Isothiourea‐Catalyzed Acylative Kinetic Resolution of Tertiary α‐Hydroxy Esters

Abstract

A highly enantioselective isothiourea‐catalyzed acylative kinetic resolution (KR) of acyclic tertiary alcohols has been developed. Selectivity factors of up to 200 were achieved for the KR of tertiary alcohols bearing an adjacent ester substituent, with both reaction conversion and enantioselectivity found to be sensitive to the steric and electronic environment at the stereogenic tertiary carbinol centre. For more sterically congested alcohols, the use of a recently‐developed isoselenourea catalyst was optimal, with equivalent enantioselectivity but higher conversion achieved in comparison to the isothiourea HyperBTM. Diastereomeric acylation transition state models are proposed to rationalize the origins of enantiodiscrimination in this process. This KR procedure was also translated to a continuous‐flow process using a polymer‐supported variant of the catalyst.

Recent Advances in Catalytic Nonenzymatic Kinetic Resolution of Tertiary Alcohols

“…In this respect, in 2020, Smith and co-workers developed an isothiourea HyperBTM 49 catalyzed acylation KR of tertiary α-hydroxy esters 53 with selectivity factors up to 200 (Scheme 10 ). 32 For more sterically congested substrates, the use of isoselenourea catalyst 51 was better. It is speculated that the efficient enantiodiscrimination of catalyst is based on the steric differences between the carbinol substituents.…”