An efficient lactamisation/N-acyliminium Pictet–Spengler domino strategy for the diasteroselective synthesis of polyhydroxylated quinoxalinone, β-carboline and quinazolinone derivatives

Abstract

A novel cascade strategy has been developed for the synthesis of polyhydroxylated tetrahydroindolo[1,2-a]pyrrolo[2,1-c]quinoxaline, tetrahydrodipyrrolo[1,2-a:2′,1′-c]quinoxaline, hexahydro-1H-indolizino[8,7-b]indole, hexahydrobenzo[6,7]pyrrolo[1′,2′:1,2]azepino[3,4-b]indole, tetrahydrobenzo[4,5]imidazo[1,2-c]pyrrolo[1,2-a]quinazoline, and tetrahydropyrrolo[1,2-a]tetrazolo[1,5-c]quinazoline scaffolds. The key step is a lactamisation/Pictet–Spengler condensation of a bifunctional sugar-derived hydroxy-γ-lactone component with an appropriate bifunctional aromatic amine component. This modular approach features the in situ-generation of a cyclic N-acyliminium intermediate that allows the diastereoselective assembly of these diverse polycyclic systems efficiently under mild and operationally simple conditions.