Synthesis of mono-fluorinated heterocycles with a ring-junction nitrogen atom via Rh(iii)-catalyzed CF3-carbenoid C–H functionalization and defluorinative annulation

Abstract

A Rh(III)-catalyzed defluorinative [4 + 2] annulation of 2-aryl indoles with ethyl 2-diazo-3,3,3-trifluoropropanoate for the synthesis of 6-fluoro-indolo[2,1-a]isoquinolines has been developed. The reaction involves the regioselective CF₃-carbenoid C–H functionalization of 2-aryl indoles and consecutive β-fluoride elimination, followed by chemoselective N-1 cyclization of indoles with the CF₂C moiety to cleave the second C–F bond. Using various azoles as the directing groups, this protocol also enables the facile assembly of the corresponding mono-fluorinated heterocycles with a ring-junction nitrogen atom, including benzoimidazo[2,1-a], imidazo[2,1-a], imidazo[5,1-a], pyrazolo[5,1-a], and triazolo[3,4-a] fused isoquinolines, as well as imidazo[1,2-a]pyridines via vinylic Csp²-H activation. Moreover, diverse functional groups were readily installed onto the resultant indolo[2,1-a]isoquinolines by their S_NAr reactions with nucleophiles.