Synthesis of 1,4-Dihydropyridines and Related Heterocycles by Iodine-Mediated Annulation Reactions of N-Cyclopropyl Enamines

The annulation of N-cyclopropyl enamines to produce 1,4-dihydropyridine (1,4-DHP) derivatives is described. In the presence of molecular iodine (I₂), an N-cyclopropyl enamine substrate undergoes iodination, opening of the cyclopropyl ring, and annulation with a second molecule of the substrate to form the 1,4-DHP product. This reaction is amenable to gram-scale operations under mild reaction conditions with no transition metals being required. Further transformations of the 1,4-DHPs leads to related pyridine and bicyclic frameworks.