Cobalt(II)-Catalyzed Proficient Synthesis of Enaminones from Aryl Alkenes and Amines

Dedicated to Professor B. C. Ranu on his 75th birthday.

Abstract

A simple, cost-effective, and modular strategy has been developed to synthesize synthetically and pharmaceutically active enaminones by oxidative amination of aryl alkenes with amines and CHCl₃, using tert-butyl hydroperoxide as an oxidant. We describe the synthesis of enaminones from vinyl arenes and sterically hindered N,N-diisopropylethylamine (DIPEA) by employing an Earth-abundant cobalt salt as a catalyst within a very short reaction period for the first time. Furthermore, nitrogen- and oxygen-containing heterocyclic compounds have been synthesized from these highly functionalized enaminones. Moreover, various control experiments, such as radical trapping reaction, along with a Hammett analysis with various types of substituents on the styrene ring unraveled the detailed mechanism of this reaction pathway.

Key words

enaminones - vinylarenes - cobalt catalysis - Hammet analysis - Oxidative amination

Publication History

Received: 18 June 2024

Accepted after revision: 31 July 2024

Accepted Manuscript online:
31 July 2024

Article published online:
22 August 2024

• References and Notes

• 1a Abbas M, Mostafa BB. Bioorg. Med. Chem. 2005; 13: 6133
• 1b Cox DS, Scott KR, Gao H, Raje S, Eddington ND. J. Pharm. Sci. 2001; 90: 1540
• 2 Abdulla R F, Morgan LA. Synth. Commun. 1982; 12: 351
• 3a Zhang Z.-H, Zhang X.-N, Mo L.-P, Li Y.-X, Ma F.-P. Green Chem. 2012; 14: 1502
• 3b Siddiqui ZN, Farooq F. J. Mol. Catal. A: Chem. 2012; 363: 451
• 4a Netto BA. D, Lapis AA. M, Bernd AB, Russowsky D. Tetrahedron 2009; 65: 2484
• 4b Cvetovich RJ, Pipik B, Hartner FW, Grabowski EJ. Tetrahedron Lett. 2003; 44: 5867
• 5a Liu J.-Y, Cao G.-E, Xu W, Cao J, Wang W.-L. Appl. Organomet. Chem. 2010; 24: 685
• 5b Burkhardt ER, Bergman RG, Heathcock CH. Organometallics 1990; 9: 30
• 5c Cámpora J, Maya CM, Palma P, Carmona E, Gutiérrez-Puebla E, Ruiz C. J. Am. Chem. Soc. 2003; 125: 1482
• 6 Braibante HT. S, Braibante ME. F, Rosso GB, Oriques DA. J. Braz. Chem. Soc. 2003; 14: 994
• 7 Brandt CA, da Silva AC. M. P, Pancote CG, Brito CL, da Silveira MA. B. Synthesis 2004; 1557
• 8 Ueno S, Shimizu R, Kuwano R. Angew. Chem. Int. Ed. 2009; 48: 4543
• 9 Schuppe AW, Cabrera JM, McGeoch CL. B, Newhouse TR. Tetrahedron 2017; 73: 3643
• 10 Shi W, Sun S, Wu M, Catano B, Li W, Wang J, Guo H, Xing Y. Tetrahedron Lett. 2015; 56: 468
• 11 Li M, Fang D, Geng F, Dai X. Tetrahedron Lett. 2017; 58: 4747
• 12 Kang Y.-W, Cho YJ, Han SJ, Jang H.-Y. Org. Lett. 2016; 18: 272
• 13 Neff RK, Su Y.-L, Liu S, Rosado M, Zhang X, Doyle MP. J. Am. Chem. Soc. 2019; 141: 16643
• 14 Zhang J, Zhou P, Yin A, Zhang S, Liu W. J. Org. Chem. 2021; 86: 8980
• 15a Pal A, Das KM, Sau S, Thakur A. Chem. Asian J. 2023; 18: e202300755
• 15b Pal A, Das KM, Thakur A. J. Org. Chem. 2023; 88: 8955
• 16a Sau S, Das KM, Mondal B, Thakur A. J. Org. Chem. 2024; 89: 7095
• 16b Das TN, Dhanasekaran T, Alfassi ZB, Neta P. J. Phys. Chem. A 1998; 102: 280
• 17 Pal A, Thakur A. Org. Biomol. Chem. 2022; 20: 8977
