Enantioconvergent iso-Pictet-Spengler Reactions: Organocatalytic Synthesis of Chiral Tetrahydro-γ-carbolines

Enantioconvergent iso-Pictet-Spenglerreactionsof chiral racemic ss-formyl esters and a ss-keto ester arereported, providing complex tetrahydro-& gamma;-carbolines containingtwo contiguous stereocenters. The reactions are catalyzed by a chiralthiourea and benzoic acid cocatalytic system and constitute rare casesof nonhydrogenative stereoconvergent additions to racemic & alpha;-stereogenic-ss-dicarbonyls.Elaboration of the products to chiral aminoalcohols and carbamatesis demonstrated.

Automated summary

Enantioconvergent iso-Pictet-Spengler reactions of chiral racemic ss-formyl esters and a ss-keto ester are reported, leading to the formation of complex tetrahydro-& gamma;-carbolines bearing two contiguous stereocenters. These reactions are catalyzed by a chiral thiourea and benzoic acid cocatalytic system, representing unusual nonhydrogenative stereoconvergent additions to racemic & alpha;-stereogenic-ss-dicarbonyls. The transformation of the products to chiral aminoalcohols and carbamates is also demonstrated.