Communications
doi.org/10.1002/ejoc.202100090
Conflict of Interest
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The authors declare no conflict of interest.
Keywords: Asymmetric catalysis
Michael reaction · Organocatalysis · Synthetic methods
· Bifunctional catalysts ·
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Scheme 3. Proposed Transition State Structure.
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particular, the use of DEMA base additive is important to
achieve excellent enantioselectivity (entries 3, 4, 7, 11, 15, and
1
8). The use of 4-substituted cyclohexanones such as 4-tert-
butyl- and 4-phenylcyclohexanone afforded the corresponding
Michael adducts 4f and 4g with both high syn- and
enantioselectivity in addition to high diastereoselectivity for the
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4
-tert-butyl or 4-phenyl substituent (entries 19~25). Again, the
use of the DEMA base additive is essential for achieving
excellent enantioselectivity for syn-4f (entries 21 and 22).
Notably, the enantioselectivity observed in the DEMA/CPME
system is almost perfect (entry 21). When heteroatoms were
incorporated into the cyclohexanone substrate, the desired
Michael adducts 4h and 4i were delivered in good to high yield
with high syn- and enantioselectivity (entries 26~32). This
approach is also applicable to an asymmetric direct Michael
reaction between an aldehyde and trans-β-nitrostyrene and
results in good enantioselectivity (entry 33).
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Based on the absolute configuration of the Michael adduct
syn-4a, a transition state structure of asymmetric Michael
reaction catalyzed by 1b was proposed to account for the
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observed absolute configuration of syn-4a (Scheme 3). Here,
+
R3NH
moiety activates trans-β-nitrostyrene for the smooth
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In summary, we have developed an asymmetric direct
Michael reaction that is applicable to several ketones and trans-
β-arylnitroethenes under the influence of commercially avail-
able L-hydroxyproline-based amino Tf-amide organocatalyst 1
in a practical manner. The use of a trialkylamine adduct, such as
triethylamine or DEMA, is of crucial importance to accelerate
the reaction and also to achieve high enantioselectivity in the
present asymmetric direct Michael reactions catalyzed by
bifunctional amino Tf-amide organocatalyst 1. Further inves-
tigations concerning the efficacy and effectiveness of organo-
catalyst 1 and other related catalysts in other asymmetric
reactions are currently in progress in our laboratories.
6
[6] Recent examples on direct asymmetric aldol reactions by proline-based
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Acknowledgements
This work was financially supported by the National Natural
Science Foundation of China (No. 21977019, 22050410279), and
the Guangdong Provincial Key Research and Development
Program (2019B020201005).
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