Enantioselective Tertiary Electrophile (Hetero)Benzylation: Pd-Catalyzed Substitution of Isoprene Monoxide with Arylacetates

The enantioselective generation of quaternary carbon centers remains challenging but is of growing importance for the preparation of functional molecules. Transition metal catalyzed allylic alkylations of tertiary electrophiles have provided access to these substructures but remain generally incompatible with organometallic benzyl nucleophiles. In this study we demonstrate that electron-deficient arylacetates can serve as benzyl nucleophile surrogates to generate enantioenriched acyclic molecules containing a quaternary carbon center via a two-step substitution-decarboxylation process using isoprene monoxide. The reaction gives products typically in >90% ee using a commercially available catalyst system and tolerates an array of electron-withdrawing functional groups on the arylacetate moiety. The lactone intermediate generated by the initial substitution reaction can be used in further stereoselective transformations to prepare molecules with acyclic vicinal quaternary stereocenters.