The optimization for cyclization reaction of 2-(2-carbomethoxyethynyl)aniline derivatives and formal synthesis of pyrroloquinoline quinone and its analogue utilizing a sequential coupling-cyclization reaction

The reaction conditions for the Pd-catalyzed cyclization reaction of 2-(2-carbomethoxyethynyl)aniline derivatives were investigated. The amounts of Pd(PPh3)4, methyl propiolate, and ZnBr2 could be significantly reduced compared with those reported in our preliminary publication by careful tuning of the solvent and the reaction temperature. In addition to the above results, formal syntheses of pyrroloquinoline quinone (PQQ) and its analogue from 2-amino-5-nitrophenol using a Pd-complex-catalyzed sequential coupling-cyclization reaction between methyl propiolate and 2-iodoaniline derivatives are described.