Formation of Seven-Membered Rings by Ring-Closing Metathesis of Vinyl Bromides

Abstract

A Grubbs II catalyst mediated ring-closing metathesis (RCM) of monobrominated dienes is reported to proceed in moderate to good yields (40–80%) where the linking chain contains five atoms, leading to carbocyclic and heterocyclic seven-membered bromoolefins. Notably, RCM to form five-, six-, or eight-membered bromoolefins was unsuccessful, with the exception of one example where RCM afforded diethyl 3-bromocyclohex-3-ene-1,1-dicarboxylate. In this case, a bromomethyl-substituted cyclohexene was obtained as a byproduct. The utility of selected bromoolefin RCM products was demonstrated through their participation in Suzuki–Miyaura reactions. Vinylic halide exchange (Br → Cl) was noted as a side reaction under RCM conditions.

Key words

ring-closing metathesis - Grubbs catalyst - vinylic bromides - carbocycles - heterocycles

Publication History

Received: 04 March 2022

Accepted after revision: 06 May 2022

Accepted Manuscript online:
06 May 2022

Article published online:
07 June 2022

• References and Notes


For selected reviews on ring-closing metathesis see:
• 1a Ogba OM, Warner NC, O’Leary DJ, Grubbs RH. Chem. Soc. Rev. 2018; 47: 4510
• 1b Cheng-Sánchez I, Sarabia F. Synthesis 2018; 50: 3749
• 1c Yu M, Lou S, Gonzalez-Bobes F. Org. Proc. Res. Dev. 2018; 22: 918
• 1d Handbook of Metathesis . 2nd, ed.; Vol. 1, Ed. Grubbs R. H., Wenzel A. G.; Wiley-VCH; Weinheim: 2015
• 1e Vougioukalakis GC, Grubbs RH. Chem. Rev. 2010; 110: 1746
• 1f Brown RC. D, Satcharoen V. Heterocycles 2006; 70: 705
• 1g Arisawa M, Nishida A, Nakagawa M. J. Organomet. Chem. 2006; 691: 5109
• 1h Conrad JC, Fogg DE. Curr. Org. Chem. 2006; 10: 185
• 1i Deiters A, Martin SF. Chem. Rev. 2004; 104: 2199

For selected reviews on transition-metal-catalyzed cross-coupling reactions see:
• 2a Miyaura N, Suzuki A. Chem. Rev. 1995; 95: 2457
• 2b Nicolaou KC, Bulger PG, Sarlah D. Angew. Chem. Int. Ed. 2005; 44: 4442
• 2c Seechurn CC. C. J, Kitching MO, Colacot TJ, Snieckus V. Angew. Chem. Int. Ed. 2012; 51: 5062
• 2d Suzuki A. Angew. Chem. Int. Ed. 2011; 50: 6722
• 3a Macnaughtan ML, Gary JB, Gerlach DL, Johnson MJ. A, Kampf JW. Organometallics 2009; 28: 2880
• 3b Macnaughtan ML, Johnson MJ. A, Kampf JW. J. Am. Chem. Soc. 2007; 129: 7708
• 4a Kirkland TA, Grubbs RH. J. Org. Chem. 1997; 62: 7310
• 4b Chao WC, Weinreb SM. Org. Lett. 2003; 5: 2505
• 5 For a more recent attempted six-membered bromo-olefin RCM, see: Heinrich CF, Durand D, Starck J, Michelet V. Org. Lett. 2020; 22: 7064
• 6 Gatti M, Drinkel E, Wu L, Pusterla I, Gaggia F, Dorta R. J. Am. Chem. Soc. 2010; 132: 15179
• 7 Salim SS, Bellingham RK, Satcharoen V, Brown RC. D. Org. Lett. 2003; 5: 3403

