N-Heterocyclic Carbene Catalyzed Asymmetric Hydration: Direct Synthesis of α-Protio and α-Deuterio α-Chloro and α-Fluoro Carboxylic Acids

摘要

The catalytic asymmetric synthesis of -halo carbonyl derivativesnhas received considerable attention in recent years.n1nApproachesnto accessing these valuable synthons currently rely on the asym-nmetric generation of the -halo aldehyde2nor estern3nand theirnsubsequent manipulation. We have previously shown that , -ndichloro aldehydes in the presence of a chiral N-heterocyclicncarbene (NHC)n4nand phenol can yield the respective -chloro arylnester in good yields and ee’s.n5 7nIn an effort to maximize bothnatom and step economy in these processes, we envisioned that waternwould be the ideal nucleophile to generate the -halo acids directly,nthe redox8nhydration of the -reducible aldehyde (Scheme 1).n9nHerein, we report the asymmetric synthesis of -chloro and -fluoroncarboxylic acids through a mild biphasic redox process. Thenversatility of the developed reaction also lends itself to thenincorporation of a deuterium by simply using D2O.