °C) (85%); IR (CDCl3)
3162, 2946, 1730, 1602 cm-1; 1H NMR (200 MHz, CDCl3) δ 7.73 (d,
8 H, J ) 8.2 Hz), 7.03 (d, 8 H, J ) 8.2 Hz), 4.43-4.28 (br s, 4 H),
3.87 (s, 12 H), 3.35-3.00 (m, 8 H), 2.20-1.73 (m, 12 H), 1.70-1.50
(s, 4 H); 13C NMR (50.3 MHz, CDCl3) δ 192.6, 162.7, 130.2, 139.7,
114.2, 61.8, 55.7, 48.2, 31.3, 24.9. Anal. Calcd for C48H56N4O20-
Rh2S4: C, 42.93; H, 4.20; N, 4.17. Found: C, 43.05; H, 4.35; N, 4.14.
Tetrakis[N-[(4-nitrophenyl)sulfonyl]-(L)-prolinato]dirhodium (6b):
(0.435 g, 1.8 mmol), (0.08 g, 0.18 mmol), (40 mL), (1:0); yield 0.048
g of a green solid (mp 228-230 °C) (19%); IR (CDCl3) 2974, 1729,
1
(CDCl3) 3278, 2966, 2260, 1597, 1466 cm-1; H NMR (200 MHz,
CDCl3) δ 7.74 (d, 8 H, J ) 8.2 Hz), 7.43 (d, 8 H, J ) 8.2 Hz), 6.25-
5.79 (bs, 4 H), 3.75-3.63 (m, 4 H), 2.60-2.29 (m, 12 H), 2.05-1.85
(m, 4 H), 1.29 (s, 36 H), 0.58 (d, 12 H, J ) 6.12 Hz); 13C NMR (50.3
MHz, CDCl3) δ 191.1, 155.9, 137.8, 127.1, 125.7, 62.4, 35.0, 31.4,
31.0, 18.9, 17.6. Anal. Calcd for C60H88N4O16Rh2S4: C, 49.52; H,
6.09; N, 3.85. Found: C, 49.50; H, 6.23 N, 3.75.
Tetrakis[N-[(4-methylphenyl)sulfonyl]-(L)-phenylalinato]dirhod-
ium (8): (1.08 g, 0.34 mmol), (0.29 g, 0.68 mmol), (30 mL), (60:40);
yield 0.723 g of a green solid (mp 270-273 °C dec) (72%); IR (CDCl3)
1
3343, 2927, 1710, 1601, 1160 cm-1; H NMR (200 MHz, CDCl3) δ
7.43 (d, 4 H, J ) 9.2 Hz), 6.95 (m, 32 H), 6.15 (br s, 4 H), 3.95 (m,
4 H), 2.80 (m, 8H), 2.28 (s, 12 H); 13C NMR (50.3 MHz, CDCl3) δ
191.4, 142.6, 136.9, 136.7, 125.6, 129.5, 129.2, 128.1, 126.8, 126.2;
HRMS (FAB) calcd for C64H65N4O16Rh2S4 (m + H), 1479.1389, found
(m + H) 1479.1426.
1
1603 1532 cm-1; H NMR (200 MHz, CDCl3) δ 8.35 (d, 8 H, J )
8.70 Hz), 8.00 (d, 8 H, J ) 8.70 Hz), 4.40-4.28 (m, 4 H), 3.37-3.15
(m, 12 H), 2.10-1.78 (m, 12 H); 13C NMR (50.3 MHz, CDCl3) δ 191.9,
150.0, 144.1, 128.7, 124.3, 61.9, 44.3, 31.4, 24.9; HRMS (FAB) calcd
for C44H45N8O24Rh2S4 (m + H), 1402.9539, found (m + H) 1402.9600.
Tetrakis[N-[(4-tert-butylphenyl)sulfonyl]-(L)-prolinato]dirhodi-
um (6c): (7.204 g, 231.3 mmol), (2.00 g, 4.62 mmol), (180 mL), (50:
50, 750 mL; 60:40, 500 mL; 70:30, 750 mL); yield 3.78 g of a green
solid (mp 279 °C dec) (56%); IR (CDCl3) 3686, 2960, 1604, 1347
Tetrakis[N-[(4-tert-butylphenyl)sulfonyl]-(L)-2-azetidinecarboxy-
lato]dirhodium (9): (70.3 mg, 0.236 mmol), (26.1 mg, 59.0 µmol),
(40 mL), (70:30); yield 50.0 mg of a green solid (mp 181-184 °C)
(63%); IR (neat) 2964, 1607, 1428, 1345, 1308, 1166, 1113, 1089 cm-1
;
1H NMR (200 MHz, CDCl3) δ 7.82-7.69 (d, 8 H, J ) 8.0 Hz), 7.69-
7.49 (d, 8 H, J ) 10.0 Hz), 4.48-4.23 (m, 4 H), 3.80-3.45 (m, 4 H),
1
cm-1; H NMR (200 MHz, CDCl3) δ 7.74 (d, 8 H, J ) 9.2 Hz), 7.53
(d, 8 H, J ) 9.2 Hz), 4.35 (m, 4 H), 3.27 (m, 4 H), 3.09 (m, 4 H), 2.07
(m, 4 H), 1.81 (m, 8 H), 1.52 (m, 4 H), 1.35 (s, 36 H); 13C NMR (50.3
MHz, CDCl3) δ 192.45, 156.13, 135.48, 127.39, 125.89, 76.37, 61.74,
48.25, 35.18, 31.18, 24.85; HRMS (FAB) calcd for C60H81N4O16Rh2S4
(m + H), 1447.2641, found (m + H) 1447.2617.
