Three-Component Synthesis of Multiply Functionalized 5,6-Dehydroisoquinuclidines through Dearomatization of Pyridine

A three-component synthesis of multiply functionalized 5,6-dehydroisoquinuclidines is described. After the formation of an <i>N</i>-alkylpyridinium salt, Grignard addition led to the formation of the corresponding 1,2-dihydropyridine bearing an alkyl, alkene, aryl, or alkynyl group. Subsequent Diels-Alder reaction with a dienophile provided functionalized dehydroisoquinuclidines in high yields (up to 93%) with <i>endo</i> selectivities (73:27 to >99:1). This reaction was applicable to the synthesis of an <i>N</i>-(4-methoxybenzyl)pyridinium salt, where the 4-methoxybenzyl group was switched to a benzyloxycarbonyl group after the formation of the dehydroisoquinuclidine.