Stereospecific Transition‐Metal‐Free Alkylation of Chiral Non‐Racemic Secondary Tosylates with Cyanohydrins: Convenient Access to Enantiomerically Enriched α‐Tertiary Ketones

Abstract A novel stereospecific, transition‐metal‐free alkylation of cyanohydrins with enantiomerically enriched secondary tosylates is described. This method enables the general, efficient, and operationally simple synthesis of enantioenriched α‐tertiary ketones by leveraging the nucleophilicity of cyanohydrin anions, which serve as umpolung carbonyl equivalents to facilitate highly stereospecific S N 2 substitutions. Reactions involving alkenyl cyanohydrins proceed through a stereoconvergent olefin synthesis (SCOS) from a geometric E/Z mixture, furnishing stereochemically defined, conjugated α‐tertiary ketones. This methodology exhibits broad functional group tolerance, accommodating unactivated and sterically hindered acyclic and cyclic secondary tosylates. The resulting chiral ketones are configurationally stable and can be readily converted into synthetically versatile intermediates using classical transformations. The utility of this approach is exemplified by a concise, stereospecific synthesis of ( R )‐cyclamen aldehyde, underscoring its potential to streamline the preparation of enantioenriched α‐tertiary ketones—structural motifs that feature prominently in both natural and non‐natural products and serve as key intermediates in target‐directed synthesis.