Synlett 2018; 29(09): 1223-1228
DOI: 10.1055/s-0036-1591956
letter
© Georg Thieme Verlag Stuttgart · New York

Efficient Access to cis-Hydrobenzo[b]oxepines: Rhodium(I)-Catalyzed Cyclization of Cyclohexadienone-Tethered o-Tolyl-Substituted Alkynes

Jia-Xin Wang
a   College of Chemistry, Jilin University, 2699 Qianjin Road, Changchun 130012, P. R. of China   Email: wliao@jlu.edu.cn
,
Yun-Xuan Tan
b   Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China   Email: tianping@sioc.ac.cn
,
Wei-Wei Liao*
a   College of Chemistry, Jilin University, 2699 Qianjin Road, Changchun 130012, P. R. of China   Email: wliao@jlu.edu.cn
,
Ping Tian  *
b   Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China   Email: tianping@sioc.ac.cn
c   Innovation Research Institute of Traditional Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, P. R. of China   Email: tianping@shutcm.edu.cn
,
Guo-Qiang Lin
b   Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China   Email: tianping@sioc.ac.cn
c   Innovation Research Institute of Traditional Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, P. R. of China   Email: tianping@shutcm.edu.cn
,
Qian Zhao*
d   Jiangsu Key Laboratory of Chiral Drug Development, Jiangsu Aosaikang Pharmaceutical Co., Ltd., Nanjing, Jiangsu 211112, P. R. of China   Email: zhaoqian@ask-pharm.com
› Author Affiliations

Financial support was generously provided by the 973 Program (2015CB856600), NSFC (21572251, 21572253, 21772063), and the Collaborative Innovation Center of Chemical Science and Engineering (Tianjin).
Further Information

Publication History

Received: 17 January 2018

Accepted after revision: 20 February 2018

Publication Date:
14 March 2018 (online)


Abstract

An efficient access to cis-hydrobenzo[b]oxepine frameworks has been established through rhodium(I)-catalyzed cyclization of cyclohexadienone-tethered o-tolyl-substituted alkynes (1,6-enynes). The cascade process involves regioselective α-arylrhodation of the alkyne, 1,4-rhodium migration, and conjugate addition to cyclohexadienone.

