Hexafluoroisopropanol as a highly versatile solvent

1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) has recently become a very popular solvent or additive with applications across the spectrum of chemistry. Analysis shows that it possesses a wide range of interesting and unique properties. In this Perspective, we detail the main uses of HFIP in the natural sciences and disclose the underlying principles that give it such wide appeal. Accordingly, we show the broad usage and beneficial effects in many areas of chemistry. Reviewing the applications of a solvent would ordinarily be an unusual thing to do, but the unique properties of hexafluoroisopropanol and its applications across a huge swathe of chemistry make that both a viable and interesting undertaking.

[1]  H. Schmickler,et al.  Baeyer-Villiger oxidations with hydrogen peroxide in fluorinated alcohols: lactone formation by a nonclassical mechanism. , 2002, Angewandte Chemie.

[2]  M. Buck,et al.  Trifluoroethanol and colleagues: cosolvents come of age. Recent studies with peptides and proteins , 1998, Quarterly Reviews of Biophysics.

[3]  R. Compton,et al.  Hydrogen Bonding to Hexafluoroisopropanol Controls the Oxidative Strength of Hypervalent Iodine Reagents. , 2016, Journal of the American Chemical Society.

[4]  A. Phillips.  1,1,1,3,3,3‐Hexafluoro‐2‐propanol , 2010, Encyclopedia of Reagents for Organic Synthesis.

[5]  Dieter Schollmeyer,et al.  Metal- and reagent-free highly selective anodic cross-coupling reaction of phenols. , 2014, Angewandte Chemie.

[6]  L. Eberson,et al.  1,1,1,3,3,3-Hexafluoropropan-2-ol as a solvent for the generation of highly persistent radical cations , 1995 .

[7]  F. Colobert,et al.  A remarkable solvent effect of fluorinated alcohols on transition metal catalysed C–H functionalizations , 2016 .

[8]  M. Peruzzini,et al.  Two pathways of proton transfer reaction to (triphos)Cu(η(1)-BH4) via a dihydrogen bond [triphos = 1,1,1-tris(diphenylphosphinomethyl)ethane]. , 2016, Dalton transactions.

[9]  G. Sotzing,et al.  Orthogonal alignment of DNA using hexafluoroisopropanol as solvent for film castings , 2014 .

[10]  H. Rehrauer,et al.  Insight into the beneficial immunomodulatory mechanism of the sevoflurane metabolite hexafluoro‐2‐propanol in a rat model of endotoxaemia , 2015, Clinical and experimental immunology.

[11]  J. Neudörfl,et al.  Unveiling the "booster effect" of fluorinated alcohol solvents: aggregation-induced conformational changes and cooperatively enhanced H-bonding. , 2006, Journal of the American Chemical Society.

[12]  N. Maiti,et al.  Correlation of an Alcohol's αC-D Stretch with Hydrogen Bond Strength in Complexes with Amines , 2003 .

[13]  M. Ratnikov,et al.  Lewis acid catalyst free electrophilic alkylation of silicon-capped pi donors in 1,1,1,3,3,3-hexafluoro-2-propanol. , 2008, Angewandte Chemie.

[14]  P. Jena.  Materials for Hydrogen Storage: Past, Present, and Future , 2011 .

[15]  T. Satoh,et al.  Synthesis of well‐defined syndiotactic poly(methyl methacrylate) with low‐temperature atom transfer radical polymerization in fluoroalcohol , 2006 .

[16]  Martin Nieger,et al.  ortho-Selective phenol-coupling reaction by anodic treatment on boron-doped diamond electrode using fluorinated alcohols. , 2009, Chemistry.

[17]  K. Ohgo,et al.  Comparative study of silk fibroin porous scaffolds derived from salt/water and sucrose/hexafluoroisopropanol in cartilage formation. , 2009, Journal of bioscience and bioengineering.

[18]  J. Ayllón,et al.  First NMR Observation of the Intermolecular Dynamic Proton Transfer Equilibrium between a Hydride and Coordinated Dihydrogen: (dppm)2HRuH···H−OR = [(dppm)2HRu(H2)]+(OR)- , 1997 .

