Photoenolization of α,β-Unsaturated Esters Enables Enantioselective Contra-Thermodynamic Positional Isomerization to α-Tertiary β,γ-Alkenyl Esters
Issued Date
2025-01-01
Resource Type
ISSN
00027863
eISSN
15205126
Scopus ID
2-s2.0-85218893750
Journal Title
Journal of the American Chemical Society
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of the American Chemical Society (2025)
Suggested Citation
Chang K.C., Chiu H.H., Huang P.G., Miñoza S., Lee W.H., Keerthipati P.K., Racochote S., Lee Y.H., Chou C.J., Hsu C.M., Chang C.W., Soorukram D., Chiu C.C., Liao H.H. Photoenolization of α,β-Unsaturated Esters Enables Enantioselective Contra-Thermodynamic Positional Isomerization to α-Tertiary β,γ-Alkenyl Esters. Journal of the American Chemical Society (2025). doi:10.1021/jacs.4c15732 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/105527
Title
Photoenolization of α,β-Unsaturated Esters Enables Enantioselective Contra-Thermodynamic Positional Isomerization to α-Tertiary β,γ-Alkenyl Esters
Corresponding Author(s)
Other Contributor(s)
Abstract
The enantioselective protonation of prochiral enolates is an ideal and straightforward platform to synthesize stereodefined α-tertiary esters, which are recurring motifs in a myriad of biorelevant molecules and important intermediates thereof. However, this approach remains onerous, particularly when dealing with α-unactivated esters and related acids, as enantioinduction on the nascent nucleophile necessitates peremptory reaction conditions, thus far only achieved via preformed enolates. A complementary and contra-thermodynamic catalytic strategy is herein described, where a transient photoenol, in the form of a ketene hemiacetal, is enantioselectively protonated with a chiral phosphoric acid (CPA). The prochiral photoketene hemiacetals are procured from excited α,β-unsaturated esters, specifically from the Z-geometric isomer through [1,5]-hydride shift as a chemically productive nonradiative relaxation pathway. Tautomerization via formal 1,3-proton transfer in the photoketene hemiacetal with CPA as a proton shuttle delivers α-branched β,γ-alkenyl esters in good to excellent yields and enantioselectivity under mild conditions. Furthermore, the current protocol was coupled to functional group interconversion experiments, as well as in a formal total synthesis of a known marine γ-butyrolactone-type metabolite. Performing the reaction in a continuous photoflow setup also enabled a gram-scale synthesis of a β,γ-alkenyl ester with up to 92% ee.