Rhodium-Catalyzed Intramolecular Acylation of 2-(Indol-1-yl)-benzoic Acids under Redox-Neutral Conditions

Abstract

We developed a novel access to indoloindolone by a rhodium-catalyzed intramolecular acylation of 2-(indol-1-yl)benzoic acids. This reaction proceeds via the in situ formation of a mixed anhydride under redox-neutral reaction conditions. Preliminary mechanistic investigations revealed that the in situ formed mixed anhydride participates in the C–H activation step, which is facilitated by a RhI catalyst. The utility of this reaction was demonstrated by a large-scale reaction.

Key words

rhodium - intramolecular acylation - redox-neutral conditions - indoloindolones - C–H activation

Publication History

Received: 28 March 2023

Accepted after revision: 08 May 2023

Accepted Manuscript online:
08 May 2023

Article published online:
14 June 2023

• References and Notes


For selected reviews, see:
• 1a Humphrey GR, Kuethe JT. Chem. Rev. 2006; 106: 2875
• 1b Bandini M, Eichholzer A. Angew. Chem. Int. Ed. 2009; 48: 9608
• 1c Liu X.-Y, Qin Y. Acc. Chem. Res. 2019; 52: 1877
• 1d Kim T, Ha MW, Kim J. Molecules 2022; 27: 2171
• 2a Giacometti RD, Ramtohul YK. Synlett 2009; 2010
• 2b Hong D, Chen Z, Lin X, Wang Y. Org. Lett. 2010; 12: 4608
• 2c Kulkarni AM, Srinivas K, Deshpande MV, Ramana CV. Org. Chem. Front. 2016; 3: 43
• 2d Liu L, Qiang J, Bai S, Li Y, Miao C, Li J. Appl. Organomet. Chem. 2017; 31: e3817
• 2e Xu H, Sun L, Song C. Helv. Chim. Acta 2019; 102: e1800195
• 3 Rogness DC, Larock RC. Tetrahedron Lett. 2009; 50: 4003
• 4a Wu X, Xiao Y, Sun S, Yu J.-T, Cheng J. Org. Lett. 2019; 21: 6653
• 4b Aher YN, Pawar AB. Chem. Commun. 2021; 57: 7164
• 5a Motiwala HF, Vekariya RH, Aubé J. Org. Lett. 2015; 17: 5484
• 5b Zou S, Liu Y, Xi C. ACS Omega 2019; 4: 18734
• 6 Wang X, Li Z, Cao S, Rao H. Adv. Synth. Catal. 2016; 358: 2059
• 7 Liu M, Liu Y.-W, Xu H, Dai H.-X. Tetrahedron Lett. 2019; 60: 151061

For our recent works on rhodium-catalyzed C–H functionalization using carboxylic acid anhydrides, see:
• 8a Suzuki H, Liao Y, Kawai Y, Matsuda T. Eur. J. Org. Chem. 2021; 4938
• 8b Suzuki H, Sasamori F, Matsuda T. Org. Lett. 2022; 24: 1141
• 8c Suzuki H, Kawai Y, Takemura Y, Matsuda T. Org. Biomol. Chem. 2022; 20: 2808
• 8d Suzuki H, Ito Y, Matsuda T. Chem. Lett. 2022; 51: 775
• 9 Hu C, Mou D, Zhang X, Fu Y, Huo C, Du Z. Org. Biomol. Chem. 2022; 20: 8120
• 10a Maetani S, Fukuyama T, Ryu I. Org. Lett. 2013; 15: 2754
• 10b Fukuyama T, Sugimori T, Maetani S, Ryu I. Org. Biomol. Chem. 2018; 16: 7583

For examples on using the mixture of PivOH and Boc₂O as an in situ formed anhydride in rhodium-catalyzed decarbonylative C–H functionalization, see:
• 11a Zhao H, Xu X, Luo Z, Cao L, Li B, Li H, Xu L, Fan Q, Walsh PJ. Chem. Sci. 2019; 10: 10089
• 11b Zhao H, Xu X, Yu H, Li B, Xu X, Li H, Xu L, Fan Q, Walsh PJ. Org. Lett. 2020; 22: 4228
• 11c Yu H, Zhao H, Xu X, Zhang X, Yu Z, Li L, Wang P, Shi Q, Xu L. Asian J. Org. Chem. 2021; 10: 879

For selected examples on catalytic fluorazone synthesis, see:
• 12a Campo MA, Larock RC. J. Org. Chem. 2002; 67: 5616
• 12b Chang J, Sun L, Dong J, Shen Z, Zhang Y, Wu J, Wang R, Wang J, Song C. Synlett 2012; 23: 2704
• 12c Wang S, Yang Q, Dong J, Li C, Sun L, Song C, Chang J. Eur. J. Org. Chem. 2013; 7631
• 12d Liao F, Shi R, Sha Y, Xia J, Liao W, Lei A. Chem. Commun. 2017; 53: 4354
• 12e Konishi H, Futamata S, Manabe K. Adv. Synth. Catal. 2018; 360: 1805

