Angewandte
Chemie
DOI: 10.1002/anie.201400236
Asymmetric Catalysis Very Important Paper
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Enantioselective N H Insertion Reaction of a-Aryl a-Diazoketones:
An Efficient Route to Chiral a-Aminoketones**
Bin Xu, Shou-Fei Zhu,* Xiao-Dong Zuo, Zhi-Chao Zhang, and Qi-Lin Zhou*
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Abstract: A highly enantioselective N H insertion reaction of
a-diazoketones was developed by using cooperative catalysis
by dirhodium(II) carboxylates and chiral spiro phosphoric
acids. The insertion reaction provides a new access route to
diverse chiral a-aminoketones, which are versatile building
blocks in organic synthesis, with fast reaction rates, good yields
and high enantioselectivity under mild and neutral conditions.
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T
he construction of carbon–heteroatom bonds (C X) is
a central task for studies in organic synthesis.[1] C X bonds
can be formed directly by transition-metal-catalyzed insertion
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of carbenes into heteroatom–hydrogen bonds (X H, where
X = N, O, S, etc.).[2] Recently, significant progress in catalytic
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asymmetric X H insertion reactions has been made, for
example, high enantioselectivities have been achieved with
Figure 1. The catalysts and ligands used in this study.
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carbene insertions into N H, O H, and S H bonds, which all
contain heteroatoms with lone-pair electrons.[3] However, a-
diazoesters are the only carbene precursors that have been
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into X H bonds in which X has lone-pair electrons is that the
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used for these asymmetric X H insertion reactions, which
strongly electron-withdrawing carbonyl group promotes the
formation of free ylide III[2,6] or enol IV,[7] and chiral catalyst
is thus not present during the chirality-determining proton-
transfer step (Scheme 1).
produce chiral a-heteroatom-substituted esters. Therefore,
the potential applications of these reactions are severely
limited. a-Diazoketones, another readily available carbene
precursor, have been used in a few rhodium-catalyzed
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asymmetric cyclopropanation reactions, in C H and Si H
insertion reactions, and in tandem reactions involving
ylides.[2,4] X H insertion reactions of a-diazoketones produce
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a-heteroatom-substituted ketones, which are useful building
blocks for organic synthesis. However, when we used 1-diazo-
1-phenylpropan-2-one (2a) in the asymmetric insertion
reaction with tert-butyl carbamate (BocNH2) catalyzed by
[Rh2(R-DOSP)4], [Rh2(S-PTAD)4], or a chiral copper com-
plex with a spirobisoxazoline ligand (4; Figure 1), no enan-
tioselectivity was observed (Table 1, entries 1–3).[5] The
problem with the asymmetric insertion of a-diazoketones
[*] B. Xu, Prof. S.-F. Zhu, X.-D. Zuo, Z.-C. Zhang, Prof. Q.-L. Zhou
State Key Laboratory and Institute of Elemento-organic Chemistry,
Nankai University, Tianjin 300071 (China)
and
Collaborative Innovation Center of Chemical Science and
Engineering, Tianjin (China)
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Scheme 1. Proposed pathway of X H insertions of a-diazoketones.
E-mail: sfzhu@nankai.edu.cn
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Herein, we report a highly enantioselective N H insertion
[**] We thank the National Natural Science Foundation of China and the
National Basic Research Program of China (2012CB821600), the
“111” project (B06005) of the Ministry of Education of China, and
the Program for New Century Excellent Talents in University (NCET-
10-0516) for financial support.
reaction of a-diazoketones co-catalyzed by dirhodium(II)
carboxylates and chiral spiro phosphoric acids (SPAs, 1), in
which chiral induction was achieved in the proton-transfer
step.[8] The mild, neutral conditions bring special advantages
for the preparation of synthetically important chiral a-
aminoketones,[9] which can epimerize under harsh conditions.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2014, 53, 3913 –3916
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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