For examples of biologically active sulfamides, see:
• 8a Mastrolorenzo A, Rusconi S, Scozzafava A, Supuran CT. Expert Opin. Ther. Pat. 2006; 16: 1067
• 8b Winum JY, Scozzafava A, Montero JL, Supuran CT. Expert Opin. Ther. Pat. 2006; 16: 27
• 8c Winum J.-Y, Scozzafava A, Montero J.-L, Supuran CT. Med. Res. Rev. 2006; 26: 767
• 8d Reitz AB, Smith GR, Parker MH. Expert Opin. Ther. Pat. 2009; 19: 1449
• 9a Dougherty JM, Probst DA, Robinson RE, Moore JD, Klein TA, Snelgrove KA, Hanson PR. Tetrahedron 2000; 56: 9781
• 9b Jun JH, Dougherty JM, del Sol Jimenez M, Hanson PR. Tetrahedron 2003; 59: 8901
• 10a Brown RC. D, Castro JL, Moriggi J.-D. Tetrahedron Lett. 2000; 41: 3681
• 10b Moriggi J.-D, Brown LJ, Castro JL, Brown RC. D. Org. Biomol. Chem. 2004; 2: 835
• 11a Salim SS, Bellingham RK, Brown RC. D. Eur. J. Org. Chem. 2004; 800
• 11b Hill-Cousins JT, Salim SS, Bakar YM, Bellingham RK, Light ME, Brown RC. D. Tetrahedron 2014; 70: 3700
• 12 Dewynter G, Aouf N, Criton M, Montero J.-L. Tetrahedron 1993; 49: 65
• 13 See the Supporting Information for full details of the synthesis of RCM substrates 2 and 5.
• 14 Miller SJ, Kim S.-H, Chen Z.-R, Grubbs RH. J. Am. Chem. Soc. 1995; 117: 2108
• 15a Basato M, Tubaro C, Biffis A, Bonato M, Buscemi G, Lighezzolo F, Lunardi P, Vianini C, Benetollo F, Del Zotto A. Chem. Eur. J. 2009; 15: 1516
• 15b Maas G. Chem. Soc. Rev. 2004; 33: 183
• 15c Simal F, Demonceau A, Noels AF, Knowles DR. T, O'Leary S, Maitlis PM, Gusev O. J. Organomet. Chem. 1998; 558: 163
• 16 Halide exchange has previously been observed in reactions of ruthenium alkylidene catalysts with vinyl bromide; see ref. 3.
• 17a Schmidt B. Angew. Chem. Int. Ed. 2003; 42: 4996
• 17b Sémeril D, Bruneau C, Dixneuf PH. Helv. Chim. Acta 2001; 84: 3335
• 17c Çetinkaya B, Demir S, Özdemir I, Toupet L, Sémeril D, Bruneau C, Dixneuf PH. New J. Chem. 2001; 25: 519
• 17d Yamamoto Y, Ohkoshi N, Kameda M, Itoh K. J. Org. Chem. 1999; 64: 2178
• 17e Yamamoto Y, Nakagai Y, Ohkoshi N, Itoh K. J. Am. Chem. Soc. 2001; 123: 6372
• 18 Peppers BP, Diver ST. J. Am. Chem. Soc. 2004; 126: 9524
• 19 2,7-Dibenzyl-4-bromo-2,3,6,7-tetrahydro-1,2,7-thiadiazepine 1,1-Dioxide (2a); Typical Procedure A solution of GII (6.0 mg, 7.0 μmol) in benzene (2 mL) was added to a solution of compound 1a (31.2 mg, 0.07 mmol) in benzene (5 mL), and the mixture was stirred and degassed for 30 s then refluxed for 18 h. A second portion of the GII (3.0 mg, 3.5 μmol) dissolved in benzene (1 mL) was then added and heating was continued for 18 h. The solution was then concentrated under reduced pressure to afford the crude product as a black oil. Purification by column chromatography [silica gel, EtOAc/hexane (2:98)] gave a white solid; yield: 26 mg (90%); mp 106–108 °C. IR (ATR): 3030, 2919, 1507, 1456, 1359 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.40–7.24 (m, 10 H), 6.24 (t, J = 5.7 Hz, 1 H), 4.52 (s, 2 H), 4.45 (s, 2 H), 4.03 (s, 2 H), 3.60 (d, J = 5.7 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 135.6 (C), 135.3 (C), 130.5 (CH), 128.8 (CH), 128.7 (CH), 128.6 (CH), 128.3 (CH), 128.2 (CH), 122.7 (C), 52.4 (CH₂), 52.1 (CH₂), 44.1 (CH₂). LRMS (ES⁺, MeCN): m/z (%): 431 (100) and 429 (100) [M + Na]⁺. HRMS (ES⁺): m/z [M + Na]⁺ calcd for C₁₈H₁₉ ⁷⁹BrN₂NaO₂S: 429.0242; found: 429.0239.