Bidirectional metalation of hydrobenzoin: direct access to new chiral ligands and auxiliaries

In the last 30 years, the development of asymmetric reactions has become one of the most important pursuits within the field of organic chemistry. In this regard, hydrobenzoin has demonstrated utility as both an auxiliary and a ligand for a variety of asymmetric transformations including aldol reactions, Diels-Alder reactions, and Evans-Tishchenko reactions. Oftentimes, however, the optimization of these processes involves the use of ortho-functionalized hydrobenzoin derivatives, the syntheses of which are often lengthy and/or proceed without complete control of absolute chemistry, detracting from the utility of this catalyst/ligand system. This thesis reports the development of a novel synthesis of ortho-substituted hydrobenzoin derivatives via a one-step process that involves a bidirectional ortho-metalation of hydrobenzoin. Further exploitation of these hydrobenzoin derivatives via Pd-catalyzed cross coupling reactions further enhances the utility of this process and provides access to a wide range of novel chiral ligands and auxiliaries in optically pure form.