An Approach to the Synthesis of Enantiopure Tetrahydroisoquinoline via a Key Asymmetric Ugi Reaction

Abstract

An approach to the synthesis of the multisubstituted ­tetrahydroisoquinoline featuring an asymmetric Ugi reaction of α-amino acid, aromatic aldehyde and an isocyanide has been developed. The promising utility of the strategy is demonstrated by a ­synthesis of an enantiopure functionalized 1,3-trans-tetrahydroisoquinolin-4-ol from natural l-valine. The configuration of the two stereocenters at C-1 and C-4, generated in the Ugi reaction and Pomeranz–Fritsch-type cyclization separately, was controlled very well and determined by NMR studies.

Key words

Ugi reaction - α-amino acid - aromatic aldehyde - tetrahydroisoquinoline - asymmetric synthesis

• References and Notes

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