Synlett, Table of Contents Synlett 2015; 26(19): 2702-2706DOI: 10.1055/s-0035-1560265 letter © Georg Thieme Verlag Stuttgart · New York Stereoselective Synthesis of Trisubstituted Vinyl Bromides by Addition of Alkynes to Oxocarbenium Ions Andrew R. Ehle Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA Email: mpwatson@udel.edu , Melissa G. Morris Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA Email: mpwatson@udel.edu , Bryan D. Klebon Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA Email: mpwatson@udel.edu , Glenn P. A. Yap Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA Email: mpwatson@udel.edu , Mary P. Watson* Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA Email: mpwatson@udel.edu › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract We have developed an efficient method for the synthesis of trisubstituted (E)-vinyl bromides by a Friedel–Crafts-type addition of alkynes to oxocarbenium ions formed in situ from acetals. The success of this reaction relies on the identification of magnesium bromide etherate as both a Lewis-acid promoter and a source of bromide. This reaction employs simple inexpensive starting materials and proceeds under mild conditions to allow the preparation of a range of vinyl bromide products in high yields and high E/Z selectivities. Furthermore, the vinyl bromides also contain an allylic ether functional group. Both the vinyl bromide and allylic ether groups are effective handles for the elaboration of these useful synthetic intermediates. Key words Key wordshaloalkenes - stereoselectivity - oxocarbenium ions - Friedel–Crafts reactions - alkynes - vinylations Full Text References References and Notes 1a Xu S, Kamada H, Kim EH, Oda A, Negishi E.-i In Metal-Catalyzed Cross-Coupling Reactions and More . Vol. 1. de Meijiere A, Brase S, Oestreich M. Chap. 3 Wiley-VCH; Weinheim: 2014: 133 1b Chemla F, Ferreira F, Jackowski O, Micouin L, Perez-Luna A In Metal-Catalyzed Cross-Coupling Reactions and More . Vol. 1. de Meijiere A, Brase S, Oestreich M. Chap. 4 Wiley-VCH; Weinheim: 2014: 279 2a Creton I, Marek I, Normant JF. Synthesis 1996; 1499 2b Fallis AG, Forgione P. Tetrahedron 2001; 57: 5899 2c Knochel P In Comprehensive Organic Synthesis . Vol. 4. Trost BM, Fleming I. Pergamon; Oxford: 1991: 865 2d Lim DS. W, Anderson EA. Synthesis 2012; 44: 983 2e Lipshutz BH, Butler T, Lower A. J. Am. Chem. Soc. 2006; 128: 15396 2f Marek I, Minko Y In Metal-Catalyzed Cross-Coupling Reactions and More . Vol. 2. de Meijiere A, Brase S, Oestreich M. Chap. 10 Wiley-VCH; Weinheim: 2014: 763 2g Murakami K, Ohmiya H, Yorimitsu H, Oshima K. Org. Lett. 2007; 9: 1569 2h Stüdemann T, Knochel P. Angew. Chem. Int. Ed. 1997; 36: 93 2i Zhang D, Ready JM. J. Am. Chem. Soc. 2006; 128: 15050 3 Tan Z, Negishi E.-i. Angew. Chem. Int. Ed. 2006; 45: 762 4a Nunes C, Steffens D, Monteiro A. Synlett 2007; 103 4b Kutsumura N, Niwa K, Saito T. Org. Lett. 2010; 12: 3316 4c Li W, Li J, Wan Z.-K, Wu J, Massefski W. Org. Lett. 2007; 9: 4607 5a Kuhl N, Schröder N, Glorius F. Org. Lett. 2013; 15: 3860 5b Jyothi D, HariPrasad S. Synlett 2009; 2309 5c Kim K.-M, Park I.