3.31-3.11 (m, 4 H), 2.39-1.93 (m, 8 H), 1.36 (s, 36 H); [R]25
)
D
-187.36° (c 0.095, CHCl3). Anal. Calcd for C56H72O16N4Rh2S4: C,
48.35; H, 5.22; N, 4.03. Found: C, 48.20; H, 5.29; N, 3.98.
Tetrakis[N-[(4-tert-butylphenyl)sulfonyl]-(L)-2-pipecolinato]dirhod-
ium (10): (40.0 mg, 0.123 mmol), (13.6 mg, 30.7 µmol), (40 mL),
(40:60); yield 40.0 mg of a green solid (mp 293-295 °C dec) (80%);
Tetrakis[N-[(4-dodecylphenyl)sulfonyl]-(L)-prolinato]dirhodi-
um (6d). The linear alkylbenzenesulfonic acid used was obtained from
Alpha Research Chemicals and consisted of a mixture of 1% C10, 40%
C11, 28% C12, and 31% C13: (14.3 g, 33.9 mmol), (3.00 g, 6.8 mmol),
(180 mL), (50:50, 500 mL; 60:40, 1000 mL; 70:30, 1000 mL); yield
8.8 g of a green solid (mp 190-194 °C) (69%); IR (CDCl3) 2928,
1
IR (neat) 2962, 1599, 1410, 1337, 1263, 1157, 1115, 1090 cm-1; H
NMR (200 MHz, CDCl3) δ 7.74-7.66 (d, 8 H, J ) 8.0 Hz), 7.53-
7.44 (d, 8 H, J ) 8.0 Hz), 4.71-4.6 (m, 4 H), 3.40-3.24 (m, 4 H),
3.18-2.90 (m, 4 H, 2.58-2.41 (m, 4 H), 2.28-2.01 (m, 4 H), 1.57-
0.74 (m, 52 H); HRMS (FAB) calcd for C64H89N4O16Rh2S4 (m + H),
1503.3267, found (m + H) 1503.3276.
General Procedure for Rhodium(II)-Catalyzed Decompositions
of Vinyldiazomethanes in the Presence of Alkenes. A mixture of
the alkene (1.2-20 equiv) and Rh(II) catalyst (0.01 equiv) in CH2Cl2
or pentane was stirred at room temperature under an argon atmosphere.
To this solution was added the vinyl diazomethane (1 equiv, 0.12 M)
1
2856, 1605, 1156 cm-1; H NMR (200 MHz, CDCl3) δ 7.74 (d, 8 H,
J ) 9.23 Hz), 7.53 (d, 8 H, J ) 9.23 Hz), 4.32 (m, 4 H), 3.25 (m, 4
H), 3.05 (m, 4 H), 2.07 (m, 4 H), 1.85 (m, 4 H), 1.57 (m, 8 H), 1.25
(bs, 36 H), 0.85 (m, 10 H); HRMS (FAB) (% relative abundance)
(44) Rapoport, H.; Cupps, T. L.; Boutin, R. H. J. Org. Chem. 1985, 50,
3972.

Decomposition of Vinyldiazomethanes
J. Am. Chem. Soc., Vol. 118, No. 29, 1996 6905
in CH2Cl2 or pentane over 10 min, and the mixture was then stirred
for 1-8 h. The mixture was then concentrated in Vacuo, and the residue
was purified on silica using ether/petroleum ether as the eluent in the
ratio specified in parentheses. The amounts of diazo compound,
rhodium(II), alkene, and solvent are presented in that order in
abbreviated form. In reactions carried out at -78 °C, the diazo
compound was added over 30 min and the reaction was the maintained
at -78 °C for 24-36 h. Compounds 18-21 were prepared from
alkenes obtained as gases by condensing a large excess of alkene with
a dry ice/acetone cup condenser into a chilled (0 °C) solvent/catalyst
solution, followed by addition of the diazo compound, and warming
to room temperature, and the reaction was worked up as above.
Enantiomeric excesses (% ee) were determined by 1H NMR at 200 or
500 MHz using tris[3-[(heptafluoropropyl)hydroxymethylene]-(-)-
camphorato]praseodymium(III) derivative (0.10-0.35 equiv) and in-
tergration of the split signals due to the methoxy or the vinyl group, or
by HPLC using a Diacel Chiralcel OJ analytical column where noted.
(1S,2S)-Methyl 2â-Phenyl-1â-(2-(Z)-styryl)cyclopropane-1r-car-
boxylate (12a): 11a (17.2 g, 84.8 mmol), 6d (1.58 g, 0.85 mmol),
(44.2 g, 424 mmol), (pentane, 350 mL), (0:100 to 10:90); yield 19.62
g (83%); mp 57-60 °C; 92% ee, determined by 1H NMR and by chiral
HPLC;30 flow rate 1.0 mL/min, 1.5% 2-propanol in hexane; UV 254
nm; TR ) 17 min (1S,2S), 27 min (1R,2R) (100% ee after 1
recrystallization from 2-propanol, giving a 70% recovery of fine white
crystals); [R]25 ) -166° (c 1.1, CHCl3) (lit. [R]25 ) -169° (c 1.1,
reaction at -78 °C, (70%) >97% ee; IR (neat) 1721, 1495, 1435, 1250,
1
737 cm-1; H NMR (200 MHz, CDCl3) δ 7.29-7.02 (m, 9 H), 6.35
(d, 1 H, J ) 15.9 Hz), 6.11 (d, 1 H, J ) 15.9 Hz), 3.75 (s, 3 H), 2.95
(app t, 1 H, J ) 8.5), 2.01 (dd, 1 H, J ) 9.1, 5.1 Hz), 1.77 (dd, 1 H,
J ) 7.1, 5.1 Hz); CD λ (mdeg) 202 (-2.1), 224 (+0.9), 258 (-0.8) (c
2.4 × 10-4 M, EtOH); HRMS (EI) calcd for C19H17O2Cl, 312.0917,
found 312.0907.
