J. Am. Chem. Soc. 2001, 123, 12907-12908
Atom Economic Asymmetric Creation of Quaternary Carbon: Regio- and Enantioselective Reactions of a Vinylepoxide with a Carbon Nucleophile Barry M. Trost* and Chunhui Jiang Department of Chemistry, Stanford UniVersity Stanford, CA 94305-5080 ReceiVed September 4, 2001 The metal-catalyzed additions of pronucleophiles to vinylepoxides with achiral phosphine ligands have a strong bias to lead to 1,4-addition (eq 1, path a), due to the electronic effect of the epoxide oxygen.1,2 On the other hand, the 1,2-adducts are
potentially valuable chiral building blocks as a result of the diverse functionality present that permits chemoselective differentiation. While the use of heteroatom pronucleophiles such as alcohols, amines, and imides has been successfully employed,3-5 the use of carbon-centered pronucleophiles has not been employed yet represents perhaps the most significant type since it builds the basic carbon framework. Particularly significant is the case of R ) alkyl since it entails creating a quaternary carbon enantioselectively. The success of heteroatom pronucleophiles has been attributed to the ability of such functionality to hydrogen bond or in some other way coordinate to the epoxide oxygen to help deliver the nucleophile to the adjacent carbon. The failure of carbon-centered pronucleophiles to participate in such hydrogen bonding would seem to make any extrapolation of results from heteroatom to carbon pronucleophiles unlikely. Despite this expectation, we explored β-ketoesters in such reactions to determine the feasibility of eq 1, path b, dominating over path a. As a probe of the effect of chiral ligands on regioselectivity, isoprene monoepoxide 1 was reacted with ethyl acetoacetate 2 in the presence of 1 mol % Pd2(dba)3‚CHCl3 (Pd(0)) and 3 mol % of racemic ligand (()-L1 (eq 2, and Table 1, entry 1). A
(1) Trost, B. M.; Molander, G. A., J. Am. Chem. Soc. 1981, 103, 5969; Trost, B. M.; Warner, R. W. J. Am. Chem. Soc. 1982, 104, 6112; Trost, B. M.; Cossy, J. J. Am. Chem. Soc. 1982, 104, 6881; Trost, B. M.; Granja, J. R. J. Am. Chem. Soc. 1991, 113, 1044; Trost, B. M.; Granja, J. R. Tetrahedron Lett. 1991, 32, 2193; Trost, B. M.; Ito, N.; Greenspan, P. D. Tetrahedron Lett. 1993, 34, 1421; Trost, B. M.; Ceschi, M. A.; Ko¨nig, B. Angew. Chem., Int. Ed. Engl. 1997, 36, 1486; Trost, B. M.; Schroeder, G. M. J. Am. Chem. Soc. 2000, 122, 3785. (2) Tsuji, J.; Kataoka, H.; Kobayashi, Y. Tetrahedron Lett. 1981, 22, 2575.
12907
Table 1. Probe Reactions of 2-Methyl-2-vinyloxirane with Ethyl Acetoacetatea entry
ligand
1 2 3 4 5 6 7 8h
(()-L1 (()-L1 (S,S)-L1 (S,S)-L1 (S,S)-L2 (S,S)-L2 (S,S)-L3 (S,S)-L3
additiveb solvent none none none TBAT none TBAT TBAT TBAT
CH2Cl2 CH2Cl2 CH2Cl2 PhH CH2Cl2 PhH PhH PhH
temp
rxn time (min)
ratioc 3:4:5
yieldd 3
eee 3
rt 0 °C rt rt rt rt 40 °C 40 °C
10 30 25 15 30
