This dissertation discusses the synthesis of ether linked analogs of annonaceous acetogenins. Utilization of ether linkages will enable rapid synthesis of a library of acetogenins with a variety of groups flanking the right and left side of the bis-adjacent THF core, which will be used for future SAR studies of acetogenins. An efficient method for regio- and stereoselective double cyclization of polyhydroxylated systems to form bis-adjacent THF rings with ether linked is developed.Several elegant reports of asymmetric halogenation of alkenes and alkynes followed by intra or inter molecular attack of a nucleophile have appeared in the literature in the last decade. We have recently disclosed catalytic asymmetric routes to chlorolactones, chlorooxazolines, and chlorooxazines. Further studies have shown the feasibility for the cyclization of carbamates to yield chlorooxazolidinone. We have observed a remarkable solvent effect that essentially reverses the chirality of the product chlorooxazolidinone with the same chiral catalyst. The results of this study along with kinetic investigations that suggest enthalpy-entropy compensation as the origin of the chirality switch are discussed in this dissertation.
Read
