A Convergent Radical Based Route to Trifluoromethyl Ketones and to α,β-Unsaturated Trifluoromethyl Ketones.

A convergent synthesis of trifluoromethyl ketones and α,β-unsaturated trifluoromethyl ketones is described, starting with aliphatic iodides and dithiocarbonates (xanthates) and exploiting both the α- and β-fragmentations of a sulfonyl radical. The transformation initially furnishes the ketones in a masked enol carbonate form, from which they can be easily regenerated.

[1]  Hong Liu,et al.  Recent advances in the trifluoromethylation methodology and new CF3-containing drugs , 2014 .

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

[3]  G. Röschenthaler,et al.  A concise approach to CF3-containing furan-3-ones, (bis)pyrazoles from novel fluorinated building blocks based on 2,3-butanedione , 2014 .

[4]  C. Olsen,et al.  The Effect of Various Zinc Binding Groups on Inhibition of Histone Deacetylases 1–11 , 2014, ChemMedChem.

[5]  P. Laurent,et al.  Synthesis of substituted 1-trifluoromethyl and 1-perfluoroalkyl-3-(arylamino)prop-2-en-1-one: advances in the mechanism of Combes 2-trifluoromethyl and 2-perfluoroalkyl quinolines synthesis , 2014 .

[6]  Trevor A. Hamlin,et al.  Methylenation of perfluoroalkyl ketones using a Peterson olefination approach. , 2014, The Journal of organic chemistry.

[7]  Hélène Jullien,et al.  Flexible routes to thiophenes. , 2014, Organic letters.

[8]  N. Leadbeater,et al.  Trifluoromethyl ketones: properties, preparation, and application. , 2013, Chemical communications.

[9]  N. Zanatta,et al.  New strategy for the regioselective synthesis of 1-phenyl-3-trifluoromethyl-1H-pyrazoles , 2013 .

[10]  Yuhan Zhou,et al.  Synthesis of trifluoromethyl ketones via tandem Claisen condensation and retro-Claisen C-C bond-cleavage reaction. , 2013, The Journal of organic chemistry.

[11]  Jinhua J. Song,et al.  Development of a large scale asymmetric synthesis of the glucocorticoid agonist BI 653048 BS H3PO4. , 2013, The Journal of organic chemistry.

[12]  Jingwei Zhao,et al.  Synthesis of trifluormethyl substituted oxetenes by the reaction of acetylenedicarboxylate with trifluoromethyl ketone in the presence of triphenylphosphine , 2013 .

[13]  S. Zard,et al.  Fun with Radicals. Some New Perspectives for Organic Synthesis , 2011 .

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

[15]  K. Nicolaou,et al.  New synthetic technologies for the construction of heterocycles and tryptamines. , 2009, Journal of the American Chemical Society.

[16]  L. Kiss,et al.  Efficient synthesis of 2-(trifluoromethyl)nicotinic acid derivatives from simple fluorinated precursors. , 2008, Organic letters.

[17]  A. Yang,et al.  Design, synthesis, and evaluation of trifluoromethyl ketones as inhibitors of SARS-CoV 3CL protease , 2008, Bioorganic & Medicinal Chemistry.

[18]  S. Purser,et al.  Fluorine in medicinal chemistry. , 2008, Chemical Society reviews.

[19]  F. Diederich,et al.  Fluorine in Pharmaceuticals: Looking Beyond Intuition , 2007, Science.

[20]  V. Nenajdenko,et al.  Recent advances in the chemistry of a,-unsaturated trifluoromethylketones , 2007 .

[21]  S. Zard,et al.  The Degenerative Radical Transfer of Xanthates and Related Derivatives: An Unusually Powerful Tool for the Creation of Carbon—Carbon Bonds , 2007 .

[22]  S. Zard New routes to organofluorine compounds based on ketenes and the radical transfer of xanthates. , 2007, Organic & biomolecular chemistry.

[23]  M. Schlosser CF(3)-bearing aromatic and heterocyclic building blocks. , 2006, Angewandte Chemie.

[24]  S. Zard,et al.  Powerful carbon-carbon bond forming reactions based on a novel radical exchange process. , 2006, Chemistry.

[25]  N. Zanatta,et al.  Regiospecific synthesis of 4-alkoxy and 4-amino substituted 2-trifluoromethyl pyrroles. , 2006, The Journal of organic chemistry.

[26]  S. Bagal,et al.  Radicals from aldehydes : A convergent access to dienes and δ-lactones , 2006 .

[27]  Minoru Yoshida,et al.  Novel histone deacetylase inhibitors: cyclic tetrapeptide with trifluoromethyl and pentafluoroethyl ketones. , 2004, Bioorganic & medicinal chemistry letters.

[28]  K. Glaser,et al.  Trifluoromethyl ketones as inhibitors of histone deacetylase. , 2002, Bioorganic & medicinal chemistry letters.

