Synlett
DOI: 10.1055/s-0036-1590907
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Internal Alkynes through an Effective Tandem ­Elimination–Hydrodebromination–Cross-Coupling of gem-­Dibromoalkenes with Halobenzenes

Yuan Jia, Ning Zhonga, Zinan Kanga, Guobing Yan*b, Ming Zhao*a
  • aSchool of Chemical Engineering, China University of Mining and Technology, No. 1 Daxue Road, Xuzhou 221116, P. R. of China
  • bDepartment of Chemistry, Lishui University, Lishui 323000, P. R. of China   Email: ming815zhao@aliyun.com   Email: gbyan@lsu.edu.cn
This work was supported by Fundamental Research Funds for the Central Universities (No. 2015XKMS048), the Natural Science Foundation of Jiangsu Province (No. BK20160254), the National Natural Science Foundation of China (No. 21572094), and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
Further Information

Publication History

Received: 17 June 2017

Accepted after revision: 24 August 2017

Publication Date:
14 September 2017 (eFirst)

Abstract

Carbon–carbon couplings are among the most important strategies for constructing functional molecules in organic synthetic chemistry, and cheap, diverse, and readily available coupling partners are crucial to these diverse reactions. In this contribution, we report the first palladium-catalyzed C–C cross-coupling reaction of two kinds of organic halide, a gem-dibromoalkene and a halobenzene, as the starting materials. Terminal alkynes were generated in situ through a tandem elimination–hydrodebromination process, and the internal alkyne final products were synthesized in one pot. The reaction proceeded under simple, facile, and classic copper-free Sonogashira coupling reaction conditions in good to excellent yields.

