Enantiodivergent Synthesis of Tertiary α-Aryl 1-Indanones: Evidence Toward Disparate Mechanisms in the Palladium-Catalyzed Decarboxylative Asymmetric Protonation

Herein, we describe a study into the scope and origin of an enantiodivergent effect in the palladium-catalyzed decarboxylative asymmetric protonation. By switching the achiral proton source, both enantiomers of a series of tertiary alpha-aryl-1indanones are readily accessed from the corresponding alpha-aryl-beta-keto allyl esters. In this example of dual stereocontrol, enantioselectivities up to 94% (S) and 92% (R) were achieved using Meldrum's acid and formic acid, respectively. In an attempt to rationalize this switch in absolute configuration an investigation of the ambiguous mechanism of the decarboxylative asymmetric protonation was conducted. A novel catalytic cycle for the reaction with formic acid is proposed and subjected to a variety of experimental studies.