Practical Pd(II)-Catalyzed C–H Alkylation with Epoxides: One-Step Syntheses of 3,4-Dihydroisocoumarins

Pd­(II)-catalyzed ortho-alkylation of benzoic acids
with both terminal and internal epoxides affords 3,4-dihydroisocoumarins
in one step. The presence of potassium countercations is crucial for
this reaction. Monoprotected amino acid ligands significantly promote
this reaction, enabling the development of a practical C–H
alkylation reaction using 0.5 mol % Pd catalyst. The inversion of
stereochemistry in the C–H alkylation step is consistent with
a redox-neutral SN2 nucleophilic ring-opening process as
opposed to a Pd­(II)/Pd­(IV) pathway.