Ligand-Controlled Copper-Catalyzed Highly Regioselective Difluoromethylation of Allylic Chlorides/Bromides and Propargyl Bromides
Yang Gu
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
Search for more papers by this authorChanghui Lu
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
Search for more papers by this authorYucheng Gu
Syngenta, Jealott's Hill International Research Cente Bracknell, Berkshire, RG42 6EY UK
Search for more papers by this authorCorresponding Author
Qilong Shen
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
E-mail: [email protected]; Tel.: 0086-021-54925197Search for more papers by this authorYang Gu
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
Search for more papers by this authorChanghui Lu
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
Search for more papers by this authorYucheng Gu
Syngenta, Jealott's Hill International Research Cente Bracknell, Berkshire, RG42 6EY UK
Search for more papers by this authorCorresponding Author
Qilong Shen
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
E-mail: [email protected]; Tel.: 0086-021-54925197Search for more papers by this authorAbstract
Highly regiodivergent copper-catalyzed allylic/propargylic difluoromethylation reactions by employing different ligands are described. When 5,6-dimethyl-1,10-phenanthroline was used as the ligand, exclusively α-difluoromethylated products were obtained, while γ-selective difluoromethylated products were generated when N-heterocyclic carbene-SIPr was used as the ligand. Likewise, high α- vs. γ-selectivities were achieved in the presence of similar copper catalysts for the reactions of propargyl bromides. Moreover, a copper-catalyzed asymmetric allylic difluoromethylation reaction with moderate to good enantioselectivity by the use of chiral ligands was developed.
Supporting Information
| Filename | Description |
|---|---|
| cjoc201700594-sup-0001-AppendixS1.pdfPDF document, 8.3 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1(a) Wong, D. T.; Perry, K. W.; Bymaster, F. P. Nat. Rev. Drug Discovery 2005, 4, 764; (b) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320; (c) Hagmann, W. K. J. Med. Chem. 2008, 51, 4359; (d) Vitaku, E.; Smith, D. T.; Njardarson, J. T. J. Med. Chem. 2014, 57, 10257.
- 2(a) Erickson, J. A.; McLoughlin, J. I. J. Org. Chem. 1995, 60, 1626; (b) Narjes, F.; Koehler, K. F.; Koch, U.; Gerlach, B.; Colarusso, S.; Steinkühler, C.; Brunetti, M.; Altamura, S.; Francesco, R. D.; Matassa, V. G. Bioorg. Med. Chem. Lett. 2002, 12, 701; (c) Xu, Y.; Prestwich, G. D. J. Org. Chem. 2002, 67, 7158; (d) Meanwell, N. A. J. Med. Chem. 2011, 54, 2529; (e) Zafrani, Y.; Yeffet, D.; Sod-Moriah, G.; Berliner, A.; Amir, D.; Marciano, D.; Gershonov, E.; Saphier, S. J. Med. Chem. 2017, 60, 797.
- 3Selected reviews for difluoromethylation: (a) Hu, J.-B.; Zhang, W.; Wang, F. Chem. Commun. 2009, 7465;
(b) Jin, Z.; Hammond, G. B.; Xu, B. Aldrichim. Acta 2012, 45, 67;
(c) Chen, B.; Vicic, D. A. Top. Organomet. Chem. 2015, 52, 113;
(d) Lu, Y.; Liu, C.; Chen, Q.-Y. Curr. Org. Chem. 2015, 19, 1638;
(e) Ni, C.-F.; Zhu, L.-G.; Hu, J.-B. Acta Chim. Sinica 2015, 73, 90;
(f) Rong, J.; Ni, C.-F.; Hu, J.-B. Asian J. Org. Chem. 2017, 6, 139;
10.1002/ajoc.201600509 Google Scholar(g) Yerine, D. E.; Barata-Vallejo, S.; Postigo, A. Chem. Eur. J. 2017, 23, 14676.
- 4Selected reports for difluoromethylation: (a) Fujikawa, K.; Fujioka, Y.; Kobayashi, A.; Amii, H. Org. Lett. 2011, 13, 5560; (b) Fujiwara, Y.; Dixon, J. A.; O'Hara, F.; Funder, E. D.; Dixon, D.; Rodriguez, R. A.; Baxter, R. D.; Herlé, B.; Sach, N.; Collins, M. R.; Ishihara, Y.; Baran, P. S. Nature 2012, 492, 95; (c) Fier, P. S.; Hartwig, J. F. J. Am. Chem. Soc. 2012, 134, 5524; (d) Prakash, G. K. S.; Ganesh, S. K.; Jones, J. P.; Kulkarni, A.; Masood, K.; Swabeck, J. K.; Olah, G. A. Angew. Chem. Int. Ed. 2012, 51, 12090; (e) Mizuta, S.; Stenhagen, I. S. R.; Duill, M. O.; Wolstenhulme, J.; Kirjavainen, A. K.; Forsback, S. J.; Tredwell, M.; Sandford, G.; Moore, P. R.; Huiban, M.; Luthra, S. K.; Passchier, J.; Solin, O.; Gouverneur, V. Org. Lett. 2013, 15, 2648; (f) Jiang, X.-L.; Chen, Z.-H.; Xu, X.-H.; Qing, F.-L. Org. Chem. Front. 2014, 1, 774; (g) Xu, P.; Guo, S.; Wang, L.-Y.; Tang, P.-P. Angew. Chem. Int. Ed. 2014, 53, 5955; (h) Xu, L.; Vicic, D. A. J. Am. Chem. Soc. 2016, 138, 2536; (i) Feng, Z.; Min, Q.-Q.; Zhang, X.-G. Org. Lett. 2016, 18, 44; (j) Deng, X.-Y.; Lin, J.-H.; Xiao, X.-C. Org. Lett. 2016, 18, 4384; (k) Serizawa, H.; Ishii, K.; Aikawa, K.; Mikami, K. Org. Lett. 2016, 18, 3686; (l) Aikawa, K.; Serizawa, H.; Mikami, K. Org. Lett. 2016, 18, 3690; (m) Feng, Z.; Min, Q.-Q.; Fu, X.-P.; An, L.; Zhang, X.-G. Nat. Chem. 2017, 9, 918.
