Angewandte
Communications
Chemie
Synthetic Methods
Use of Trifluoromethyl Groups for Catalytic Benzylation and
Alkylation with Subsequent Hydrodefluorination
Jiangtao Zhu+, Manuel PØrez+, Christopher B. Caputo, and Douglas W. Stephan*
[13]
À
Abstract: The electrophilic organofluorophosphonium cata-
lyst [(C6F5)3PF][B(C6F5)4] is shown to effect benzylation or
alkylation by aryl and alkyl CF3 groups with subsequent
hydrodefluorination, thus resulting in a net transformation of
CF3 into CH2–aryl fragments. In the case of alkyl CF3 groups,
Friedel–Crafts alkylation by the difluorocarbocation pro-
ceeded without cation rearrangement, in contrast to the
corresponding reactions of alkyl monofluorides.
C F bonds in the presence of silanes and silylium cations.
The following year, Müller and co-workers reported the use
of disilyl cations in related dehydrofluorination reactions of
C F bonds. In 2007, Terao and co-workers described the
alkylation of a CF3 species in a stoichiometric reaction with an
aluminum alkyl species.[15] In 2008, Douvris and Ozerov
reported the use of a trialkylsilylium cation in the hydro-
defluorination of trifluoromethyl and nonafluorobutyl groups
by silanes under mild conditions.[16] The Ozerov group
subsequently described the use of AlMe3 and an alumenium
[14]
À
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C
F bonds are thermodynamically strong and generally
[17]
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kinetically inert. These attributes together with increased
hydrophobicity and metabolic stability are important features
that have led to the incorporation of fluorine into over 200
pharmaceuticals currently in use.[1] This resistance to reac-
tivity has also been exploited for materials development.
Perhaps the best known example is the perfluorinated
polymer Teflon,[2] which is used as a chemically resistant
coating or as a container for corrosive materials. On the other
hand, the lack of reactivity means that organofluorocarbons
are environmentally persistent and pervasive.[3] For example,
the highly toxic perfluorooctanoic acid derivatives used in
surfactants and the production of fluorinated polymers have
been found even in arctic snow.[4] Furthermore, the adverse
effects of chlorofluorocarbons (CFCs) and other low-molec-
ular-weight fluorinated alkanes, which act as potent green-
house gases, are well-established.[5]
cation to alkylate C F bonds.
In 2012 and 2013, our
research group reported the use of the electrophilic Lewis
acid catalysts B(C6F5)3 and [(C6F5)3PF][B(C6F5)4] in hydro-
defluorination reactions of fluoroalkanes.[18] Whereas the
former is a classic Lewis acid based on the vacant p orbital on
B, the latter exploits the s* orbital oriented opposite to the
À
P F bond. A recent review by Oestreich et al. provides an
excellent overview of main-group Lewis acids for C F bond
À
activation.[19]
Friedel–Crafts products were identified in several of the
above studies,[13,16,17,20] although it was Olah and Kuhn in 1964
who first reported the Friedel–Crafts alkylation of alkyl
fluorides by the use of BF3.[21] In 2011, Siegel and co-workers
exploited Friedel–Crafts reactions of polyaromatic mono-
fluoroarenes initiated by protons or silylium cations to effect
intramolecular cyclization reactions affording polyaromatic
species.[22] Kemnitz and co-workers reported C C bond
À
À
Strategies for the installation of C F bonds or fluorinated
organic fragments have drawn considerable attention in
recent years, largely because of the potential for pharma-
ceutical applications.[6] On the other hand, strategies designed
formation through reactions of fluoromethanes and benzene
in the presence of the heterogeneous catalyst aluminum
chlorofluoride.[20b] Recently, Paquin and co-workers devel-
oped an acid-mediated Friedel–Crafts arylation of benzyl
fluorides that was enabled by hydrogen bonding.[23] We
previously observed that whereas [(C6F5)3PF][B(C6F5)4]
mediated hydrodefluorination in CD2Cl2, the use of arene
solvents afforded Friedel–Crafts by-products. In this study, we
optimized the use of [(C6F5)3PF][B(C6F5)4] as a catalyst for
Friedel–Crafts benzylation or alkylation with aryl or alkyl
trifluoromethyl derivatives and subsequent hydrodefluorina-
tion. In this fashion, CF3 groups were converted catalytically
into a variety of CH2–aryl fragments.
We explored the notion of the Lewis acid activation of CF3
fragments by treating p-BrC6H4CF3 in C6D6 in the presence of
Et3SiH (3.6 equiv) with 10 mol% of the Lewis acids B(C6F5)3,
FeCl3, InCl3, and ZnCl2. In these cases, no reaction was
observed over the course of 16 h at 808C. In contrast, the use
of AlCl3 (1.5 mol%) as the catalyst under the same conditions
afforded the product p-BrC6H4CH2C6D5 (1) in 15% yield
after 16 h at 258C. Furthermore, the use of the Lewis acid
[(C6F5)3PF][B(C6F5)4] (1.5 mol%) gave the product
À
to cleave C F bonds for the degradation of environmental
toxins have seen more limited development.[7] The research
groups of Jones,[8] Grushin,[9] Oestreich,[10] and others[1,11] have
developed transition-metal species that activate aryl or
À
monofluoroalkyl C F bonds stoichiometrically, whereas
a recent report described the abstraction of fluoride by
B(C6F5)3 from a hexafluoropropylene–palladium species to
give a cationic perfluoroallylpalladium complex.[12]
À
An alternative strategy for C F bond activation involves
the use of main-group reagents or catalysts. To this end,
Ozerov and co-workers described the hydrodefluorination of
[*] Dr. J. Zhu,[+] Dr. M. PØrez,[+] Dr. C. B. Caputo, Prof. Dr. D. W. Stephan
Department of Chemistry, University of Toronto
80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada)
E-mail: dstephan@chem.utoronto.ca
[+] These authors contributed equally.
Supporting information and ORCID(s) from the author(s) for this
Angew. Chem. Int. Ed. 2016, 55, 1417 –1421
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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