Three-Component\nSynthesis of Multiply Functionalized\n5,6-Dehydroisoquinuclidines through Dearomatization of Pyridine

A three-component synthesis of multiply functionalized\n5,6-dehydroisoquinuclidines\nis described. After the formation of an <i>N</i>-alkylpyridinium\nsalt, Grignard addition led to the formation of the corresponding\n1,2-dihydropyridine bearing an alkyl, alkene, aryl, or alkynyl group.\nSubsequent Diels–Alder reaction with a dienophile provided\nfunctionalized dehydroisoquinuclidines in high yields (up to 93%)\nwith <i>endo</i> selectivities (73:27 to >99:1). This\nreaction\nwas applicable to the synthesis of an <i>N</i>-(4-methoxybenzyl)pyridinium\nsalt, where the 4-methoxybenzyl group was switched to a benzyloxycarbonyl\ngroup after the formation of the dehydroisoquinuclidine.