For examples on 8H-indolo[3,2,1-de]acridin-8-one synthesis by annulation, see:
• 13a Zhao J, Li R, Ai W, Dong D, Li J, Chen L, Xie L, Yu T, Huang W. Chem. Asian J. 2016; 11: 1382
• 13b Zhou L, Zhang G. Angew. Chem. Int. Ed. 2020; 59: 8963
• 13c Song Y, Zhang G. Org. Lett. 2021; 23: 491
• 13d Zhang G, Zhu G. Org. Chem. Front. 2021; 8: 5336
• 13e Zhao Y.-H, Chen J.-H, Liu M.-C, Zhou Y.-B, Wu H.-Y. Adv. Synth. Catal. 2022; 364: 2939
• 14a Lu J, Zhang H, Chen X, Liu H, Jiang Y, Fu H. Adv. Synth. Catal. 2013; 355: 529
• 14b Pan F, Lei Z.-Q, Wang H, Li H, Sun J, Shi Z.-J. Angew. Chem. Int. Ed. 2013; 125: 2117
• 14c Mamone P, Danoun G, Gooßen LJ. Angew. Chem. Int. Ed. 2013; 125: 6836
• 14d Xiang K, Zhang S, Liu L, Huang T, Tang Z, Li C, Xu K, Chen T. Org. Chem. Front. 2021; 8: 2543
• 15 Typical Experimental Procedure for the Rhodium-Catalyzed Intramolecular Acylation of 2-(Indol-1-yl)benzoic Acid (1) To an oven-dried test tube equipped with a stirring bar were added 2-(indol-1-yl)benzoic acid (1, 0.3 mmol), [RhCl(CO)₂]₂ (5.8 mg, 0.015 mmol), NaI (13.5 mg, 0.09 mmol), and 1,4-dioxane (0.6 mL). Subsequently, Piv₂O (83.8 mg, 0.45 mmol) was injected to the solution via a syringe, and the tube was sealed with a PTFE cap. The reaction mixture was stirred at 150 °C for 18 h. After cooling to room temperature, the reaction mixture was filtered through a pad of silica gel (hexane/EtOAc = 1:1). The filtrate was concentrated under reduced pressure, and the residue was purified by preparative thin-layer chromatography (dichloromethane) or flush column chromatography (dichloromethane/hexane = 1:1) to give the product 2. 4-Methyl-10H-indolo[1,2-a]indol-10-one (2f) The title compound was obtained as an orange solid (43.5 mg, 62%); purified by preparative TLC (Et₂O/toluene = 1/19); mp 174.0–175.0 °C. ¹H NMR (500 MHz, CDCl₃): δ = 7.78 (d, J = 8.6 Hz, 1 H), 7.64 (dd, J = 7.4, 1.1 Hz, 1 H), 7.47–7.42 (m, 2 H), 7.17–7.12 (m, 2 H), 7.06 (t, J = 7.4 Hz, 1 H), 7.01 (t, J = 7.7 Hz, 1 H), 2.91 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 181.4, 145.3, 138.8, 135.3, 135.2, 134.7, 130.3, 129.4, 124.9, 124.4, 123.8, 123.6, 111.2, 111.2, 108.1, 22.2. IR (neat): 3027, 2970, 2323, 1741, 1686, 1614, 1560, 1472, 1446, 1376, 1217, 1133, 928, 756 cm^–1. HRMS (ESI-TOF): m/z calcd for C₁₆H₁₂NO⁺ [M + H]⁺: 234.0913; found: 234.0905. 8-Methyl-10H-indolo[1,2-a]indol-10-one (20) The title compound was obtained as an orange solid (61.0 mg, 87%); purified by preparative TLC (dichloromethane); mp 143.5–144.5 °C. ¹H NMR (500 MHz, CDCl₃): δ = 7.55 (d, J = 8.0 Hz, 1 H), 7.36–7.29 (m, 3 H), 7.17 (d, J = 8.0 Hz, 1 H), 7.08–7.02 (m, 2 H), 6.99 (s, 1 H), 2.25 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 181.6, 143.2, 135.8, 135.7, 134.0, 133.5, 132.3, 129.3, 127.8, 125.3, 124.8, 121.6, 111.1, 110.8, 107.3, 20.7. IR (neat): 2919, 1687, 1623, 1539, 1488, 1439, 1388, 1321,1234, 1033, 800, 780, 740, 518 cm^–1. HRMS (ESI-TOF): m/z calcd for C₁₆H₁₂NO⁺ [M + H]⁺: 234.0913; found: 234.0924.