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

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.

Key words

fluorination - decarboxylation - α-fluoroketones - noncatalytic reaction - tertiary fluorides

• 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.