A Highly Diastereoselective and Enantioselective Synthesis of Polysubstituted Pyrrolidines via an Organocatalytic Dynamic Kinetic Resolution Cascade

Abstract

Highly functionalized pyrrolidine and piperidine analogues, with up to three stereogenic centers, were synthesized in good yield (50–95%), excellent dr (single isomer), and high ee (>90%) using a <i>Cinchona</i> alkaloid-derived carbamate organocatalyst. High stereoselective synergy was achieved by combining a reversible <i>aza</i>-Henry reaction with a dynamic kinetic resolution (DKR)-driven <i>aza</i>-Michael cyclization. Whereas both reactions proceed with moderate enantioselectivities (50–60% for each step), high enantioselectivities are obtained for the overall products devoid of dr sacrifice