Angewandte
Communications
Chemie
Aminations
Mild and Selective Cobalt-Catalyzed Chemodivergent Transfer
Hydrogenation of Nitriles
+
+
Zhihui Shao , Shaomin Fu , Mufeng Wei, Shaolin Zhou,* and Qiang Liu*
[
4]
Abstract: Herein, we describe a selective cobalt-catalyzed
chemodivergent transfer hydrogenation of nitriles to synthesize
primary, secondary, and tertiary amines. The solvent effect
plays a key role for the selectivity control. The general
applicability of this procedure was highlighted by the synthesis
of more than 70 amine products bearing various functional
groups in high chemoselectivity. Moreover, this mild system
achieved > 2000 TONs (turnover numbers) for the transfer
hydrogenation of nitriles.
amines via catalytic reduction of nitriles has been much less
explored, and noble metal catalysts are requisite for the
known examples. To date, a general chemodivergent synthesis
of primary and secondary amines via selective hydrogenation
of nitriles has not been established, which is a significant but
challenging goal in organic synthesis.
Nitriles are conventionally reduced using stoichiometric
amounts of sensitive metal hydrides, which suffers from low
atom-efficiency and functional group tolerance. Clearly, the
catalytic hydrogenation of nitriles is a more sustainable
synthetic route. Direct hydrogenation with H2 gas and
transfer hydrogenation are two parallel strategies for hydro-
genation reactions. Although heterogeneous catalysts are
T
he catalytic reduction of nitriles represents an efficient and
[
1]
green one-step synthesis of valuable amine products. How-
ever, there is a crucial selectivity problem for this reaction
owing to the formation of mixtures of primary amines,
commonly used for the direct hydrogenation of nitriles with
H to produce primary amines in industry, homogeneous
[2]
[5]
secondary amines, imines,
and even tertiary amines
2
(
Scheme 1). Within these possibilities, the selective synthesis
catalysts can be more selective and milder. However, these
reactions are almost limited to the precious metals (mainly
[
6]
based on ruthenium). Very recently, noteworthy progress
has been made by Bellerꢀs and Milsteinꢀs groups in this
respect. They independently developed molecular-defined
[7]
[8]
[9]
iron, manganese, and cobalt catalysts for the direct
hydrogenation of nitriles to primary amines under over 30 bar
H pressure and 1008C. Complementary to the direct hydro-
2
genation, the transfer hydrogenation could allow for reduc-
tions under ambient conditions without the need for hazard-
[10]
ous pressurized H gas nor elaborate experimental setups.
2
Scheme 1. Possible reaction pathways for the hydrogenation of nitriles.
Nevertheless, very limited studies on the transfer hydro-
genation of nitriles have been reported, which are all
restricted to the use of noble metal catalysts.
[11]
of a certain amine product constitutes a particular challenge,
especially for secondary and tertiary amines. This is because
at least four steps are involved in the reaction sequence for
the generation of secondary or tertiary amines via nitrile
reduction. Consequently, a high degree of selectivity control is
required for these reactions. Considering the intricate selec-
Herein, we describe the first cobalt-catalyzed transfer
hydrogenation of nitriles for a chemodivergent synthesis of
[
9,12]
primary and secondary amines.
The selectivity control was
achieved by using different solvents and cobalt catalysts.
Moreover, a reductive amination of nitriles has been also
realized in the presence of various amine substrates to
produce unsymmetric secondary and tertiary amines
[
3]
tivity control, a direct synthesis of secondary or tertiary
(
Scheme 2). Based on this strategy, over 70 amine products
[
+]
[+]
were synthesized selectively with well-defined cobalt catalysts
and ammonia borane (NH -BH , AB) as a practical hydrogen
donor. These reactions could proceed under mild condi-
[
*] Z. Shao, Dr. S. Fu, M. Wei, Prof. Dr. Q. Liu
Center of Basic Molecular Science (CBMS)
Department of Chemistry, Tsinghua University
Beijing 100084 (China)
3
3
[
13]
[14]
tions without any additives.
E-mail: qiang_liu@mail.tsinghua.edu.cn
Following our interests for the development of new cobalt
[
+]
Z. Shao, Prof. Dr. S. Zhou
[15]
catalysts, this investigation began with the preparation of
a series of well-defined NNP
catalysts I–VIII. After having these catalysts in hand, we
studied their reactivity in transfer hydrogenation of benzoni-
trile 1a using AB as the hydrogen donor in methanol
Key Laboratory of Pesticide & Chemical Biology
Ministry of Education, College of Chemistry
Central China Normal University (CCNU) (China)
E-mail: szhou@mail.ccnu.edu.cn
[16]
and PNP pincer cobalt
+
[
] These authors contributed equally to this work.
(
Table S1). The use of NNP pincer catalysts I and II afforded
Supporting information and the ORCID identification number(s) for
the best yields and selectivity for the formation of benzyl-
amine 2a and dibenzylamine 3a, respectively. However, the
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!