Direct Catalytic Asymmetric Addition of α-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 α-fluoronitriles and aldehydes promoted by a chiral CuI /Barton's base catalytic system, delivering α-tetrasubstituted α-fluoro-β-hydroxynitriles with satisfactory stereoselection. The stereochemical course was positively biased by the combined use of asymmetrical achiral thiourea as a supplementary ligand for CuI , 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.