Angewandte
Chemie
DOI: 10.1002/anie.201405058
Synthetic Methods
Copper-Catalyzed Aerobic Oxidative Transformation of Ketone-
Derived N-Tosyl Hydrazones: An Entry to Alkynes**
Xianwei Li, Xiaohang Liu, Huoji Chen, Wanqing Wu, Chaorong Qi, and Huanfeng Jiang*
Abstract: A novel strategy involving Cu-catalyzed oxidative
transformation of ketone-derived hydrazone moiety to various
synthetic valuable internal alkynes and diynes has been
developed. This method features inexpensive metal catalyst,
green oxidant, good functional group tolerance, high regio-
selectivity and readily available starting materials. Oxidative
deprotonation reactions were carried out to form internal
alkynes and symmetrical diynes. Cross-coupling reactions of
hydrazones with halides and terminal alkynes were performed
to afford functionalized alkynes and unsymmetrical conju-
gated diynes. A mechanism proceeding through a Cu-carbene
applicability in synthetic chemistry. Another challenge faced
in ketone-to-alkyne transformations includes the selective
deprotonation of proximal hydrogen atoms.
In contrast, N-tosylhydrazones derived from simple
ketones, which were utilized as the precursors of diazo
compounds, have been widely exploited in modern synthetic
chemistry, especially in transition-metal-catalyzed reactions.[2]
Barluenga, Wang and others have demonstrated the synthetic
utility of metal/carbene species (derived from N-tosylhydra-
zones) in cross-coupling reactions. Such a methodology has
emerged as a powerful strategy for the construction of
structurally diverse molecules which might be difficult to
access by other cross-couplings.[3]
ꢀ
intermediate is proposed for the C C triple bond formation.
T
he hydration reaction of alkynes is a well-studied subject in
organic chemistry. However, the retrohydration reaction,
namely the conversion of ketones into alkynes, still remains
underdeveloped (Scheme 1). Previous synthetic protocols[1]
typically involved the enolization of the carbonyl group and
subsequent induced enol elimination induced by a sterically
ꢁ
hindered base to give the C C bond. These known methods
have drawbacks, such as low efficiency, requiring stepwise
a procedure, and harsh reaction conditions, which limit their
Scheme 2. Catalytic transformations of N-tosylhydrazones.
Despite these excellent developments, the cross-coupling
reactions involving N-tosylhydrazones as coupling partners
are still limited. Thus, developing new strategies combining
the chemistry of N-tosylhydrazones with other concepts, such
as aerobic oxidative transformations, might be one exciting
and desirable direction. However, the troublesome compat-
ibility of the stoichiometric amount of oxidant and harsh
reaction conditions in these processes might be the major
challenges.[4] During our search for more selective aerobic
oxidative transformations,[5] we reasoned that a copper/car-
bene species could be a versatile precursor in such conver-
sions. Herein, we would like to present an example of ketone-
to-alkyne (via hydrazones) transformation by selective depro-
tonation in the presence of O2.[3,6]
This copper-catalyzed selective oxidation of N-tosyl-
hydrazones occurs under an atmosphere of oxygen, thus
generating the corresponding internal alkynes or copper
acetylide intermediates in situ (Scheme 2), which could
subsequently participate in oxidative homocouplings, cross-
couplings with halides, and oxidative cross-couplings with
terminal alkynes to afford various symmetrical diynes,
internal alkynes, and unsymmetrical diynes. We speculate
Scheme 1. Retro alkyne hydration strategy: from ketones to alkynes.
[*] X. Li, X. Liu, H. Chen, Dr. W. Wu, Dr. C. Qi, Prof. Dr. H. Jiang
School of Chemistry and Chemical Engineering, South China
University of Technology
Guangzhou 510640 (P.R. China)
E-mail: jianghf@scut.edu.cn
[**] We are grateful to Dr. Liangbin Huang for helpful suggestions and
comments on this manuscript. This work was supported by the
National Basic Research Program of China (973 Program)
(2011CB808600), the National Natural Science Foundation of China
(21172076), the Guangdong Natural Science Foundation
(10351064101000000), and the Fundamental Research Funds for
the Central Universities (2014ZP0004).
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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