-H. Synthesis 2004; 2641 For other methods, see: 6a Stanforth SP In Comprehensive Functional Group Transformations II . Vol. 2. Katritzky AR, Taylor RJ. K. Elsevier; Oxford: 2005: 561 6b Huang X, Fu W.-J. Synthesis 2006; 1016 6c Hodgson DM, Arif T. J. Am. Chem. Soc. 2008; 130: 16500 6d Imazaki Y, Shirakawa E, Ueno R, Hayashi T. J. Am. Chem. Soc. 2012; 134: 14760 6e Pan J, Wang X, Zhang Y, Buchwald SL. Org. Lett. 2011; 13: 4974 7a Maity P, Srinivas HD, Watson MP. J. Am. Chem. Soc. 2011; 133: 17142 7b Srinivas HD, Maity P, Yap GP. A, Watson MP. J. Org. Chem. 2015; 80: 4003 MgBr2 has been previously employed as both a Lewis acid and as a source of bromide; see: 8a Wang Y, Lam HW. J. Org. Chem. 2009; 74: 1353 8b Wei H.-X, Jasoni RL, Hu J, Li G, Paré PW. Tetrahedron 2004; 60: 10233 For three-component couplings of alkynes, metal halides, and nonoxocarbenium, benzylic carbocations, see: 9a Liu Z.-Q, Wang J, Han J, Zhao Y, Zhou B. Tetrahedron Lett. 2009; 50: 1240 9b Marcuzzi F, Melloni G, Modena G. J. Org. Chem. 1979; 44: 3022 9c Yao M.-L, Quick TR, Wu Z, Quinn MP, Kabalka GW. Org. Lett. 2009; 11: 2647 10 For a three-component coupling of alkynes, metal halides, and nonbenzylic oxocarbenium ions derived from glycals, see: Tatina M, Kusunuru AK, Yousuf SK, Mukherjee D. Chem. Commun. 2013; 49: 11409 For examples of intramolecular Prins cyclizations of alkynes with trapping by a metal halide, see: 11a Melany ML, Lock GA, Thompson DW. J. Org. Chem. 1985; 50: 3925 11b Kim Y.-H, Lee K.-Y, Oh C.-Y, Yang J.-G, Ham W.-H. Tetrahedron Lett. 2002; 43: 837 11c Miranda PO, Díaz DD, Padrón JI, Bermejo J, Martín VS. Org. Lett. 2003; 5: 1979 11d Takami K, Yorimitsu H, Shinokubo H, Matsubara S, Oshima K. Synlett 2001; 293 11e Xu T, Yu Z, Wang L. Org. Lett. 2009; 11: 2113 For examples of divinylation of benzylic oxocarbenium ions, see: 12a Kabalka GW, Wu Z, Ju Y. Org. Lett. 2002; 4: 3415 12b Kabalka GW, Yao M.-L, Borella S, Wu Z, Ju Y.-H, Quick T. J. Org. Chem. 2008; 73: 2668 12c Miranda PO, Díaz DD, Padrón JI, Ramírez MA, Martín VS. J. Org. Chem. 2005; 70: 57 12d Shimizu M, Okura K, Arai T, Hachiya I. Chem. Lett. 2010; 39: 1052 12e Shimizu M, Toyoda T, Baba T. Synlett 2005; 2516 12f Yadav JS, Reddy BV. S, Eeshwaraiah B, Gupta MK, Biswas SK. Tetrahedron Lett. 2005; 46: 1161 13a Price CC, Pappalardo JA. J. Am. Chem. Soc. 1950; 72: 2613 13b Martens H, Janssens F, Hoornaert G. Tetrahedron 1975; 31: 177 13c Kokubo K, Matsumasa K, Miura M, Nomura M. J. Org. Chem. 1996; 61: 6941 13d Zhou H, Zeng C, Ren L, Liao W, Huang X. Synlett 2006; 3504 13e Iwai T, Fujihara T, Terao J, Tsuji Y. J. Am. Chem. Soc. 2009; 131: 6668 14a Zi W, Toste FD. J. Am. Chem. Soc. 2013; 135: 12600 14b Zhang M, Wang Y, Yang Y, Hu X. Adv. Synth. Catal. 2012; 354: 981 14c Schultz DM, Babij NR, Wolfe JP. Adv. Synth. Catal. 2012; 354: 3451 15 Reactions were conducted in 1-dram vials capped with Teflon-lined caps and heated by using aluminum heating blocks deep enough to enclose the glass of the vial completely. 