Lewis base catalyzed trialkylsilylcyanide additions to cyclic 2-fluoroketones: nucleophile directed access to both cis- and trans-stereoisomers

Abstract

An efficient method for the Lewis base-catalyzed addition of trialkylorganosilanes (TMSCN & TBSCN) to cyclic 2-fluoroketones has been developed producing the TMS- or TBS-protected cyanohydrins in good yields and diastereoselectivity. The Lewis base, solvent, and trialkylorganosilane have a dramatic effect on the reaction time and stereoselectivity for these reactions. TMSCN reacted the fastest using DIPEA as the Lewis base, and favored the cis product (up to 22:1), whereas methoxide-catalyzed reactions with TBSCN yielded the trans stereoisomer (up to 18:1).