Photoenolization of <i>α,β</i>-Unsaturated Esters Enables Enantioselective Contra-Thermodynamic Positional Isomerization to α-Tertiary <i>β,γ</i>-Alkenyl Esters

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 <i>α,β</i>-unsaturated esters, specifically from the <i>Z</i>-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 <i>β,γ</i>-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 <i>β,γ</i>-alkenyl ester with up to 92% <i>ee</i>.