Rh(III)-Catalyzed [4 + 2] Annulation of Indoles with Diazo Compounds: Access to Pyrimido[1,6-a]indole-1(2H)-ones

Abstract

The Rh(III)-catalyzed regioselective C2-H bond carbenoid insertion/cyclization of N-amidoindoles with α-acyl diazo compounds has been developed. This method provides a novel approach to 2H-pyrimido[1,6-a]indol-1-ones with a broad range of functional group tolerance. The synthetic utilities of the approach are demonstrated by versatile chemical transformations.

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…The group of Wei Zeng reported an alkylation/annulation sequence towards pyrimido[1,6- a ]indole-1(2 H )-ones under [Cp*RhCl 2 ] 2 catalysis with α-diazocarbonyl reagents ( Scheme 26D ). 206 The method gave good access to this scaffold with the majority of examples in yields >70%. In the indole substrate Br and COOMe was tolerated amongst other less reactive FGs.…”

Synthesis of [5,6]‐Bicyclic Heterocycles with a Ring‐Junction Nitrogen Atom: Rhodium(III)‐Catalyzed C−H Functionalization of Alkenyl Azoles

“…These compounds have emerged in the past several years as competent coupling partners for heterocycles ynthesis by rhodium(III)-catalyzed C À Hf unctionalization. [10] Unlike for alkyne coupling,t he reaction of alkenyl azoles with diazoketones is redox-neutral and requires no stoichiometric oxidant. ForC-alkenyl imidazoles,s imple heating at 40 8 8Ci nT HF was effective (see Table S2 for optimization).…”

Regioselective Direct C‐Alkenylation of Indoles

“…Reaction of N ‐alkylcarbamoyl indoles with α‐diazoketones 128 under Rh III catalysis is able to provide pyrimidoindolones in satisfactory yields (Scheme ) . The plausible mechanism entails as first step the cyclometalation of the indole leading to intermediate 129 which reacts with α‐diazoketone giving the rhodium–carbene species 130 .…”

“…Reaction of N-alkylcarbamoyl indoles with a-diazoketones 128 under Rh III catalysis is able to provide pyrimidoindolones in satisfactory yields (Scheme 98). [195] The plausible mechanism entails as first step the cyclometalation of the indole leading to intermediate 129 which reacts with a-diazoketone giving the rhodium-carbenes pecies 130.T he latter adduct undergoes to an indole shift anda fter protonolysis of the rhodacycle 131 the obtained open-chain intermediate 132 gives ac ondensation reactionleadingt othe final product.…”