Tin or gallium-catalyzed cyanide-transition metal-free synthesis of nitriles from aldehydes or oximes

Article abstract of DOI:10.1016/j.tetlet.2016.11.034

Tin or gallium chloride catalyzed transformation of oximes or aldehydes to nitriles is described. Various nitriles were obtained in up to 99% of yields. The gram-scale reaction or the optically active dinitrile was also available. This synthetically useful method has avoided toxic organic or inorganic cyanides as well as transition or noble metal catalysts.

Full text of DOI:10.1016/j.tetlet.2016.11.034

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Accepted Manuscript
Tin or Gallium-Catalyzed Cyanide-Transition Metal-Free Synthesis of Nitriles
from Aldehydes or Oximes
Yan-Jun Zhuang, Jie Liu, Yan-Biao Kang
PII:
S0040-4039(16)31490-3
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.11.034
TETL 48320
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
20 September 2016
4 November 2016
7 November 2016
Please cite this article as: Zhuang, Y-J., Liu, J., Kang, Y-B., Tin or Gallium-Catalyzed Cyanide-Transition Metal-
Free Synthesis of Nitriles from Aldehydes or Oximes, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/
j.tetlet.2016.11.034
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Tetrahedron Letters
Tin or Gallium-Catalyzed Cyanide-Transition Metal-Free Synthesis of Nitriles from
Aldehydes or Oximes
Yan-Jun Zhuang, Jie Liu, and Yan-Biao Kang
Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Tin or gallium chloride catalyzed transformation of oximes or aldehydes to nitriles is described.
Various nitriles were obtained in up to 99% of yields. The gram-scale reaction or the optically
active dinitrile was also available. This synthetically useful method has avoided toxic organic or
inorganic cyanides as well as transition or noble metal catalysts.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Nitriles
Aldehydes
Oximes
Tin
Gallium
———
 Corresponding author. e-mail: ybkang@ustc.edu.cn

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Nitriles are important and useful intermediates for the synthesis of amides, amines, carboxylic acids, oxazolines and ketones.1
Among conventional approaches,2,3 The transformation of aldoximes to nitriles has been established in 1881.3 The conversion of
cheap and easily available oximes to nitriles is a straight forward synthetic strategy and a variety of catalysts have been developed.3
Besides oximes, ketones,4 aldehydes4,5 and methylarenes6 are all suitable starting materials for nitriles. The coupling reactions have
also been applied in the synthesis of nitriles from various [CN]-sources.7 In our previous work of the synthesis of nitriles from
methylarenes or carbonyl compounds, AlCl3 has proven to be an efficient catalyst or reagent for promoting these reactions.4,6a In
this work, gallium and tin chlorides were found even more efficient than AlCl3 as Lewis acids in the conversion of oximes to
nitriles.
Scheme 1. Group 13 metal-catalyzed synthesis of nitriles.
Initially, various Lewis acids were investigated (Scheme 2). Several catalysts such as GaCl3, SnCl2, Zn(OTf)2, and Ga(OTf)3
were all found to be efficient, whereas GaCl3 and SnCl2 were proven to be the best. In the transformation of oximes to nitriles,
GaCl3 and SnCl2 were both selected as the catalysts, whereas only SnCl2 was selected for the synthesis nitriles from aldehydes.
Compared with GaCl3, SnCl2 was not sensitive to moisture, therefore reactions could be carried out in the open air in the presence of
SnCl2.
Scheme 2. Reaction conditions.
Various oximes bearing different substituents were subjected to the reaction conditions catalyzed by tin(II) chloride (method 1A)
or gallium(III) (method 1B) (Scheme 3).8 Either aliphatic or aromatic oximes were smoothly converted to desired nitriles in
generally high yields. Even if the substrates bearing strong electron-withdrawing groups such as nitryl or trifluoromethyl gave
corresponding nitriles in 75-86% of yields (2c and 2d). Heteroaryl nitriles such as 2e and 2f were obtained in high yields with
gallium catalyst. Nicotinonitrile 2f is the precursor of Niacin or nicotine derivatives. Dinitrile 2g was obtained in up to 99% of yield.
With respect to aliphatic nitriles, all nitriles (2h, 2i, 2j and 2k) examined were isolated in more than 80% of yields with gallium
catalyst. Cinnamonitrile 2l and 3-phenylpropiolonitrile 2m were readily synthesized from corresponding oximes in good to high
yields. Chiral dinitriles 2n was obtained in 86% of yield with more than 99% ee for corresponding enantioenriched dioxime. In the
transformation of oximes to nitriles, SnCl2 generally demonstrated lower efficiency compared with GaCl3.

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Scheme 3. Synthesis of nitriles from oximes (method 1, for the procedure, see ref. 8).
The direct synthesis of nitriles from aldehydes is more convenient in organic synthesis. In the aforementioned optimization of
reaction conditions, SnCl2 was found to be more efficient than GaCl3 in the direct synthesis of nitriles from aldehydes (Scheme 2)
due to its tolerance to moisture. Thus SnCl2 was employed to investigate the direct synthesis of nitriles from aldehydes (method 2).9
Comparable yields were obtained for SnCl2 in the catalysis in conversion of oximes and aldehydes to nitriles. For example, nitrile
2a was obtained in 80% yield for both cases. Normally longer reaction time was needed for the direct transformation of aldehydes
to nitriles.