Programmable Access to α‐Quaternary Ketones and Aldehydes via Stereodefined β‐Oxy Vinylbenziodoxoles

ABSTRACT

Fully substituted acyclic enolates are valuable intermediates for the enantioselective construction of α‐quaternary carbonyl compounds, yet reliable control of enolate geometry—particularly for aldehydes—remains difficult under conventional deprotonation conditions. β‐Oxy vinylbenziodoxoles (VBXs), accessible through two complementary pathways, provide stereodefined acyclic enolate precursors that retain alkene geometry through subsequent cross‐coupling and carbonate formation. These VBXs undergo configuration‐retentive Sonogashira coupling, enabling modular installation of alkynyl substituents. Subsequent conversion to allyl enol carbonates furnishes ketone‐ and aldehyde‐type enolate surrogates with defined E / Z configuration. Under Pd/Trost‐ligand conditions, these carbonates participate in enantioselective decarboxylative allylic alkylation to deliver α‐quaternary ketones and aldehydes in high yields and enantioselectivities. The decisive role of enolate geometry is demonstrated by the opposite sense of asymmetric induction for E ‐ and Z ‐isomers of the carbonate precursor. The resulting alkynyl‐substituted products are readily diversified through manipulation of the allyl, alkynyl, and carbonyl groups.