Scandium Triflate Catalyzed Nazarov Cyclization of Arylvinyl Epoxides Derived from Alkoxides and Chloro(aryl)carbenes: A Facile Access to Resveratrol-Derived Natural Products

Abstract

The reaction of arylvinyl alkoxides with chloro(aryl)carbenes provided the corresponding arylvinyl epoxides that underwent Nazarov cyclization in a catalytic amount of scandium triflate, providing easy access to several highly substituted indenes, including some resveratrol-derived natural products.

Key words

Nazarov cyclization - arylvinyl alcohol - arylvinyl epoxides - indenes - resveratrol-derived natural products - scandium triflate - chloro(aryl)carbenes

Publication History

Received: 14 September 2020

Accepted after revision: 15 October 2020

Article published online:
13 November 2020

• References and Notes

• 1 Keylor MH, Matsuura BS, Stephenson R. J. Chem. Rev. 2015; 115: 8976
• 2 He S, Yan X. Curr. Med. Chem. 2013; 20: 1005
• 3a Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW. W, Fong HH. S, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM. Science 1997; 275: 218
• 3b Xiao Q, Zhu W, Feng W, Lee SS, Leung AW, Shen J, Gao L, Xu C. Front. Pharmacol. 2019; 9: 1534
• 4a Banks AS, Kon N, Knight C, Matsumoto M, Gutiérrez-Juárez R, Rossetti L, Gu W, Accili D. Cell Metab. 2008; 8: 333
• 4b Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek MR, Elliott PJ, Westphal CH. Nature 2007; 450: 712
• 5 Frankel EN, Waterhouse AL, Kinsella JE. Lancet 1993; 341: 1103
• 6 Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Nature 2006; 444: 337
• 7 Nonomura S, Kanagawa H, Makimoto A. Yakugaku Zasshi 1963; 83: 988
• 8a Langcake P, Pryce RJ. Physiol. Plant Pathol. 1976; 9: 77
• 8b Langcake P, McCarthy WV. Vitis 1979; 18: 244
• 9 Xiao K, Zhang H.-J, Xuan L.-J, Zhang J, Xu Y.-M, Bai D.-L. In Studies in Natural Products Chemistry, Bioactive Natural Products, Part N, Vol. 34 . Atta-ur-Rahman, Eds.: Elsevier; New York: 2008: 453-646
• 10a Aguirre JM, Alesso EN, Iglesias GY. M. J. Chem. Soc., Perkin Trans. 1 1999; 1353
• 10b Li X.-C, Ferreira D. Tetrahedron 2003; 59: 1501
• 10c Takaya Y, Terashima K, Ito J, He Y.-H, Takeoka M, Yamaguchi N, Niwa M. Tetrahedron 2005; 61: 10285
• 10d Langcake P, Pryce RJ. J. Chem. Soc., Chem. Commun. 1977; 208
• 10e Sako M, Hosokawa H, Ito T, Iinuma M. J. Org. Chem. 2004; 69: 2598
• 10f Wenling L, Li H, Li Y, Hou Z. Angew. Chem. Int. Ed. 2006; 45: 7609
• 11a Klotter F, Studer A. Angew. Chem. Int. Ed. 2014; 53: 2473
• 11b Li W, Yang S, Lv T, Yang Y. Org. Biomol. Chem. 2014; 12: 2273
• 11c Zhong C, Zhu J, Chang J, Sun X. Tetrahedron Lett. 2011; 52: 2815
• 11d Snyder SA, Brill ZG. Org. Lett. 2011; 13: 5524
• 11e Keffrey JL, Sarpong R. Org. Lett. 2009; 11: 5450
• 11f Snyder SA, Breazzano SP, Ross AG, Lin Y, Zografos AL. J. Am. Chem. Soc. 2009; 131: 1753
• 11g Jeffrey JL, Sarpong R. Tetrahedron Lett. 2009; 50: 1969
• 11h Snyder SA, Zografos L, Lin Y. Angew. Chem. Int. Ed. 2007; 46: 8186
• 12a Mahesh SK, Nanubolu JB, Sudhakar G. J. Org. Chem. 2019; 84: 7815
• 12b Sudhakar G, Mahesh SK, Vemulapalli SP. B, Nanubolu JB. Org. Lett. 2017; 19: 4500
