Synthesis 2017; 49(22): 4978-4985
DOI: 10.1055/s-0036-1588527
paper
© Georg Thieme Verlag Stuttgart · New York

Visible-Light-Induced Trifluoromethylation of Highly Functionalized Arenes and Heteroarenes in Continuous Flow

Irini Abdiaja, Cecilia Bottecchiab, Jesus Alcazar*a, Timothy Noёl*b
  • aJanssen Research & Development, Jarama 75A, 45007 Toledo, Spain   Email: jalcazar@its.jnj.com
  • bDepartment of Chemical Engineering and Chemistry, Micro Flow Chemistry & Process Technology, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands   Email: t.noel@tue.nl
The authors acknowledge the European Union for a Marie Curie ITN Grant (Photo4Future, Grant No. 641861). Further financial support for this work was provided by a VIDI grant (T.N., SensPhotoFlow, No. 14150).
Further Information

Publication History

Received: 07 June 2017

Accepted after revision: 07 July 2017

Publication Date:
09 August 2017 (eFirst)

Abstract

We report a continuous-flow protocol for the trifluoromethylation of arenes, heteroarenes, and benzofused heterocycles. This photoredox methodology relies on the use of solid sodium trifluoromethanesulfinate (CF3SO2Na) as the trifluoromethylating agent and the iridium complex [Ir{dF(CF3)ppy}2](dtbpy)]PF6 as the photoredox catalyst. A diverse set of highly functionalized heterocycles proved compatible with the methodology, and moderate to good yields were obtained within 30 minutes of residence time.