[19]  Siegfried R. Waldvogel,et al.  Efficient anodic and direct phenol-arene C,C cross-coupling: the benign role of water or methanol. , 2012, Journal of the American Chemical Society.

[20]  W. Herrebout,et al.  Lewis acid mediated vinyl-transfer reaction of alkynes to N-alkylimines by using the N-alkyl residue as a sacrificial hydrogen donor. , 2013, Chemistry.

[21]  D. Schollmeyer,et al.  Synthesis of meta-Terphenyl-2,2''-diols by Anodic C-C Cross-Coupling Reactions. , 2016, Angewandte Chemie.

[22]  Fei Li,et al.  Insight into the structures of the second and fifth transmembrane domains of Slc11a1 in membrane mimics , 2014, Journal of peptide science : an official publication of the European Peptide Society.

[23]  A. V. Miroshnichenko,et al.  Case of an acid-free cationic polymerization of alkenes. An efficient preparation of poly-β-pinene in hexafluoroisopropanol medium , 2012, Journal of Polymer Research.

[24]  M. Ratnikov,et al.  Elaboration of a Lewis acid-free protocol for the alkylation of silicon-containing π-donors by β-arylthioalkyl chlorides , 2010 .

[25]  R. Bates,et al.  Determination of pH;: Theory and practice , 1964 .

[26]  D. Schollmeyer,et al.  Access to Pyrazolidin-3,5-diones through Anodic N-N Bond Formation. , 2016, Angewandte Chemie.

[27]  M. Peruzzini,et al.  Dihydrogen bonding in complex (PP3)RuH(η(1)-BH4) featuring two proton-accepting hydride sites: experimental and theoretical studies. , 2014, Inorganic chemistry.

[28]  J. Aubé,et al.  Intramolecular Friedel-Crafts Acylation Reaction Promoted by 1,1,1,3,3,3-Hexafluoro-2-propanol. , 2015, Organic letters.

[29]  F. Toste,et al.  Enantioselective Oxidative Homocoupling and Cross-Coupling of 2-Naphthols Catalyzed by Chiral Iron Phosphate Complexes. , 2016, Journal of the American Chemical Society.

[30]  J. Qu,et al.  Friedel-Crafts alkylation of arenes with epoxides promoted by fluorinated alcohols or water. , 2010, Chemical communications.

[31]  Xiulin Zhu,et al.  Single electron transfer‐living radical polymerization of methyl methacrylate in fluoroalcohol: Dual control over molecular weight and tacticity , 2009 .

[32]  D. M. Kuznetsov,et al.  Acetal-induced cationic polymerization of styrene and indene in hexafluoroisopropanol , 2013 .

[33]  A. Berkessel,et al.  Efficient catalytic methods for the Baeyer–Villiger oxidation and epoxidation with hydrogen peroxide , 2001 .

[34]  D. M. Kuznetsov,et al.  Cationic polymerization of styrenes under essentially neutral conditions , 2013, Journal of Polymer Research.

[35]  Pavel A. Dub,et al.  Experimental and computational studies of hydrogen bonding and proton transfer to [Cp*Fe(dppe)H]. , 2005, Chemistry.

[36]  Geniece L. Hallett-Tapley,et al.  Absolute reactivity of arylallyl carbocations , 2009 .

[37]  F. Walther,et al.  NMR structures of the C-terminal segment of surfactant protein B in detergent micelles and hexafluoro-2-propanol. , 2004, Biochemistry.

[38]  Sharon J. Sequeira,et al.  Novel Modeling Approach to Generate a Polymeric Nanofiber Scaffold for Salivary Gland Cells. , 2010, Journal of nanotechnology in engineering and medicine.

[39]  Ignacio Colomer,et al.  Catalytic Hypervalent Iodine Promoters Lead to Styrene Dimerization and the Formation of Tri- and Tetrasubstituted Cyclobutanes. , 2016, Angewandte Chemie.

[40]  C. Jeffrey,et al.  Dearomative Indole Cycloaddition Reactions of Aza-Oxyallyl Cationic Intermediates: Modular Access to Pyrroloindolines. , 2015, Journal of the American Chemical Society.

