Synthesis 2014; 46(14): 1859-1870
DOI: 10.1055/s-0033-1338637
special topic
© Georg Thieme Verlag Stuttgart · New York

Copper-Mediated Direct Functionalization of Unsaturated C–C Bonds with Ethyl Bromo(difluoro)acetate: A Straightforward Access to Highly Valuable Difluoromethylated Alkenes

Marie-Charlotte Belhomme
,
Delphine Dru
,
Heng-Ying Xiong
,
Dominique Cahard
,
Tatiana Besset*
,
Thomas Poisson*
,
Xavier Pannecoucke
Further Information

Publication History

Received: 27 February 2014

Accepted after revision: 13 April 2014

Publication Date:
28 May 2014 (eFirst)

Abstract

A copper-mediated fluorofunctionalization of alkenes and alkynes has been developed. This method provides ready access to trisubstituted difluoromethylated olefins (from dihydropyrans, glycal derivatives, or terminal alkynes) or to tetrasubstituted olefins (from disubstituted alkynes). The products were obtained in good to high yields with acceptable E/Z selectivities. Finally, a first direct route to difluoromethylated alkynes is reported, albeit with low yields.

Supporting Information

 
  • References

  • 1 These authors contributed equally.
    • 4a Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
    • 4b O’Hagan D. Chem. Soc. Rev. 2008; 37: 308
    • 4c Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
    • 4d Jeschke P. ChemBioChem 2004; 5: 570
    • 4e Böhm H.-J, Banner D, Bendels S, Kansy M, Kuhn B, Müller K, Obst-Sander U, Stahl M. ChemBioChem 2004; 5: 637

      For some reviews, see:
    • 5a Besset T, Schneider C, Cahard D. Angew. Chem. Int. Ed. 2012; 51: 5048
    • 5b Liu H, Gu Z, Jiang X. Adv. Synth. Catal. 2013; 355: 617
    • 5c Wu X.-F, Neumann H, Beller M. Chem. Asian J. 2012; 7: 1744
    • 5d Landelle G, Panossian A, Pazenok S, Vors J.-P, Leroux FR. Beilstein J. Org. Chem. 2013; 9: 2476.

      For selected examples of trifluoromethylation reactions, see:
    • 6a Miura M, Feng C.-G, Ma S, Yu J.-Q. Org. Lett. 2013; 15: 5258
    • 6b Wang X, Truesdale L, Yu J.-Q. J. Am. Chem. Soc. 2010; 132: 3648
    • 6c Zhang X.-G, Dai H.-X, Wasa M, Yu J.-Q. J. Am. Chem. Soc. 2012; 134: 11948
    • 6d Chu L, Qing F.-L. J. Am. Chem. Soc. 2012; 134: 1298
    • 6e Xu J, Fu Y, Luo D.-F, Jiang Y.-Y, Xiao B, Liu Z.-J, Gong T.-J, Liu L. J. Am. Chem. Soc. 2011; 133: 15300
    • 6f Parsons AT, Buchwald SL. Angew. Chem. Int. Ed. 2011; 50: 9120

    • For selected examples of fluorination reactions, see:
    • 6g Hull KL, Anani WQ, Sanford MS. J. Am. Chem. Soc. 2006; 128: 7134
    • 6h McMurtrey KB, Racowski JM, Sanford MS. Org. Lett. 2012; 14: 4094
    • 6i Vigalok A. Organometallics 2011; 30: 4802
    • 6j Zhao S.-B, Becker JJ, Gagné MR. Organometallics 2011; 30: 3926
    • 6k Kaspi AW, Goldberg I, Vigalok A. J. Am. Chem. Soc. 2010; 132: 10626
    • 6l Chan KS. L, Wasa M, Wang X, Yu J.-Q. Angew. Chem. Int. Ed. 2011; 50: 9081
    • 6m Ichiishi N, Canty AJ, Yates BF, Sanford MS. Org. Lett. 2013; 15: 5134
  • 7 Surapanich N, Kuhakarn C, Pohmakotr M, Reutrakul V. Eur. J. Org. Chem. 2012; 5943
  • 8 For a preliminary communication from our group regarding the direct introduction of the CF2CO2Et moiety, see: Belhomme M.-C, Poisson T, Pannecoucke X. Org. Lett. 2013; 15: 3428
    • 9a Murakami S, Ishii H, Tajima T, Fuchigami T. Tetrahedron 2006; 62: 3761

    • For a photocatalytic approach, see:
    • 9b Wallentin C.-J, Nguyen JD, Finkbeiner P, Stephenson CR. J. J. Am. Chem. Soc. 2012; 134: 8875
    • 9c Jiang H, Huang C, Guo J, Zeng C, Zhang Y, Yu S. Chem. Eur. J. 2012; 18: 15158
    • 10a Taguchi T, Kitagawa O, Morikawa T, Nishiwaki T, Uehara H, Endo H, Kobayashi Y. Tetrahedron 1986; 27: 6103
    • 10b Ashwood MS, Cottrell IF, Cowden CJ, Wallace DJ, Davies AJ, Kennedy DJ, Dolling UH. Tetrahedron Lett. 2002; 43: 9271
    • 11a Qi Q, Shen Q, Lu L. J. Am. Chem. Soc. 2012; 134: 6548
    • 11b Schwaebe MK, McCarthy JR, Whitten JP. Tetrahedron Lett. 2000; 41: 791
    • 11c Feng Z, Min Q.-Q, Xiao Y.-L, Zhang B, Zhang X. Angew. Chem. Int. Ed. 2014; 53: 1669
    • 12a Poisson T, Belhomme M.-C, Pannecoucke X. J. Org. Chem. 2012; 77: 9277
    • 12b Lemonnier G, Poisson T, Couve-Bonnaire S, Pannecoucke X. Tetrahedron Lett. 2013; 54: 2821
    • 12c Lemonnier G, Poisson T, Couve-Bonnaire S, Jubault P, Pannecoucke X. Eur. J. Org. Chem. 2013; 3278
    • 12d Ferrary T, David E, Milanole G, Besset T, Jubault P, Pannecoucke X. Org. Lett. 2013; 15: 5598
  • 13 Besset T, Cahard D, Pannecoucke X. J. Org. Chem. 2014; 79: 413
  • 14 Others radical inhibitors or radical scavengers such as butylated hydroxytoluene (TBHT), benzoquinone, or diphenylethene had no effect on the outcome of the reaction.

