Carbon-Carbon Coupling of C(sp 3 )-F Bonds Using Alumenium Catalysis Weixing Gu, †,‡ Mason R. Haneline, ‡,§ Christos Douvris, ‡,| and Oleg V. Ozerov* ,†,‡ Departments of Chemistry, Texas A&M UniVersity, College Station, Texas 77842, and Brandeis UniVersity, 415 South Street, Waltham, Massachusetts 02454 Received May 14, 2009; E-mail: ozerov@mail.chem.tamu.edu Abstract: Dialkylalumenium cation equivalents coupled with the hexabromocarborane anion function as efficient and long-lived catalysts for alkylation of aliphatic C-F bonds (alkylative defluorination or AlkDF) by alkylaluminum compounds. Only C(sp 3 )-F bonds undergo AlkDF; C(sp 2 )-F bonds are unaffected. Examples of compounds undergoing AlkDF include monofluoroalkanes, gem-difluorocyclopentane, and compounds containing a CF 3 group attached to either an aryl or an alkyl substituent. Conversion of C-F bonds to C-Me bonds is accomplished with high fidelity using Me 3 Al as the stoichiometric reagent. In reactions with Et 3 Al, hydrodefluorination of the C-F bonds is competitive with alkylation, indicative presumably of competitive hydride vs alkyl transfer from Et 3 Al. In a trialkylaluminum reagent, 1.1-1.4 alkyl groups per Al can be used to replace C-F bonds. Organoaluminum compounds efficiently remove water from the reaction mixture, obviating the need for rigorously dry solvents. Some organoaluminum compounds, especially methylaluminoxane, are capable of AlkDF with more reactive substrates, but catalysis by alumenium offers an advantage over the uncatalyzed C-F activation in terms of both increased rate and, in some cases, a dramatically increased selectivity. Introduction Carbon-fluorine bonds are among the most robust function- alities in chemistry. 1 Activation of C-F bonds is thus a fundamental challenge of note. 2 It is also often viewed through the prism of remediation of polyfluoroorganic atmospheric pollutants such as chlorofluorocarbons (CFCs), hydrofluorocar- bons (HFCs), and perfluorocarbons (PFCs), all of which are very potent greenhouse gases. 3 Reductive removal of fluorine can be accomplished by strong reductants with or without a transition-metal catalyst. 2 Selective replacement of F in a C-F bond with another substituent presents a separate challenge. In particular, catalytic conversion of C(sp 3 )-F bonds to C-C bonds is especially rare. 4 Transition-metal catalysis of C-F activation generally relies on the reductive cleavage of the C-F bond, either in an oxidative addition process or by electron transfer. 2 In 2005, we reported on a new approach for hydrodefluorination (HDF) of aliphatic C-F bonds in which the critical C-F cleavage step is a nonredox process of abstraction of fluoride by a highly Lewis acidic silylium cation. 5,6 Reed and co-workers reported on the stoichiometric abstraction of fluoride with silylium reagents paired with the undecaiodocarborane. 7 We recently demonstrated that utilization of halogenated carboranes as companion anions (instead of [B(C 6 F 5 ) 4 ] - ) led to the dramatic improvement of the longevity of the catalytic C-F activation. 8 We conceived of a related “alkylative defluorination” (AlkDF) process mediated by R 2 Al + equivalents (in place of R 3 Si + ) paired with a carborane anion (Scheme 1). Given the greater polarity of Al-C bonds, it seemed reasonable to expect that an alkyl group transfer from Al would be more facile and a catalytic replacement of C-F by an alkyl group can be realized. Trialkylaluminum compounds are readily available and thus are a very reasonable stoichiometric reagent. Here we report on the success of our strategy. Our work here benefits significantly from the knowledge available through the accomplishments of other groups. The guiding precedent for the use of a Lewis acidic main group † Texas A&M University. ‡ Brandeis University. § Current address: Heraeus Metal Processing Inc., Santa Fe Springs, CA 90670. | Current address: University of Colorado, Boulder, CO 80309. (1) (a) Hudlicky, M. Chemistry of Organic Fluorine Compounds; Prentice- Hall: New York, 1992; p 175. (b) Hiyama, T. Organofluorine Compounds Chemistry and Applications; Springer: New York, 2000. (2) (a) Kiplinger, J. L.; Richmond, T. G.; Osterberg, C. E. Chem. ReV. 1994, 94, 373. (b) Burdeniuc, J.; Jedlicka, B.; Crabtree, R. H. Chem. Ber. 1997, 130, 145. (c) Richmond, T. G. In Topics in Organometallic Chemistry; Murai, S., Ed.; Springer: New York, 1999; Vol. 3, p 243. (d) Reinhold, M.; McGrady, J. E.; Perutz, R. N. J. Am. Chem. Soc. 2004, 126, 5268, and references within. (e) Torrens, H. Coord. Chem. ReV. 2005, 249, 1957. (f) Amii, H.; Uneyama, K. Chem. ReV. 2009, 109, 2119. (3) (a) Shine, K. P.; Sturges, W. T. Science 2007, 315, 1804. (b) Burdeniuc, J.; Crabtree, R. H. Science 1996, 271, 340. (4) For recent examples of C(sp 3 )-F to C-C conversion, see: (a) Terao, J.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J. Am. Chem. Soc. 2003, 125, 5646. (b) Terao, J.; Todo, H.; Watanabe, H.; Ikumi, A.; Kambe, N. Angew. Chem., Int. Ed. 2004, 42, 3412. (c) Terao, J.; Watabe, H.; Kambe, N. J. Am. Chem. Soc. 2005, 127, 3656. (d) Hatakeyama, T.; Ito, S.; Nakamura, M.; Nakamura, E. J. Am. Chem. Soc. 2005, 127, 14192. (e) Fuchibe, K.; Akiyama, T. J. Am. Chem. Soc. 2006, 128, 1434. (f) Fuchibe, K.; Mitomi, K.; Suzuki, R.; Akiyama, T. Chem.sAsian J. 2008, 3, 261. (5) Scott, V. J.; C ¸ elenligil-C ¸ etin, R.; Ozerov, O. V. J. Am. Chem. Soc. 2005, 127, 2852. (6) Panisch, R.; Bolte, M.; Mueller, T. J. Am. Chem. Soc. 2006, 128, 9676. (7) Douvris, C.; Stoyanov, E. S.; Tham, F. S.; Reed, C. A. Chem. Commun. 2007, 1145. (8) Douvris, C.; Ozerov, O. V. Science 2008, 328, 1188. Published on Web 07/14/2009 10.1021/ja903927c CCC: $40.75  2009 American Chemical Society J. AM. CHEM. SOC. 2009, 131, 11203–11212 9 11203