Nitric Acid Promoted Metal-Free Bromothiolation of Internal Alkynes with Hydrobromic Acid and Disulfides

Abstract

A novel, metal-free bromo-thiolation of internal alkynes with hydrobromic acid and disulfides has been developed. The reaction is promoted by commercial-grade nitric acid and is used to construct a series of unexplored β-bromoalkenyl sulfides in moderate to good yield. Most products were obtained with high stereoselectivity as syn-configured tetrasubstituted alkenes. Both sulfide groups of the disulfide reagent were used in this method.

Key words

bromo-thiolation - internal alkynes - hydrobromic acid - disulfides - nitric acid - β-bromoalkenyl sulfides - syn-configuration

Publication History

Received: 06 March 2022

Accepted after revision: 01 June 2022

Article published online:
20 July 2022

• References and Notes

• 1a Kondo T, Mitsudo T.-A. Chem. Rev. 2000; 100: 3205
• 1b Kuniyasu H, Kambe N. Chem. Lett. 2006; 35: 1320
• 1c Marcantoni E, Massaccesi M, Petrini M, Bartoli G, Bellucci MC, Bosco M, Sambri L. J. Org. Chem. 2000; 65: 4553
• 1d Li Q, Dong T, Liu X, Lei X. J. Am. Chem. Soc. 2013; 135: 4996
• 1e Itami K, Higashi S, Mineno M, Yoshida J.-I. Org. Lett. 2005; 7: 1219
• 2a Nieves I, Garrido M, Abad JL, Delgado A. Synlett 2010; 2950
• 2b Allan RD, Duke RK, Hambley TW, Johnston GA. R, Mewett KN, Quickert N, Tran HW. Aust. J. Chem. 1996; 49: 785
• 3a Yu G, Ou Y, Chen D, Huang Y, Yan Y, Chen Q. Synlett 2020; 31: 83
• 3b Mulina OM, Doronin MM, Kostyagina VA, Timofeev GP. Russ. J. Org. Chem. 2021; 57: 1302
• 3c Lu F, Xu J, Li H, Wang K, Ouyang D, Sun L, Huang M, Jiang J, Hu J, Alhumade H, Lu L, Lei A. Green Chem. 2021; 23: 7982
• 3d Li X, Zhang B, Yu Z, Zhang D, Shi H, Xu L, Du Y. Synthesis 2022; 54: 1375
• 3e Zhang D, Zhang J, Li X, Yu Z, Li Y, Sun F, Du Y. Synthesis 2022; 54: 411
• 4a Miyaura N, Suzuki A. Chem. Rev. 1995; 95: 2457
• 4b Negishi E.-I, Anastasia L. Chem. Rev. 2003; 103: 1979
• 4c Nicolaou KC, Bulger PG, Sarlah D. Angew. Chem. Int. Ed. 2005; 44: 4442
• 4d Johansson Seechurn CC. C, Kitching MO, Colacot TJ, Snieckus V. Angew. Chem. Int. Ed. 2012; 51: 5062
• 4e Wu W, Jiang H. Acc. Chem. Res. 2014; 47: 2483
• 5 Calo V, Scorrano G, Modena G. J. Org. Chem. 1969; 34: 2020
• 6a Lucchini V, Modena G, Valle G, Capozzi G. J. Org. Chem. 1981; 46: 4720
• 6b Capozzi G, Caristi C, Lucchini V, Modena G. J. Chem. Soc., Perkin Trans. 1 1982; 2197
• 6c Capozzi G, Romeo G, Lucchini V, Modena G. J. Chem. Soc., Perkin Trans. 1 1983; 831
• 6d Iwasaki M, Fujii T, Nakajima K, Nishihara Y. Angew. Chem. Int. Ed. 2014; 53: 13880
• 6e Iwasaki M, Fujii T, Yamamoto A, Nakajima K, Nishihara Y. Chem. Asian J. 2014; 9: 58
• 6f Surineni N, Buragohain P, Saikia B, Barua NC, Baruah RK. Tetrahedron Lett. 2015; 56: 6965
• 6g Liang S, Jiang L, Yi W.-B, Wei J. Org. Lett. 2018; 20: 7024
• 7a Benati L, Montevecchi PC, Spagnolo P. Tetrahedron 1993; 49: 5365
• 7b Zyk NV, Beloglazkina EK, Belova MA, Zefirov NS. Russ. Chem. Bull. 2000; 49: 1846
• 7c Taniguchi N. Synlett 2008; 849
• 7d Taniguchi N. Tetrahedron 2009; 65: 2782
• 7e Bao Y, Zhong L, Hou Q, Zhou Q, Yang F. Chin. J. Chem. 2018; 36: 1063
• 7f Liu S, Zheng X, Xu B. Org. Chem. Front. 2020; 7: 1690
• 8a Lin Y.-M, Lu G.-P, Cai C, Yi W.-B. Org. Lett. 2015; 17: 3310
• 8b Bao Y, Yang X, Zhou Q, Yang F. Org. Lett. 2018; 20: 1966