(1S,2S)-Methyl 2â-(4-Methoxyphenyl)-1â-(2-(Z)-styryl)cyclopro-
pane-1r-carboxylate (14). 11a (0.15 g, 0.74 mmol), 6c (10.7 mg,
7.4 mmol), (1.99 g, 14.8 mmol), (pentane, 30 mL), (5:95); yield 0.20
g (87%); 83% ee, [R]25 ) -123° (c 1.184, MeOH); reaction at -78
D
°C, (41%) 90% ee; IR (neat) 2952, 1718, 1515, 1303, 1283, 1248, 1179,
1
1145, 910 cm-1; H NMR (200 MHz, CDCl3) δ 7.20-7.13 (m 5 H),
7.03 (d, 2 H, J ) 8.5 Hz), 6.74 (d, 2 H, J ) 8.6 Hz), 6.33 (d, 1 H, J
) 16.0 Hz), 6.14 (d, 1 H, J ) 16.0 Hz), 3.73 (s, 3 H), 3.70 (s, 3 H),
2.95 (app t, 1 H, J ) 8.6, Hz), 1.99 (dd, 1 H, J ) 9.3, 5.1 Hz), 1.74
(dd, 1 H, J ) 7.3, 5.1 Hz); 13C NMR (50.3 MHz, DEPT, CDCl3) δ
174.0 (4°), 158.3 (4°), 137.0 (4°), 132.7 (3°), 130.0 (4°), 128.3 (3°),
127.3 (4°), 127.2 (3°), 126.1 (3°), 124.1 (3°), 113.3 (3°), 55.0, 52.2
(1°), 34.5 (3°), 33.0 (4°), 18.6 (2°); CD λ (mdeg) 204 (-2.3), 221
(+0.7), 256 (-0.9) (c 2.4 × 10-4 M, EtOH); HRMS (EI) calcd for
C20H20O3, 308.1412, found 308.1398.
Methyl 2â-Acetoxy1-1â-(2-(Z)-styryl)cyclopropane-1r-carboxy-
late (15). 11a (0.12 g, 0.593 mmol), 6c (8.5 mg, 5.95 mmol), (1.02 g,
11.86 mmol), (pentane, 30 mL), (10:90); yield 0.06 g as an oil (40%);
D
D
CHCl3),30 for enantiomer [R]25 ) +157.1° (c 1.1, CHCl3)16); CD λ
76% ee, [R]25 ) +55° (c 0.221, MeOH); reaction at -78 °C, (26%)
D
D
(mdeg) 202 (-2.9), 220 (+1.1), 255 (-1.0) (c 2.7 × 10-4 M, EtOH);
reaction at -78 °C, (68%) 98% ee. The spectral data were consistent
with the previously reported data.16
95% ee; IR (neat) 3050, 2950, 1751, 1724, 1254, 1221 cm-1; 1H NMR
(200 MHz, CDCl3) δ 7.42-7.23 (m, 5 H), 6.54 (d, 1 H, J ) 16.1 Hz),
6.36 (d, 1 H, J ) 16.1 Hz), 4.44 (dd, 1 H, J ) 6.9, 4.6 Hz), 3.75 (s,
3 H), 1.95 (s, 3 H), 1.89 (dd, 1 H, J ) 6.9, 6.2 Hz), 1.68 (dd, 1 H, J
) 6.2, 4.6 Hz); 13C NMR (50.3 MHz, CDCl3) δ 172.1, 170.9, 136.8,
132.0, 128.6, 127.6, 126.3, 121.0, 59.5, 52.5, 31.1, 20.4, 18.3; HRMS
(EI) calcd for C15H16O4, 260.1049, found 260.1038.
(1R,2R)-Methyl 2â-Phenyl-1â-(2-(Z)-styryl)cyclopropane-1r-car-
boxylate (ent-12a) was prepared by a procedure similar to that described
above using ent-6d as catalyst. [R]25 ) +164° (c 1.1, CHCl3) (lit.
