Nickel-catalyzed alkenylation and alkylation of fluoroarenes via activation of C-H bond over C-F bond

Article abstract of DOI:10.1021/ja807258m

Nickel/P(c-C₅H₉)₃ (PCyp₃) catalyst effects the addition reactions of fluoroarenes across alkynes, 1,3-dienes, and vinylarenes via the activation of C-H bonds over C-F bonds. The acidic C-H bonds located ortho to fluorine are exclusively activated to afford a range of alkenylated and alkylated fluoroarenes. Copyright

Full text of DOI:10.1021/ja807258m

Published on Web 11/11/2008
Nickel-Catalyzed Alkenylation and Alkylation of Fluoroarenes via Activation of
C-H Bond over C-F Bond
Yoshiaki Nakao,* Natsuko Kashihara, Kyalo Stephen Kanyiva, and Tamejiro Hiyama*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity, Kyoto 615-8510, Japan
Received September 13, 2008; E-mail: yoshiakinakao@npc05.mbox.media.kyoto-u.ac.jp;
thiyama@z06.mbox.media.kyoto-u.ac.jp
Table 1. Alkenylation of Pentafluorobenzene Catalyzed by Nickel
There has been an increasing demand for methods to introduce
F-containing groups into organic molecules because of the unique
effects of F-substituents in pharmaceutical, agrochemical, and
materials science.1 Polyfluoroarenes are a representative class of
such fluoroorganic molecules, and thus, the development of efficient
methods for their introduction has been an important issue for
synthetic chemists. Although polyfluoroarenes can be functionalized
via deprotonation of their acidic hydrogens with a stoichiometric
amount of organometalic bases followed by the reactions with
electrophiles,2 the use of a catalytic amount of metal to effect direct
functionalization of C-H bonds of polyfluoroarenes is highly
desired. While recent work by Fagnou3 and Daugulis4 allows the
direct coupling reactions of C-H bonds of polyfluoroarenes with
aryl and alkenyl halides with Pd and Cu catalysts, respectively, a
repertoire for catalytic direct transformations of such highly
electron-deficient arenes remains unexplored in spite of the recent
extensive studies on the catalytic C-H activation of arenes.5 Herein,
we report that Ni/P(c-C5H9)3 (PCyp3) catalyst is highly effective
for direct alkenylation and alkylation of polyfluoroarenes via C-H
activation followed by the insertion of alkynes, 1,3-dienes, and
vinylarenes.6
Whereas many late transition metal complexes undergo the
oxidative addition of C-H bonds of polyfluoroarenes over C-F
bonds,7 experimental8 and theoretical9 studies have shown that Ni(0)
complexes favor oxidative insertion into C-F bonds of poly-
fluoroarenes exclusively rather than C-H bonds.10 Nevertheless,
the reaction of pentafluorobenzene (1a, 1.0 mmol) with 4-octyne
(2a, 1.5 mmol) in the presence of Ni(cod)2 (3 mol %) and PCyp3
(3 mol %) in toluene at 80 °C for 3 h gave (E)-pentafluoro(octen-
4-yl)benzene (3aa) quantitatively (entry 1 of Table 1). Other tri(sec-
alkyl)phosphines including P(i-Pr)3 and PCy3 were also compara-
a Isolated yields. b Reaction run with a 3 mol % catalyst. c Slow
addition of 2c over 2.5 h. d Reaction run at 100 °C.
which were also observed competitively even in the presence of
polyfluorobenzenes in excess to give monoalkenylated products in
modest yields (entries 2-5). Among possible reaction sites, the
C-H bonds ortho to a F substituent are exclusively activated
(entries 6-9). The selective alkenylation at the ortho-position of
fluoro groups was also achieved in the presence of an electron-
withdrawing ester group (entry 10). These data clearly suggest that
the activation of C-H bonds ortho to F is preferred kinetically
and/or thermodynamically.7,13 The electron-donating methoxy group
of 1j did not affect the reaction (entry 11). Similar trends were
also seen in the alkenylation of polyfluoropyridines to give the
corresponding adducts in good yields (entries 12 and 13).
To extend the present alkenylation catalysis to catalytic direct