Supporting Information

 
  • References and Notes

    • 1a Chinchilla R. Nájera C. Chem. Rev. 2014; 114: 1783
    • 1b Boyarskiy VP. Ryabukhin DS. Bokach NA. Vasilyev AV. Chem. Rev. 2016; 116: 5894
    • 2a Doucet H. Hierso JC. Angew. Chem. Int. Ed. Engl. 2007; 46: 834
    • 2b Chinchilla R. Nájera C. Chem. Soc. Rev. 2011; 40: 5084
    • 3a Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett. 1975; 16: 4467
    • 3b Cassar L. J. Organomet. Chem. 1975; 93: 253
    • 3c Dieck HA. Heck FR. J. Organomet. Chem. 1975; 93: 241
  • 4 Liu J. Zhang X. Shi L. Liu M. Yue Y. Li F. Zhuo K. Chem. Commun. 2014; 50: 9887
    • 5a Legrand F. Jouvin K. Evano G. Isr. J. Chem. 2010; 50: 588
    • 5b Chelucci G. Chem. Rev. 2012; 112: 1344
    • 6a Desai NB. McKelvie N. Ramirez F. J. Am. Chem. Soc. 1962; 84: 1745
    • 6b Corey EJ. Fuchs PL. Tetrahedron Lett. 1972; 13: 3769
  • 7 1-(2,2-Dibromovinyl)-4-methylbenzene (1a); Typical Procedure CBr4 (3.316 g, 10 mmol) was added to a solution of Ph3P (5.246 g, 20 mmol) in CH2Cl2 (15 mL) at 0 °C, and the mixture was stirred for 10 min. 4-Tolualdehyde (0.601 g, 5 mmol) was added, and the mixture was stirred at r.t. for 1 h. After removal of solvent, hexane (30 mL) was added and the mixture was filtered through Celite. The filtrate was concentrated under reduced pressure, and the product was purified by flash column chromatography to give a yellow oil; yield: 1.325 g (96%).
    • 8a Aziz J. Baladi T. Piguel S. J. Org. Chem. 2016; 81: 4122
    • 8b Berciano BP. Lebrequier S. Besselièvre F. Piguel S. Org. Lett. 2010; 12: 4038
    • 8c Shi W. Lei AW. Tetrahedron Lett. 2014; 55: 2763
    • 8d Ye S. Yang X. Wu J. Chem. Commun. 2010; 46: 2950
    • 8e Riveiros R. Saya L. Sestelo JP. Sarandeses LA. Eur. J. Org. Chem. 2008; 2008: 1959
    • 9a Coste A. Karthikeyan G. Couty F. Evano G. Angew. Chem. Int. Ed. Engl. 2009; 48: 4381
    • 9b Coste A. Couty F. Evano G. Org. Lett. 2009; 11: 4454
    • 9c Jouvin K. Coste A. Bayle A. Legrand F. Karthikeyan G. Tadiparthi K. Evano G. Organometallics 2012; 31: 7933
    • 9d Das B. Salvanna N. Reddy GC. Balasubramanyam P. Tetrahedron Lett. 2011; 52: 6497
    • 9e Huh DH. Ryu H. Kim YG. Tetrahedron 2004; 60: 9857
    • 9f Fayol A. Fang Y.-Q. Lautens M. Org. Lett. 2006; 8: 4203
    • 9g Beltrán-Rodil S. Edwards M. Pugh D. Reid M. Taylor RJ. K. Synlett 2009; 2010: 602
    • 10a Li P. Alper H. J. Org. Chem. 1986; 51: 4354
    • 10b Shen W. Kunzer A. Org. Lett. 2002; 4: 1315
    • 10c Ye W. Mo J. Zhao T. Xu B. Chem. Commun. 2009; 3246
    • 10d Jouvin K. Bayle A. Legrand F. Evano G. Org. Lett. 2012; 14: 1652
    • 11a Murahashi SI. Yamamura M. Yanagisawa KI. Nobuaki M. Kondo K. J. Org. Chem. 1979; 44: 2408
    • 11b Cristau HJ. Chabaud B. Labaudiniere R. Christol H. J. Org. Chem. 1986; 51: 875
    • 11c Jin H. Yang YW. Kuang CX. Yang Q. Synlett 2011; 2011: 2886
    • 11d Ni Z. Wang S. Mao H. Pan Y. Tetrahedron Lett. 2012; 53: 3907
    • 12a Lera M. Hayes CJ. Org. Lett. 2000; 2: 3873
    • 12b Wang Y. Gan J. Liu L. Yuan H. Gao Y. Liu Y. Zhao Y. J. Org. Chem. 2014; 79: 3678
    • 12c Liu L. Wang Y. Zeng Z. Xu P. Gao Y. Yin Y. Zhao Y. Adv. Synth. Catal. 2013; 355: 659
    • 12d Evano G. Tadiparthi K. Couty F. Chem. Commun. 2011; 47: 179
  • 13 Seregin IV. Gevorgyan V. Chem. Soc. Rev. 2007; 36: 1173
    • 14a Rahimi A. Schmidt A. Synthesis 2010; 2010: 2621
    • 14b Liu J. Dai F. Yang Z. Wang S. Xie K. Wang A. Chen X. Tan Z. Tetrahedron Lett. 2012; 53: 5678
    • 14c Yan H. Lu L. Sun P. Zhu Y. Yang H. Liu D. Rong G. Mao J. RSC Adv. 2013; 3: 377
    • 15a Chelucci G. Capitta F. Baldino S. Pinna GA. Tetrahedron Lett. 2007; 48: 6514
    • 15b Chelucci G. Capitta F. Baldino S. ­Tetrahedron 2008; 64: 10250
  • 16 Shen W. Wang L. J. Org. Chem. 1999; 64: 8873
    • 17a Rao ML. N. Jadhav DN. Dasgupta P. Org. Lett. 2010; 12: 2048
