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
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.