For alkynes thiolation see:
• 9a Truce WE, Tichenor GJ. W. J. Org. Chem. 1972; 37: 2391
• 9b Ogawa A, Ikeda T, Kimura K, Hirao T. J. Am. Chem. Soc. 1999; 121: 5108
• 9c Taniguchi T, Fujii T, Idota A, Ishibashi H. Org. Lett. 2009; 11: 3298
• 9d Shiu H.-Y, Chan T.-C, Ho C.-M, Liu Y, Wong M.-K, Che C.-M. Chem. Eur. J. 2009; 15: 3839
• 9e Jim CK. W, Qin A, Lam JW. Y, Mahtab F, Yu Y, Tang BZ. Adv. Funct. Mater. 2010; 20: 1319
• 9f Banerjee B, Litvinov DN, Kang J, Bettale JD, Castle SL. Org. Lett. 2010; 12: 2650
• 9g Jin Z, Xu B, Hammond GB. Eur. J. Org. Chem. 2010; 168
• 9h Minozzi M, Monesi A, Nanni D, Spagnolo P, Marchetti N, Massi A. J. Org. Chem. 2011; 76: 450
• 9i Nurhanna Riduan S, Ying JY, Zhang Y. Org. Lett. 2012; 14: 1780
• 9j Singh R, Raghuvanshi DS, Singh KN. Org. Lett. 2013; 15: 4202
• 9k Truong VX, Dove AP. Angew. Chem. Int. Ed. 2013; 52: 4132
• 9l Chen J, Chen S, Xu X, Tang Z, Au C.-T, Qiu R. J. Org. Chem. 2016; 81: 3246
• 9m Ye Y, Huang C, Zhao C, Ren B, Xiao H, Li X. Synth. Commun. 2016; 46: 1634
• 9n Pramanik M, Choudhuri K, Chakraborty S, Ghosh A, Mal P. Chem. Commun. 2020; 56: 2991
• 10 Synthesis of 3; General procedure: Alkyne 1 (0.40 mmol) and disulfide 2 (0.22 mmol) were added into a 25 mL oven-dried flask and dissolved in dichloromethane (4 mL), then hydrobromic acid (40% aqueous, 10 equiv) mixed with nitric acid (65% aqueous, 0.5 equiv) was added dropwise. The solution was then stirred for 8 h at 40 °C. After the reaction was finished, the reaction mixture was cooled to room temperature, diluted in diethyl ether (15 mL), and washed with brine (2 × 15 mL). The aqueous phase was re-extracted with diethyl ether (15 mL). The combined organic extracts were dried over Na₂SO₄ and concentrated in vacuum and the resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to afford product 3. Spectroscopic data of (Z)-(2-bromo-1,2-diphenylvinyl)(p-tolyl)-sulfane (3a): Yield: 136.7 mg (91%); white solid; mp 105.0–106.1 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.56 (d, J = 8.0 Hz, 2 H), 7.34–7.43 (m, 5 H), 7.17–7.27 (m, 3 H), 7.00 (d, J = 8.0 Hz, 2 H), 6.88 (d, J = 8.0 Hz, 2 H), 2.19 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 140.7, 139.7, 137.2, 136.4, 131.9, 130.1, 129.7, 129.3, 129.2, 128.6, 128.2, 127.8, 127.7, 121.5, 21.0. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₁H₁₈ ^78.9183BrS: 381.0307; found: 381.0298. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₁H₁₈ ^80.9163BrS: 383.0287; found: 383.0273. See the Supporting Information for 3a–s.
• 11 Song M, Hu Q, Li Z.-Y, Sun X, Yang K. Chin. Chem. Lett. 2022; 33: 4269
• 12a Dénès F, Pichowicz M, Povie G, Renaud P. Chem. Rev. 2014; 114: 2587
• 12b Zhou S.-F, Pan X.-Q, Zhou Z.-H, Shoberu A, Zhang P.-Z, Zou J.-P. J. Org. Chem. 2015; 80: 5348
• 12c Lin Y.-M, Lu G.-P, Wang G.-X, Yi W.-B. J. Org. Chem. 2017; 82: 382
• 12d Fındık V, Varinca BT, Degirmenci I, Sag Erdem S. J. Phys. Chem. A 2021; 125: 3556
• 13 Ratcliffe CT, Shreeve JN. M, Wynne KJ. Nitrosyl Halides, inInorganic Syntheses, vol. 11. Jolly WL. Wiley; Weinheim: 1968: 194
• 14a Kroll FE. K, Morphy R, Rees D, Gani D. Tetrahedron Lett. 1997; 38: 8573
• 14b Schlosser KM, Krasutsky AP, Hamilton HW, Reed JE, Sexton K. Org. Lett. 2004; 6: 819
• 14c Yadav JS, Subba Reddy BV, Jain R, Baishya G. Tetrahedron Lett. 2008; 49: 3015