Synthesis and reactivity of enantiomerically pure 2-fluoromethyl-2-(1′- p-tolylsulfinyl)alkyl oxiranes

Abstract

This paper presents an efficient procedure for preparing enantio- and diastereomerically pure 2-fluoromethyl-2-(1′- p-tolylsulfinyl)alkyl oxiranes, designed as versatile chirons to be transformed to a series of synthetically useful and biologically relevant compounds. In particular, (2 S)-2-fluoromethyl-2-(1′- p-tolylsulfinyl)alkyl oxiranes, prepared by the reaction between ( R S)-α-alkyl-β-keto-γ-fluoro sulfoxides and diazomethane, can be efficiently obtained in diastereomerically pure state via formation, purification and re-cyclization of the corresponding bromohydrins. Synthetic value of these oxiranes was demonstrated by their transformation to various sulfur-free synthetically and biologically interesting compounds via the reductive desulfurization, Pummerer, ring-opening and syn-elimination reactions. The presence of the methyl in α-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-elimination reaction of the p-tolyl sulfoxide group provided an efficient entry to the sulfur-free vinyl derivatives.