Monocationic Cinchoninium Catalyzed Asymmetric Oxohydroxylation of Enoates

Asymmetric dihydroxylation and epoxidation
are well-developed and
widely used approaches to introduce chiral oxygenated functional groups
with an alkene substrate. However, oxohydroxylation of an alkene,
furnishing adjacent oxo and hydroxy groups, is less explored. In this
paper, asymmetric oxohydroxylation of α-alkyl enoates with potassium
permanganate catalyzed by monocationic quaternary ammonium salts derived
from cinchona alkaloid is reported. A series of α-hydroxy-β-keto
esters were obtained in up to 96% yield and 98% ee under user-friendly
conditions. Synthetic application of oxohydroxylation was demonstrated
in the synthesis of key chiral building blocks for thapsigargin and
camptothecin synthesis. Control experiments indicated that, compared
with tetrabutylammonium, monocationic chiral cinchoninium has a dramatic
rate acceleration effect on catalytic permanganate oxidation.