Access to Quaternary Stereogenic Centers via Rhodium(III)-Catalyzed Annulations between 2-Phenylindoles and Ketenes

Abstract

Rh(III)-catalyzed C-H activation of arenes and mild oxidative [4 + 2] annulative coupling with ketenes have been realized. The uniquely high reactivity of the C(3) of 2-phenylindoles was successfully utilized to facilitate the reductive elimination process, leading to efficient synthesis of cyclic products with a quaternary carbon stereocenter.

Rh(III)‐Catalyzed Reaction of 2‐Aryl‐3‐acyl‐1H‐indoles with α‐Diazo Carbonyl Compounds: Synthesis of 5‐Carbonyl Substituted Benzo[a]carbazoles via [5+1] Annulation

“…On the basis of the above mechanistic studies and literature reports, [6][7][8][9][10][11][12][13][14] a plausible mechanism is depicted in Scheme 6.…”

“…To our delight, 2 eq. of H 2 O could effectively promote the reaction and afford 3 a with a higher yield of 77% (entries [11][12]. Further studies showed that the best result was obtained when the reaction was conducted at 80 °C (entries 13 and 15).…”

“…[3] Recently, great efforts have been made in the selective C(sp 2 )À H functionalization of NÀ H indoles for the synthesis of various indole-containing compounds since the free À NH unit of indoles can not only direct a specific CÀ H bond activation but also participate in the following transformation (Scheme 1). [4][5][6][7][8][9][10][11][12][13][14] For example, in 2010, Miura reported the Rh(III)-catalyzed oxidative coupling/cyclization of 2-phenylindoles with alkynes to generate indolo [2,1-a]isoquinolines. [4] Later, Huang et al disclosed an efficient method for the synthesis of 6Hisoindolo [2,1-a]indol-6-ones through rhodium-catalyzed NHindole-directed CÀ H carbonylation of 2-arylindoles with carbon monoxide.…”

“…[5] In 2017, our group described Rh(III)-catalyzed cascade reactions of 2-arylindoles with α-diazo carbonyl compounds, leading to the production of benzo[a]carbazoles containing an unprotected NH unit. [6] Since then, (NH)-indole was found to be a good directing group for transition-metalcatalyzed arene C(sp 2 )À H functionalization with various coupling partners such as alkenes, [7] sulfoxonium ylides, [8] benzoquinones, [9] quinone monoacetals, [10] ketenes, [11] dioxazolones [12] and 4-hydroxy-2-alkynoates [13] to afford isoindolo [2,1-a]indoles, 6-substituted benzo[a]carbazoles, dibenzo[a,c]carbazoles, indole-containing bridged compounds, indolo[1,2-c]quinazolines, furo [3,4-c]indolo [2,1-a]isoquinolines, etc. [14] (Scheme 1a).…”

“…Recently, great efforts have been made in the selective C(sp 2 )−H functionalization of N−H indoles for the synthesis of various indole‐containing compounds since the free −NH unit of indoles can not only direct a specific C−H bond activation but also participate in the following transformation (Scheme 1). [4–14] For example, in 2010, Miura reported the Rh(III)‐catalyzed oxidative coupling/cyclization of 2‐phenylindoles with alkynes to generate indolo[2,1‐ a ]isoquinolines [4] . Later, Huang et al.…”