Enantioselective Synthesis of Quaternary α-Fluoroketones via Decarboxylation

Significance

Quaternary α-fluoroketones were synthesized via a Pd-catalyzed decarboxylation of racemic allyl α-fluoro ketoesters. Cyclic ketoesters of different ring sizes (5-7) and benzo-annulated systems worked well to give excellent yields and ee’s. Linear α-fluoro ketoesters gave moderate ee’s, although yields remained excellent. In analogy to Stoltz’s findings (J. T. Mohr, D. C. Behenna, A. M. Harned, B. M. Stoltz Angew. Chem. Int. Ed. 2005, 44, 6924-6927), the t-Bu-phox ligand was optimal and etherate solvents such as Et₂O or THF were the solvent of choice, while non-polar solvents like CH₂Cl₂ gave poor enantioselectivity.