- 5Selected recently reported methods for radical difluoromethylation of alkenes for the construction of C(sp3)-C bonds: (a) Thomoson, C. S.; Tang, X.-J.; Dolbier, W. R. J. Org. Chem. 2015, 80, 1264; (b) Tang, X.-J.; Dolbier, W. R. Angew. Chem. Int. Ed. 2015, 54, 4246; (c) Fu, W.-J.; Han, X.; Zhu, M.; Xu, C.; Wang, Z.-Q.; Ji, B.-M.; Hao, X.-Q.; Song, M.-P. Chem. Commun. 2016, 52, 13413; (d) Ran, Y.; Lin, Q.-Y.; Xu, X.-H.; Qing, F.-L. J. Org. Chem. 2016, 81, 7001; (e) Lin, Q.-Y.; Ran, Y.; Xu, X.-H.; Qing, F.-L. Org. Lett. 2016, 18, 2419; (f) Arai, Y.; Tomita, R.; Ando, G.; Koike, T.; Akita, M. Chem. Eur. J. 2016, 22, 1262; (g) Lin, Q.-Y.; Xu, X.-H.; Zhang, K.; Qing, F.-L. Angew. Chem. Int. Ed. 2016, 55, 1479.
- 6Selected other methods for the construction of C(sp3)-CF2H bonds: (a) Nawrot, E.; Jonczyk, A. J. Fluorine Chem. 2009, 130, 466; (b) Lida, T.; Hashimoto, R.; Aikawa, K.; Ito, S.; Mikami, K. Angew. Chem. Int. Ed. 2012, 51, 9535; (c) Liu, G.; Wang, X.; Lu, X.; Xu, X.-H.; Tokunaga, E.; Shibata, N. ChemistryOpen 2012, 1, 227; (d) He, Z.-B.; Hu, M.-Y.; Luo, T.; Li, L.-C.; Hu, J.-B. Angew. Chem. Int. Ed. 2012, 51, 11545; (e) Wang, X.; Liu, G.; Xu, X.-H.; Shibata, N.; Tokunaga, E.; Shibata, N. Angew. Chem. Int. Ed. 2014, 53 1827; (f) Aikawa, K.; Maruyama, K.; Honda, K.; Mikami, K. Org. Lett. 2015, 17, 4882; (g) Banik, S. M.; Medley, J. W.; Jacobsen, E. N. Science 2016, 353, 51; (h) Wei, Y.; Yu, L.-Y.; Lin, J.-H.; Zhang, X.; Xiao, J.-C. Chin. J. Chem. 2016, 34, 481.
- 7Selected recent reviews on copper-catalyzed allylic substitution: (a) Alexakis, A.; Bäckvall, J. E.; Krause, N.; Pàmies, O.; Diéhuez, M. Chem. Rev. 2008, 108, 2796; (b) Harutyunyan, S. R.; den Hartog, T.; Geurts, K.; Minnaard, A. J.; Feringa, B. L. Chem. Rev. 2008, 108, 2824.
- 8Interestingly, reported copper-catalyzed allylic trifluoromethylation reactions occurred exclusively to form the trifluoromethylated products at the less hindered position: (a) Burton, D. J.; Wiemers, D. M. J. Am. Chem. Soc. 1985, 107, 5014; (b) Miyake, Y.; Ota, S.; Nishibayashi, Y. Chem. Eur. J. 2012, 18, 13255; (c) Larsson, J. M.; Pathipati, S. R.; Szabo, K. J. J. Org. Chem. 2013, 78, 7330.
- 9For Pd-catalyzed γ-selective trifluoromethylation of allylic bromides, see: Kitazume, T.; Ishikawa, N. J. Am. Chem. Soc. 1985, 107, 5186.
- 10Examples for copper-catalyzed propargylic trifluoromethylation: (a) Zhao, T. S. N.; Szabo, K. J. Org. Lett. 2012, 14, 3966; (b) Miyake, Y.; Ota, S.-I.; Shibata, M.; Nakajima, K.; Nishibayashi, Y. Chem. Commun. 2013, 49, 7809; (c) Ji, Y.-L.; Kong, J.-J.; Lin, J.-H.; Xiao, J.-C.; Gu, Y.-C. Org. Biomol. Chem. 2014, 12, 2903; (d) Ambler, B. R.; Peddi, S.; Altman, R. A. Org. Lett. 2015, 17, 2506.
- 11 Burton, D. J.; Hartgraves, G. A. J. Fluorine Chem. 2007, 128, 1198.
- 12 Aikawa, K.; Ishii, K.; Endo, Y.; Mikami, K. J. Fluorine Chem. 2017, doi: https://doi.org/10.1016/j.jfluchem.2017.07.018.
- 13(a) Gu, Y.; Leng, X.-B.; Shen, Q. Nat. Commun. 2014, 5, 6405, DOI: https://doi.org/10.1038/ncomms6405; (b) Gu, Y.; Chang, D.-L.; Leng, X.-B.; Gu, Y.-C.; Shen. Q. Organometallics 2015, 34, 3065; (c) Chang, D.-L.; Gu, Y.; Shen, Q. Chem. Eur. J. 2015, 21, 6074.