[29]  H. Lebel,et al.  Highly chemoselective rhodium-catalyzed methylenation of fluorine-containing ketones. , 2002, Organic letters.

[30]  B. Crousse,et al.  Anhydrodihydroartemisinin and its 10-trifluoromethyl analogue: access to novel d-ring-contracted artemisinin trifluoromethyl ketones. , 2002, The Journal of organic chemistry.

[31]  V. Kesavan,et al.  New catalytic oxidation of trifluoromethyl carbinols by a ruthenium(II) complex , 2000 .

[32]  S. Zard,et al.  A New Radical Vinylation Reaction of Iodides and Dithiocarbonates. , 1999, Angewandte Chemie.

[33]  K. Tornheim,et al.  Synthesis of potent and selective inhibitors of human plasma kallikrein. , 1999, Bioorganic & medicinal chemistry letters.

[34]  James R. Moore,et al.  Practical asymmetric synthesis of Efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor , 1998 .

[35]  G. Olah,et al.  Direct Preparation of Trifluoromethyl Ketones from Carboxylic Esters: Trifluoromethylation with (Trifluoromethyl)trimethylsilane. , 1998, Angewandte Chemie.

[36]  V. Nenajdenko,et al.  Preparation of α,β-Unsaturated Ketones Bearing a Trifluoromethyl Group and Their Application in Organic Synthesis , 1997 .

[37]  P. Fuchs,et al.  Stereospecific Alkenylation of C−H Bonds via Reaction with β-Heteroatom-Functionalized Trisubstituted Vinyl Triflones1 , 1997 .

[38]  Philip L. Fuchs,et al.  Alkenylation of C−H Bonds via Reaction with Vinyl and Dienyl Triflones. Stereospecific Synthesis of Trisubstituted Vinyl Triflones via Organocopper Addition to Acetylenic Triflones1 , 1996 .

[39]  R. Chambers,et al.  2h-heptafluorobut-2-ene as a synthon for hexafluorobut-2-yne , 1996 .

[40]  S. Zard,et al.  A new and efficient synthesis of trifluoromethyl ketones from carboxylic acids. Part I , 1995 .

[41]  M. Hisamatsu,et al.  One-Step Synthesis of Novel Carbonates: Alkoxymethyl Carbonates, from Alcohols and Chloromethyl Alkyl , 1995 .

[42]  C. Bryant,et al.  Non-peptidic inhibitors of human leukocyte elastase. 4. Design, synthesis, and in vitro and in vivo activity of a series of beta-carbolinone-containing trifluoromethyl ketones. , 1995, Journal of medicinal chemistry.

[43]  Cynthia L. Powell,et al.  A novel fluoride ion mediated olefination of electron-deficient aryl ketones by alkanesulfonyl halides , 1994 .

[44]  M. Bernstein,et al.  NMR structural studies of the tight complex between a trifluoromethyl ketone inhibitor and the 85-kDa human phospholipase A2. , 1993, Biochemistry.

[45]  S. Zard,et al.  An expedient access to trifluoromethyl ketones from carboxylic acids , 1992 .

[46]  D. Bonnet-Delpon,et al.  Preparation of trifluoromethyl ketones and related fluorinated ketones , 1991 .

[47]  D. Bonnet-Delpon,et al.  Determination of Z and E configurations in trifluoromethylated vinyl compounds: 3J(CF) coupling constants as a criterion for configurational assignments , 1991 .

[48]  D. M. Graves,et al.  Oxidation of fluoroalkyl-substituted carbinols by the Dess-Martin reagent , 1989 .

[49]  T. Liang,et al.  Complex of alpha-chymotrypsin and N-acetyl-L-leucyl-L-phenylalanyl trifluoromethyl ketone: structural studies with NMR spectroscopy. , 1987, Biochemistry.

[50]  Xavier Creary,et al.  Reaction of organometallic reagents with ethyl trifluoroacetate and diethyl oxalate. Formation of trifluoromethyl ketones and .alpha.-keto esters via stable tetrahedral adducts , 1987 .

[51]  B. Hammock,et al.  Transition state analogs as ligands for affinity purification of juvenile hormone esterase. , 1986, Science.

[52]  M. Gelb,et al.  Fluoro ketone inhibitors of hydrolytic enzymes. , 1985, Biochemistry.

[53]  Ulrich-Christian Vögeli,et al.  Vicinal C,H spin coupling in substituted alkenes. Stereochemical significance and structural effects†‡ , 1975 .

[54]  S. Zard,et al.  Trifluoroacetonyl radicals: a versatile approach to trifluoromethyl ketones , 1996 .

[55]  A. Lovey,et al.  Decarbalkoxylations of geminal diesters, β-keto esters and α-cyano esters effected by sodium chloride in dimethyl sulpoxide , 1973 .