Supporting Information

 
  • References and Notes

  • 8 Murthy AS. Donikela S. Reddy CS. Chegondi R. J. Org. Chem. 2015; 80: 5566
  • 9 Fukui Y. Liu P. Liu Q. He Z.-T. Wu N.-Y. Tian P. Lin G.-Q. J. Am. Chem. Soc. 2014; 136: 15607
  • 11 Clarke C. Incerti-Pradillos CA. Lam HW. J. Am. Chem. Soc. 2016; 138: 8068
  • 13 CCDC 1816856, 1816857, and 1816858 (3cj) contain the supplementary crystallographic data for compounds 3aa, 3cj, and 3cj, respectively. The data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
  • 14 cis-Hydrobenz[b]oxepines 3; General Procedure To a dried Schlenk flask charged with substrate 1 (0.2 mmol), arylboronic acid 2 (0.6 mmol, 3.0 equiv), and [Rh(COD)OH]2 (2.3 mg, 2.5 mol%) under argon was added toluene (8 mL) followed by degassed H2O (10.8 μL, 3.0 equiv), and the resulting mixture was stirred at 70 °C overnight. The reaction was quenched with sat. aq NH4Cl (30 mL), and the mixture was extracted with EtOAc (2 × 30 mL). The organic phases were combined, washed with brine (50 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, hexane–EtOAc). (4aS*,7Z,11bS*)-4a-Methyl-7-(2-methylbenzylidene)-4a,6,7,11b-tetrahydrodibenzo[b,d]oxepin-2(1H)-one (3ca) Yellow oil; yield: 44.9 mg (68%). IR (KBr): 3059, 3018, 2973, 2925, 1682, 1599, 1487, 1371, 1266, 1237, 1168, 1131, 1116, 1099, 1029, 912, 890, 791, 738, 658 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.45 (dd, J = 7.4, 1.6 Hz, 1 H), 7.38 (td, J = 7.5, 1.4 Hz, 1 H), 7.34 (td, J = 7.4, 1.5 Hz, 1 H), 7.23–7.15 (m, 4 H), 7.00 (d, J = 7.4 Hz, 1 H), 6.71 (s, 1 H), 6.55 (d, J = 10.2 Hz, 1 H), 6.02 (d, J = 10.1 Hz, 1 H), 4.50 (s, 2 H), 3.46–3.33 (m, 1 H), 3.11 (dd, J = 17.7, 10.0 Hz, 1 H), 2.53 (dd, J = 17.7, 5.4 Hz, 1 H), 2.24 (s, 3 H), 1.37 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 199.0, 151.7, 142.1, 140.9, 137.0, 136.4, 135.5, 130.2, 129.3, 128.8, 128.4, 128.0, 128.0, 127.6, 125.9, 72.6, 62.7, 49.3, 40.0, 24.9, 20.0. ESI-MS: m/z = 353.1 [M + Na]+. HRMS (ESI): m/z [M + H]+ calcd for C23H23O2: 331.1693; found: 331.1690. (4aS*,7Z,11bS*)-4a-Ethyl-7-(2-methylbenzylidene)-4a,6,7,11b-tetrahydrodibenzo[b,d]oxepin-2(1H)-one (3fa) Light-yellow oil; yield: 48.8 mg (71%). IR (KBr): 2965, 2925, 2374, 2349, 2316, 1683, 1486, 1116, 1098, 765, 738, 672, 664 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.45 (dd, J = 7.4, 1.5 Hz, 1 H), 7.39–7.26 (m, 2 H), 7.24–7.16 (m, 4 H), 7.06 (d, J = 7.3 Hz, 1 H), 6.72 (s, 1 H), 6.67 (d, J = 10.3 Hz, 1 H), 6.15 (d, J = 10.3 Hz, 1 H), 4.48 (dd, J = 16.3, 1.8 Hz, 2 H), 3.52–3.38 (m, 1 H), 3.20 (dd, J = 17.7, 10.1 Hz, 1 H), 2.61 (dd, J = 17.7, 5.3 Hz, 1 H), 2.31 (s, 3 H), 1.94–1.71 (m, 2 H), 0.93 (t, J = 7.5 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 199.1, 150.3, 142.0, 141.0, 137.1, 136.4, 135.5, 130.1, 128.8, 128.4, 128.0, 127.9, 127.6, 125.9, 75.0, 62.5, 47.7, 40.0, 29.6, 20.0, 7.9. ESI-MS: m/z = 367.2 [M + Na]+. HRMS (ESI): m/z [M + Na]+ calcd for