• 18 Enaminones 4a–q; General Procedure An oven-dried round-bottomed flask equipped with a stirrer bar was charged with CoCl₂·6H₂O (0.1 equiv, 0.1 mmol, 23.8 mg), DIPEA (3 equiv, 3 mmol, 0.52 mL), TBHP (3 equiv, 3 mmol, 0.29 mL), and toluene (1 mL). CHCl₃ (3 equiv, 3 mmol, 0.24 mL) was added to the mixture, followed by the appropriate styrene derivative 1 (1.0 equiv, 1.0 mmol). The mixture was stirred for 3 h in a preheated oil bath at 60 °C, then cooled to r.t. H₂O was added, and the mixture and extracted with CH₂Cl₂ (3 × 10 mL) and H₂O. The organic phase was washed with brine, dried (Na₂SO₄), and concentrated under reduced pressure. The crude product was purified by column chromatography [silica gel (100–200 mesh), EtOAc–PE (3:7 to 4:6)].
• 19 3-[(2E)-3-(Diisopropylamino)prop-2-enoyl]benzonitrile (4d) Purified by column chromatography (silica gel, 30% EtOAc–PE) to give a yellow oil; yield: 204.92 mg (0.80 mmol, 80%). ¹H NMR (300 MHz, CDCl₃): δ = 8.14–8.11 (m, 2 H), 7.98 (d, J = 12 Hz, 1 H), 7.72 (d, J = 9 Hz, 1 H), 7.52 (t, J = 7.5 Hz, 1 H), 5.70 (d, J = 12 Hz, 1 H), 3.33 (q, J = 7 Hz, 2 H), 1.32–1.27 (m, 12 H). ¹³C{¹H} NMR (75 MHz, CDCl₃): δ = 185.9, 151.7, 144.8, 141.8, 133.9, 131.8, 131.3, 129.5, 129.2, 112.4, 90.9, 57.7, 52.5, 41.6, 22.1, 12.7. Anal. Calcd for C₁₆H₂₀N₂O: C, 74.97; H, 7.86; N, 10.93. Found: C, 74.71; H, 7.60; N, 11.06. (1E)-1-(Diisopropylamino)hept-1-en-3-one (4g) Purified by column chromatography (silica gel, 20% EtOAc–PE) to give a yellow oil; yield: 133.44 mg (0.65 mmol, 65%). ¹H NMR (300 MHz, CDCl₃): δ = 7.50 (d, J = 9 Hz, 1 H), 4.62 (d, J = 9 Hz, 1 H), 2.29 (t, J = 6 Hz, 2 H), 1.44–1.17 (m, 21 H). ¹³C{¹H} NMR (75 MHz, CDCl₃): δ = 170.3, 146.8, 84.9, 71.4, 68.9, 51.0, 37.3, 28.8, 27.6, 22.7, 14.1. Anal. Calcd for C₁₃H₂₅NO: C, 73.88; H, 11.92; N, 6.63. Found: C, 73.55; H, 11.65; N, 6.44. 3-[(2E)-3-(Diethylamino)prop-2-enoyl]benzonitrile (4o) Purified by column chromatography (silica gel, 40% EtOAc–PE) to give a yellow liquid; yield: 159.80 mg (0.70 mmol, 70%). ¹H NMR (300 MHz, CDCl₃): δ = 8.15–8.11 (m, 2 H), 7.90 (d, J = 12 Hz, 1 H), 7.73–7.70 (m, 1 H), 7.53 (t, J = 7.5 Hz, 1 H), 5.70 (d, J = 12 Hz, 1 H), 3.43–3.31 (m, 4 H), 1.28 (s, 6 H). ¹³C {¹H} NMR (75 MHz, CDCl₃): δ = 185.9, 153.5, 141.8, 133.9, 131.8, 131.3, 129.2, 118.9, 112.4, 90.9, 51.0, 43.2, 14.9, 14.2. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₄H₁₇N₂O; 229.1341; found: 229.1340. (2E)-3-(Diethylamino)-1-(3-nitrophenyl)prop-2-en-1-one (4q) Purified by column chromatography (silica gel, 30% EtOAc–PE) to give a yellow liquid; yield: 176.28 mg (0.71 mmol, 71%). ¹H NMR (300 MHz, CDCl₃): δ = 8.67 (t, J = 3 Hz, 1 H), 8.31–8.23 (m, 2 H), 7.90 (d, J = 15 Hz, 1 H), 7.59 (t, J = 9 Hz, 1 H), 5.76 (d, J = 12 Hz, 1 H), 3.41–3.35 (m, 4 H), 1.28 (t, J = 6 Hz, 6 H). ¹³C {¹H} NMR (75 MHz, CDCl₃): δ = 185.6, 153.6, 148.3, 142.4, 133.6, 129.4, 125.4, 122.4, 90.8, 50.9, 43.2, 14.9, 11.8. Anal. Calcd for C₁₃H₁₆N₂O₃: C, 62.89; H, 6.50; N, 11.28. Found: C, 62.60; H, 6.22; N, 11.01.
• 20a Yadav N, Khan J, Tyagi A, Singh S, Hazra CK. J. Org. Chem. 2022; 87: 6886
• 20b Das KM, Pal A, Surya TL, Roy L, Thakur A. Chem. Eur. J. 2023; 30: e202303776
• 21 Ying J, Liu T, Liu Y, Wang J.-P. Org. Lett. 2022; 24: 2404
• 22 Jiang T.-S, Zhou Y, Dai L, Liu X, Zhang X. Tetrahedron Lett. 2019; 60: 2078
• 23a Chen C, Tan H, Liu B, Yue C, Liu W. Org. Chem. Front. 2018; 5: 3143
• 23b Chen C, Li Y, Pan Y, Duan L, Liu W. Org. Chem. Front. 2019; 6: 2032
• 24a Pan C, Huang B, Hu W, Feng X, Yu J.-T. J. Org. Chem. 2016; 81: 2087
• 24b Wang Q.-Q, Wang Z.-X, Zhang X.-Y, Fan X.-S. Asian J. Org. Chem. 2017; 6: 1445
• 24c Chudasama V, Fitzmaurice RJ, Caddick S. Nat. Chem. 2010; 2: 592
• 25a Ling J, Zhang J, Zhao Y, Xu Y, Wang H, Lv Y, Ji M, Ma L, Ma M, Wan X. Org. Biomol. Chem. 2016; 14: 5310
• 25b Wu C.-S, Liu R.-X, Ma D.-Y, Luo C.-P, Yang L. Org. Lett. 2019; 21: 6117