Benzyne Cyclization Route to Benzophenanthridine Alkaloids. Synthesis of Chelerythrine, Decarine, and Nitidine

Article abstract of DOI:10.1021/jo00243a020

The alkaloids chelerythrine (8b) and decarine (7c) have been synthesized through a benzyne-mediated cyclization of N-(2-halobenzyl)-1-naphthylamines 4 with KNH2 in ammonia/ether.The 7-hydroxybenzophenanthridine structure 16a proposed for the alkaloid fagaridine is questioned on the basis of comparison with a model compound (16b) synthesized by benzyne cyclization.For the 8,9-oxygenated alkaloids like nitidine (8i), this cyclization proceeded poorly, but a dramatic improvement occurred when LDA/THF at -78 deg C was used instead of KNH2/NH3.