| The overarching goal of this dissertation is the development of strategies and methodologies aimed at the diversity-oriented synthesis of benzofused sultam libraries utilizing the ability of alpha-fluorobenzenesulfonamides to undergo nucleophilic aromatic substitution (SNAr). The development of a new method for the synthesis of benzofused sultams via a strategy termed as complementary ambiphile pairing (CAP) is described. This approach entails the complementary pairing of two ambiphilic synthons, alpha-fluorobenzenesulfonamides and ortho-quinone methides (o-QM's) in a formal one-pot, hetero [4+4] approach to afford the novel dibenzo[b,g][1,4,5]oxathiazocine-5,5-dioxide ring system. An orthogonal reaction pairing strategy based on the ability of alpha-fluorobenzenesulfonamides to undergo facile nucleophilic aromatic substitution to generate diverse polycyclic benzofused sultams is also reported. Several reaction pathways that are orthogonal to the SNAr reaction are paired with the SNAr pathway, including intramolecular Mitsunobu alkylation, epoxide ring opening and [3+2] azide-alkyne Huisgen cycloadditions to generate an array of diverse benzofused sultams. Lastly, a strategy termed "click, cyclize, click" to afford an array of benzofused sultams is described. This approach entails amino alcohol sulfonylation (Click) utilizing alpha-fluorobenzenesulfonyl chlorides and subsequent intramolecular SNAr O-arylation to afford benzofused sultams containing 2° sulfonamide N-H's. A number of reaction pathways including Mitsunobu alkylation, conventional alkylations, acylations and SNAr additions are subsequently utilized in diversification of the core scaffold. The utilization of ROMP-derived oligomeric triphenylphosphine (OTPP) in the production of a prototype benzyl benzothiaoxazepine-1,1-dioxide library is also described. |
