Direct Catalytic Asymmetric Addition Of Alpha-Fluoronitriles To Aldehydes

A fluorine-containing tetrasubstituted stereogenic center is a highly valued structural feature in medicinal chemistry. Herein, we describe the direct coupling of racemic alpha-fluoronitriles and aldehydes promoted by a chiral Cu-I/Barton's base catalytic system, delivering alpha-tetrasubstituted alpha-fluoro-beta-hydroxynitriles with satisfactory stereoselection. The stereochemical course was positively biased by the combined use of asymmetrical achiral thiourea as a supplementary ligand for Cu-I, which significantly enhanced the stereoselectivity. Both aromatic and aliphatic aldehydes were implemented to provide densely and stereoselectively functionalized chiral building blocks with aliphatic and aromatic tails.