Angewandte
Communications
Chemie
À
C H Alkenylation
Chelation versus Non-Chelation Control in the Stereoselective Alkenyl
2
À
sp C H Bond Functionalization Reaction
Qiu-Ju Liang, Chao Yang, Fei-Fan Meng, Bing Jiang, Yun-He Xu,* and Teck-Peng Loh*
Abstract: A hydroxy group chelation-assisted stereospecific
oxidative cross-coupling reaction between alkenes was devel-
oped under mild reaction conditions. In the presence of
palladium catalyst, the alkenes tethered with hydroxy function-
ality can couple efficiently with electron-deficient alkenes to
form the corresponding multi-substituted olefin products. The
hydroxy group on the substrate could play dual roles in
À
reaction, acting as the directing group for alkenyl C H bond
activation and controlling the stereoselectivity of the products.
O
lefins are a very important class of compounds in organic
chemistry. Accordingly, it is not surprising that many methods,
including the highly stereoselective methods, have been
developed towards their synthesis.[1] Among them, the
Wittig reactions,[2] transition metal-catalyzed cross-coupling
reactions,[3] and olefin methathesis[4] represent the most
commonly used approaches. Unfortunately, these methods
still suffer from poor atom economy, poor selectivities with
highly substituted alkenes, high cost of starting materials, and/
or the need to use expensive metal catalyst. Therefore, novel
and highly atom-economical method for the stereoselective
synthesis of alkenes utilizing cheap and easily available
starting materials that is amenable to large scale production
is highly desirable.[5] An attractive strategy to overcome these
Scheme 1. Palladium-catalyzed oxidative cross-coupling between
alkenes.
À
a selective alkenyl C H bond functionalization and tandem
cross-coupling reaction. Herein, we report for the first time
À
the realization of this concept for direct site-selective C H
bond functionalization and the tandem coupling reaction.
This method provides easy and practical access to highly
substituted alkenes with very high stereoselectivities.
To test the feasibility of this concept, we commenced the
hypothesized coupling reaction using homoallylic alcohol 1a
as the model substrate to couple with n-butyl acrylate in the
presence of palladium catalyst. It has been well established
that the combined catalytic system of palladium catalyst with
limitations is to develop transition-metal-catalyzed selective
sp2 alkenyl C H bond coupling reactions. While the
[6]
À
2
À
À
(hetero)aryl sp C H bond using transition-metal catalysts
amino acid ligand could mediate efficient direct C H bond
have witnessed significant progress in recent years,[7] stereo-
functionalization.[11] Therefore, we tested our model reaction
with this established procedure.
2
À
À
selective C H bond functionalization of alkenyl sp C H
bond remains elusive.[8] We envisage that the selective C H
Gratifyingly, the desired product 3a could be obtained in
59% yield with 84:16 (Z/E) stereoselectivity when 10 mol%
of Pd(OAc)2 and 50 mol% of N-acetyl-l-valine[12] were used
in the presence of 1.5 equiv Ag2CO3 as oxidant (Table 1,
entry 1). Furthermore, various amino acids were added to this
reaction, it was encouraging to find that N-acetyl-l-phenyl-
alanine could provide 76% (1H NMR yield) of product in
dioxane (Table 1, entry 5). Control experiments carried out
has validated the mandatory presence of palladium catalyst,
silver oxidant, ligand, and base to furnish the cross-coupling
product.
Under the optimized reaction conditions, we turned our
attention to explore the substrate scope of the olefinic
coupling partners (Scheme 2). As expected, good stereose-
lectivities of the products could be obtained when different
acrylates were coupled with alkene 1a. It is noteworthy that
the vinyltrimethylsilane was also an effective substrate for the
coupling reaction with 1a albeit in moderate yield of 48%.[13]
When other carbonyl derivatives such as ethyl vinylketone,
acroleine, and N,N-dimethylacrylamide were examined for
their compatibility as coupling partners in this reaction, the
À
bond functionalization of cheap and commercially available
homoallylic or allylic alcohols could be attained by judicious
choice of reaction conditions (Scheme 1).[9] Although this
chelation versus non-chelation concept has been used widely
in asymmetric synthesis,[10] it has never been utilized for
[*] Q.-J. Liang, C. Yang, F.-F. Meng, B. Jiang, Prof. Dr. Y.-H. Xu,
Prof. Dr. T. P. Loh
Department of Chemistry
University of Science and Technology of China
96 Jinzhai Road, Hefei, Anhui 230026 (China)
E-mail: xyh0709@ustc.edu.cn
Prof. Dr. T. P. Loh
Institute of Advanced Synthesis, Jiangsu National Synergetic Inno-
vation Center for Advanced Materials, Nanjing Tech University
30 South Puzhu Road Nanjing, Jiangsu 210009 (China)
and
Division of Chemistry and Biological Chemistry, School of Physical
and Mathematical Sciences, Nanyang Technological University
Singapore 637616 (Singapore)
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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