Supporting Information

 
  • References

    • 1a Zhou Y. Wang J. Gu Z. Wang S. Zhu W. Aceña JL. Soloshonok VA. Izawa K. Liu H. Chem. Rev. 2016; 116: 422
    • 1b Purser S. Moore PR. Swallow S. Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
    • 1c Müller K. Faeh C. Diederich F. Science 2007; 317: 1881
    • 2a Ilardi EA. Vitaku E. Njardarson JT. J. Med. Chem. 2014; 57: 2832
    • 2b Huchet QA. Kuhn B. Wagner B. Kratochwil NA. Fischer H. Kansy M. Zimmerli D. Carreira EM. Müller K. J. Med. Chem. 2015; 58: 9041
    • 3a Barata-Vallejo S. Postigo A. Coord. Chem. Rev. 2013; 257: 3051
    • 3b Tomashenko OA. Grushin VV. Chem. Rev. 2011; 111: 4475
    • 3c Huiban M. Tredwell M. Mizuta S. Wan Z. Zhang X. Collier TL. Gouverneur V. Passchier J. Nat. Chem. 2013; 5: 941
    • 4a Straathof NJ. W. Cramer SE. Hessel V. Noël T. Angew. Chem. Int. Ed. 2016; 55: 15549
    • 4b Bottecchia C. Wei XJ. Kuijpers KP. Hessel V. Noel T. J. Org. Chem. 2016; 81: 7301
    • 4c Lefebvre Q. Hoffmann N. Rueping M. Chem. Commun. 2016; 52: 2493
    • 4d Chatterjee T. Iqbal N. You Y. Cho EJ. Acc. Chem. Res. 2016; 49: 2284
    • 4e Beatty JW. Douglas JJ. Cole KP. Stephenson CR. J. Nat. Commun. 2015; 6
    • 4f Straathof NJ. W. Gemoets HP. L. Wang X. Schouten JC. Hessel V. Noël T. ChemSusChem 2014; 7: 1612
    • 4g Prier CK. Rankic DA. MacMillan DW. C. Chem. Rev. 2013; 113: 5322
    • 4h Nagib DA. MacMillan DW. C. Nature 2011; 480: 224
    • 4i Iqbal N. Choi S. Kim E. Cho EJ. J. Org. Chem. 2012; 77: 11383
    • 4j Cui L. Matusaki Y. Tada N. Miura T. Uno B. Itoh A. Adv. Synth. Catal. 2013; 355: 2203
    • 5a Pan X. Xia H. Wu J. Org. Chem. Front. 2016; 3: 1163
    • 5b Barata-Vallejo S. Lantaño B. Postigo A. Chem. Eur. J. 2014; 20: 16806
    • 6a Ji Y. Brueckl T. Baxter RD. Fujiwara Y. Seiple IB. Su S. Blackmond DG. Baran PS. Proc. Natl. Acad. Sci. U.S.A. 2011; 108: 14411
    • 6b Wang D. Deng G.-J. Chen S. Gong H. Green Chem. 2016; 18: 5967
    • 6c Langlois BR. Billard T. Mulatier J.-C. Yezeguelian C. J. Fluorine Chem. 2007; 128: 851
    • 6d Langlois BR. Laurent E. Roidot N. Tetrahedron Lett. 1991; 32: 7525
    • 6e Tordeux M. Langlois B. Wakselman C. J. Org. Chem. 1989; 54: 2452
    • 7a Lefebvre Q. Synlett 2016; 28: 19
    • 7b Zhang C. Adv. Synth. Catal. 2014; 356: 2895
    • 8a Huck L. Berton M. de la Hoz A. Diaz-Ortiz A. Alcazar J. Green Chem. 2017; 19: 1420
    • 8b Wirth T. ChemSusChem 2012; 5: 215
    • 8c Galloway WR. J. D. Isidro-Llobet A. Spring DR. Nat. Commun. 2010; 1: 1
    • 9a Teders M. Gómez-Suárez A. Pitzer L. Hopkinson MN. Glorius F. Angew. Chem. Int. Ed. 2017; 56: 902
    • 9b Hopkinson MN. Gómez-Suárez A. Teders M. Sahoo B. Glorius F. Angew. Chem. Int. Ed. 2016; 55: 4361
    • 9c Demissie TB. Hansen JH. Dalton Trans. 2016; 45: 10878
  • 10 Teegardin K. Day JI. Chan J. Weaver J. Org. Process Res. Dev. 2016; 20: 1156
  • 11 Cambié D. Bottecchia C. Straathof NJ. W. Hessel V. Noël T. Chem. Rev. 2016; 116: 10276
    • 12a Brown DG. Boström J. J. Med. Chem. 2016; 59: 4443
    • 12b Alonso N. Miller LZ. de M Muñoz J. Alcázar J. McQuade DT. Adv. Synth. Catal. 2014; 356: 3737
    • 12c Egle B. Muñoz J. Alonso N. De Borggraeve W. de la Hoz A. Díaz-Ortiz A. Alcázar J. J. Flow Chem. 2014; 4: 22
    • 12d de M Muñoz J. Alcázar J. de la Hoz A. Díaz-Ortiz A. Adv. Synth. Catal. 2012; 354: 3456
    • 12e Noël T. Musacchio AJ. Org. Lett. 2011; 13: 5180
    • 12f Cooper TW. J. Campbell IB. Macdonald SJ. F. Angew. Chem. Int. Ed. 2010; 49: 8082
  • 13 Gao G.-L. Yang C. Xia W. Chem. Commun. 2017; 53: 1041
    • 14a Linghu X. Wong N. Iding H. Jost V. Zhang H. Koenig SG. Sowell CG. Gosselin F. Org. Process Res. Dev. 2017; 21: 387
    • 14b Peng A. Jiang J. Hu P. Luo Y. J. Chromatogr., B 2010; 878: 2442
    • 15a Chang B. Shao H. Yan P. Qiu W. Weng Z. Yuan R. ACS Sustainable Chem. Eng. 2017; 5: 334
    • 15b Li L. Mu X. Liu W. Wang Y. Mi Z. Li C.-J. J. Am. Chem. Soc. 2016; 138: 5809
    • 16a Noёl T. Photochemical Processes in Continuous-Flow Reactors. World Scientific; New Jersey; 2017
    • 16b Tucker JW. Zhang Y. Jamison TF. Stephenson CR. J. Angew. Chem. Int. Ed. 2012; 51: 4144
    • 16c Elliott LD. Knowles JP. Koovits PJ. Maskill KG. Ralph MJ. Lejeune G. Edwards LJ. Robinson RI. Clemens IR. Cox B. Pascoe DD. Koch G. Eberle M. Berry MB. Booker-Milburn KI. Chem. Eur. J. 2014; 20: 15226
    • 16d Knowles JP. Elliott LD. Booker-Milburn KI. Beilstein J. Org. Chem. 2012; 8: 2025
    • 17a Elliott LD. Berry M. Harji B. Klauber D. Leonard J. Booker-Milburn KI. Org. Process Res. Dev. 2016; 20: 1806
    • 17b Abdiaj I. Alcázar J. Bioorg. Med. Chem. 2016; DOI: in press; DOI: 10.1016/j.bmc.2016.12.041.
    • 17c Su Y. Kuijpers K. Hessel V. Noël T. React. Chem. Eng. 2016; 1: 73
  • 18 Pitre SP. McTiernan CD. Ismaili H. Scaiano JC. ACS Catal. 2014; 4: 2530
  • 19 Gleave RJ. Beswick PJ. Brown AJ. Giblin GM. P. Haslam CP. Livermore D. Moses A. Nicholson NH. Page LW. Slingsby B. Swarbrick ME. Bioorg. Med. Chem. 2009; 19: 6578