Conformational memory in enantioselective radical reductions and a novel synthesis of contrathermodynamic spiroketals

The discovery of novel stereoselective reactions of α-oxygenated radicals is the general theme of this dissertation. Chapter 1 introduces some of the fundamental principles governing the conformation of various α-oxygenated radicals as well as the stereoselectivity of their reactions. One of these principles holds that the stereoselectivity of free radical reactions is governed by the equilibrium distribution of the radical intermediates. However, the development of non-equilibrium radical reactions (chapter 2) serves as an important exception to this postulate which helps to re-define the model for stereoselectivity for these radical reactions. The overall process involves a reaction of radical intermediates which occurs faster than their equilibration. A related, but altogether separate distinction of 2-tetrahydropyranyl radicals is that these intermediates effectively exhibit a ‘memory of chirality’ (chapter 3). In this process, a radical generated at a chiral center reacts to generate an optically active product (in up to 90% ee) with retention of configuration. A slow rate of conformational interconversion relative to radical reaction is responsible for this memory effect.; Chapter 4 deals mainly with the equilibrations and couplings of equatorial and axial 4-lithio-1,3-dioxanes, which are synthons for syn- and anti-1,3-diols derived from α-oxygenated radical intermediates. Equilibration studies proved that the equilibrium strongly favors the equatorial alkyllithium. Furthermore, transmetalation to copper enhances the range of electrophiles which react effectively with 4-lithio-1,3-dioxanes. Chapter 5 unifies the principles introduced in preceding chapters in the effective demonstration of a novel stereoselective synthesis of contrathermodynamic spiroketals. Using this method, contrathermodynamic and/or thermodynamic spiroketals can be stereoselectively synthesized from a common precursor.