Chiral sulfoxide controlled asymmetric additions to CN double bond. An efficient approach to stereochemically defined α-fluoroalkyl amino compounds

Abstract

This paper presents a full account of studies into the asymmetric addition reactions between α-lithium derivatives of enantiomerically pure methyl and benzyl p-tolyl sulfoxides and the N-( p-methoxyphenyl)aldimines, bearing trifluoromethyl, pentafluoroethyl and ω-hydrotetrafluoroethyl groups, to afford the corresponding α-fluoroalkyl β-sulfinylamines, synthetically versatile precursors of a series of enantiomerically pure biomedicinally important α-fluoroalkylalkylamines and α-fluoroalkyl-β-hydroxyalkylamines. The addition reactions were found to proceed under mild conditions allowing for convenient preparation of the corresponding α-fluoroalkyl β-sulfinylamines in excellent yields and good enantiomeric purity. The stereochemical outcomes of these reactions were shown to be subject to kinetic control, that is in sharp contrast to the corresponding reactions of fluorine-free imines. The absolute configurations of the addition products suggest that the fluoroalkyl group on starting imines plays a role of enantiodirecting, sterically larger substituent causing realization of an unusual for this type of reactions transition states.