One-Pot Synthesis of Optically Active Cyanohydrin Acetates from Aldehydes via Quinidine-Catalyzed Transhydrocyanation Coupled with Lipase-Catalyzed Kinetic Resolution in Organic Solvent

Article abstract of DOI:10.1246/bcsj.65.111

A novel one-pot synthetic method was developed for the preparation of optically active cyanohydrin acetates.Racemic cyanohydrins were generated from aldehydes and acetone cyanohydrin by quinidine-catalyzed transhydrocyanation, and the resulting cyanohydrins 2a-j were then acetylated by lipase in a stereoselective manner using isopropenyl acetate as an acylating reagent.A variety of aldehydes 1a-j were successfully transformed into the corresponding cyanohydrin acetates 3a-j having 47-95percent e.e. without isolating the unstable cyanohydrins 2.Moreover, the reversible nature of base-catalyzed transhydrocyanation allows for in situ racemization of the unreacted cyanohydrins and concurrent kinetic resolution by lipase enabled the preparation of (S)-3b-d with 40-82percent e.e. in more than 50percent yield.Polymer-supported cinchona alkaloid was also used as a catalyst for this one-pot reaction and showed the comparable chemical and optical yield to that for the soluble monomeric alkaloid.The insoluble polymer and lipase were recovered by filtration and found to have almost the same catalytic activity even after four times of reuse.