Enaminone-Directed Rh(III)-Catalyzed Hydroarylation Reaction of Oxa/azabenzonorbornadienes through C–H Bond Functionalization

Abstract

We report an Rh(III)-catalyzed hydroarylation of oxa- and azabenzonorbornadienes directed by enaminones through C–H activation. The reaction proceeds under mild conditions with broad substrate scope and excellent regioselectivity. Diverse polycyclic products are obtained in high yields. A representative structure was confirmed by X-ray analysis.

Keywords

C–H activation - Rhodium catalysis - Enaminone - Hydroarylation - Oxa/azabenzonorbornadienes

Publikationsverlauf

Eingereicht: 25. Juli 2025

Angenommen nach Revision: 18. August 2025

Accepted Manuscript online:
19. August 2025

Artikel online veröffentlicht:
18. September 2025

• References

• 1a Crabtree RH, Lei A. Chem Rev 2017; 117 (13) 8481-8482
• 1b Goswami N, Bhattacharya T, Maiti D. Nat Rev Chem 2021; 5 (09) 646-659
• 2a Dalton T, Faber T, Glorius F. ACS CentrSci 2021; 7 (02) 245-261
• 2b Sinha SK, Ghosh P, Jain S. et al. Chem Soc Rev 2023; 52 (21) 7461-7503
• 3 Hartwig JF, Larsen MA. ACS CentrSci 2016; 2 (05) 281-292
• 4 Davies HML. J Org Chem 2016; 81 (02) 343-350
• 5a Rej S, Ano Y, Chatani N. Chem Rev 2020; 120 (03) 1788-1887
• 5b Das J, Guin S, Maiti D. Chem Sci 2020; 11 (40) 10887-10909
• 6 Liu B, Romine AM, Rubel CZ, Engle KM, Shi B-F. Chem Rev 2021; 121 (24) 14957-15074
• 7 Gandeepan P, Müller T, Zell D, Cera G, Warratz S, Ackermann L. Chem Rev 2019; 119 (04) 2192-2452
• 8 Cabré A, Verdaguer X, Riera A. Chem Rev 2022; 122 (01) 269-339
• 9 Wang Y, Liao W, Wang Y, Jiao L, Yu Z-X. J Am Chem Soc 2022; 144 (06) 2624-2636
• 10 von Delius M, Le CM, Dong VM. J Am Chem Soc 2012; 134 (36) 15022-15032
• 11 Kakiuchi F, Takano S, Kochi T. ACS Catal 2018; 8 (07) 6127-6137
• 12 Qi X, Lan Y. Acc Chem Res 2021; 54 (14) 2905-2915
• 13 Begum T, Prakash R, Duarah G, Gogoi S. Chapter 10 – Utilization of Rh-Carbenoid CH Insertion Reactions for the Synthesis of Bioactive Natural Products. In Studies in Natural Products Chemistry. Atta ur R. ed. Vol. 65. Elsevier; 2020: 349-380
• 14a Piou T, Rovis T. Acc Chem Res 2018; 51 (01) 170-180
• 14b Liu C-X, Yin S-Y, Zhao F. et al. Chem Rev 2023; 123 (16) 10079-10134
• 15 Qi X, Li Y, Bai R, Lan Y. Acc Chem Res 2017; 50 (11) 2799-2808
• 16 Roy P, Mahato K, Shrestha D, Mohandoss S, Lee SW, Lee YR. Org Biomol Chem 2025; 23 (01) 36-58
• 17 Chen D, Dong D-Q, Qiu Z-X. et al. Eur J Org Chem 2025; 28 (04) e202401177
• 18 Zhou S, Wang J, Wang L, Song C, Chen K, Zhu J. Angew Chem Int Ed 2016; 55 (32) 9384-9388
• 19 Huang J, Yu F. Synthesis 2020; 53 (04) 587-610
• 20 Chen D, Wan J-P, Liu Y. Org Lett 2025; 27 (10) 2371-2376
• 21 Nagireddy A, Dattatri, Kotipalli R, Nanubolu JB, Reddy MS. J Org Chem 2022; 87 (02) 1240-1248
• 22a Gaber HM, Bagley MC, Muhammad ZA, Gomha SM. RSC Adv 2017; 7 (24) 14562-14610
• 22b General Procedure for C–H Activation/Hydroarylation (1 mmol scale): Enaminone 1a (175 mg, 1 mmol), [RhCp*Cl₂]₂ (2.5 mol %), AgSbF₆ (15 mol %), NaOAc (1.5 equiv), and dioxazolone 2a (144 mg, 1 mmol) were weighed into a pressure tube, to which was added DCE (10 mL). The reaction mixture was stirred for 24 h at 110 ^°C. Purification was performed by flash column chromatography on silica gel using EtOAc and petroleum ether to afford product 3
• 22c (E)-3-(dimethylamino)-1-(2-((2R)-1,2,3,4-tetrahydro-1,4-epoxynaphthalen-2-yl)phenyl)prop-2-en-1-one (3aa): Reaction Time: 24 h.; viscous oil; 240 mg, 75% yield; ¹H NMR (400 MHz, CDCl₃) δ 7.70 (d, J = 8.0 Hz, 1H), 7.36 (t, J = 7.5 Hz, 1H), 7.33–7.16 (m, 5H), 7.16–7.08 (m, 2H), 5.48 (d, J = 4.5 Hz, 1H), 5.28 (d, J = 12.2 Hz, 1H), 5.27 (s, 1H), 3.21 (dd, J = 8.1, 4.3 Hz, 1H), 2.90 (s, 6H), 2.14–1.95 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 194.5, 154.9, 146.3, 146.2, 142.6, 142.3, 129.4, 127.1, 126.7, 126.51, 126.46, 125.6, 119.1, 118.9, 98.5, 85.4, 79.3, 44.9, 41.7, 38.6, 37.0; HRMS (ESI⁺) m/z calcd for (M + H)⁺ [C₂₁H₂₁O₂N + H]⁺ : 320.1651, found 320.1653