Development of a practical method for the asymmetric synthesis of quaternary carbon centers: A second generation auxiliary

Despite significant progress in the field of organic chemistry, the asymmetric formation of all-carbon quaternary centers still represents a considerable challenge. Our group previously reported the stereocontrolled generation and alkylation of alpha,alpha-disubstituted amide enolates to form quaternary centers. This reaction takes place via the reduction of bicyclic alpha,alpha-dialkylated alpha-thioglycolate lactams using one-electron transfer reagents.; This method suffered from several limitations to practicality, thus this research project has focused on the development of a second-generation chiral auxiliary system which would overcome the first generation auxiliary shortcomings.; The design and synthesis of a new chiral auxiliary system is described. The design is modular and allows the auxiliary to be synthesized in a few shorts steps from commercially available materials. Alkylation of the new auxiliary, reductive enolization and the subsequent final alkylation to form quaternary centers is achieved with high levels of stereocontrol for both enolate intermediates. Two sets of conditions are described to cleave the auxiliary and liberate the products containing the quaternary centers.; The methodology that has been developed is versatile and represents a practical solution to the enantioselective formation of quaternary carbon centers. It also overcomes all the shortcomings of the first generation.