Expedient entry to the piperazinohydroisoquinoline ring system using a sequential Ugi/Pictet–Spengler/reductive methylation reaction protocol

Abstract

An expedient entry to the piperazinohydroisoquinoline ring system present in the tetrahydroisoquinoline antitumor alkaloids family is described. The synthetic sequence involves: a sequential Ugi reaction followed by an N-Boc-deprotection process and iminium formation with a spontaneous Pictet–Spengler cyclization and reductive N-methylation, with all these processes performed in a two-operation protocol in the same reaction flask.