Accessing Stereochemically Rich Sultams via Microwave-assisted, Continuous-flow Organic Synthesis (MACOS) Scale-out

The generation of stereochemically rich benzothiaoxazepine-1,1′-dioxides for enrichment of high-throughput screening collections is reported. Utilizing a microwave-assisted, continuous-flow organic synthesis platform (MACOS), scale-out of core benzothiaoxazepine-1,1′-dioxide scaffolds has been achieved on multigram scale using an epoxide opening/SNAr cyclization protocol. Diversification of these sultam scaffolds was attained via a microwave-assisted intermolecular SNAr reaction with a variety of amines. Overall, a facile, two-step protocol generated a collection of benzothiaoxazepine-1,1′-dioxides possessing stereochemical complexity in rapid fashion, where all eight stereoisomers were accessed from commercially available starting materials.