Base-catalyzed Asymmetric Diels-Alder Reaction of N-Nosyl-3-hydroxy-2-pyridone with a Chiral Acrylate, and Its Application to the Synthesis of Aminocarbasugars

Abstract

A base-catalyzed asymmetric Diels-Alder
reaction of N-sulfonylated 3-hydroxy-2-pyridone and a
chiral acrylate has been developed. In the presence of a
catalytic amount of cinchona alkaloid, the reaction
proceeded smoothly in aqueous tetrahydrofuran and gave a
highly functionalized bicyclolactam in good yield with up to
91% diastereoselectivity (de). Absolute configuration of the
adduct was established as 1R, 4S, 8R, based on
transformation to compounds with known configuration. Its
synthetic utility was demonstrated by preparing 2-
epivalidamine, 2,3-epivalidamine, and an enantiomer of a
Tamiflu intermediate, in short steps.