Herein we report the first highly enantioselective allenoate-Claisen rearrangement using doubly axially chiral phosphate sodium salts as catalysts. This synthetic method provides access to β-amino acid derivatives with vicinal stereocenters in up to 95% ee. We also investigated the mechanism of enantioinduction by transition state (TS) computations with DFT as well as statistical modeling of the relationship between selectivity and the molecular features of both the catalyst and substrate. The mutual interactions of charge-separated regions in both the zwitterionic intermediate generated by reaction of an amine to the allenoate and the Na+-salt of the chiral phosphate leads to an orientation of the TS in the catalytic pocket that maximizes favorable noncovalent interactions. Crucial arene-arene interactions at the periphery of the catalyst lead to a differentiation of the TS diastereomers. Finally, these interactions were interrogated using DFT calculations and validated through statistical modeling of parameters describing noncovalent interactions.
Miró, Javier, et al. "Enantioselective Allenoate-Claisen Rearrangement Using Chiral Phosphate Catalysts." Journal of the American Chemical Society, vol. 142, no. 13, Mar. 2020. https://doi.org/10.1021/jacs.0c01637
Miró, Javier, Gensch, Tobias, Ellwart, Mario, Han, Seo-Jung, Lin, Hsin-Hui, Sigman, Matthew S., & Toste, F. Dean (2020). Enantioselective Allenoate-Claisen Rearrangement Using Chiral Phosphate Catalysts. Journal of the American Chemical Society, 142(13). https://doi.org/10.1021/jacs.0c01637
Miró, Javier, Gensch, Tobias, Ellwart, Mario, et al., "Enantioselective Allenoate-Claisen Rearrangement Using Chiral Phosphate Catalysts," Journal of the American Chemical Society 142, no. 13 (2020), https://doi.org/10.1021/jacs.0c01637
@article{osti_1984041,
author = {Miró, Javier and Gensch, Tobias and Ellwart, Mario and Han, Seo-Jung and Lin, Hsin-Hui and Sigman, Matthew S. and Toste, F. Dean},
title = {Enantioselective Allenoate-Claisen Rearrangement Using Chiral Phosphate Catalysts},
annote = {Herein we report the first highly enantioselective allenoate-Claisen rearrangement using doubly axially chiral phosphate sodium salts as catalysts. This synthetic method provides access to β-amino acid derivatives with vicinal stereocenters in up to 95% ee. We also investigated the mechanism of enantioinduction by transition state (TS) computations with DFT as well as statistical modeling of the relationship between selectivity and the molecular features of both the catalyst and substrate. The mutual interactions of charge-separated regions in both the zwitterionic intermediate generated by reaction of an amine to the allenoate and the Na+-salt of the chiral phosphate leads to an orientation of the TS in the catalytic pocket that maximizes favorable noncovalent interactions. Crucial arene-arene interactions at the periphery of the catalyst lead to a differentiation of the TS diastereomers. Finally, these interactions were interrogated using DFT calculations and validated through statistical modeling of parameters describing noncovalent interactions.},
doi = {10.1021/jacs.0c01637},
url = {https://www.osti.gov/biblio/1984041},
journal = {Journal of the American Chemical Society},
issn = {ISSN 0002-7863},
number = {13},
volume = {142},
place = {United States},
publisher = {American Chemical Society (ACS)},
year = {2020},
month = {03}}
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division (CSGB); National Institutes of Health (NIH); European Commission; Ministry of Science and Technology, China; National Science Foundation (NSF)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1984041
Journal Information:
Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 13 Vol. 142; ISSN 0002-7863