Synlett 2018; 29(18): 2408-2411
DOI: 10.1055/s-0037-1611019
letter
© Georg Thieme Verlag Stuttgart · New York

Catalyst-Free Decarboxylative Fluorination of Tertiary β-Keto Carboxylic Acids

Misaki Katada
,
Kazumasa Kitahara
,
Seiji Iwasa
,
Department of Environmental and Life Sciences, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi 441-8580, Japan   Email: shiba@ens.tut.ac.jp
› Author Affiliations
This study was supported by the Grants-in-Aid for Scientific Research (B) (18H01974), the Grant-in-Aid for Research Fellow of JSPS (No. 18J12369), and the Tatematsu Foundation.
Further Information

Publication History

Received: 21 August 2018

Accepted after revision: 17 September 2018

Publication Date:
16 October 2018 (eFirst)

Abstract

Decarboxylative fluorination of tertiary β-keto carboxylic ­acids was performed using an electrophilic fluorinating reagent. The reaction proceeded in the absence of a catalyst or base to yield the corresponding α-fluoroketones with tertiary fluorocarbons in good to high yields. Considering that the α-fluorination of asymmetrical ketones ­often causes problems with the regioselectivity between the α- and α′-positions, this method could be a good alternative to the α-fluorination of simple ketones for the synthesis of tertiary fluoroketones.

Supporting Information

 
  • References and Notes

    • 1a Ojima I. Fluorine in Medicinal Chemistry and Chemical Biology . Wiley-Blackwell; Chichester: 2009
    • 1b Müller K. Faeh C. Diederich F. Science 2007; 317: 1881
    • 1c Purser S. Moore PR. Swallow S. Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
    • 1d O’Hagan D. Chem. Soc. Rev. 2008; 37: 308
    • 1e Wang J. Sánchez-Roselló M. Aceña JL. del Pozo C. Sorochinsky AE. Fustero S. Soloshonok VA. Liu H. Chem. Rev. 2013; 114: 2432
  • 2 Zhu Y. Han J. Wang J. Shibata N. Sodeoka M. Soloshonok VA. Coelho JA. S. Toste FD. Chem. Rev. 2018; 118: 3887
    • 3a Baudoux J. Cahard D. Org. React. 2007; 69: 347
    • 3b Ma J.-A. Cahard D. Chem. Rev. 2008; 108: PR1
    • 3c Furuya T. Kuttruff CA. Ritter T. Curr. Opin. Drug Discovery Dev. 2008; 11: 803
    • 3d Furuya T. Kamlet AS. Ritter T. Nature 2011; 473: 470
    • 3e Yang X. Wu T. Phipps RJ. Toste FD. Chem. Rev. 2015; 115: 826
    • 4a Pedersen KJ. J. Am. Chem. Soc. 1929; 51: 2098
    • 4b Pedersen KJ. J. Phys. Chem. 1933; 38: 559
    • 4c Pedersen KJ. J. Am. Chem. Soc. 1938; 60: 595
    • 4d Westheimer FH. Jones WA. J. Am. Chem. Soc. 1941; 63: 3283
    • 4e Swain CG. Bader RF. W. Esteve RM. Jr. Griffin RN. J. Am. Chem. Soc. 1961; 83: 1951
    • 4f Brower KP. Gay B. Konkol TL. J. Am. Chem. Soc. 1966; 88: 1681
    • 4g Straub TS. Bender ML. J. Am. Chem. Soc. 1972; 94: 8881
    • 4h Logue MW. Pollack RM. Vitullo VP. J. Am. Chem. Soc. 1975; 97: 6868

      For reviews, see:
    • 5a Pan Y. Tan C.-H. Synthesis 2011; 2044
    • 5b Bernardi L. Fochi M. Franchini MC. Ricci A. Org. Biomol. Chem. 2012; 2911
    • 5c Wang Z.-L. Adv. Synth. Catal. 2013; 355: 2745
    • 5d Nakamura S. Org. Biomol. Chem. 2014; 12: 394
    • 5e Bae HY. Synlett 2015; 26: 705
    • 6a Li J. Li Y.-L. Jin N. Ma A.-L. Huang Y.-N. Deng J. Adv. Synth. Catal. 2015; 357: 2474
    • 6b Li Y.-L. Li J. Deng J. Adv. Synth. Catal. 2017; 359: 1407
  • 7 Zhang R. Ni C. He Z. Hu J. J. Fluorine Chem. 2017; 203: 166
  • 8 Shibatomi K. Kitahara K. Sasaki N. Kawasaki Y. Fujisawa I. Iwasa S. Nat. Commun. 2017; 8: 15600
  • 9 Shibatomi K. Kitahara K. Okimi T. Abe Y. Iwasa S. Chem. Sci. 2016; 7: 1388
  • 10 Typical Procedure of Decarboxylative Fluorination of 1 A dried flask was charged with 1a (0.5 mmol), Selectfluor (0.75 mmol), and DMF (2.5 mL) under argon atmosphere. The mixture was stirred at ambient temperature for 24 h. The mixture was subjected to silica gel column chromatography purification (hexane/EtOAc = 20:1) to give 86% yield of 2a as a colorless liquid.
  • 11 Characterization Data of 2a 1H NMR (500 MHz, CDCl3): δ = 8.07 (d, J = 7.6 Hz, 1 H), 7.52 (dt, J = 7.5, 1.5 Hz, 1 H), 7.35 (t, J = 7.5 Hz, 1 H), 7.26 (d, J = 7.6 Hz, 1 H), 3.18 (dt, J = 17.2, 5.4 Hz, 1 H), 3.01 (ddd, J = 17.2, 9.6, 5.2 Hz, 1 H), 2.53–2.46 (m, 1 H), 2.33–2.24 (m, 1 H), 1.60 (d, J = 22.2 Hz, 3 H). 13C NMR (126 MHz, CDCl3): δ = 194.3 (J = 19.2 Hz), 142.7, 134.0, 130.7, 128.7, 128.3, 127.1, 93.8 (J = 179.9 Hz), 35.0 (J = 22.8 Hz), 26.2 (J = 9.6 Hz), 20.9 (J = 25.2 Hz). 19F NMR (470 MHz, CDCl3): δ = –153.1. HRMS (DART): m/z [M + NH4]+ calcd for C11H15F1N1O1 +1: 196.1138; found: 196.1138.