Expedient C–H Chalcogenation of Indolines and Indoles by Positional-Selective Copper Catalysis

Abstract

A versatile protocol for the C–H chalcogenation of indolines and indoles by means of copper catalysis was established. The C–H functionalization occurred selectively at the C7 position of indolines and exclusively at the C(2)–H bonds of indoles. The robust copper catalyst tolerated a wide range of functional groups and set the stage for the synthesis of diversely decorated indoles. Mechanistic studies were indicative of a SET-type mechanism and a facile C–H metalation being operative.

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

“…The C7 thiolation of indolines reported by Ackermann is also particularly interesting since no stoichiometric oxidant was used apart from air, requiring only a catalytic amount of Cu ( Scheme 145B ). 860 The same conditions proved effective also for thiolation and selenylation of indoles. Drawbacks of this protocol are the high temperature required and the relatively modest yields obtained for most examples.…”

Cu‐Catalyzed Directed C7−H Imidation of Indolines via Cross‐Dehydrogenative Coupling

“…Based on the literature and our experimental data, a plausible reaction pathway is outlined in Scheme . The first step is likely the oxygen mediated oxidation of Cu(I) catalyst, generating the active Cu(II) species.…”

C−H Functionalization of Indoles by 3d Transition‐Metal Catalysis

“…A copper‐catalyzed C(7)−H functionalization of indoline was reported by Ackermann (Scheme ) . The authors demonstrated the thiolation of both the indoline and indole C−H bonds with excellent regio and chemoselectivity.…”

“…A copper-catalyzed C(7)À H functionalization of indoline was reported by Ackermann (Scheme 40). [78] The authors demon- strated the thiolation of both the indoline and indole CÀ H bonds with excellent regio and chemoselectivity. Diverse substituents like À Br, À Cl, À F, À Me on indole and/or indolines were well tolerated under optimized reaction conditions.…”