[41]  J. Qu,et al.  Tetraphenylphosphonium Tetrafluoroborate/1,1,1,3,3,3-Hexafluoroisopropanol (Ph4PBF4/HFIP) Effecting Epoxide-Initiated Cation-Olefin Polycyclizations. , 2016, Organic letters.

[42]  B. Carré,et al.  The acidity functions of trifluoroethanol and hexafluoroisopropanol, and their mixtures with water , 1981 .

[43]  Sarah E. Wengryniuk,et al.  Access to Diverse Oxygen Heterocycles via Oxidative Rearrangement of Benzylic Tertiary Alcohols. , 2016, Organic letters.

[44]  Xiulin Zhu,et al.  RAFT polymerization of N-vinylpyrrolidone mediated by cyanoprop-2-yl-1-dithionaphthalate in the presence of a fluoroalcohol: the possibility of altering monomer properties by hydrogen bonding? , 2016 .

[45]  T. W. Bentley,et al.  Relatively fast solvolytic reactions of 1-adamantyl mesylate. Further development of the YOTs scale of solvent ionizing power and the NOTs scale of solvent nucleophilicity , 1983 .

[46]  K. Morimoto,et al.  Organo-Iodine(III)-Catalyzed Oxidative Phenol-Arene and Phenol-Phenol Cross-Coupling Reaction. , 2016, Angewandte Chemie.

[47]  R. Hughes,et al.  Dearomative Indole (3 + 2) Reactions with Azaoxyallyl Cations – New Method for the Synthesis of Pyrroloindolines , 2015, Journal of the American Chemical Society.

[48]  S. Denmark,et al.  On the absolute configurational stability of bromonium and chloronium ions. , 2010, Journal of the American Chemical Society.

[49]  Y. Kita,et al.  A novel oxidative azidation of aromatic compounds with hypervalent iodine reagent, phenyliodine(III) bis(trifluoroacetate) (PIFA) and trimethylsilyl azide , 1991 .

[50]  F. Proft,et al.  Metal-Free Synthesis of Chlorinated β-Amino Ketones via an Unexpected Reaction of Imines with Arylacetylenes in 1,1,1,3,3,3-Hexafluoro-2-propanol , 2016 .

[51]  J. D. Bois,et al.  Organocatalytic C–H hydroxylation with Oxone® enabled by an aqueous fluoroalcohol solvent system , 2014 .

[52]  Huali Yu,et al.  Simultaneously improving controls over molecular weight and stereoregularity of Poly(4-vinylpyridine) via a hydrogen bonding-facilitated controlled radical polymerization , 2013 .

[53]  B. Kirchner,et al.  The Catalytic Effect of Fluoroalcohol Mixtures Depends on Domain Formation , 2017 .

[54]  Ignacio Colomer,et al.  Orthogonally Protected 1,2-Diols from Electron-Rich Alkenes Using Metal-Free Olefin syn-Dihydroxylation. , 2016, Organic letters.

[55]  H. Sakurai,et al.  Hypervalent Iodine-Induced Nucleophilic Substitution of para-Substituted Phenol Ethers. Generation of Cation Radicals as Reactive Intermediates , 1994 .

[56]  C. Beaumont,et al.  Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. , 2006, Blood.

[57]  I. Larrosa,et al.  Room-Temperature Direct β-Arylation of Thiophenes and Benzo[b]thiophenes and Kinetic Evidence for a Heck-type Pathway , 2016, Journal of the American Chemical Society.

[58]  D. Schollmeyer,et al.  Source of Selectivity in Oxidative Cross-Coupling of Aryls by Solvent Effect of 1,1,1,3,3,3-Hexafluoropropan-2-ol. , 2015, Chemistry.

[59]  A. Berkessel,et al.  Dramatic acceleration of olefin epoxidation in fluorinated alcohols: activation of hydrogen peroxide by multiple h-bond networks. , 2006, Journal of the American Chemical Society.

[60]  W. Stark,et al.  Fluorinated groups mediate the immunomodulatory effects of volatile anesthetics in acute cell injury. , 2011, American journal of respiratory cell and molecular biology.