    • 17b Rao ML. N. Dasgupta P. Murty VN. RSC Adv. 2015; 5: 24834
  • 18 Yan JC. Wang ZY. Wang L. J. Chem. Res. 2004; 71 ; DOI: 10.3184/030823404323000864
    • 19a Habrant D. Rauhala V. Koskinen AM. P. Chem. Soc. Rev. 2010; 39: 2007
    • 19b Zhao M. Kuang C. Yang Q. Cheng X. Tetrahedron Lett. 2011; 52: 992
    • 19c Liu S. Chen X. Hu Y. Yuan L. Chen S. Wu P. Wang W. Zhang S. Zhang W. Adv. Synth. Catal. 2015; 357: 553
  • 20 Morri AK. Thummala Y. Doddi VR. Org. Lett. 2015; 17: 4640
    • 21a Shirakawa E. Itoh K.-i. Higashino T. Hayashi T. J. Am. Chem. Soc. 2010; 132: 15537
    • 21b Sun C.-L. Shi Z.-J. Chem. Rev. 2014; 114: 9219
  • 22 Cross-Coupling of gem-Dibromoalkenes with Iodobenzene; General Procedure A mixture of the appropriate gem-dibromoalkene 1 (0.68 mmol), Cs2CO3 (2.4 mmol), and DMSO (2 mL) was stirred at 115 °C for 15 h. When 1 was completely consumed, PhI (0.4 mmol) and Pd/C (5 mol%) were added and the mixture was deaerated with N2 and stirred at 80 °C for 25 h. The mixture was then cooled to r.t., diluted with EtOAc (30 mL), and washed with H2O (3 × 10 mL). The organic phases were combined, dried (MgSO4), and concentrated, and the residue was purified by column chromatography (silica gel, hexane). 1,2-Dichloro-4-(phenylethynyl)benzene (3m) White solid; yield: 47.4 mg (48%). 1H NMR (400 MHz, CDCl3): δ = 7.60 (t, J = 5.6 Hz, 1 H), 7.54–7.48 (m, 2 H), 7.43–7.27 (m, 5 H). 13C NMR (101 MHz, CDCl3): δ = 133.1, 132.5, 132.5, 131.6, 130.6, 130.3, 128.7, 128.3, 123.2, 122.4, 91.2, 86.9. HRMS (EI): m/z [M]+ calcd for C14H8Cl2: 246.0003; found: 246.0012.
  • 23 Palladium-Catalyzed Cross-Coupling of gem-Dibromoalkenes 1 with Bromobenzene or 1-Chloro-4-nitrobenzene; General Procedure A mixture of the appropriate gem-dibromoalkene 1 (0.68 mmol), Cs2CO3 (2.4 mmol), and DMSO (2 mL) was stirred at 115 °C for 15 h. When the alkene 1 was completely consumed, bromobenzene (4) or 1-chloro-4-nitrobenzene (5) (0.4 mmol), Pd(OAc)2 (5 mol%), and PPh3 (10 mol%) were added and the mixture was deaerated with N2 gas and stirred at 60 °C or 80 °C for 25 h. When the reaction was complete, the product was isolated and purified as described above. 1-Chloro-4-[(4-methoxyphenyl)ethynyl]benzene (3x) Brown solid; yield: 81.5 mg (84%). 1H NMR (400 MHz, CDCl3): δ = 7.50–7.36 (m, 4 H), 7.32–7.25 (m, 2 H), 6.92–6.77 (m, 2 H), 3.83–3.69 (m, 3 H). 13C NMR (101 MHz, CDCl3): δ = 160.0, 133.2, 132.8, 131.8, 128.8, 128.5, 122.3, 114.2, 90.5, 87.2, 55.5. HRMS (EI): m/z [M]+ calcd for C15H11ClO: 242.0498; found: 242.0506. Methyl 4-[(4-Chlorophenyl)ethynyl]benzoate (3y) Brown solid; yield: 88.1 mg (82%). 1H NMR (400 MHz, CDCl3): δ = 8.10–7.96 (m, 2 H), 7.61–7.50 (m, 2 H), 7.44 (t, J = 13.1 Hz, 2 H), 7.36–7.27 (m, 2 H), 3.98–3.83 (m, 3 H). 13C NMR (101 MHz, CDCl3): δ = 166.6, 134.9, 133.0, 131.6, 129.8, 129.7, 128.9, 127.7, 121.3, 91.2, 89.6, 52.3. HRMS (EI): m/z [M]+ calcd for C16H11ClO2 [M]+ 270.0448; found: 270.0459. 1-Fluoro-4-[(4-methoxyphenyl)ethynyl]benzene (3z) Brown solid; yield: 76.8 mg (85%). 1H NMR (400 MHz, CDCl3): δ = 7.53–7.35 (m, 4 H), 7.06–6.95 (m, 2 H), 6.85 (d, J = 8.5 Hz, 2 H), 3.81 (d, J = 14.4 Hz, 3 H). 13C NMR (101 MHz, CDCl3): δ = 162.3 (J CF = 249.2 Hz), 159.7, 133.3 (J CF = 7.6 Hz), 133.0, 119.7 (J CF = 3.0 Hz), 115.7, 115.4 (J CF = 22.7 Hz), 114.1, 89.1, 87.0, 55.3.HRMS (EI): m/z [M]+ calcd for C15H11FO: 226.0794; found: 226.0800. Methyl 4-[(4-Fluorophenyl)ethynyl]benzoate (3za) Brown solid; yield: 60.0 mg (59%). 1H NMR (400 MHz, CDCl3): δ = 8.01 (d, J = 8.2 Hz, 2 H), 7.64–7.41 (m, 4 H), 7.05 (t, J = 8.6 Hz, 2 H), 3.90 (d, J = 12.0 Hz, 3 H). 13C NMR (101 MHz, CDCl3): δ = 166.5, 162.8 (J CF = 250.7 Hz), 133.7 (J CF = 9.01 Hz), 131.5, 129.6, 128.4, 127.8, 118.8 (J CF = 3.0 Hz), 115.8 (J CF = 22.7 Hz), 91.3, 88.4, 52.2. HRMS (EI): m/z [M]+ calcd for C16H11FO2: 254.0743; found: 254.0750.