SYNTHESIS AND REACTIVITY OF ENANTIOMERICALLY PURE 2-FLUOROMETHYL-2-(1'-P-TOLYLSULFINYL)ALKYL OXIRANES

This paper presents an efficient procedure for preparing enantio- and diastereomerically pure 2-fluoromethyl-2- (1'-p-tolylsulfinyl)alkyl ox iranes, designed as versatile chirons to be transformed to a series of synthetically useful and biologically relevant compounds. In particul ar, (2S)-2-fluorometbyl-2-(1'-p-tolylsulfinyl)alkyl oxiranes, prepared by the reaction between (RS)reaction between (R-S)-alpha-alkyl-beta-k eto-gamma-fluoro sulfoxides and diazomethane, can be efficiently obtai ned in diastereomerically pure state via formation, purification and r e-cyclization of the corresponding bromohydrins. Synthetic value of th ese oxiranes was demonstrated by their transformation to various sulfu r-free synthetically and biologically interesting compounds via the re ductive desulfurization, Pummerer, ring-opening and syn-elimination re actions. The presence of the methyl in alpha-position to the sulfoxide group in the starting compounds was found to interfere with a normal course of the Pummerer rearrangement giving rise to the corresponding vinyl sulfides in low chemical yield. By contrast the thermal syn-elim ination reaction of the p-tolyl sulfoxide group provided an efficient entry to the sulfur-free vinyl derivatives. (C) 1998 Elsevier Science Ltd. All rights reserved.