Asymmetric Construction of α,α‐Disubstituted Piperazinones Enabled by Benzilic Amide Rearrangement
An unprecedent asymmetric catalytic benzilic amide rearrangement for the synthesis of α,α-disubstituted piperazinones is reported. The reaction proceeds via a domino [4+1] imidazolidination/formal 1,2-nitro- gen shift/1,2-aryl or alkyl migration sequence, employing readily available vicinal tricarbonyl compounds and 1,2- diamines as starting materials. This approach provides an efficient access to chiral C3-disubsituted piperazin-2-ones with high enantiocontrol, which are exceedingly difficult to access from the existing synthetic method- ologies. The observed enantioselectivity was proposed to be controlled by dynamic kinetic resolution in the 1,2- aryl/alkyl migration step. The resulting densely function- alized products are versatile building blocks to bioactive natural products, drug molecules and their analogues.
Cite this item
He, Y.-P., Quan, R., Li, X.-Z., Zhu, J., & Wu, H. (2023). Asymmetric Construction of α,α‐Disubstituted Piperazinones Enabled by Benzilic Amide Rearrangement. Angewandte Chemie International Edition, 62(18). https://doi.org/10.1002/anie.202217954
Click Copy to copy the citation, or select the text manually.
WOS:000956183100001
2023-04-24
62
18
REVIEWED
EPFL