Catalytic Functionalization of Indoles by Copper‐Mediated Carbene Transfer

Abstract

The complex [TpBr3Cu(NCMe)] (TpBr3=hydrotris(3,4,5‐tribromo)pyrazolylborate) efficiently catalyzes the CH functionalization of indole derivatives at C3 by carbene transfer from different diazoesters in a high‐yield transformation involving low catalyst loadings and short reaction times. This system has shown that the previously proposed dichotomy of carbene addition (to the double bond) vs carbene insertion (to the CH bond) corresponds to two consecutive reaction steps: the cyclopropane intermediates, observed in the reaction mixtures, are the precursors of the final CH functionalization derivatives in a ring‐opening process involving acid catalysis. Those in situ generated cyclopropanes undergo nucleophilic ring opening with Me2CuLi to afford both C2 and C3 functionalized indoles.

Ring-opening, cycloaddition and rearrangement reactions of nitrogen-substituted cyclopropane derivatives

“…167 168,169,170,171 Scheme 56. Ring-opening isomerisation of donor-acceptor aminocyclopropane derivatives.…”

“…It is worth pointing out that starting from certain substrates, unusual selectivity can be observed with respect to the cyclopropane ring-opening, i.e. with cleavage of the distal cyclopropane bond relative to the nitrogen atom(Schemes 60 and 61) 161,167,174,175,176. Direct heterolytic rupture of this bond is a distinct possibility in these examples, the resulting cationic centre being tertiary and stabilised by mesomeric effect.…”

“…gives good results with the indole-derived cyclopropanes 133, although these reactions proceed with poor diastereoselectivity (Scheme 87) 167. Scheme 87.…”

(Acetonitrile)[hydrotris(3,4,5-tribromo)-pyrazolylborate]copper, TpBr3Cu(NCMe)

“…The complex [Tp Br3 Cu(NCMe)] has also been employed in the C-H bond functionalization of indoles at C3 by carbene transfer from different diazoesters (eq 15). 19 The reaction occurs through initial cyclopropanation of the heterocyclic double bond followed by ring opening. Catalytic Nitrene-Transfer Reaction.…”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…979), which afforded furanones fused to bicyclic ring systems (e.g. 982)[1058];(6) net C-H functionalization of indoles via opening of the indole cyclopropanation product[1059];(7)sequential formation of carbene complexes from double diazo compounds (e.g. 981) and demonstration of a tandem N-H insertion (e.g.…”