Pentafluorophenyl acetate

Stereodivergent Coupling for Vicinal Stereocenter Construction Using Pentafluorophenyl Acetate in Dual Pd/Lewis Base Catalysis

Zhang Q, et al. Chem, 2022, 8(10), 2784-2796.

Pentafluorophenyl acetate has proven to be a highly effective carbonyl electrophile in the stereodivergent coupling with 1,3-dienes, enabling precise control over vicinal stereocenter formation. In a recent study, a dual catalytic system combining chiral palladium complexes and Lewis base catalysts was developed to modulate both diastereo- and enantioselectivity.
The optimized reaction employed (R)-DTBM-Segphos-ligated Pd(0) [(R)-Pd-1] with (S)-Bn-BTM in 1,4-dioxane at room temperature, coupling 1,3-diene 1a with pentafluorophenyl acetate 2a to afford the syn-product syn-3aa in 87% yield, 20:1 dr, and 99% ee. Anti-diastereomers were obtained by simply inverting catalyst chirality, with (S)-Pd-2 and (S)-Et-BTM giving anti-3aa in 83% yield and 10:1 dr. The use of pentafluorophenyl esters was critical for activation toward nucleophilic attack while allowing subsequent transformation of the leaving group. This methodology not only highlights the synthetic value of pentafluorophenyl acetate in asymmetric synthesis but also demonstrates a powerful approach for stereodivergent reaction control via catalyst-catalyst chirality tuning.