    • For a review, see:
    • 15a Casitas A, Ribas X. Chem. Sci. 2013; 4: 2301
    • 15b Phipps RJ, Gaunt MJ. Science 2009; 323: 1593
    • 15c Phipps RJ, McMurray L, Ritter S, Duong HA, Gaunt MJ. J. Am. Chem. Soc. 2012; 134: 10773
    • 15d Chen B, Hou X.-L, Li Y.-X, Wu Y.-D. J. Am. Chem. Soc. 2011; 133: 7668
    • 15e Barton DH. R, Finet J.-P, Khamsi J. Tetrahedron Lett. 1988; 29: 1115
    • 15f Gigant N, Chausset-Boissarie L, Belhomme M.-C, Poisson T, Pannecoucke X, Gillaizeau I. Org. Lett. 2013; 15: 278

    • For selected examples involving a well-defined Cu(III) species, see:
    • 15g Casitas A, King AE, Parella T, Costas M, Stahl SS, Ribas X. Chem. Sci. 2010; 1: 326
    • 15h Huffman LM, Casitas A, Font M, Canta M, Costas M, Ribas X, Stahl SS. Chem. Eur. J. 2011; 17: 10643
    • 15i Casitas A, Canta M, Solà M, Costas M, Ribas X. J. Am. Chem. Soc. 2011; 133: 19386
  • 16 We cannot exclude the possibility that the reductive elimination precedes the proton abstraction.
    • 17a Suero MG, Bayle ED, Collins BS. L, Gaunt MJ. J. Am. Chem. Soc. 2013; 135: 5332
    • 17b Walkinshaw AJ, Xu W, Suero MG, Gaunt MJ. J. Am. Chem. Soc. 2013; 135: 12532

      For selected examples, see:
    • 18a Egami H, Shimizu R, Sodeoka M. Tetrahedron Lett. 2012; 53: 5503
    • 18b Janson PG, Ghoneim I, Ilchenko NO, Szabό KJ. Org. Lett. 2012; 14: 2882
    • 18c Mizuta S, Verhoog S, Engle KM, Khotavivattana T, O’Duill M, Wheelhouse K, Rassias G, Médebielle M, Gouverneur V. J. Am. Chem. Soc. 2013; 135: 2505
    • 18d Wang X.-P, Lin J.-H, Zhang C.-P, Xiao J.-C, Zheng X. Beilstein J. Org. Chem. 2013; 9: 2635
  • 19 Fanga X, Yanga X, Mao S, Wanga Z, Chena G, Wu F. Tetrahedron 2007; 63: 10684
  • 20 No improvement was observed under an inert atmosphere.

    • For selected examples, see:
    • 21a Chu L, Qing F.-L. J. Am. Chem. Soc. 2010; 132: 7262
    • 21b Liu C, Ma H, Nie J, Ma J. Chin. J. Chem. 2012; 30: 47
    • 21c Baert F, Colomb J, Billard T. Angew. Chem. Int. Ed. 2012; 51: 10382
    • 21d Alazet S, Zimmer L, Billard T. Angew. Chem. Int. Ed. 2013; 52: 10814
    • 21e Chen C, Chu L, Qing F.-L. J. Am. Chem. Soc. 2012; 1324: 12454

      For some example of applications, see:
    • 22a Fustero S, Fernández B, Bello P, del Pozo C, Arimitsu S, Hammond GB. Org. Lett. 2007; 9: 4251
    • 22b Arimitsu S, Fernández B, Bello P, del Pozo C, Fustero S, Hammond GB. J. Org. Chem. 2008; 73: 2656
    • 22c Kizirian J.-C, Aiguabella N, Pesquer A, Fustero S, Bello P, Verdaguer X, Riera A. Org. Lett. 2010; 12: 5620
  • 23 CF2Br2 is banned under the Montreal Protocol, see: http://ozone.unep.org/Publications/MP_Handbook/Section_1.1_The_Montreal_Protocol/ (accessed May 5, 2014).

    • The crucial roles of Cu(OAc)2 and of carboxylate as a ligand in several transformations have been previously reported. For a review, see:
    • 24a Ackermann L. Chem. Rev. 2011; 111: 1315
    • 24b For selected examples, see references 6a and 6b.
  • 25 When the reaction was carried out with three equivalents of NaOAc in the absence of any other additive, no alkyne 5a was formed, and 33% of alkene (E)-4a was detected.
  • 26 A substantial amount of a product resulting from homocoupling of alkyne 3 was obtained.
  • 27 When a mixture of 68:32 mixture of alkenes (E)- and (Z)-4a was treated under the standard conditions, only traces of 5a were detected by 19F NMR spectroscopy.
  • 28 Bucher C, Gilmour R. Angew. Chem. Int. Ed. 2010; 49: 8724
  • 29 Leonelli F, Capuzzi M, Calcagno V, Passacantilli P, Piancatelli G. Eur. J. Org. Chem. 2005; 2671