10.1002/ejoc.201900431
European Journal of Organic Chemistry
COMMUNICATION
withdrawing 6o and 6p to electron-donating group 6q (entries
15-17). When Y1 was hydrogen, 6b and 6c, the activity and
enantioselectivity were lower (entries 2, 3). Posssibly, the
electronic effect of the aromatic ring stabilized the adjacent
olefins and then increased the activity of the olefin insertion
reaction, while the aromatic ring steric hindrance effect
increased the stereoselectivity and enantioselectivity of the
product. When Y2 was methyl, 3- methoxyphenyl (Y1) substituted
substrate 6s did not recieved the corresponding product with
higher enantioselectivity (57% ee) (entry 17 vs. 19). Importantly,
this reaction tolerated structural diversity in the desired products,
which is significant for further synthesis and transformations.
To validate the practicality of our method, we attempted to
perform reactions on a gram-scale. Product 6a (1.1g) was
obtained with 68% yield and 95% ee, while 6g (1.4g) was
obtained with 80% yield and 90% ee (Scheme 4), which were
consistent with the results shown in Scheme 3.
Furthermore, environmentally friendly oxidant molecular oxygen
was applied in this approach, which corresponds to the concept
of green chemistry. Use of this protocol to synthesize biologically
active molecules is ongoing in our laboratory.
Acknowledgements
We thank the National Science and Technology Major Project of
China on “Key New Drug Creation and Development Program”
(Project No. 2014ZX09J14104-06C), Shaanxi Province Key
Research and Development Program (S2019-YF-ZDCXL-
ZDLSF-0138) and the Key Research and Development Project
of Shaanxi Province (2017SF-226). We also thank Professor
Shengyong Zhang for valuable discussion.
Keywords: asymmetric catalysis • cinchona alkaloid • oxazoline
ligands • cascade cyclization • aza-wacker
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Scheme 4. Gram-scale reactions.
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Scheme 5. Further conversion of reaction product.
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In summary, a series of novel chiral cinchona alkaloid
oxazoline ligands were designed and synthesized in high yields.
The catalytic system of Pd(TFA)2/chiral cinchona alkaloid
oxazoline was applied to achieve the highly efficient
enantioselective oxidative cascade cyclization of aromatic
alkenyl amides under mild reaction condition, affording high
diastereoselectivities
(>95:5
dr)
and
excellent
enantioselectivities (up to 97% ee) with good yields (up to 83%).
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