A convenient entry into the rhoeadan skeleton. Total synthesis of (±) cis-alpinigenine

Abstract

Condensation of 4-bromoisochroman-3-one (8a) with N-methyl-3,4-dimethoxy-β-phenethylamine (7) provides the aminolactone 9a which by diisobutylaluminum hydride reduction followed by polyphosphoric acid mediated cyclization gives the tetracyclic product 10a, thus constituting a convergent, short entry into the rhoeadan alkaloid skeleton. Chromium trioxide oxidation of 10a affords a low yield of the corresponding lactone 11a. A parallel series of reactions starting from 7,8-dimethoxy-4-bromoisochroman-3-one (8b), prepared either via Baeyer–Villiger oxidation of 4,5-dimethoxy-2-indanone (14) or, more conveniently, via benzeneboronic acid assisted condensation of 3-hydroxy-4-methoxyphenylacetic acid (18) with formaldehyde, yields 7,8,12,13-tetramethoxy-3-methylrhoeadan (10b). Oxidation of compound 10b with chromium trioxide gives the corresponding lactone 11b also in low yield. Since 11b has been previously converted into (±)-cis-alpinigenine (11c) and (±)-cis-alpinine(11d), this work constitutes total syntheses of these alkaloids.