Access to [4,3,1]-Bridged Carbocycles via Rhodium(III)-Catalyzed C–H Activation of 2-Arylindoles and Annulation with Quinone Monoacetals

Abstract

Reported herein is the Rh­(III)-catalyzed annulation of N-unprotected 2-arylindoles with quinone monoacetals for the straightforward synthesis of [4,3,1]-bridged carbocycles with exclusive C(3) selectivity. Mechanistic studies, particularly deuterium-labeling experiments, suggest that the coupling likely proceeds via two-fold C–H activation with two-fold migratory insertion into the enone moieties.

Construction of Bridged Carbocycles and Heterocycles via Rh(III)-Catalyzed C–H Alkylation/Michael Addition of 2-Arylindoles with Quinone Monoacetals

“…It should be noted that, during the submission of this paper, Zheng and co-workers reported a similar method for the synthesis of bridged nine-membered carbocyclic compounds . Compared with the reported work, the present protocol exhibits the following advantages.…”

“…Meanwhile, the Rh­(III)-catalyzed annulations using quinone monoacetals as coupling partners, on the other hand, have rarely been explored (Scheme , eq 2). As a continuation of our recent interest in Rh­(III)-catalyzed annulation reactions, we disclosed herein a Rh­(III)-catalyzed formal [4 + 5] annulation reaction of 2-arylindoles with quinone monoacetals, thus offering an efficient and straightforward strategy for the selective synthesis of hard-to-prepare bridged nine-membered carbocyclic and heterocyclic compounds (Scheme , eq 3). Intriguingly, the regioselectivity of C(3) and N(1) annulation can be easily controlled by simply using 2-substituted or 2,3-disubstituted indoles as the substrates.…”

Recent advances in rhodium-catalysed cross-dehydrogenative-coupling between two C(sp2)–H bonds

“…A Rh( iii )-catalysed annulative coupling between unprotected 2-arylindoles and quinone monoacetals was performed to access the [4,3,1]-bridged carbocycles with exclusive C3 selectivity (Scheme 40). 58 Mechanistic investigation of H/D exchange suggested that the annulation reaction proceeded through a two-fold C–H activation/formal Michael addition pathway. The main challenge of this reaction is that it may stop at C–H alkylation without further cyclization and both C3 and NH of the indole may be involved in the formal Michael addition.…”

Recent Advances in the Synthesis of 5‐MemberedN‐Heterocycles via Rhodium Catalysed Cascade Reactions

“…The role of directing group assisted Rh catalyzed C−H activation/annulations of unsaturated bonds in the chemistry of hetero and carbocycles is unparalleled [61a,b] . Lately, N−O bond containing DGs are become familiar in rhodium catalyzed reactions, as the latter makes the reaction redoxneutral assisting the catalyst turnover without an external oxidant and also facilitating the additional cyclisation after the alkyne insertion [61c,d] .…”