A New General Method for the Asymmetric Synthesis of 4-Alkyl-3-aryl-1,2,3,4-tetrahydroisoquinolines.
A highly enantioselective method for the synthesis of 4-alkyl substituted 1,2,3,4-tetrahydroisoquinolines is reported. The key step relies on the asymmetric synthesis of alpha-alkylarylacetic acids by alkylation of their corresponding amides employing (S,S)-(+)-pseudoephedrine as chiral inductor. Subsequent Friedel-Crafts acylation, stereocontrolled reductive amination and Pictet-Spengler cyclization affords the title compounds in excellent yields and enantioselectivities.
Vicario
Jose L.
JL
Departamento de Química Orgánica, Facultad de Ciencias, Universidad del Pais Vasco, P.O. Box 644, 48080 Bilbao, Spain.
Badía
Dolores
D
Domínguez
Esther
E
Carrillo
Luisa
L