Selective Synthesis of Benzo[a]Carbazoles and Indolo[2,1‐a]‐Isoquinolines via Rh(III)‐Catalyzed C−H Functionalizations of 2‐Arylindoles with Sulfoxonium Ylides

Abstract

A highly chem-and regioselective synthesis of diversely substituted benzo[a]carbazoles and indolo[2,1-a]-isoquinolines through Rh(III)catalyzed cascade reactions of 2-arylindoles with sulfoxonium ylides is presented. To be specific, treatment of 2-arylindoles, 2-arylindole-3-carbaldehydes, 2-arylindole-3-carbonitriles or 2-aryl-3-methylindoles with sulfoxonium ylides under the catalysis of Rh(III) led to the selective formation of 6aryl/alkyl benzo[a]carbazoles, 5-acylbenzo[a]carbazoles, 6-amino-5-acylbenzo[a]carbazoles or 12methylindolo[2,1-a]isoquinolines, respectively. Mechanistically, the formation of the title compounds involves a cascade process including metalation of the inert C(sp 2 )ÀH bond, migratory insertion of ylide into the carbon-metal bond via an in situ carbenoid formation, protodemetalation, and condensation. To our knowledge, this is the first example in which b-carbonyl sulfoxonium ylides were used as stable carbene precursors and bifunctional C2 synthons to afford benzo[a]carbazoles and indolo[2,1-a]isoquinolines.

Sulfoxonium Ylide Derived Metal Carbenoids in Organic Synthesis

“…In 2018, Fan's group developed a highly chemo-and regioselective synthesis of benzo[a]carbazoles 73a-c and indolo[2,1-a]isoquinolines 73d through coupling of 2-aryl indoles with sulfoxonium ylide derived Rh(III)-carbenoids (Scheme 33). 52 By strategically placing substituents with suitable reactivity at the 3-position of indoles 72a-d, diverse heterocyclic products were obtained. 3-Unsubstituted indole 72a provided benzo[a]carbazoles 73a, while formyl or cyano groups at C3 afforded 5-acylbenzo[a]carbazoles 73b and 6-amino-5-acylbenzo[a]carbazoles 73c, respectively.…”

Ruthenium(II)-Catalyzed Homocoupling of α-Carbonyl Sulfoxonium Ylides Under Mild Conditions: Methodology Development and Mechanistic DFT Study

“…It was generally proposed that the cyclic product was formed by the first generation of an acylmethylation intermediate in similar cascade reactions. (Chen et al, 2018;Hu et al, 2018aHu et al, ,b, 2019Liang et al, 2018;Shi et al, 2018;Xiao et al, 2018;Xie et al, 2018bXie et al, , 2019Xie H. et al, 2018;Xu et al, 2018;Zhou et al, 2018;Cai et al, 2019;Chen P. et al, 2019;Cui et al, 2019;Huang et al, 2019;Lai et al, 2019;Liu et al, 2019;Luo et al, 2019;Lv et al, 2019;Nie et al, 2019;Shen et al, 2019;Wu C. et al, 2019;Zhang et al, 2019Zhang et al, , 2020Wu et al, 2020). Further transformations from IM6 were explored theoretically to confirm whether the acylmethylation intermediate (IM8) is key in the formation of 2a (Figure 2).…”

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

“…[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).…”