• 12c Sudhakar G, Raghavaiah J, Mahesh G, Singarapu KK. Org. Biomol. Chem. 2016; 14: 2866
• 12d Sudhakar G, Reddy KJ, Nanubolu JB. Org. Biomol. Chem. 2015; 13: 8875
• 12e Sudhakar G, Satish K. Chem. Eur. J. 2015; 21: 6475
• 13a Zhao Y, Kang J, Park C.-M, Bagdon PE, Peng B, Xian M. Org. Lett. 2014; 16: 4536
• 13b Hoffmann RW, Brumm K, Bewersdorf M, Mikolaiski W, Kusche A. Chem. Ber. 1992; 125: 2741
• 14 Harada T, Akiba E, Oku A. J. Am. Chem. Soc. 1983; 105: 2771
• 15a Chen J, Lin J.-H, Xiao J.-C. Org. Lett. 2018; 20: 3061
• 15b Kaballa GW, Wu Z. Tetrahedron Lett. 2000; 41: 579
• 15c Han GY, Han PF, Perkins J, McBay HC. J. Org. Chem. 1981; 46: 4695
• 16 Typical Procedure for the Synthesis of 2 To a mixed suspension of potassium hydride (2.5 equiv) and potassium tert-butoxide (2.5 equiv) in THF was added a THF (2.5 mL) solution of 8 (1.0 equiv), and the mixture was stirred at 0 °C under an argon atmosphere for 5 min after that was added a THF (2.5 mL) solution of benzal chloride (2.5 equiv). After completing the starting material, the reaction was quenched with aq NH₄Cl and extracted with EtOAc. The organic layer was washed with aq NaCl, dried over Na₂SO₄, and concentrated under reduced pressure. The crude product was purified by using basic Al₂O₃ column chromatography to isolate 2. Characterization Data of 2a 123.5 mg, 90% yield, dr 1:1 based on ¹H NMR spectroscopy. ¹H NMR (500 MHz, CDCl₃): δ = 7.25–7.14 (m, 5 H), 6.41 (d, J = 2.3 Hz, 2 H), 6.22 (t, J = 2.3 Hz, 1 H), 4.37 (s, 1 H), 3.66 (s, 6 H), 2.08 (s, 3 H), 1.76 (s, 3 H), 1.74 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 160.0, 139.1, 135.3, 128.9, 128.7, 127.8, 127.5, 126.7, 105.8, 99.2, 69.6, 68.3, 55.2, 22.5, 20.3, 15.0. IR (neat): ν_max = 2927, 1594, 1454, 1425, 1345, 1202, 1152, 1063, 842, 737, 697. HRMS (ESI): m/z calcd for C₂₁H₂₅O₃ [M + H]: 325.1798; found: 325.1791. Typical Procedure for the Synthesis of 3 To a stirred solution of above-obtained 2 (1.0 equiv) in dry CH₂Cl₂ (3.7 mL) was added Sc(OTf)₃ (0.1 equiv) at 0 °C, and stirring was continued at the same temperature. After completing the starting material, the reaction was quenched with water or saturated aq NaHCO₃ solution and extracted with CH₂Cl₂. The organic layer was washed with aq NaCl solution, dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The crude product was purified by using silica gel column chromatography (EtOAc/hexanes) to give 3. Characterization Data of 3a 118 mg, 96% yield. ¹H NMR (400 MHz, CDCl₃): δ = 7.44 (d, J = 7.6 Hz, 2 H), 7.3 (t, J = 7.6 Hz, 2 H), 7.2 (t, J = 7.6 Hz, 1 H), 6.34 (d, J = 2.0 Hz, 1 H), 6.15 (d, J = 2.0 Hz, 1 H), 5.93 (s, 1 H), 3.73 (s, 3 H), 3.58 (s, 3 H), 2.1 (br s, 1 H), 1.92 (s, 3 H), 1.32 (s, 3 H), 1.30 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 159.9, 155.7, 153.2, 143.2, 142.4, 134.2, 131.5, 128.3, 126.9, 125.7, 98.5, 95.2, 69.4, 55.4, 55.1, 50.3, 21.8, 21.2, 9.9. IR (neat): ν_max = 3395, 2956, 2925, 2855, 1595, 1454, 1349, 1203, 1152, 1090, 699. HRMS (ESI): m/z calcd for C₂₁H₂₃O₂ [M – OH]: 307.1698; found: 307.1692.
• 17 Majetich G, Shimkus JM. J. Nat. Prod. 2010; 73: 284