D
[R]25D ) +157.1° (c 1.1, CHCl3)); CD λ (mdeg) 202 (+2.9), 220 (-1.1),
255 (+1.0) (c 2.7 × 10-4 M, EtOH).16
Methyl 2â-Ethoxy-1â-(2-(Z)-styryl)cyclopropane-1r-carboxylate
(16). 11a (0.15 g, 0.742 mmol), 6c (10.7 mg, 7.4 mmol), (1.07 g,
14.8 mmol), (pentane, 30 mL), (5:95); yield 0.15 g as an oil (83%);
(1S,2S)-Ethyl 2â-Phenyl-1â-(2-(Z)-styryl)cyclopropane-1r-car-
boxylate (12b). 11b (0.35 g, 1.62 mmol), 6c (10.7 mg, 7.4 mmol),
(3.37 g, 32.4 mmol), (pentane, 50 mL), (2:98); yield 0.35 g as a pale
yellow solid (mp 37-40 °C) (73%); 84% ee, [R]25D ) -98° (c 0.301,
MeOH); IR (neat) 3027, 2980, 1713, 1246 cm-1; 1H NMR (200 MHz,
CDCl3) δ 7.28-7.08 (m, 10 H), 6.34 (d, 1 H, J ) 15.9 Hz), 6.13 (d,
1 H, J ) 15.9 Hz), 4.21 (q, 2 H, J ) 7.1 Hz), 2.02 (dd, 1 H, J ) 9.1,
5.0 Hz), 3.00 (dd, 1H, J ) 9.0, 7.3 Hz), 1.81 (dd, 1 H, J ) 7.3, 5.1
Hz), 1.29 (t, 3 H, J ) 7.1 Hz); CD λ (mdeg) 200 (-3.2), 220 (+1.2),
256 (-1.0) (c 2.5 × 10-4 M, EtOH). Anal. Calcd for C20H20O2: C,
82.16; H, 6.89. Found: C, 82.11; H, 6.87.
59% ee, [R]25 ) -7° (c 0.997, MeOH); reaction at -78 °C, (65%)
D
93% ee; IR (neat) 2978, 1717, 1437, 1348, 1290, 1250 cm-1; 1H NMR
(200 MHz, CDCl3) δ 7.43-7.21 (m, 5 H), 6.74 (d, 1 H, J ) 16.3 Hz),
6.33 (d, 1 H, J ) 16.2 Hz), 4.45 (dd, 1 H, J ) 7.0, 4.9 Hz), 3.74 (s,
3 H), 3.33 (q, 2 H, J ) 7.2 Hz), 1.88 (dd, 1 H, J ) 7.0, 5.5 Hz), 1.64
(dd, 1 H, J ) 5.5, 4.9 Hz), 1.11 (t, 3 H, J ) 7.1 Hz); 13C NMR (50.3
MHz, DEPT, CDCl3) δ 172.7 (4°), 137.5 (4°), 129.5 (3°), 128.4 (3°),
127.0 (3°), 126.0 (3°), 121.6 (3°), 67.9 (3°), 67.1 (2°), 52.0 (1°), 31.6
(4°), 21.6 (2°), 14.7 (1°). Anal. Calcd for C15H18O3: C, 73.15; H,
7.37. Found: C, 72.87; H, 7.38.
(1S,2S)-1-Methylethyl 2â-Phenyl-1â-(2-(Z)-styryl)cyclopropane-
1r-carboxylate (12c). 11c (0.25 g, 1.09 mmol), 6c (10.7 mg, 7.4
mmol), (2.27 g, 21.8 mmol), (pentane, 50 mL), (10:90); yield 0.25 g
as a pale yellow solid (mp 38-41 °C) (76%); 76% ee, [R]25D ) -109°
Methyl 2â-Butyl-1â-(2-(Z)-styryl)cyclopropane-1r-carboxylate
(17). 11a (0.15 g, 0.742 mmol), 6c (10.7 mg, 7.4 mmol), (25 g, 14.8
mmol), (pentane, 30 mL), (5:95); yield 0.12 g as an oil (63%); >90%
ee, [R]25D ) -93° (c 0.255, MeOH); IR (neat) 2955, 2930, 1724, 1246
1
(c 0.633, MeOH); IR (neat) 2361, 1715, 1250 cm-1; H NMR (200
1
MHz, CDCl3) δ 7.45-7.05 (m, 10 H), 6.31 (d, 1 H, J ) 16.0 Hz),
6.12 (d, 1 H, J ) 16.0 Hz), 5.10 (m, 1 H), 2.98 (app t, 1 H, J ) 8.1
Hz), 2.00 (dd, 1 H, J ) 9.2, 5.1 Hz), 1.79 (dd, 1 H, J ) 7.1, 5.1 Hz),
1.28 (t, 6 H, J ) 8.2 Hz); CD λ (mdeg) 202 (-2.2), 220 (+0.9), 255
(-1.0) (c 2.7 × 10-4 M, EtOH). Anal. Calcd for C21H22O2: C, 82.32;
H, 7.24. Found: C, 82.17; H, 7.22.
cm-1; H NMR (200 MHz, CDCl3) δ 7.41-7.22 (m, 5 H), 6.65 (d, 1
H, J ) 16.0 Hz), 6.32 (d, 1 H, J ) 16.0 Hz), 3.70 (s, 3 H), 1.62-1.58
(m, 3 H), 1.32-1.26 (m, 5 H), 1.14-1.11 (m, 1 H), 0.89-0.82 (m, 3
H); 13C NMR (50.3 MHz, CDCl3) δ 175.0, 137.1, 131.7, 128.5, 127.4,
126.3, 124.7, 52.2, 31.7, 31.6, 30.5, 27.8, 22.4, 19.4, 14.0; HRMS (EI)
calcd for C17H22O2, 258.1620, found 258.1616.
