Influence of the Bridgehead Substituent on the Stereoselective Leuckart Reaction of 2-Norbornanones − Skeletal Rearrangement versus Structural Retention

Abstract

The synthesis of chiral amine norbornane derivatives has been achieved by means of the Leuckart reaction of various 2-norbornanones. We propose an ionic mechanism for this process in which the formation of a 2-formylamino-2-norbornyl cation is the common initial step. The reaction pathway and the isolated products are strongly dependent on the nature of the bridgehead substituents; hydrogen and alkyl groups yield only enantiopure 2-norbornyl formamides with structural retention, whereas O-acyl or N-acyl groups favour a pinacol-type skeleton rearrangement through a cascade of Wagner−Meerwein rearrangements and intramolecular transamidations.