Hydrodefluorination

Hydrodefluorination (HDF) is a type of organic reaction in which in a substrate a carbon–fluorine bond is replaced by a carbon–hydrogen bond.^[1][2] The topic is of some interest to scientific research. In one general strategy for the synthesis of fluorinated compounds with a specific substitution pattern, the substrate is a cheaply available perfluorinated hydrocarbon. An example is the conversion of hexafluorobenzene (C₆F₆) to pentafluorobenzene (C₆F₅H) by certain zirconocene hydrido complexes. In this type of reaction the thermodynamic driving force is the formation of a metal-fluorine bond that can offset the cleavage of the very stable C-F bond. Other substrates that have been investigated are fluorinated alkenes. Another reaction type is oxidative addition of a metal into a C-F bond ^[3] followed by a reductive elimination step in presence of a hydrogen source. For example perfluoronated pyridine reacts with bis(cyclooctadiene)nickel(0) and triethylphosphine to the oxidative addition product and then with HCl to the ortho-hydrodefluorinated product. In reductive hydrodefluorination the fluorocarbon is reduced in a series of single electron transfer steps through the radical anion, the radical and the anion with ultimate loss of a fluorine anion. An example is the conversion of pentafluorobenzoic acid to 3,4,5-tetrafluorobenzoic acid in a reaction of zinc dust in aqueous ammonia.

Specific systems that have been reported for fluoroalkyl group HDF are triethylsilane / carborane acid,^[4][5] and NiCl₂(PCy₃)₂ / (LiAl(O-t-Bu)₃H) ^[6]

References

1. Kuehnel, M. F., Lentz, D. and Braun, T. (2013), Synthesis of Fluorinated Building Blocks by Transition-Metal-Mediated Hydrodefluorination Reactions. Angew. Chem. Int. Ed., 52: 3328–3348. doi:10.1002/anie.201205260
2. C−F and C−H Bond Activation of Fluorobenzenes and Fluoropyridines at Transition Metal Centers: How Fluorine Tips the Scales Eric Clot, Odile Eisenstein, Naseralla Jasim, Stuart A. Macgregor, John E. McGrady, and Robin N. Perutz Accounts of Chemical Research 2011 44 (5), 333-348 doi:10.1021/ar100136x
3. Activation of Carbon-Fluorine Bonds by Metal Complexes Jaqueline L. Kiplinger, Thomas G. Richmond, and Carolyn E. Osterberg Chemical Reviews 1994 94 (2), 373-431 doi:10.1021/cr00026a005
4. Meier, G. and Braun, T. (2009), Catalytic C[BOND]F Activation and Hydrodefluorination of Fluoroalkyl Groups. Angew. Chem. Int. Ed., 48: 1546–1548. doi:10.1002/anie.200805237
5. Hydrodefluorination and Other Hydrodehalogenation of Aliphatic Carbon−Halogen Bonds Using Silylium Catalysis Christos Douvris, C. M. Nagaraja, Chun-Hsing Chen, Bruce M. Foxman, and Oleg V. Ozerov Journal of the American Chemical Society 2010 132 (13), 4946-4953 doi:10.1021/ja100605m
6. Juan Xiao, Jingjing Wu, Wenwen Zhao, Song Cao and NiCl2(PCy3)2-catalyzed hydrodefluorination of fluoroarenes with LiAl(O-t-Bu)3H, Journal of Fluorine Chemistry, Volume 146, February 2013, Pages 76-79, ISSN 0022-1139, doi:10.1016/j.jfluchem.2012.12.002.