(1S,2S)-1,1-Dimethylethyl 2â-Phenyl-1â-(2-(Z)-styryl)cyclopro-
pane-1r-carboxylate (12d). 11d (0.20 g, 0.82 mmol), 6c (10.7 mg,
7.4 mmol), (1.71 g, 16.4 mmol), (pentane, 50 mL), (10:90); yield 75%
as a pale yellow solid (mp 71-74 °C); 50% ee, [R]25D ) -45° (c 0.444,
MeOH); IR (neat) 2978, 2361, 2342, 1709, 1144 cm-1; 1H NMR (200
MHz, CDCl3) δ 7.26-7.08 (m, 10 H), 6.30 (d, 1 H, J ) 16.1 Hz),
6.12 (d, 1 H, J ) 16.1 Hz), 2.92 (dd, 1 H, J ) 9.0, 7.4 Hz), 1.95 (dd,
1 H, J ) 9.0, 5.0 Hz), 1.73 (dd, 1 H, J ) 7.4, 5.0 Hz), 1.50 (s, 9 H);
CD λ (mdeg) 202 (-1.1), 222 (+3.8), 255 (-0.3) (c 2.3 × 10-4 M,
EtOH); HRMS (EI) calcd for C18H16O2 (m - C4H8), 264.1150, found
(m - C4H8) 264.1156. Anal. Calcd for C22H24O2‚0.3H2O: C, 80.95;
H, 7.62. Found: C, 80.94; H, 7.43.
Methyl 2â-Ethyl-1â-(2-(Z)-styryl)cyclopropane-1r-carboxylate
(18). 11a (0.20 g, 0.989 mmol), 6c (14.2 mg, 9.8 mmol), 1-butene in
excess, (pentane, 25 mL), (2:98 to 5:95); yield 0.16 g as a yellow oil;
(69%); >95% ee, [R]25 ) -128° (c 0.53, MeOH); IR (neat) 2960,
D
1
1720, 1250, 1150, 965 cm-1; H NMR (200 MHz, CDCl3) δ 7.32-
7.14 (m, 5 H), 6.80 (d, 1 H, J ) 16.2 Hz), 6.15 (d, 1 H, J ) 16.2 Hz),
3.68 (s, 3 H), 1.53-1.20 (m, 5 H), 0.91 (t, 3 H, J ) 7.2 Hz); 13C NMR
(50.3 MHz, CDCl3) δ 174.9, 137.0, 131.6, 128.5, 127.3, 126.2, 124.5,
52.1, 33.3, 30.6, 21.5, 19.3, 13.7; MS (EI) m/z (relative intensity) 230
(33), 199 (9), 187 (62), 171 (36), 141 (24), 129 (100), 115 (47), 91
(99), 65 (31), 55 (36); HRMS (EI) calcd for C15H18O2: 230.1307, found
230.1307.
(1S,2S)-Methyl 2â-(4-Chlorophenyl)-1â-(2-(Z)-styryl)cyclopro-
pane-1r-carboxylate (13). 11a (0.15 g, 0.74 mmol), 6c (10.7 mg,
7.4 mmol), (2.05 g, 14.8 mmol), (pentane, 30 mL), (5:95); yield 0.21
Methyl 2â-(1-Methylethyl)-1â-(2-(Z)-styryl)cyclopropane-1r-car-
boxylate (19). 11a (0.20 g, 0.989 mmol), 6c (14.2 mg, 9.8 mmol),
3-methyl-1-butene in excess, (pentane, 30 mL), (2:98 to 5:95); yield
g as a yellow oil (91%); 89% ee, [R]25 ) -101° (c 2.118, MeOH);
0.14 g as a yellow oil; (58%); 95% ee, [R]25 ) -115° (c 0.186,
D
D

6906 J. Am. Chem. Soc., Vol. 118, No. 29, 1996
DaVies et al.
MeOH); IR (neat) 3026, 2956, 2928, 2870, 1723, 1435, 1294, 1247,
1202, 1149, 968 cm-1; 1H NMR (200 MHz, CDCl3) δ 7.44-7.19 (m,
5 H), 6.74 (d, 1 H, J ) 18.0 Hz), 6.35 (d, 1 H, J ) 18.0 Hz), 3.71 (s,
3 H), 1.62-1.38 (m, 2 H), 1.29-1.06 (m, 2 H), 1.02 (d, 3 H, J ) 8.0
Hz), 0.95-0.91 (d, 3 H, J ) 8.0 Hz); 13C NMR (50.3 MHz, CDCl3) δ
174.8, 137.0, 131.4, 128.5, 127.3, 126.2, 124.5, 52.1, 39.7, 30.9, 28.0,
22.4, 22.0, 18.7; MS m/z (relative intensity) 244 (19), 188 (21), 169
(5), 155 (7), 129 (100), 115 (12), 91 (5), 77 (4), 41 (12); HRMS calcd
for C16H20O2, 244.1463, found 244.1474.
Methyl 2,2-Dimethyl-1â-(2-(Z)-styryl)cyclopropane-1r-carboxy-
late (20). 11a (0.20 g, 0.989 mmol), 6c (14.7 mg, 9.8 µmol),
2-methylpropene in excess, (pentane, 30 mL), (2:98 to 5:95); yield 0.12
g as a yellow oil; (52%); 95% ee; IR (neat) 3027, 3000, 2984, 2950,
1728, 1434, 1294, 1231, 1196, 1187, 1106 cm-1; 1H NMR (200 MHz,
CDCl3) δ 7.40-7.25 (m, 5 H), 6.71-6.63 (d, 1 H, J ) 16.0 Hz), 6.36
(d, 1 H, J ) 16.0 Hz), 3.71 (s, 3 H), 1.53 (d, 1 H, J ) 5.0 Hz), 1.21
(s, 3 H) 1.13 (d, 1 H, J ) 5.0 Hz), 1.11 (s, 3 H); 13C NMR (50.3 MHz,
CDCl3) δ 172.5, 137.1, 128.5, 127.3, 126.7, 126.2, 51.8, 37.2, 27.9,
23.6, 21.5, 20.9; MS (EI) m/z (relative intensity) 230 (64), 197 (16),
183 (32), 171 (22), 155 (41), 128 (32), 115 (43), 91 (100), 65 (37), 41
(53). Anal. Calcd for C15H18O2: C, 78.23; H, 7.88. Found: C, 78.08;
H, 7.96.
