Catalytic Enantioselective Protonation of Gold Enolates Enabled by Cooperative Gold(I) Catalysis
Kaylaa L. Gutman, Carlos D. Quintanilla, Liming Zhang*
*Department of Chemistry & Biochemistry, University of California, Santa Barbara, Santa Barbara, California 93106, United States,
Email: zhangchem.ucsb.edu
K. L. Gutman, C. D. Quintanilly, L. Zhang, J. Am. Chem. Soc., 2024, 146, 3598-3602.
DOI: 10.1021/jacs.3c11919
see article for more reactions
Abstract
From cyclic ketone enol carbonates, cooperative gold(I) catalysis provides highly enantioselective access to cyclic ketones featuring an α tertiary chiral center, including challenging 2-methylsuberone. In combination with a gold-catalyzed formation of cyclopentadienyl carbonates in a one-pot, two-step process, this chemistry enables expedient access to synthetically versatile α'-chiral cyclopentenones.
see article for more examples
Details
The document discusses a study on the catalytic enantioselective protonation of gold enolates using cooperative gold(I) catalysis. This method provides a mild and highly enantioselective approach to constructing tertiary α-stereocenters, which are common in natural products and biologically relevant compounds. The research highlights the use of bifunctional phosphine ligands to enable gold-ligand cooperation, leading to the formation of enantiomerically enriched cyclic ketones from cyclic ketone enol carbonates. The study also explores a one-pot, two-step process combining gold-catalyzed formation of cyclopentadienyl carbonates with enantioselective protonation, resulting in chiral cyclopentenones with excellent enantiomeric excesses. The method demonstrates high levels of facial selectivity and accommodates various substituents, achieving up to 97% ee. The research provides a new strategy for synthesizing chiral tertiary carbon centers and expands the scope of enantioselective protonation under mild conditions. The study was conducted by Kaylaa L. Gutman, Carlos D. Quintanilla, and Liming Zhang, and was published in the Journal of the American Chemical Society in 2024. The authors acknowledge financial support from NIGMS and NSF.
General Procedure
4Å MS were added to a solution of carbonate (0.325 mmol, 1 eq.) in DCM (1.3 mL, 0.25 M) and allowed to stir at room temperature for 30 minutes. IPrAuCl (10.09 mg, 5 mol %) and NaBARF (14.40 mg, 5 mol %) were added and the reaction was stirred at room temperature for 3 hours. (An aliquot was taken out when preliminary studies were performed on an analytical scale for NMR to establish conversion to dienyl carbonate). LigandAuCl (13.89 mg, 5 mol %) and NaBARF (14.40 mg, 5 mol %) were then added and the reaction was stirred for 16 hours at room temperature and monitored by TLC for completion. The crude reaction mixture was then concentrated in vacuo and purified on flash column chromatography using hexanes and ethyl acetate as the eluent (5:1).
Key Words
ID: J48-Y2024