Short and convenient synthesis of two natural phthalides by a copper(I) catalysed Sonogashira/oxacyclisation copper(I) process

Total synthesis of (+/-)-herbaric acid and (+/-)-(4-methoxybenzyl)-5,7-dimethoxyphthalide, two natural phthalide products, was achieved in 8 steps and 5 steps, respectively, starting from commercially available 3,5-dimethoxyaniline. The key step of the sequence included a copper-catalysed tandem cross-coupling and oxacylisation reaction of terminal alkynes and 2-iodobenzok acid derivatives via 5-exo-dig cyclisation with high stereo-, regio- and chemoselectivities. This straightforward method allows the preparation of diverse phthalides, which belong to a group of pharmacologically important compounds. (C) 2013 Elsevier Ltd. All rights reserved.