Angewandte
Chemie
DOI: 10.1002/anie.201301509
Organocatalysis
Construction of Enantiomerically Enriched Diazo Compounds Using
Diazo Esters as Nucleophiles: Chiral Lewis Base Catalysis**
Haibin Mao, Aijun Lin, Yan Shi, Zhijie Mao, Xuebin Zhu, Weipeng Li, Hongwen Hu,
Yixiang Cheng, and Chengjian Zhu*
Diazo compounds are remarkably versatile metal carbene
precursors which participate in metal-catalyzed rearrange-
ments, cycloadditions, XÀH (X = C, N, O, Si, S, etc.) bond
insertions, and ylide-forming reactions with concomitant
[
1]
expulsion of N2. These compounds also take part in 1,3-
dipolar cycloaddition reactions of a wide range of dipolar-
[
2]
ophiles with retention of the CN moiety. Because of their
2
unique properties and extensive applications, the interest in
[
1e,3]
the chemistry of diazo compounds has been long standing.
However, efficient synthesis of chiral diazo compounds,
especially those with delicate functionalities, is still in
[
4]
urgent need. Enantioselective CÀC bond formation employ-
ing diazo esters as nucleophilic reaction partners provides
[
5]
a straightforward approach to chiral diazo compounds.
Nevertheless, the instability of the diazo moiety to transition
[
1,6]
metals
catalysis, and the nature of the esters makes them less
renders them unmanageable in organometallic
[
7,8]
reactive in organocatalysis.
successful examples are focused on aldol /Mannich-type
Until now, the described
[
8,9]
[10]
[
9a]
reactions under the catalysis of chiral zirconium, magne-
Scheme 1. Asymmetric reactions using diazo esters as nucleophiles.
a) Enantioselective aldol-type reactions of diazo esters with carbonyl
compounds catalyzed by chiral Lewis acids (groups of Wang, Feng,
[
8a]
[9b]
[9c]
sium, scandium, and zinc complexes or chiral Brønsted
acids with simple electrophiles, such as carbonyl compounds
and imines (Scheme 1a,b). Exploitation of diazo esters as
nucleophiles in asymmetric catalysis remains a significant
challenge.
[8, 9]
Cozzi, and Trost). b) Enantioselective Mannich-type reactions of
diazo esters with imines catalyzed by chiral Bronsted acids (groups of
[
10]
Terada and Maruoka). c) Chiral Lewis base catalyzed allylic alkylation
of diazo esters with MBH carbonates. Boc=tert-butoxycarbonyl.
Recently, chiral Lewis bases were used to catalyze
asymmetric allylic alkylation, with Morita-Baylis–Hillman
(
MBH) adducts as electrophiles, through a S 2’/S 2’ cascade
conjunction with our efforts on asymmetric transformations
N
N
[12]
and has emerged as a powerful strategy for the construction of
multifunctional compounds.
reactions using diazo esters as nucleophiles, and also in
of modified MBH esters, we describe herein our results on
chiral Lewis base catalyzed allylic alkylation of diazo esters
with MBH carbonates (Scheme 1c). The desired diazo
compounds could be synthesized in good yields with excellent
enantioselectivities (up to 96% ee), even on a preparative
scale. We also demonstrate the utility of these diazo
compounds by expedient the synthesis of a number of
optically pure N heterocycles.
Initial examination was carried out by using ethyl
diazoacetate (EDA; 2a; 0.10 mmol) and the MBH carbonate
3a (0.12 mmol) in the presence of DABCO (20 mol%) in
0.5 mLTHFat room temperature. The corresponding racemic
product was isolated in 95% yield (Table 1, entry 1). Encour-
aged by this preliminary result, we examined a number of
chiral tertiary amines for enantioinduction of the reaction.
This effort led to the identification of 1e, which provided
access to 4aa in 91% ee even though the yield (35%)
remained relatively low (Table 1, entry 6). To increase the
reaction yield and enantioselectivity, various solvents were
screened with catalyst 1e. The experimental results revealed
that increased solvent polarity led to an increased yield.
[11]
To expand the number of
[*] H. Mao, A. Lin, Y. Shi, Z. Mao, X. Zhu, W. Li, Prof. Dr. H. Hu,
Prof. Dr. Y. Cheng, Prof. Dr. C. Zhu
State Key Laboratory of Coordination Chemistry
School of Chemistry and Chemical Engineering
Nanjing University, Nanjing, 210093 (P. R. China)
E-mail: cjzhu@nju.edu.cn
Prof. Dr. C. Zhu
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
345 Lingling Road, Shanghai, 200032 (P. R. China)
[
**] We gratefully acknowledge the National Natural Science Foundation
of China (21172106, 21074054), the National Science Fund for
Talent Training in Basic Science (No. J1103310), the National Basic
Research Program of China (2010CB923303), and the Research
Fund for the Doctoral Program of Higher Education of China
(
20120091110010) for their financial support.
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
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