Enantioselective Synthesis of Cyclic, Quaternary Oxonitriles

Quaternary oxonitriles are stereoselectively generated from the union of five-, six-, and seven-membered 2-chloroalkenecarbonitriles with chiral alcohols via a Claisen rearrangement. The strategy rests on a new conjugate addition elimination of allylic alkoxides to 2-chlorocycloalkenecarbonitriles to afford substituted 2-alkoxyalkenenitriles. Subsequent thermolysis unmasks a cyclic oxonitrile while selectively forming a new quaternary center with enantiomeric ratios typically greater than 9:I. The overall alkylation strategy addresses the challenge of enantioselectively generating hindered, quaternary centers while simultaneously installing ketone, nitrite, and olefin functionalities.