The development of new oxabicyclic-based strategies for the stereo- and enantioselective synthesis of azepines, thiepines and thiocines, polysubstituted decalins and related fused polycycles

grantor: University of TorontoThe development of new oxabicyclic-based enantio- and stereoselective synthetic strategies are described in this thesis. Their synthetic potential, versatility and flexibility were demonstrated by the preparation of seven- and eight-membered nitrogen and sulfur heterocycles, polysubstituted decalins and related fused polycycles. In Chapter 1, the tandem "pincer" Diels-Alder reaction, consisting of two consecutive [4+2] cycloadditions between two dienes and an acetylenic bis-dienophile was applied toward the rapid construction of bridged polyoxacyclic ring systems when furan derivatives are used as the diene components. The study has demonstrated the stereoselectivity ('exo-exo' adduct), the chemoselectivity ("pincer" 'vs' "domino") as well as the regioselectivity of the reaction. The reaction has been successfully applied to a variety of 2-substituted furans and tethered bis-furans in combination with monoactivated and diactivated dienophiles. Chapter 2 describes a chemo-, regio- and stereocontrolled methodology for the simple and efficient synthesis of a large variety of 'cis'-decalins and related fused polycyclic systems with control at up to six stereocenters, based on the sequential ring opening of dioxacyclic: templates. We have established that the most useful feature of the reactivity of the dioxacyclic compounds is that the first ring opening reaction is significantly faster than the second allowing the sequential transformation of the oxabicyclic moieties. The flexibility of the sequential ring opening process and its limitations have been demonstrated and a new enantioselective mode of opening was reported. The base-promoted desymmetrization of 'meso' aza[3.2.1]oxabicyclic and thia[3.2.1] and oxa[3.3.1]bicyclic compounds has been exploited in Chapter 3 to give enantioenriched azepines, thiepines and thiocines. The regioselective opening of unsymmetrical aza[3.2.1]oxabicyclic and thia[3.2.1] and [3.3.1]oxabicyclic compounds bearing a methyl substituent at the bridgehead as well as the mechanism of deprotonation have also been investigated. In Chapter 4, we have briefly studied the intramolecular anionic ring opening of oxabicyclo[2.2.1] systems as a route to bicyclo[4.3.0]nonenes which are trans fused. The influence of the length of the all-carbon tether on the cyclization has been investigated. Cyclization of the 2-carbon tether substrate via an unexpected SN2 endo attack gave access to the spiro [5.2.0] skeleton. Stabilized anions have also been successfully cyclized.Ph.D