alkylation of polyfluorobenzenes, we examined the addition of 1a
across other unsaturated compounds. The reaction of 1a (1.0 mmol)
with 1-phenyl-1,3-butadiene under identical conditions proceeded
at its terminal double bond to give 5 in 67% yield (Scheme 1).
Likewise, 2-vinylnaphthalene also inserted into the C-H bond of
1a under Ni catalysis to give 1,1-diarylethane 6 in 83% yield.
The catalytic reactions should be initiated by the formation of
η2-arene complex A followed by the oxidative addition of the C-H
bond of the polyfluoroarene to give B (Scheme 2).6,9 The insertion
of an alkyne into the Ni-H bond occurs after the preceding
coordination in the direction avoiding steric repulsion between the
bulkier R2 and the polyfluorophenyl group on the Ni center.
1
tively effective to give 3aa in >85% yields as estimated by H
NMR, whereas use of PMe3, PBu3, and P(t-Bu)3 as a ligand afforded
only a trace amount of the adduct. A catalyst prepared in situ from
bench-stable Ni(acac)2, [HPCyp3]BF4, and AlMe36e with a standard
Schlenck technique effectively gave 3aa in 87% yield.11 Bis(silyl-
methyl)acetylene 2b underwent the reaction with 1a to give
pentafluorophenyl-substituted allylsilane 3ab (entry 2). Diphenyl-
acetylene (2c) also gave the corresponding cis-adduct, although slow
addition of the alkyne was essential to diminish the competitive
tri- and oligomerization of the alkyne (entry 3). Sterically biased
unsymmetrical alkynes underwent the addition reaction with
excellent regioselectivities to give cis-adducts having a bulkier
substituent trans to the pentafluorophenyl group exclusively (entries
4-6).
Other polyfluorobenzenes also underwent the addition reaction
across 2a (Table 2). Substrates with a lower number of F gave the
corresponding adducts in lower yields possibly due to the lower
acidity of the C-H bond to be activated (entries 1-9).12 Using
excess 2a generally gave good yields of dialkenylated products,
9
16170 J. AM. CHEM. SOC. 2008, 130, 16170–16171
10.1021/ja807258m CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Nickel-Catalyzed Alkenylation of Fluoroarenes
in the formation of the alkylation products and regenerates Ni(0).
The reaction of 1a, 1j-d1, and 2a gave only a small amount (<10%)
of crossover products, supporting the proposed catalytic cycle.11
Here, we have uncovered a Ni catalyst for the activation of C-H
over C-F bonds of polyfluoroarenes and demonstrated their direct
alkenyl- and alkylation to allow efficient synthesis of a variety of
polyfluoroarenes having alkenyl and alkyl groups in regio- and
stereoselective manners. Experimental and theoretical mechanistic
studies determining the origin of the dramatic ligand effect on the
Ni catalysis for C-H activation of polyfluoroarenes and further
development of other C-H functionalizations of F-containing
substrates via Ni catalysis are being pursued in our laboratories.
Acknowledgment. We thank Professor James P. Stambuli for
proofreading the manuscript and helpful comments. This work has
been supported financially by a Grant-in-Aid for Creative Scientific
Research from MEXT. K.S.K. acknowledges Honjo International
Scholarship Foundation for financial support.
Supporting Information Available: Detailed experimental proce-
dures including spectroscopic and analytical data. This material is
available free of charge via the Internet at http:/pubs.acs.org.
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a Isolated yields. b Reaction run with a 3 mol % catalyst.
Reductive elimination gives alkenylated polyfluoroarene 3 and
regenerates the Ni(0) species. The insertion of 1,3-dienes and
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Scheme 1. Alkylation of 1a Catalyzed by Nickel
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Scheme 2. Plausible Mechanism
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