Stereoselective oxirane formation by reaction of diazomethane on 1-fluoro-3-[(4-methylphenyl)sulfinyl]-3-phenylpropan-2-one

Abstract

(2S, 2′R,RS)-2-(Fluoromethyl)-2-{[(4-methylphenyl)sulfinyl][phenyl]methyl}oxirane (4) was obtained in high chemical yield and with high diastereoselectivity by reacting diazomethane with pure (3R, RS)-1-fluoro-3-[(4-methylphenyl)sulfinyl]-3-phenylpropan-2-one (3), but also with its (3S, RS)-3-diastereoisomer, in the latter case through inversion of the configuration at carbon 3. The corresponding methyl enol ethers 6 were isolated as by-products. NMR experiments and molecular modelling calculations were performed in order to clarify the equilibria in solution and the preferred conformations of both ketones 3. Several variously substituted, sulfur-free tertiary α-(fluoromethyl)carbinols were obtained from the main reaction product (2S, 2′R,RS)-4 through appropriate elaborations of the sulfinyl group and of the oxirane ring. The structure of (2S, 2′R,RS)-4 was established by X-ray analysis of the open-chain derivative (2S, 2′R,RS)-1-bromo-3-fluoro-2′-{[(4-methylphenyl)sulfinyl][phenyl]methyl}propan-2-ol (7).