as an inert reaction partner. In this field, the structural specific
substrates are the first choices, and many relative transforma-
tions have been developed through the skeleton reorganiza-
tion.4 Many efforts have also been made to the cleavage and
transformation of nitriles due to their availability and
stability.5
C-CN for the further cross coupling. We set out to further
explore the reactivity of arylnitriles in the presence of
different aryl boronic species to facilitate the construction
of the C-C bond.
2-Naphthylnitrile 1a was first chosen as a studying
objective. After the screening, we found that the best base
for this transformation was t-BuOK, in the presence of CuF2
as an additive. On the other hand, aryl boronic ester 2b seems
to be the best partner for this cross coupling (Table 1). It is
Previous studies also indicated that the CN group could
be applied as a leaving group in cross couplings with more
active Grignard reagents and organo zinc reagents via Ni
catalysis.6 During those transformations, active organome-
tallic reagents first played the critical role to reduce the Ni(II)
to Ni(0) to initiate the catalytic cycle as a reducing reagent
other than a coupling partner. However, cross coupling of
arylnitriles with relatively unreactive organo species, such
as organoboronic species, has never been reported. Not only
does it arise from the difficulty of transmetalation between
the unreactive organometallic species and organonickel
intermediates but also the poor reductivity of unreactive
species may not reduce Ni(II) species to initiate the oxidative
addition.7
Table 1. Cross Coupling between 1a with Phenyl Boronic Acid
Derivativesa
To our interest, when we studied Ni-catalyzed C-O
cleavage of aryl carboxylate to cross couple with boroxine
2a,8 in the presence of a cyano group on substrate 1, two
different coupling products were isolated in comparable
yields (Scheme 1). It implied that the same condition not
Scheme 1
a All the reactions were carried out in 0.2 mmol scale of 1a with 4.0
equiv of 2. b GC yields with n-dodecane as an internal standard. c 1.3 equiv
of 2a was used. d Isolated yield.
only activated the aryl C-O bond but also induced the cross
coupling between arylnitriles and phenylboroxine. This
observation also showed the potential ability of aryl boroxine
to reduce Ni(II) to Ni(0) to initiate the oxidative addition of
pointed out that only Ni catalyst is sufficient for this
transformation, and Pd, Fe, and the other transition metal
species were tested but failed. The efficiency was further
promoted by the addition of excess PCy3 (please refer to
Table S1, Supporting Information).
Different arylnitriles were further surveyed (Table 2).
Other than the naked naphthyl group, both the electron-
donating group and the electron-deficient group on the
naphthyl skeleton did not obviously affect the efficiency. The
good reactivity of the phenyl derivative showed a broad
generality of the substrate scope. Similarly, the electron-
withdrawing group and electron-donating group survived
well. The presence of the MeO, PhO, ester, and amide group
offers the great chance to further functionalize the products
with developed methods. It is noteworthy that the hetero-
cyclic substrates showed even better reactivity, which
expanded the substrate scope much broader.
(4) (a) Jun, C.-H. Chem. Soc. ReV. 2004, 33, 610. (b) Winter, C.; Krause,
N. Angew. Chem., Int. Ed. 2009, 48, 2460. (c) Bonesi, S. M.; Fagnoni, M.;
Albini, A. Angew. Chem., Int. Ed. 2008, 47, 10022.
(5) (a) Tobisu, M.; Chatani, N. Chem. Soc. ReV. 2008, 37, 300. (b) Taw,
F. L.; White, P. S.; Bergman, R. G.; Brookhart, M. J. Am. Chem. Soc.
2002, 124, 4192. (c) Nakao, Y.; Kanyiva, K. S.; Oda, S.; Hiyama, T. J. Am.
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(e) Tobisu, M.; Kita, Y.; Chatani, N. J. Am. Chem. Soc. 2006, 128, 8152.
(f) Tobisu, M.; Nakamura, R.; Kita, Y.; Chatani, N. J. Am. Chem. Soc.
2009, 131, 3174. (g) Burmeister, J. L.; Edwards, L. M. J. Chem. Soc. A
1971, 1663. (h) Na´jera, C.; Sansano, J. M. Angew. Chem., Int. Ed. 2009,
48, 2452. (i) Nakao, Y.; Oda, S.; Hiyama, T. J. Am. Chem. Soc. 2004, 126,
13904. (j) Watson, M. P.; Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130,
12594. (k) Nakao, Y.; Ebata, S.; Yada, A.; Hiyama, T.; Ikawa, M.; Ogoshi,
S. J. Am. Chem. Soc. 2008, 130, 12874. (l) Blum, J.; Oppenheimer, E.;
Bergmann, E. D. J. Am. Chem. Soc. 1967, 89, 2338. (m) Garcia, J. J.;
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Further studies also showed the wide range of boronic ester
derivatives for this transformation (Table 3). Electron-
donating groups facilitated this transformation well, and
desired cross coupling products were isolated in good yields
(entries 1-4 and 6-7). It is important to note that the steric
(6) (a) Miller, J. A. Tetrahedron Lett. 2001, 42, 6991. (b) Miller, J. A.;
Dankwardt, J. W. Tetrahedron Lett. 2003, 44, 1907. (c) Miller, J. A.;
Dankwardt, J. W.; Penney, J. M. Synthesis 2003, 1643. (d) Penney, J. M.;
Miller, J. A. Tetrahedron Lett. 2004, 45, 4989.
Org. Lett., Vol. 11, No. 15, 2009
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