DOI: 10.1002/open.201900130
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A Cyanide-Free Synthesis of Acylcyanides through
Ru-Catalyzed C(sp3)-H-Oxidation of Benzylic Nitriles
Pascal Eisele, Michael Bauder, Shih-Fan Hsu, and Bernd Plietker*[a]
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A practical method for generation of acylcyanides devoid of any
external cyanide sources is presented that relies on a mild Ru-
catalyzed selective CÀ H-oxidation of benzylic nitriles. The
starting materials are smoothly generated through condensa-
tion of the corresponding carboxylic acid amides using silanes.
The obtained acylcyanides can be employed in a plethora of
transformation as exemplified to some larger extend in the
sequence of CÀ H-oxidation-Tischenko-rearrangement for the
generation of structurally diverse benzoyloxycyanohydrines.
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Acylcyanides are versatile building blocks in Organic synthesis.[1]
They can be used as both acylating reagents but also in cross-
couplings[2] and addition reactions[3] but also in carbonylcyana-
tion of alkynes[4] or the formation of cyanohydrines (Figure 1).[5]
At the outset of our studies 4-methoxyphenylacetonitrile
and the conditions for the previously reported benzylic CÀ H
oxidation were chosen for the initial experiments and further
optimized. We were delighted to find that after a slight
modification of the previously established reactions conditions
the corresponding acylcyanide 2 was obtained in 97% yield. As
expected, electron-rich acetonitriles give higher yields but
moderately electron withdrawing groups like halides are
tolerated as well. Interestingly, even acetals are stable under
the conditions, neither hydrolysis nor oxidation to the corre-
sponding carbonates were observed. As acylcyanides are highly
reactive,[1] the crude acylcyanides were trapped as t-butylesters
by simple treatment with t-butanol in the presence of base
(Table 1).
Figure 1. Ru-catalyzed selective CÀ H-oxidation of benzylnitriles.
Table 1. Ru-catalyzed oxidation of benzylnitriles and in-situ trapping.
As pointed out above, acylcyanides are highly reactive
intermediates which are difficult to isolate. In the fate of
practicability we subsequently wondered, whether the reaction
mixture could be quenched through the addition of
nucleophiles.[11] While in the case of t-butanol a switch of
solvents proved necessary, both secondary and primary alco-
hols could be added directily after full conversion in the
[a] M. Sc. P. Eisele, M. Sc. M. Bauder, Dr. S.-F. Hsu, Prof. Dr. B. Plietker
Institute of Organic Chemistry
University of Stuttgart
Pfaffenwaldring 55, DE-70569 Stuttgart, Germany
E-mail: bernd.plietker@oc.uni-stuttgart.de
Supporting information for this article is available on the WWW under
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This
is an open access article under the terms of the Creative Commons Attri-
bution Non-Commercial NoDerivs License, which permits use and distribu-
tion in any medium, provided the original work is properly cited, the use is
non-commercial and no modifications or adaptations are made.
ChemistryOpen 2019, 8, 1–4
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© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA