Benzylic Fluorination Induced by a Charge-Transfer Complex with a Solvent-Dependent Selectivity Switch

We present a divergent strategy for the fluorination of phenylacetic acid derivatives that is induced by a charge-transfer complex between Selectfluor and 4-(dimethylamino)pyridine. A comprehensive investigation of the conditions revealed a critical role of the solvent on the reaction outcome. In the presence of water, decarboxylative fluorination through a single-electron oxidation is dominant. Non-aqueous conditions result in the clean formation of α-fluoro-α-arylcarboxylic acids.

[1]  M. Fagnoni,et al.  Generation of Alkyl Radicals: From the Tyranny of Tin to the Photon Democracy , 2020, Chemical reviews.

[2]  Adrián Gómez‐Suárez,et al.  Selectfluor® Radical Dication (TEDA 2+. ) – A Versatile Species in Modern Synthetic Organic Chemistry , 2020 .

[3]  Mingbin Yuan,et al.  Engaging α-Fluorocarboxylic Acids Directly in Decarboxylative C–C Bond Formation , 2020 .

[4]  R. Yazaki,et al.  Chemoselective Catalytic α-Oxidation of Carboxylic Acids: Iron/Alkali Metal Cooperative Redox Active Catalysis. , 2020, Journal of the American Chemical Society.

[5]  L. Ye,et al.  Enantioselective Copper(I)/Chiral Phosphoric Acid Catalyzed Intramolecular Amination of Allylic and Benzylic C−H Bonds , 2019, Angewandte Chemie.

[6]  I. Leito,et al.  On the Basicity of Organic Bases in Different Media , 2019, European Journal of Organic Chemistry.

[7]  A. Sterling,et al.  The fluorination of C-H bonds: developments and perspectives. , 2019, Angewandte Chemie.

[8]  Zhen Wang,et al.  Ag-Catalyzed Chemoselective Decarboxylative Mono- and gem-Difluorination of Malonic Acid Derivatives. , 2019, Journal of the American Chemical Society.

[9]  Samantha L. Bidwell,et al.  Experimental and Theoretical Evidence for Nitrogen–Fluorine Halogen Bonding in Silver-Initiated Radical Fluorinations , 2019, ACS Catalysis.

[10]  C. Kee,et al.  Synthesis of 18F-difluoromethylarenes using aryl boronic acids, ethyl bromofluoroacetate and [18F]fluoride† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c8sc05096a , 2019, Chemical science.

[11]  C. Hammond,et al.  Catalytic Formation of C(sp3)–F Bonds via Heterogeneous Photocatalysis , 2018, ACS Catalysis.

[12]  M. Antonietti,et al.  Continuous Heterogeneous Photocatalysis in Serial Micro-Batch Reactors. , 2018, Angewandte Chemie.

[13]  Jeffrey F. Van Humbeck,et al.  Benzylic Fluorination of Aza-Heterocycles Induced by Single-Electron Transfer to Selectfluor. , 2018, Angewandte Chemie.

[14]  T. Truong,et al.  Decarboxylative fluorination of aliphatic carboxylic acids under heterogeneous delafossite AgFeO2 nanoparticle catalysis: The utilization of bimetallic cooperativity , 2018 .

[15]  N. Meanwell.  Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design. , 2018, Journal of medicinal chemistry.

[16]  R. Baxter,et al.  Radical C-H Fluorination Using Unprotected Amino Acids as Radical Precursors. , 2017, Organic letters.

[17]  G. Sammis,et al.  Recent Advances in Radical Fluorination , 2015, Synthesis.

[18]  M. D. Hill,et al.  Applications of Fluorine in Medicinal Chemistry. , 2015, Journal of medicinal chemistry.

[19]  D. MacMillan,et al.  Decarboxylative Fluorination of Aliphatic Carboxylic Acids via Photoredox Catalysis. , 2015, Journal of the American Chemical Society.

[20]  P. Champagne,et al.  Monofluorination of Organic Compounds: 10 Years of Innovation. , 2015, Chemical reviews.

[21]  T. Lectka,et al.  Photocatalyzed benzylic fluorination: shedding "light" on the involvement of electron transfer. , 2014, Organic letters.

[22]  D. O'Hagan,et al.  Successful fluorine-containing herbicide agrochemicals , 2014 .

[23]  P. Tang,et al.  Silver-catalyzed oxidative activation of benzylic C-H bonds for the synthesis of difluoromethylated arenes. , 2014, Angewandte Chemie.

[24]  Chuo Chen,et al.  Visible light-promoted metal-free C-H activation: diarylketone-catalyzed selective benzylic mono- and difluorination. , 2013, Journal of the American Chemical Society.

[25]  J. Passchier,et al.  Catalytic decarboxylative fluorination for the synthesis of tri- and difluoromethyl arenes. , 2013, Organic letters.

[26]  M. Inoue,et al.  Metal-free fluorination of C(sp3)-H bonds using a catalytic N-oxyl radical. , 2013, Organic letters.

[27]  John M. Brown,et al.  Palladium-catalyzed substitution and cross-coupling of benzylic fluorides. , 2012, Organic Letters.

[28]  D. O'Hagan.  Fluorine in health care: Organofluorine containing blockbuster drugs , 2010 .

[29]  O. Solin,et al.  Radiosynthesis and evaluation of [18F]Selectfluor bis(triflate). , 2010, Angewandte Chemie.

[30]  S. Kalaichelvan,et al.  FT-IR, FT-Raman spectra and ab initio HF and DFT calculations of 4-N,N'-dimethylamino pyridine. , 2008, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[31]  Fei Zhang,et al.  A novel general method for preparation of α-fluoro-α-arylcarboxylic acid. Direct fluorination of silyl ketene acetals with Selectfluor® , 2006 .

[32]  S. P. Porras,et al.  Nitromethane as solvent in capillary electrophoresis. , 2005, Journal of chromatography. A.

[33]  G. Olah,et al.  Synthetic methods and reactions , 1988, Proceedings / Indian Academy of Sciences.

[34]  J. Olah,et al.  Synthetic methods and reactions. 63. Pyridinium poly(hydrogen fluoride) (30% pyridine-70% hydrogen fluoride): a convenient reagent for organic fluorination reactions , 1979 .

[35]  Chi‐Huey Wong,et al.  Selectfluor: mechanistic insight and applications. , 2004, Angewandte Chemie.