Asymmetric Synthesis of All-Carbon Quaternary Stereocenters via Desymmetrization of 2,2-Disubstituted 1,3-Propanediols

A novel enantioselective desymmetrization of 2,2-disubstituted 1,3-propanediols has been established to generate all-carbon quaternary stereocenters, which has been implemented with BzCl and Et3N in the presence of Pybox(6)-CuCl2 complex in CH2Cl2 or PhMe at −78°C. While all the cyanide-comprising diols were desymmetrized with superb enantioselectivity (higher than 98% ee), the stereoinduction of the other substrates greatly depends on the size difference between the two substituents at the 2-position. When the size difference becomes larger, the corresponding substrates tend to engender enhanced enantioselectivity (up to 99% ee).