Stereodivergent Enantioselective Synthesis by Exploiting Unusually Large Kinetic H/D Isotope Effects on Deprotonation

Abstract

On deprotonation of chiral deuterated carbamates like the reaction of (S)-1 with sec-butyllithium to form (R)-2, unusually high kinetic isotope effects kH/kD of 70 or greater are observed. These point to the participation of a quantum mechanical tunnel effect and can be exploited for enantioselective transformations based on the discrimination by the base of H and D in otherwise identical environments. The procedure is particularly suitable for highly selective syntheses of stereospecific deuterium- and tritium-labeled alcohols.