DOI: 10.1002/chem.201404780
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Synthetic Methods
Straightforward Synthesis of 1,2-Dicyanoalkanes from
Nitroalkenes and Silyl Cyanide Mediated by
Tetrabutylammonium Fluoride
Kensuke Kiyokawa, Takaya Nagata, Junpei Hayakawa, and Satoshi Minakata*[a]
Abstract: A straightforward synthesis of 1,2-dicyanoalkanes
by reacting nitroalkenes with trimethylsilyl cyanide in the
presence of tetrabutylammonium fluoride is described. The
reaction proceeds through a tandem double Michael addi-
tion under mild conditions. Employing the hypervalent sili-
cate generated from trimethylsilyl cyanide and tetrabutylam-
monium fluoride is essential for achieving this transforma-
tion. Mechanistic studies suggest that a small amount of
water included in the reaction media plays a key role. This
protocol is applicable to various types of substrates includ-
ing electron-rich and electron-deficient aromatic nitroal-
kenes, and aliphatic nitroalkenes. Moreover, vinyl sulfones
were found to be good alternatives, particularly for electron-
deficient nitroalkenes. The broad substrate scope and func-
tional group tolerance of the reaction makes this approach
a practical method for the synthesis of valuable 1,2-dicya-
noalkanes.
Introduction
knowledge, no straightforward synthesis of 1,2-dicyanoalkanes
has yet been established.
Nitriles are undoubtedly an important class of compounds in
organic synthesis and they have been recognized as versatile
synthetic intermediates for the preparation of other useful
building blocks.[1] Therefore, numerous efforts have been dedi-
cated to the development of methods for introducing cyano
groups into organic molecules.[2] Despite the significant ach-
ievements made in cyanation reactions, there are only a limited
number of examples of dicyanation reactions. Such reactions
can provide 1,2-dicyanoalkanes (succinonitrile derivatives) that
could be transformed into highly valuable compounds such as
1,2-dicarboxylic acids,[3a] 1,2-diamides,[3b] 1,4-diamines,[3c,d] and
various heterocycles (pyrrolidines, succinimides, and pyr-
roles).[3d–i] Bailey and Jackson reported on the synthesis of 1,2-
dicyanoalkanes by the sequential one-pot Michael addition of
lithium cyanide (LiCN) to a vinyl sulfone.[4] However, only one
example of a substrate was described and this gave only mod-
erate yield. Although Arai and Nishida recently reported on the
palladium-catalyzed 1,2-dicyanation of alkynes, and also dem-
onstrated the reduction of the resulting dicyanoalkene to pro-
vide a 1,2-dicyanoalkane, the method requires a two-step pro-
tocol involving a transition-metal-catalyzed reaction.[5] To our
Nitroalkenes, which are easily prepared by nitro-aldol reac-
tions,[6] have been widely used as Michael acceptors in organic
synthesis.[7–9] Conjugate addition of a cyanide anion to a nitroal-
kene derivative is the simplest route to b-nitronitriles,[10] which
are suitable precursors of cyanoalkenes. Corey and Estreicher
reported that the Michael addition of sodium cyanide (NaCN)
to 1-nitrocyclohexene under acidic conditions provided the
corresponding b-nitronitrile, which, after treatment with 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU), gave the corresponding
1-cyanocycloalkene.[11] Although a few examples of the Michael
addition of cyanide anions to nitroalkenes to produce cyanoal-
kenes through the elimination of HNO2 in situ have been re-
ported,[12] the direct use of such cyanoalkenes in further trans-
formations has not been recorded. We have now designed
a new strategy for the straightforward synthesis of 1,2-dicya-
noalkanes from nitroalkenes by a tandem double Michael addi-
tion. The first Michael addition involves the addition of a cya-
nide anion to nitroalkene I (Scheme 1, I to II) and the second
involves the addition of a cyanide anion to cyanoalkene III
formed in situ from the b-nitronitrile II through the elimination
of HNO2 (Scheme 1, III to IV). Thus, we report a novel synthetic
method for the preparation of 1,2-dicyanoalkanes from nitroal-
[a] Dr. K. Kiyokawa, T. Nagata, J. Hayakawa, Prof. Dr. S. Minakata
Department of Applied Chemistry
Graduate School of Engineering
Osaka University, Yamadaoka 2-1
Suita, Osaka 565-0871 (Japan)
Fax: (+81)6-6879-7402
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201404780.
Scheme 1. Strategy for the straightforward synthesis of 1,2-dicyanoalkanes
from nitroalkenes.
Chem. Eur. J. 2014, 20, 1 – 7
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