16 1-Bromo-4-[(2E)-3-bromo-1-methoxy-3-phenylprop-2-en-1-yl]benzene (3Ba); Typical Procedure In a N2-filled glovebox, MgBr2·OEt2 (30.9 mg, 0.12 mmol, 1.2 equiv) was weighed into a 1-dram vial equipped with a magnetic stirrer bar. Na2CO3 (13.3 mg, 0.10 mmol, 1.0 equiv), acetal 1B (23.1 mg, 0.10 mmol, 1.0 equiv), alkyne 2a (15.3 mg, 0.30 mmol, 1.5 equiv), and CHCl3 (0.5 mL) were successively added. The vial was capped with a Teflon-lined cap and heated in an aluminum heating block at 60 °C with vigorous stirring (700 rpm) for 24 h. The vial was removed from the glovebox, and the mixture was filtered through a plug of silica gel that was rinsed with Et2O to remove insoluble salts. A minimal amount of silica gel was added to the filtrate. The mixture was then concentrated and loaded directly onto a silica gel column and purified by chromatography (5% Et2O–hexanes) to give a yellow solid; yield: 34.8 mg (91%) (run 1); 34.2 mg (90%) (run 2); mp 73–82 °C. 1H NMR analysis showed that 3Ba was isolated as a 13:1 ratio of olefin isomers; FTIR (thin film): 1010, 1071, 1443, 1485, 2820, 2902, 2925 cm–1. 1H NMR (400 MHz, CDCl3): δ (major isomer) = 7.54–7.49 (m, 2 H), 7.46–7.34 (m, 5 H), 7.18 (d, J = 8.3 Hz, 2 H), 6.33 (d, J = 9.6 Hz, 1 H), 4.58 (d, J = 9.6 Hz, 1 H), 3.26 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ (major isomer) =139.1, 138.1, 133.8, 131.8, 129.1, 128.7, 128.5, 128.4, 125.0, 121.9, 80.0, 56.0. HRMS (EI+): m/z [M+] calcd for C16H14Br2: 365.9554; found: 365.9550. 1,1′-[(1E)-1-Bromo-3-methoxyprop-1-ene-1,3-diyl]dibenzene (3Aa) FTIR (thin film): 700, 768, 1088, 1099, 1444, 2819, 2889, 3029, 3060 cm–1. 1H NMR (400 MHz, CDCl3): δ (major isomer) = 7.47–7.26 (m, 10 H), 6.42 (d, J = 9.6 Hz, 1 H), 4.63 (d, J = 9.6 Hz, 1 H), 3.27 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ (major isomer) = 140.0, 138.3, 134.3, 129.0, 128.8, 128.7, 128.4, 128.1, 126.7, 124.5, 80.6, 56.0. HRMS (EI+): m/z [M+] calcd for C16H15O: 223.1119; found: 223.1123. {3-[(2E)-3-Bromo-1-methoxy-3-phenylprop-2-en-1-yl]phenoxy}(tert-butyl)dimethylsilane (3Ea) FTIR (thin film): 699, 782, 1257, 1277, 1444, 1600, 2857, 2895, 2929, 3060 cm–1. 1H NMR (400 MHz, CDCl3): δ (major isomer) = 7.39 (d, J = 3.2 Hz, 5 H), 7.21 (t, J = 7.7 Hz, 1 H), 6.86 (d, J = 7.6 Hz, 1 H), 6.77 (m, 2 H), 6.35 (d, J = 9.6 Hz, 1 H), 4.51 (d, J = 9.6 Hz, 1 H), 3.22 (s, 3 H), 0.98 (s, 9 H), 0.21 (s, 6 H). 13C NMR (101 MHz, CDCl3): δ (major isomer) = 155.9, 141.5, 138.2, 134.3, 129.7, 129.0, 128.8, 128.3, 128.2, 124.4, 119.7, 118.4, 80.5, 56.1, 25.7, 18.2, –4.3. HRMS (EI+): m/z [M+] calcd for C15H26O3Si: 282.1651; found: 282.1655. 17 Crystallographic data for compound 3Ba have been deposited with the accession numbers CCDC 973170, and can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk; Web site: www.ccdc.cam.ac.uk/conts/retrieving.html. 18 Antiperiplanar addition of halide and a cation across an alkyne has been proposed, particularly for reactions conducted at low temperatures; see: Yeh M.-CP, Fang C.-W, Lin H.-H. Org. Lett. 2012; 14: 1830 19 Kuznetsov A, Gevorgyan V. Org. Lett. 2012; 14: 914 20 Wang J, Zhang L, Jing Y, Huang W, Zhou X. Tetrahedron Lett. 2009; 50: 4978 21a Karaguni I.-M, Glüsenkamp K.-H, Langerak A, Geisen C, Ullrich V, Winde G, Möröy T, Müller O. Bioorg. Med. Chem. Lett. 2002; 12: 709 21b Kolanos R, Siripurapu U, Pullagurla M, Riaz M, Setola V, Roth BL, Dukat M, Glennon RA. Bioorg. Med. Chem. Lett. 2005; 15: 1987 Supplementary Material Supplementary Material Supporting Information
