Vinyl azides in heterocyclic synthesis. Part 9. Synthesis of the isoquinolone alkaloid siamine by intramolecular aza-Wittig reaction

Abstract

The isoquinolone alkaloid siamine (1) has been synthesised from 3,5-dibenzyloxybenzoic acid (2) by a route which incorporates an intramolecular aza-Wittig reaction as the key step. The benzaldehyde (5), prepared from the benzoic acid (2) by the dihydro-oxazole method, is converted into the vinyl azides (6) and (7), which on treatment with triethyl phosphite give the isoquinolone (8) and the 1-ethoxyisoquinoline (9) respectively. The synthesis is completed by transformation of the isoquinoline 3-ester (9) into the corresponding 3-methylisoquinoline (12), complete dealkylation of which with boron tribromide gives siamine (1).