1. Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo, 141-0021 Japan
These authors contributed equally to this work.;2. Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo, 141-0021 Japan
Abstract:
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.