washed successively with 5% citric acid, H2O, NaHCO3 (saturated
aqueous solution), and brine (25 mL each). The excess dicarbonate
was removed by Kugelrohr distillation (80 °C at 0.7 mmHg), and the
residue was purified by chromatography on silica using EtOAc/hexanes
(0:100 to 20:80) to give 0.453 g of a white solid (68%): [R]25
)
D
-86.8° (c 0.98, CH2Cl2); IR (neat) 3367, 2987, 2954, 1721, 1693 cm-1
;
1H NMR (400 MHz, DMSO, 125 °C) δ 7.23-7.17 (m, 5 H), 6.76 (br
s, 1 H), 3.66 (s, 3 H), 3.01-2.91 (m, 1 H), 1.66 (br s, 2 H), 1.14 (s, 9
H); 13C (75 MHz, CDCl3) δ 173.1, 155.7, 134.7, 128.8, 128.4, 127.3,
79.8, 52.3, 39.6, 32.6, 27.9, 21.0. Anal. Calcd for C16H21NO4: C,
65.96; H, 7.27; N, 4.81. Found: C, 65.85; H, 7.25; N, 4.88.
(1R,2R)-(Z)-Methyl 1-[N-[[(1,1-Dimethylethyl)oxy]carbonyl]amino]-
2-phenylcyclopropane-1-carboxylate (ent-25) was prepared by a
procedure similar to that described above using ent-24 as substrate
(83%): [R]25 ) +88.6° (c 1.2, CH2Cl2).
D
(1S,2S)-(Z)-1-[N-[[(1,1-Dimethylethyl)oxy]carbonyl]amino]-2-
phenylcyclopropane-1-carboxylic Acid (26). KOH (0.34 g, 6.1 mmol)
was added to a solution of 25 (0.443 g, 1.5 mmol) in THF/H2O (20
mL, 1:1), and the resulting mixture was stirred at ambient temperature
for 18 h. H2O (10 mL), followed by a small portion of 2 M HCl, was
added, and the resulting mixture was extracted with ethyl acetate. The
process was repeated until the aqueous layer was acidified to pH 2.
The combined organic layers were dried (MgSO4) and reduced. The
crude material was recrystallized (EtOAc/hexanes) to give 0.323 g of
fine white crystals (mp 179-181 °C) (77%): [R]25D ) -106.8° (c 1.4,
CH2Cl2); IR (neat) 3263, 2979, 2929, 1703 cm-1; 1H NMR (300 MHz,
CDCl3) δ 7.39-7.17 (m, 5 H), 4.62 (br s, 1 H), 3.03 (t, 1 H, J ) 9.87
Hz), 2.15 (br s, 1 H), 1.80 (br s, 1 H), 1.33 (s, 9 H); 13C (75 MHz,
CDCl3) δ 178.2, 156.3, 134.6, 128.9, 128.4, 127.4, 80.1, 39.5, 33.2,
27.9, 21.6. Anal. Calcd for C15H19NO4: C, 64.97; H, 6.91; N, 5.05.
Found: C, 64.89; H, 6.88; N, 5.01.
Methyl 2â,3â-Dimethyl-1â-(2-(Z)-styryl)cyclopropane-1r-car-
boxylate (21). 11a (0.50 g, 2.5 mmol), 6d (46.6 mg, 2.5 µmol), cis-
2-butene in excess (approximately 5 mL), (pentane, 40 mL), (5:95);
yield 0.46 g as a yellow oil; (80%); IR (CDCl3) 3029, 2933, 1710 cm-1
;
1H NMR (200 MHz, CDCl3) δ 7.44-7.23 (m, 5 H), 6.59 (d, 1 H, J )
16.4 Hz), 6.02 (d, 1 H, J ) 16.4 Hz), 3.65 (s, 3 H), 1.85 (m, 2 H),
1.10-1.05 (m, 6 H); 13C NMR (50.3 MHz, CDCl3) δ 175.4, 137.4,
137.1, 128.5, 127.4, 126.1, 121.0, 52.1, 30.8, 26.2, 8.9. Anal. Calcd
for C15H18O2: C, 78.23; H, 7.88. Found: C, 78.13; H, 7.93.
(1R,2R)-(Z)-1-[N-[[(1,1-Dimethylethyl)oxy]carbonyl]amino]-2-
phenylcyclopropane-1-carboxylic Acid (ent-26) was prepared by a
procedure similar to that described above using ent-25 as substrate
Methyl 6-(2-(Z)-Styryl)-2-oxabicyclo[3.1.0]hexane-6-carboxylate
(23). 11a (0.15 g, 0.74 mmol), 6c (10.7 mg, 7.4 µmol), (1.04 g, 14.8
mmol), (40 mL), (10:90 to 20:80); yield 0.17 g as an oil (94%); 68%
ee; reaction at -78 °C, (84%) 86% ee; IR (neat) 3020, 2950, 2890,
(90%): [R]25 ) +108.9° (c 1.1, CH2Cl2).