[61]  T. Mei,et al.  Activation of remote meta-C–H bonds assisted by an end-on template , 2012, Nature.

[62]  D. Pappo,et al.  Significant enhancement in the efficiency and selectivity of iron-catalyzed oxidative cross-coupling of phenols by fluoroalcohols. , 2015, Angewandte Chemie.

[63]  jin-quan yu,et al.  Functionalization of C(sp3)–H bonds using a transient directing group , 2016, Science.

[64]  Zhihong Liu,et al.  Effect of Hexafluoroisopropanol on the Thermodynamics of Peptide Secondary Structure Formation , 1999 .

[65]  V. Nesterov,et al.  Additive- and Metal-Free, Predictably 1,2- and 1,3-Regioselective, Photoinduced Dual C-H/C-X Borylation of Haloarenes. , 2016, Journal of the American Chemical Society.

[66]  Jean-Pierre Bégué,et al.  Fluorinated Alcohols: A New Medium for Selective and Clean Reaction , 2004 .

[67]  K. Neimann,et al.  Electrophilic activation of hydrogen peroxide: selective oxidation reactions in perfluorinated alcohol solvents. , 2000, Organic letters.

[68]  A. Börner,et al.  Fluorinated Alcohols as Solvents, Cosolvents and Additives in Homogeneous Catalysis , 2007 .

[69]  B. Dempsey,et al.  Ionisation constants of organic acids in aqueous solution , 1979 .

[70]  R. Kötz,et al.  Novel electrolytes for electrochemical double layer capacitors based on 1,1,1,3,3,3-hexafluoropropan-2-ol , 2012 .

[71]  Pavel A. Dub,et al.  Protonation of Cp*M(dppe)H Hydrides: Peculiarities of the Osmium Congener , 2010 .

[72]  T. Rovis,et al.  Expedient Access to 2,3-Dihydropyridines from Unsaturated Oximes by Rh(III)-Catalyzed C-H Activation. , 2015, Journal of the American Chemical Society.

[73]  J. Aubé,et al.  Remodeling and Enhancing Schmidt Reaction Pathways in Hexafluoroisopropanol. , 2016, The Journal of organic chemistry.

[74]  Steven J. Brenek,et al.  Development of a Practical and Convergent Process for the Preparation of Sulopenem , 2012 .

[75]  N. Novoselov,et al.  Study of a possibility of applying the films of the silk fibroin and its mixtures with synthetic polymers for creating the materials of contact lenses , 2009 .

[76]  W. Middleton,et al.  Hydrogen Bonding in Fluoro Alcohols , 1964 .

[77]  K. Morimoto,et al.  Organocatalytic C–H/C–H' cross-biaryl coupling: C-selective arylation of sulfonanilides with aromatic hydrocarbons. , 2013, Journal of the American Chemical Society.

[78]  P. Champagne,et al.  Friedel-Crafts reaction of benzyl fluorides: selective activation of C-F bonds as enabled by hydrogen bonding. , 2014, Angewandte Chemie.

[79]  J. T. Gerig,et al.  Structure and solvation of melittin in 1,1,1,3,3,3-hexafluoro-2-propanol/water. , 2004, Biophysical journal.

[80]  Xiaohong Li,et al.  Hydrogen bonding promoting the controlled radical polymerization of 2-vinyl pyridine: supramonomer for better control , 2015 .

[81]  Gang Li,et al.  Ether-directed ortho-C-H olefination with a palladium(II)/monoprotected amino acid catalyst. , 2013, Angewandte Chemie.

[82]  F. Zhang,et al.  Study on the structure of SF fiber mats electrospun with HFIP and FA and cells behavior , 2009 .

[83]  S. Waldvogel,et al.  Anodic phenol-arene cross-coupling reaction on boron-doped diamond electrodes. , 2010, Angewandte Chemie.

[84]  Chunhua Wang,et al.  Samarium powder as catalyst for SET‐LRP of acrylonitrile in 1,1,1,3,3,3‐hexafluoro‐2‐propanol for control of molecular weight and tacticity , 2011 .

[85]  R. Kuboi,et al.  Clustering of Fluorine-Substituted Alcohols as a Factor Responsible for Their Marked Effects on Proteins and Peptides , 1999 .

