Synthesis of 2,3-Disubstituted NH Indoles via Rhodium(III)-Catalyzed C–H Activation of Arylnitrones and Coupling with Diazo Compounds

Abstract

A rhodium-catalyzed intermolecular coupling between arylnitrones and diazo compounds by C-H activation/[4 + 1] annulation with a C(N)-C(acyl) bond cleavage is reported, and 2,3-disubstituted NH indoles are directly synthesized in up to a 94% yield. A variety of functional groups are applicable to this reaction to give the corresponding products with high selectivity. Compared to other previously reported Rh(III)-catalyzed synthesis of homologous series, this method is simpler, more general, and more efficient.

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

“…Alternatively, indole synthesis may also be achieved using a RhCp*-catalyst in combination with diazo compounds as coupling partners ( Scheme 182C ). 1169 In contrast to the previous examples, this transformation requires a substoichiometric amount of Cu(OAc) 2 as oxidant but the substituent present on the nitrone is conserved in a final product (as C2-substituent of the indole scaffold). Accordingly, this strategy is of particular interest if indoles bearing an aromatic moiety at C2 position and an ester group at C3 are targeted.…”

Cp*IrIII‐Catalyzed [3+2] Annulations of N‐Aryl‐2‐aminopyrimidines with Sulfoxonium Ylides to Access 2‐Alkyl Indoles Through C–H Bond Activation

“…Inspired by this work, various elegant strategies have been reported for constuctiong the indole skeleton. Untill now, besides alkynes, alkenes, and diazo compounds have also been reported as efficient coupling partners (Scheme ). However, most of synthetic approaches require oxidants to induce catalytic turnovers.…”

Diazo Compounds: Versatile Synthons for the Synthesis of Nitrogen Heterocycles via Transition Metal‐Catalyzed Cascade C–H Activation/Carbene Insertion/Annulation Reactions

“…In 2017, Chen and co‐workers also demonstrated an efficient Rh(III)‐catalyzed synthesis of 2,3‐disubstituted NH indoles 16 using arylnitrones 25 as substrates (Scheme ) . In contrast to previous approaches, the yield of desired product improved significantly in the presence of 2 equiv.…”