Synthesis 2019; 51(23): 4385-4392
DOI: 10.1055/s-0039-1690009
special topic
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Synthesis of α-Chloro-α-halo Ketones by Decarboxylative Chlorination of α-Halo-β-ketocarboxylic Acids

Kazumasa Kitahara
,
Haruna Mizutani
,
Seiji Iwasa
,
Department of Applied Chemistry and Life Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi 441-8580, Japan   Email: shiba@chem.tut.ac.jp
› Author Affiliations
This study was supported by the Grants-in-Aid for Scientific Research (B) (18H01974) and the Grant-in-Aid for Research Fellow of JSPS (18J12369), and Tatematsu Foundation.
Further Information

Publication History

Received: 06 June 2019

Accepted after revision: 05 July 2019

Publication Date:
23 July 2019 (online)

Published as part of the Special Topic Halogenation methods (with a view towards radioimaging applications)

Abstract

Chiral α-chloro-α-fluoro ketones were synthesized by enantio­selective decarboxylative chlorination of α-chloro-β-ketocarboxylic acids in the presence of a chiral amine catalyst. The reaction yielded the corresponding α-chloro-α-fluoro ketones with moderate-to-high enantioselectivity (up to 90% ee). The method was also applied to the synthesis of α-bromo-α-chloro ketones with 90% ee.

Supporting Information

 
  • References

  • 2 Zhu Y, Han J, Wang J, Shibata N, Sodeoka M, Soloshonok VA, Coelho JA. S, Toste FD. Chem. Rev. 2018; 118: 3887
    • 3a Shibatomi K, Yamamoto H. Angew. Chem. Int. Ed. 2008; 47: 5796
    • 3b Shibatomi K, Narayama A, Soga Y, Muto T, Iwasa S. Org. Lett. 2011; 13: 2944
    • 3c Shibatomi K, Okimi T, Abe Y, Narayama A, Nakamura N, Iwasa S. Beilstein J. Org. Chem. 2014; 10: 323
    • 4a Shibatomi K, Tsuzuki Y, Nakata S.-I, Sumikawa Y, Iwasa S. Synlett 2007; 551
    • 4b Shibatomi K, Tsuzuki Y, Iwasa S. Chem. Lett. 2008; 37: 1098
    • 4c Shibatomi K, Futatsugi K, Kobayashi F, Iwasa S, Yamamoto H. J. Am. Chem. Soc. 2010; 132: 5625
    • 4d Shibatomi K, Narayama A, Abe Y, Iwasa S. Chem. Commun. 2012; 48: 7380
    • 4e Shibatomi K, Kobayashi F, Narayama A, Fujisawa I, Iwasa S. Chem. Commun. 2012; 48: 413
    • 4f Narayama A, Shibatomi K, Soga Y, Muto T, Iwasa S. Synlett 2013; 24: 375
    • 4g Shibatomi K, Kawasaki Y, Iwasa S. J. Fluorine Chem. 2015; 179: 77
    • 4h Shibatomi K, Kitahara K, Okimi T, Abe Y, Iwasa S. Chem. Sci. 2016; 7: 1388

      Earlier and/or representative studies on the asymmetric synthesis of α-chloro-α-fluorocarbonyl compounds, see:
    • 5a Frantz R, Hintermann L, Perseghini M, Broggini D, Togni A. Org. Lett. 2003; 5: 1709
    • 5b Cho MJ, Kang YK, Lee NR, Kim DY. Bull. Korean Chem. Soc. 2007; 28: 2191
    • 5c Kanga SH, Kim DY. Adv. Synth. Catal. 2010; 352: 2783
    • 5d Yi W.-B, Huang X, Zhang Z, Zhu D.-R, Cai C, Zhang W. Beilstein J. Org. Chem. 2012; 8: 1233
    • 5e Hayes MD, Rodriguez-Alvarado M, Brenner-Moyer SE. Tetrahedron Lett. 2015; 56: 4718
    • 6a Shibatomi K, Kitahara K, Sasaki N, Kawasaki Y, Fujisawa I, Iwasa S. Nat. Commun. 2017; 8: 15600
    • 6b See ref. 4h for the synthesis of chiral primary amine catalyst C1.
  • 7 Naruse A, Kitahara K, Iwasa S, Shibatomi K. Asian J. Org. Chem. 2019; 8: 691
  • 8 Wang X, Lan Q, Shirakawa S, Maruoka K. Chem. Commun. 2010; 46: 321
  • 9 Deng Q.-H, Wadepohl H, Gade LH. Chem. Eur. J. 2011; 17: 14922
  • 10 Hamashima Y, Yagi K, Takano H, Tamás L, Sodeoka M. J. Am. Chem. Soc. 2002; 124: 14530
  • 11 Ding C, Maruoka K. Synlett 2009; 664