[86]  Zhao Gao,et al.  Bis[alkynylplatinum(ii)] terpyridine molecular tweezer with conformationally-rigid spacer: modulating the binding selectivity in a three-component supramolecular recognition system. , 2016, Dalton transactions.

[87]  V. Percec,et al.  Ultrafast synthesis of ultrahigh molar mass polymers by metal-catalyzed living radical polymerization of acrylates, methacrylates, and vinyl chloride mediated by SET at 25 degrees C. , 2006, Journal of the American Chemical Society.

[88]  David E. Schwartz,et al.  Intravenous Application of a Primary Sevoflurane Metabolite Improves Outcome in Murine Septic Peritonitis: First Results , 2013, PloS one.

[89]  L. Ackermann,et al.  Selective Synthesis of Indoles by Cobalt(III)-Catalyzed C–H/N–O Functionalization with Nitrones , 2016 .

[90]  A. Modak,et al.  Remote para-C-H Functionalization of Arenes by a D-Shaped Biphenyl Template-Based Assembly. , 2015, Journal of the American Chemical Society.

[91]  Julian L. Roberts,et al.  Electrochemistry for Chemists , 1995 .

[92]  J. Aubé,et al.  Hexafluoro-2-propanol-Promoted Intermolecular Friedel-Crafts Acylation Reaction. , 2016, Organic letters.

[93]  J. Aubé,et al.  Overcoming product inhibition in catalysis of the intramolecular Schmidt reaction. , 2013, Journal of the American Chemical Society.

[94]  A. Baeza,et al.  Fluorinated alcohols as promoters for the metal-free direct substitution reaction of allylic alcohols with nitrogenated, silylated, and carbon nucleophiles. , 2012, The Journal of organic chemistry.

[95]  S. Kozuch,et al.  Synthetic and Predictive Approach to Unsymmetrical Biphenols by Iron-Catalyzed Chelated Radical-Anion Oxidative Coupling. , 2015, Journal of the American Chemical Society.

[96]  Agustí Lledós,et al.  First investigation of non-classical dihydrogen bonding between an early transition-metal hydride and alcohols: IR, NMR, and DFT approach. , 2004, Chemistry.

[97]  M. Kamigaito,et al.  Bio-Based Polyketones by Selective Ring-Opening Radical Polymerization of α-Pinene-Derived Pinocarvone. , 2016, Angewandte Chemie.

[98]  H. Mayr,et al.  Solvent nucleophilicities of hexafluoroisopropanol/water mixtures , 2013 .

[99]  T. Nakano,et al.  Free-radical copolymerization of vinyl esters using fluoroalcohols as solvents : The solvent effect on the monomer reactivity ratio , 2000 .

[100]  W. Gong,et al.  Site-Selective C(sp3)–H Functionalization of Di-, Tri-, and Tetrapeptides at the N-Terminus , 2014, Journal of the American Chemical Society.

[101]  C. Reichardt.  Solvents and Solvent Effects in Organic Chemistry , 1988 .

[102]  J. Qu,et al.  Intramolecular etherification and polyene cyclization of π-activated alcohols promoted by hot water. , 2015, The Journal of organic chemistry.

[103]  J. T. Gerig,et al.  Interactions of hexafluoro-2-propanol with the Trp-cage peptide. , 2006 .

[104]  L. Eberson,et al.  Detection and Reactions of Radical Cations Generated by Photolysis of Aromatic Compounds with Tetranitromethane in 1,1,1,3,3,3‐Hexafluoro‐2‐propanol at Room Temperature , 1995 .

[105]  H. Baltruschat,et al.  The electro-oxidation of water and alcohols at BDD in hexafluoroisopropanol , 2013 .

[106]  G. Kubas,et al.  Hydrogen activation on organometallic complexes and H2 production, utilization, and storage for future energy , 2009 .

[107]  M. Peruzzini,et al.  In-depth NMR and IR study of the proton transfer equilibrium between ({(MeC(CH 2 PPh 2 ) 3 }Ru(CO)H 2 ) and hexafluoroisopropanol , 2001 .