Fukuyama Reduction and Integrated Thioesterification/Fukuyama Reduction of Thioesters and Acyl Chlorides Using Continuous Flow

Fukuyama reduction of thioesters has been achieved using a polymer-supported Pd[O] catalyst (Pd/XAD-4), and continuous flow conditions. The generality of this reaction is good with a range of aldehydes prepared in excellent yields. In addition, an integrated multistep thioesterfication/Fukuyama reduction has been developed that allows acyl chlorides to be directly converted to the corresponding aldehydes. Integral to this process is the use of polymer-supported amine and isocyanate reagents to achieve thioesterification and scavenge unreacted thiol. In addition, catch-and-release purification has been employed to enable isolation of the aldehyde from silylthioether byproducts without the need for chromatographic purification.