10.1002/anie.201814272
Angewandte Chemie International Edition
COMMUNICATION
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The kinetic preference to form the (S)-enantiomer at the
enantioselectivity-determining
protodepalladation
step
is
consistent with experimental selectivity.[25]
In conclusion, we have demonstrated
a
catalytic,
non-
enantioselective α-alkylation of azlactones with
a
conjugated alkenes that proceeds via stereoselective
carbopalladation. The resulting products can be conveniently
deprotected to reveal useful α-quaternary amino acid derivatives.
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Acknowledgements
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[16] Across several representative examples, we found that yields and er
values were consistent in reaction performed on 0.05-mmol scale to
0.3-mmol scale. On larger scale (1.0 mmol), the reaction progressed
more slowly, leading to slightly lower yields, while maintaining similar er.
We elected to perform the examples in Tables 2 and 3 on 0.05-mmol
scale due to the valuable nature of PA7 and because all of the reaction
components have high formula weights, allowing for accurate
measurement even on small scale.
[17] The 4-OPh group appears to be relatively close to the CPA ligand in the
calculated enantioselectivity-determining transition state, TS2_S,
supporting this explanation.
[18] Over several trials, yields ranged from 10–35%, with d.r. values ranging
from 2:1 to >20:1.
This work was financially supported by Scripps Research, Pfizer,
Inc., Bristol-Myers Squibb (Unrestricted Grant), the NIH
(5R35GM125052-02 and 1R35GM128779) and the NSF (NSF-
DBI 1759544, SURF fellowship to O.A.). Calculations were
performed at the Extreme Science and Engineering Discovery
Environment (XSEDE) supported by the NSF and the HPC
Garibaldi cluster at Scripps Research. We thank Dr. Milan
Gembicky and Dr. Curtis E. Moore (UCSD) for X-ray
crystallographic analysis and Prof. Zachary K. Wickens (UW
Madison) for helpful discussion.
Keywords: palladium • directing group • chiral phosphoric acid
(CPA) • enantioselective • C–C bond formation
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