J. Am. Chem. SOC.1995,117, 11367-11368
11367
A New Strategy for the Lewis Acid-Catalyzed Cyclopropanation of Allylic Alcohols Andr6 B. Charette* and Christian Brochu
Dkpartement de Chimie, Uniuersitk de Montrkal Montrkal, Qulbec, Canada H3C 3J7 Received August 21, 1995
The efficient enantioselective synthesis of organic compounds using chiral catalysts is of great current interest.' The enantioselective (iodomethy1)zinc-mediated cyclopropanationof allylic alcohols has been the subject of relatively few investigations compared to most other carbon-carbon bond forming reactions. Kobayashi and co-workers recently found that good enantioselectivities were observed if a C2-symmetric chiral disulfonamide was added in catalytic amounts to the (iodomethy1)zinc-mediated cyclopropanation of allylic alcohols (eq l).293 R3
CH3l
CH3CH2l e f
d h
3
d f
ZnEt2 (2.0 equiv) CH212(3.0 equiv)
66-82% ee
R276,"H R'
One of the major drawbacks of this approach for obtaining high enantioselectivities is that the rate of the uncatalyzed reaction is not overwhelmingly different from that of the catalyzed process. For example, Kobayashi reported that a 20% yield of the cyclopropyl derivative was obtained in the absence of the chiral Lewis acid. In this communication, we unveil a new strategy for the Lewis acid-catalyzed cyclopropanation of allylic alcohols in which the rate of the uncatalyzed process is significantly slower than that of the catalyzed reaction. The basis of the project lies on the fact that treatment of an allylic alcohol with 1 equiv of Zn(CH2I)z should produce the (iodomethy1)zinc alkoxide and CH31 (Scheme 1). Based on observations made during the course of studies directed toward the development of a chiral auxiliary for the cyclopropanation reaction: we had evidence that these alkoxides do not undergo rapid cyclopropanation at low temperature (vide infra). We reasoned that the addition of a Lewis acid could trigger the subsequent cyclopropanation reaction by increasing the electrophilicity of the methylene group upon complexation. Subsequent formation of the halozinc alkoxide and regeneration of the Lewis acid would complete the catalytic cycle. (1) (a) Catalytic Asymmetric Synthesis; Ojima, I . , Ed.; VCH: New York, 1993. (b) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley Interscience: New York, 1994. (2) (a) Kobayashi, S.; Takahashi, H.; Yoshioka, M.; Ohno, M. Tetrahedron Lett. 1992,33,2575-2578. (b) Kobayashi, s.;Takahashi, H.; Imai, N. Chem. Lett. 1994, 177-180. (c) Kobayashi, S.; Takahashi, H.; Imai, N.; Sakamoto, K. Tetrahdron Lett. 1994, 35, 7045-7048. (3) (a) Denmark, S. E.; Christenson, B. L.; Coe, D. M.; O'Connor, S. P. Tetrahedron Lett. 1995, 36, 2215-2218. (b) Denmark, S. E.; Christenson, B. L.; O'Connor, S. P. Tetrahedron Lett. 1995, 36, 2219-2222. (4) (a) Charette, A. B.; Juteau, H. J. Am. Chem. SOC. 1994, 116, 26512652. (b) Charette, A. B.;Prescott, S.; Brochu, C. J. Org. Chem. 1995, 60, 1081-1083. (c) Charette, A. B.; CBte, B.; Marcoux, J.-F. J. Am. Chem. SOC. 1991, 113, 8166-8167. (5) 'H NMR spectra are provided in the supporting information. (6) (a) Furukawa, J.; Kawabata, N.; Nishimura, J. Tetrahedron Lett. 1966, 28, 3353-3354. (b) Furukawa, J.; Kawabata, N.; Nishimura, J. Tetrahedron 1968, 24, 53-58.
+
Figure 1. 400 MHz ' H NMR of (A) ROH Zn(CH21)2 ( 1 equiv), CD&, -20 "C, 30 min, and (B) A Tic14 (0.15 equiv), 2 h, -20
+
OC.
Scheme 1 -OH
Zn(CH2b2 (l equivl e O Z n C H 2 i
A
Initially, several 'H NMR control experiments were performed with cinnamyl alcohol and different (iodomethy1)zinc species. First, the treatment of cinnamyl alcohol with ZnEt2 (1 equiv) in CDzCl2 at 0 "C resulted in the rapid formation of the ethylzinc alkoxide (ROZnEt). Subsequent addition of CH212 (1 equiv) did not produce any cyclopropanes, the ROZnCH2I moiety, or Et1 (2 h, 0 0C).5 As expected, the addition of a second equivalent of ZnEt:! and CH212 induced rapid cyclopropane formation.6 Conversely, treatment of cinnamyl alcohol with the Simmons-Smith reagent? IZnCH21s (1 equiv, -20 "C, CD2C12), resulted in the formation of the corresponding cyclopropane (-60%) and CH31 ( ~ 4 0 % ) The ~ cyclopropanation is, therefore, competitive with the formation of the zinc (7) Simmons, H. E.; Caims, T.L.; Vladuchick, S. V.; Hoiness, C. M. Org. React. 1973, 20, 1-131. (8) IZnCH2I was prepared by adding CH212 (1 equiv) to EtZnIeDME ( 1 equiv). For the spectroscopic characterization of this reagent, see: Charette, A. B.; Marcoux, J.-F. J. Am. Chem. SOC., in press. (9) (a) Denmark, S. E.; Edwards, J. P.; Wilson, S. R. J. Am. Chem. SOC. 1992, 114,2592-2602. (b) Denmark, S . E.; Edwards, J. P. J. Org. Chem. 1991, 56, 6974-6981.
0002-7863/95/1517-11367$09.00/0 0 1995 American Chemical Society
11368 J. Am. Chem. Soc., Vol. 117, No. 45, 1995
Communications to the Editor
Table 1. Lewis Acid-Catalyzed Cyclopropanation" P h A O H
Table 2. TiCL-Catalyzed Cyclopropanation Reactiona
1. Zn(CH21)2 2. Lewis acid
1. Zn(CH2I) 2. -78 to -20 'c
e
OH
* Ph*oH
3. Tic14
conversion entry
Lewis acid
0°C
-20°C
1 2 3 4 5
none BBr3 B(OMe13 TiC1dd Ti(Oi-Pr)4 TiClz(Oi-Pr)z Sic14 SnC14 Et2A1Cld Zn(OT02 ZnI2
23' 93 50 94' 50 85 90 83 93' 45 50
