Synthesis of Chiral Tetrahydroisoquinoline and C 2-Symmetric Bistetrahydroisoquinoline Ligands and Their Application in the Enantioselective Henry Reaction

Abstract

Application of chiral tetrahydroisoquinoline and bistetrahydroisoquinoline scaffolds in asymmetric reactions is limited by the inefficient synthesis of their chiral structural variants. We have conveniently synthesized 24 such variants and applied them as ligands in the enantioselective Henry reaction. The conformational rigidity of these ligands and the size of the coordination sphere control the enantioselectivity of the products. The conformationally rigid chiral tetrahydroisoquinoline THIQ-Cu(OAc) 2 •H 2 O complex successfully catalyzed the enantioselective Henry reaction between various aldehydes and nitromethane and gives the β-nitro alcohol adducts in up to 96% yield and 80% ee.