Angewandte
Communications
Chemie
Kinetic Resolution
Atroposelective Synthesis of Axially Chiral Biaryls by
ꢀ
Palladium-Catalyzed Asymmetric C H Olefination Enabled by
a Transient Chiral Auxiliary
Dedicated to Professor Biao Yu on the occasion of his 50th birthday
Abstract: Atroposelective synthesis of axially chiral biaryls by
[1,1’-biphenyl]-2-carboxylic acid in the presence of a tripepti-
palladium-catalyzed C H olefination, using tert-leucine as an
de.[8b] The major breakthrough in this area was made
independently by Zheng and You,[8c] and Wencel-Delord,
Colobert, and co-workers[8f] in 2014. The group of You
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inexpensive, catalytic, and transient chiral auxiliary, has been
realized. This strategy provides a highly efficient and straight-
forward access to a broad range of enantioenriched biaryls in
good yields (up to 98%) with excellent enantioselectivities (95
to > 99% ee). Kinetic resolution of trisubstituted biaryls
bearing sterically more demanding substituents is also oper-
ative, thus furnishing the optically active olefinated products
with excellent selectivity (95 to > 99% ee, s-factor up to 600).
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elegantly demonstrated the rhodium(III)-catalyzed C H
olefination/DKR reaction of 1-(naphthalene-1-yl)isoquino-
lines, using a C2-symmetric chiral Cp ligand, with moderate to
good enantioselective control (58–86% ee).[8c] They further
improved the enantioselectivity by the design and application
of a chiral spiro Cp ligand.[8g] Meanwhile, Wencel-Delord,
Colobert and co-workers reported a seminal work on the
ꢀ
A
xially chiral biaryl scaffolds are commonly occurring
palladium-catalyzed diastereoselective C H functionaliza-
structural motifs in natural products and advanced materials,
and they play an important role in synthetic chemistry as
privileged chiral ligands and catalysts.[1] Accordingly, great
efforts have been devoted to the efficient synthesis of these
chiral frameworks,[2] including asymmetric coupling of two
arenes by oxidative dimerization or cross-coupling,[3] atropo-
selective aryl formation by cycloaddition,[4] asymmetric ring-
opening of bridged biaryls,[5] asymmetric transfer hydrogena-
tion,[6] stereoselective functionalization of prochiral or race-
mic biaryls,[7,8] and others.[9] In particular, the atroposelective
tion of a range of S-stereogenic biarylsulfoxides by a DKR
strategy.[8f,h] Although these achievements are significant,
some of them are still limited to narrow substrate scope, low
efficiency, and/or moderate stereocontrol. Therefore, the
development of novel strategies to access valuable axially
chiral biaryls using readily available starting materials and
chiral ligands is highly desirable and challenging. Herein, we
report the synthesis of axially chiral biaryls by a palladium-
ꢀ
catalyzed C H olefination/DKR reaction. This strategy
employs commercially available tert-leucine as an inexpen-
sive, catalytic, and transient chiral auxiliary, thus enabling the
efficient synthesis of enantioenriched biaryls in good yields
(up to 98%) with excellent enantioselectivities (95 to > 99%
ee).
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C H functionalization through dynamic kinetic resolution
(DKR) of biaryls has become one of the most economical and
powerful strategies to access these axially chiral biaryls.[8,10]
Compared to the others, this strategy enables the conversion
of both enantiomers of the racemic biaryls into axially chiral
biaryls in a theoretically quantitative yield without the
prefuctionalization of starting materials.[8] In 2000, Murai
and co-workers reported the rhodium(I)-catalyzed atropose-
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Recently, transition metal catalyzed C H functionaliza-
tion employing catalytic, transient directing groups (DGs) has
been realized as a promising strategy since it obviates extra
steps to install and remove the external DGs.[11] Yu and co-
workers have achieved the creation of central chirality using
this elegant strategy.[11d] Motivated by these reports, we
envisioned that judicious choice of a transient chiral auxiliary
would enable the construction of axial chirality, an approach
which has not been realized so far. As shown in Figure 1, we
rationalized that a chiral amino acid would reversibly react
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lective C H alkylation of biaryls with olefins, using a chiral
ferrocenyl phosphine ligand, with moderate stereoinduction
(up to 49% ee).[8a] In 2010, Miller and co-workers reported
the atroposelective electrophilic bromination of 3’-hydroxy-
ꢀ
[*] Q.-J. Yao, S. Zhang, B.-B. Zhan, Prof. Dr. B.-F. Shi
Department of Chemistry, Zhejiang University
Hangzhou 310027 (China)
with rac-1 to form the imines IM-A and IM-B. C H cleavage
of one diastereomer (IM-B) occurred preferentially because
of the steric interaction, thus affording an axially stereo-
enriched biaryl palladacycle intermediate (C), which under-
goes a typical Heck-type reaction with olefin 2 to give D. In
situ hydrolysis of the intermediate D and reoxidation of Pd0 to
PdII would afford chiral biaryls (Ra)-3 and close the catalytic
cycle.
E-mail: bfshi@zju.edu.cn
Prof. Dr. B.-F. Shi
State Key Laboratory of Elemento-organic Chemistry, Nankai Uni-
versity, Tianjin 300071 (China)
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
To test the feasibility of this hypothesis, we initiated our
research on identification of a proper chiral amino acid which
Angew. Chem. Int. Ed. 2017, 56, 1 – 7
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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