D
1
1710, 1430, 1290, 1230, 1110, 1070, 965, 940 cm-1; H NMR (200
(1S,2S)-(Z)-(-)-1-Amino-2-phenyl-1-cyclopropane-1-carboxylic
Acid (1a) Hydrochloride Salt. 26 (0.050 g, 0.18 mmol) was dissolved
in 3 M HCl (2.5 mL, concentrated HCl diluted in ethyl acetate33), and
stirred at room temperature for 1 h. The solvent was removed under
reduced pressure, and the crude material was recrystallized (EtOH/
Et2O) to give 0.031 g of fine white crystals (mp 199-202 °C dec (lit.
mp 199 °C dec)) (83%): [R]25 ) -112.1° (c 0.81, H2O) (lit. [R]23
MHz, CDCl3) δ 7.45-7.20 (m, 5 H), 6.75 (d, 1 H, J ) 16.2 Hz), 6.21
(d, 1 H, J ) 16.2 Hz), 4.36 (d, 1 H, J ) 5.6 Hz), 4.06 (ddd, 1 H, J )
10.1, 6.9, 5.0 Hz), 3.79-3.54 (m, 1 H), 3.64 (s, 3 H), 2.52 (dd, 1 H,
J ) 6.0, 5.6 Hz), 2.36-2.18 (m, 1 H), 1.97 (ddd, 1 H, J ) 13.0, 9.2,
5.0 Hz); MS (EI) m/z (relative intensity) 244 (100), 212 (20), 185 (37),
155 (33), 129 (40), 115 (41), 91 (30), 77 (35), 51 (24). Anal. Calcd
for C15H16O3: C, 73.75; H, 6.60. Found: C, 73.48; H, 6.65.
D
D
) -103° (c 0.76, H2O),7c [R]25 ) -104.6° (c 0.26, H2O)16). The
D
spectral data were consistent with the previously reported data.16
(1R,2R)-(Z)-(+)-1-Amino-2-phenyl-1-cyclopropane-1-carboxy-
lic Acid (1b) Hydrochloride Salt was prepared by a procedure similar
(1R,2S)-(E)-1-Carboxy-1-(methoxycarbonyl)-2-phenylcyclopro-
pane (24). A mixture of 12a (8.46 g, 30.3 mmol), CH3CN (60 mL, 2
mL/mmol), CCl4 (60 mL, 2 mL/mmol), H2O (90 mL, 3 mL/mmol),
and NaIO4 (52.03 g, 243.4 mmol) was stirred to a uniform suspension.
RuCl3‚H2O (0.2145 g, 0.91 mmol) was added, and the reaction was
stirred for 8 h at rt.31 The reaction was quenched with 2 M HCl (400
mL) and then extracted with EtOAc (4 × 200 mL). The organic layers
were filtered through a Celite/charcoal cake, dried (MgSO4), and
reduced. The crude material was purified by chromatography on a
silica column using EtOAc/hexanes/AcOH (14:85:1) as the eluent, and
then recrystallized from ethyl acetate/hexenes to form 4.68 g of a white
solid (94-96 °C) (70%): [R]25 ) -124.2° (c 1.1, PhH); (lit. [R]23
to that described above using ent-26 as substrate (84%): [R]25
+112.3° (c 1.2, H2O).
)
D
(S)-1,1-Bis(methoxycarbonyl)-2-phenylcyclopropane (27) was pre-
pared from 24 (3.00 g, 13.6 mmol) by the procedure described by Corey:
30 mp 63-65 °C (lit. mp 61-62 °C30); [R]25D ) -137.2° (c 1.1, PhH)
(lit. [R]23D ) -124° (c 2.2, PhH)30). The spectral data were consistent
with the previously reported data.30
(R)-1,1-Bis(methoxycarbonyl)-2-phenylcyclopropane (ent-27) was
prepared by a procedure similar to that described above using ent-24
as substrate (91%): [R]25D ) +137.5° (c 1.0, PhH). Anal. Calcd for
C13H14O4: C, 66.66; H, 6.02. Found: C, 66.52; H, 6.04.
D
D
) -104.2° (c 0.89, PhH)). The spectral data were in agreement with
previously reported data.30
(1S,2R)-(E)-1-Carboxy-1-(methoxycarbonyl)-2-phenylcyclopro-
pane (ent-24) was prepared by a procedure similar to that described
above using ent-12a as substrate (69%): [R]25D ) +125.6° (c 1.0, PhH).