C24H24NaO2 367.1669; found: 367.1667. (4aS*,7Z,11bS*)-4a-Cyclohexyl-7-(2-methylbenzylidene)-4a,6,7,11b-tetrahydrodibenzo[b,d]oxepin-2(1H)-one (3ga) Light-yellow oil; yield: 51.1 mg (64%). IR (KBr): 3661, 3228, 2925, 2851, 2375, 2349, 2316, 2286, 1681, 1598, 1486, 1450, 1259, 1047, 814, 700, 672, 664 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.44 (dd, J = 7.5, 1.5 Hz, 1 H), 7.34 (td, J = 7.4, 1.4 Hz, 1 H), 7.30–7.25 (m, 2 H), 7.22–7.17 (m, 3 H), 7.11 (d, J = 6.7 Hz, 1 H), 6.89–6.80 (m, 2 H), 6.19 (d, J = 10.3 Hz, 1 H), 4.70–4.18 (m, 2 H), 3.64–3.51 (m, 1 H), 3.36 (dd, J = 17.1, 13.1 Hz, 1 H), 2.46 (dd, J = 17.1, 4.6 Hz, 1 H), 2.31 (s, 3 H), 1.86–1.60 (m, 7 H), 1.19–0.93 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 199.8, 148.5, 137.5, 136.4, 135.4, 131.5, 130.2, 130.0, 128.9, 128.7, 128.0, 127.8, 127.6, 125.9, 75.9, 62.3, 47.4, 40.9, 29.7, 28.1, 26.5, 26.3, 26.0, 25.7, 20.0. ESI-MS: m/z = 421.1 [M + Na]+. HRMS (ESI): m/z [M + Na]+ calcd for C28H30NaO2: 421.2138; found: 421.2135. (4aS*,7Z,11bS*)-4a-Benzyl-7-(2-methylbenzylidene)-4a,6,7,11b-tetrahydrodibenzo[b,d]oxepin-2(1H)-one(3ha) Light-yellow oil; yield: 35.7 mg (44%). IR (KBr): 3066, 3023, 2850, 2922,2850, 2389, 2374, 2348, 2316, 1682, 1486, 1453, 1383, 1095, 911, 766, 737, 701, 673, 664 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.52 (dd, J = 7.4, 1.6 Hz, 1 H), 7.38 (td, J = 7.5, 1.5 Hz, 1 H), 7.33 (td, J = 7.4, 1.6 Hz, 1 H), 7.30–7.26 (m, 1 H), 7.25–7.11 (m, 9 H), 6.74 (s, 1 H), 6.55 (d, J = 10.3 Hz, 1 H), 6.13 (d, J = 10.3 Hz, 1 H), 4.76–4.50 (m, 2 H), 3.60–3.48 (m, 1 H), 3.27–3.08 (m, 2 H), 2.90 (d, J = 13.9 Hz, 1 H), 2.59 (dd, J = 17.7, 5.6 Hz, 1 H), 2.31 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 198.8, 149.5, 142.1, 140.7, 136.7, 136.4, 135.7, 135.5, 130.7, 130.2, 129.4, 129.0, 128.8, 128.3, 128.2, 128.1, 128.0, 127.6, 126.9, 125.9, 75.3, 63.2, 47.0, 43.7, 40.3, 20.0. ESI-MS: m/z = 429.1 [M + Na]+. HRMS (ESI): m/z [M + Na]+ calcd for C29H26NaO2: 429.1825; found: 429.1822. (4aS*,7Z,11bS*)-7-(2-Methylbenzylidene)-4a-phenyl-4a,6,7,11b-tetrahydrodibenzo[b,d]oxepin-2(1H)-one (3ia) Light-yellow oil; yield: 54.1 mg (69%). IR (KBr): 2931, 2383, 2376, 2357, 1924, 1865, 1730, 1716, 1683, 1670, 1561, 1456, 1267, 1160, 1065, 800, 700, 668, 656 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.48 (dd, J = 7.6, 1.4 Hz, 1 H), 7.36–7.26 (m, 6 H), 7.24–7.16 (m, 5 H), 6.86 (d, J = 7.5 Hz, 1 H), 6.78 (s, 1 H), 6.75 (d, J = 10.2 Hz, 1 H), 6.27 (d, J = 10.1 Hz, 1 H), 4.62–4.38 (m, 2 H), 4.00–3.89 (m, 1 H), 3.35 (dd, J = 17.6, 11.0 Hz, 1 H), 2.68 (dd, J = 17.6, 5.4 Hz, 1 H), 2.32 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 198.9, 150.3, 142.6, 142.0, 140.8, 136.4, 136.4, 135.5, 130.2, 130.0, 129.5, 129.0, 128.7, 128.4, 127.9, 127.8, 127.6, 126.5, 125.9, 76.5, 63.3, 48.9, 40.6, 20.0. ESI-MS: m/z = 415.1 [M + Na]+. HRMS (ESI): m/z [M + Na]+ calcd for C28H24NaO2: 415.1669; found: 415.1660.