velopments are represented by the cyanation of aryl bromides
through a copper-catalyzed domino halide exchange and the
use of specific amines (TMEDA or 1,1-methylenedipiperi-
dine) as co-catalysts.9,10 Herein is reported the cyanide-free
cyanation of boronic acids with organic thiocyanates as a
complementary method for the synthesis of nitriles. This mild
and general protocol is an extension of a growing family of
thioorganic/boronic acid cross-couplings discovered in this
laboratory11 and extended in others.12
With these results in hand, the scope and the possible
limitations of this new protocol were studied. As shown in
Table 1, a variety of different boronic acids were tested in
Table 1. Pd-Catalyzed Cyanation of Boronic Acids Mediated
by CuTC16
Initially, the coupling of boronic acids with several
thiocyanates was investigated (Scheme 1). Both catalytic
Scheme 1. Variation of Thiocyanates for the Cyanation of
Boronic Acids
palladium and stoichiometric copper(I) carboxylate are
required for the cross-coupling of boronic acids and organic
thiocyanates, just as with other thioorganic-boronic acid
cross-couplings.11,12 Among the systems studied for the
cyanative cross-coupling, the Pd(PPh3)4/CuTC system gave
the best results, and 1.5 equiv of boronic acids was used to
optimize the cross-coupling yields. In all cases, the cyanation
products were obtained in good to excellent yields (70-92%)
in THF at 50 °C.
As probed by the examples depicted in Scheme 1, the
nature of the organic thiocyanate did not seem critical to
the reaction, so commercially available benzyl thiocyanate
was employed as the cyanide source in subsequent experi-
ments and served as an excellent cyanide source in boronic
acid cross-coupling reactions.13
(8) (a) Schareina, T.; Zapf, A.; Beller, M. Chem. Commun. 2004, 1388.
(b) Weissman, S. A.; Zewge, D.; Chen, C. J. Org. Chem. 2005, 70, 1508.
(c) Grossman, O.; Gelman, D. Org. Lett. 2006, 8, 1189.
(9) Zanon, J.; Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2003,
125, 2890.
(10) Sundermeier, M.; Zapf, A.; Mutyala, S.; Baumann, W.; Sans, S.;
Weiss, S.; Beller, M. Chem.sEur. J. 2003, 9, 165.
a 1.5 equiv of CuTC. b 2.0 equiv of CuTC. c 3.0 equiv of CuTC. d Isolated
yield. e Detected by GC-MS.
(11) (a) Srogl, J.; Liebeskind, L. S. J. Am. Chem. Soc. 2000, 122, 11260.
(b) Savarin, C.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2001, 3, 91. (c)
Savarin, C.; Liebeskind, L. S. Org. Lett. 2001, 3, 2149. (d) Srogl, J.;
Liebeskind, L. S. Org. Lett. 2002, 4, 979. (e) Kusturin, C. L.; Liebeskind,
L. S.; Neumann, W. L. Org. Lett. 2002, 4, 983. (f) Liebeskind, L. S.; Srogl,
J.; Savarin, C.; Polanco, C. Pure Appl. Chem. 2002, 74, 115. (g) Kusturin,
C.; Liebeskind, L. S.; Rahman, H.; Sample, K.; Schweitzer, B.; Srogl, J.;
Neumann, W. L. Org. Lett. 2003, 5, 4349. (h) Lory, P.; Gilbertson, S. R.
Chemtracts 2005, 18, 569.
(12) (a) Alphonse, F.-A.; Suzenet, F.; Keromnes, A.; Lebret, B.;
Guillaumet, G. Org. Lett. 2003, 5, 803. (b) Alphonse, F.-A.; Suzenet, F.;
Keromnes, A.; Lebret, B.; Guillaumet, G. Synlett 2002, 3, 447. (c) Lengar,
A.; Kappe, C. O. Org. Lett. 2004, 6, 771. (d) Oumouch, S.; Bourotte, M.;
Schmitt, M.; Bourguignon, J.-J. Synthesis 2005, 25. (e) Morita, A.;
Kuwahara, S. Org. Lett. 2006, 8, 1613.
the copper-mediated, palladium-catalyzed cyanation reaction.
Very efficient transformations of unactivated (electron-
neutral) (entries 1-3) and activated (electron-rich) aryl
boronic acids (entries 4-6) were observed under the above
conditions (1.5 equiv of CuTC, THF, 50 °C). However,
deactivated (electron-deficient) aryl and heteroaryl boronic
(13) Ethyl and benzyl thiocyanates are commercially available; phe-
nylthiocyanate and p-nitrophenylthiocyanate were prepared from the cor-
responding thiol according to: Still, I. W. J.; Watson, I. D. G. Synth.
Commun. 2001, 31, 1355.
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Org. Lett., Vol. 8, No. 19, 2006