Sulfoxides as ‘traceless’ resolving agents for the synthesis of atropisomers by dynamic or classical resolution

Abstract

Reacting (−)-menthyl sulfinate with an atropisomeric but racemic aryllithium gives two atropdiastereoisomeric sulfoxides. Separation (by chromatography or crystallisation) and sulfoxide–lithium exchange of each diastereoisomer regenerates the aryllithium in enantiomerically pure form which can be quenched with a range of electrophiles with retention of stereochemical integrity. Overall the reaction sequence is a resolution but without the need for an acidic or basic substituent—a ‘traceless’ method. In certain instances, for example when the nucleophile is an ortholithiated peri-substituted 1-naphthamide, the diastereoisomeric sulfoxides may be interconverted thermally. This allows a dynamic resolution, under thermodynamic control, and hence in principle can give yields of the final products of greater than 50%. The utility of the method is demonstrated by the synthesis of a known atropisomeric phosphine ligand.