Highly enantioselective undirected catalytic hydroxylation of benzylic CH2 groups with H2O2

Article abstract of DOI:10.1016/j.jcat.2020.08.005

Chiral bis-amine-bis-pyridine Mn complexes of the type [LMn^II(OTf)₂] (L is 2,2?-bipyrrolidine derived chiral ligand, bearing trifluoroethoxy and methyl substituents), efficiently catalyze the enantioselective hydroxylation of organic substrates at benzylic CH₂ positions with H₂O₂. The use of β-polyfluorinated alcohols instead of CH₃CN as the reaction solvents enhances the yield of chiral secondary alcohol from 5–6percent up to 50–70percent. The enantiomeric purity of the alcohol can be further increased (up to 97percent ee) by diluting the mixture with CH₃CN at late stage, which facilitates stereoconvergent oxidative kinetic resolution of the alcohol formed. Using this one-pot sequential asymmetric hydroxylation/oxidative kinetic resolution approach, the oxidation of a series of 3,4-dihydrocoumarin derivatives and 3,4-dihydroquinolinone has been realized, affording the target 4-hydroxo compounds in 40–60percent isolated yield and in up to 93percent ee. Besides the 4-hydroxo derivatives, formation of 3,4-epoxidation and 3,4-desaturation byproducts has been observed in some cases, thus providing evidence for unprecedented substrate-dependent hydroxylase/desaturase/epoxidase reactivity of bis-amine-bis-pyridine Mn complexes.