(1S,2S)-(Z)-Methyl 1-[N-[[(1,1-Dimethylethyl)oxy]carbonyl]amino]-
2-phenylcyclopropane-1-carboxylate (25). A two-neck 100 mL flask,
which was thoroughly dried, pumped, and purged with argon, was
charged with 24 (0.50 g, 2.3 mmol), dry hexanes (25 mL), NEt3 (0.364
mL, 2.6 mmol, freshly distilled from CaH2), t-BuOH (2.2 mL, 23 mmol,
fractionally distilled from CaH2), and diphenylphosphoryl azide (0.52
mL, 2.5 mmol, freshly distilled via vacuum short path 140 °C at 2
mmHg).32 The mixture was heated under reflux for 18 h under argon
and then di-tert-butyl dicarbonate (0.783 mL, 3.4 mmol) was added,
and the mixture was refluxed for a further 2 h. The reaction was then
cooled to room temperature, and the solvent was removed, leaving a
thick oil. Ethyl acetate (40 mL) was added, and the organic layer was
(1S,2S)-(Z)-1-Carboxy-1-(methoxycarbonyl)-2-phenylcyclopro-
pane (28). NaOH (1 N) (16.61 mL, 16.6 mmol) was added to a stirred
mixture of 27 (2.99 g, 12.7 mmol) in MeOH (20 mL), and the resulting
solution was stirred at ambient temperature for 2 h.34 The mixture
was reduced to dryness, H2O (50 mL) was added, and the resulting
mixture was extracted with ethyl acetate (3 × 75 mL). The combined
organic layers were dried (MgSO4) and reduced. The crude material
was recrystallized (EtOAc/hexanes) to give 2.12 g of fine white crystals
(mp 60-62 °C) (75%): [R]25D ) -146.2° (c 1.1, PhH); IR (neat) 3032,
1
2948, 1739, 1688, 1429 cm-1; H NMR (400 MHz, CDCl3) δ 7.32-
7.23 (m, 5 H), 3.41 (dd, 1 H, J ) 8.8, 7.8 Hz), 3.25 (s, 3 H), 2.41 (dd,
1 H J ) 7.8, 4.9 Hz), 1.31 (dd, 1 H J ) 8.8, 4.9 Hz); 13C (75 MHz,
CDCl3) δ 172.6, 171.6, 134.1, 129.1, 128.4, 127.9, 52.3, 39.4, 33.9,
20.7. Anal. Calcd for C12H12O4: C, 65.45; H, 5.49. Found: C, 65.42;
H, 5.53.

Decomposition of Vinyldiazomethanes
J. Am. Chem. Soc., Vol. 118, No. 29, 1996 6907
(1R,2R)-(Z)-1-Carboxy-1-(methoxycarbonyl)-2-phenylcyclopro-
pane (ent-28) was prepared by a procedure similar to that described
above using ent-27 as substrate (73%): [R]25D ) +147.6° (c 1.0, PhH).
(1R,2S)-(E)-Methyl 1-[N-[[(1,1-Dimethylethyl)oxy]carbonyl]amino]-
2-phenylcyclopropane-1-carboxylate (29) was prepared from 28 (1.00
g, 4.5 mmol) by a procedure similar to that used to prepare 2532 to
give 1.00 g of a white solid (mp 85-86 °C) (76%): [R]25D ) -79.6°
(c 0.95, CH2Cl2) (lit. for enantiomer [R]25D ) +74.8° (95% ee) (c 1.1,
h.7c The reaction was then cooled, and the solvent was evaporated
under reduced pressure. The residue was dissolved in H2O (10 mL),
and the resulting solution was acidified to pH 2 with 2M HCl and then
extracted with ethyl acetate (4 × 30 mL). The organic layer was dried
(MgSO4) and reduced. The crude material was dissolved in 3 M HCl
(10 mL, concentrated HCl diluted in ethyl acetate), and the resulting
solution was stirred at rt for 1 h.33 The solvent was then removed
under reduced pressure, and the crude material was recrystallized
(EtOH/Et2O) to give 0.132 g of fine white crystals (mp 219-221 °C)
(83%): [R]25D ) -80.9° (c 1.2, H2O) (enantiomer lit. [R]25D ) +74.4°
1
CH2Cl2)7b); IR (neat) 3353, 2972, 1721, 1498 cm-1; H NMR (300
MHz, CDCl3) δ 7.34-7.21 (m, 5 H), 5.37 (br s, 1 H), 3.57 (s, 3 H),
2.85 (dd, 1 H, J ) 9.5, 8.2 Hz), 2.18 (dd, 1 H J ) 8.2, 5.7 Hz), 1.61
(dd, 1 H J ) 9.5, 5.7 Hz), 1.14 (s, 9 H); 13C (75 MHz, CDCl3) δ 170.7,
156.0, 135.4, 129.1, 127.7, 126.7, 79.5, 51.3, 40.7, 34.5, 27.9, 20.0.
Anal. C16H21NO4: C, 65.96; H, 7.27; N, 4.81. Found: C, 65.82; H,
7.26; N, 4.87.
(c 1.0, H2O),7d lit. [R]25 ) +72.7° (95% ee) (c 1.0, H2O)7d). The
D
spectral data were consistent with the previously reported data.30
(1S,2R)-(E)-(+)-1-Amino-2-phenyl-1-cyclopropane-1-carboxy-
lic Acid (1d) Hydrochloride Salt was prepared by a procedure similar
to that described above using ent-29 as substrate (92%): [R]25
+80.3° (c 1.2, H2O).
)
D
(1S,2R)-(E)-Methyl 1-[N-[[(1,1-Dimethylethyl)oxy]carbonyl]amino]-
2-phenylcyclopropane-1-carboxylate (ent-29)7b was prepared by a
procedure similar to that described above using ent-28 as substrate
(75%): [R]25 ) +88.6° (c 1.2, CH2Cl2).
Acknowledgment. Financial support of this work by the
National Science Foundation (Grant CHE 9421649) is gratefully
acknowledged.
D
(1R,2S)-(E)-(-)-1-Amino-2-phenyl-1-cyclopropane-1-carboxy-
lic Acid (1c) Hydrochloride Salt. LiOH‚H2O (0.3104 g, 7.4 mmol)
was added to a solution of 29 (0.2155 g, 0.74 mmol) in MeOH/H2O (9
mL, 2/1), and the resulting solution was heated under reflux for 2.5
JA9604931