Organ Michael G, Hanson Paul R, Rolfe Alan, Samarakoon Thiwanka B, Ullah Farman
Department of Chemistry, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada.
J Flow Chem. 2011 Aug;1(1):32-39. doi: 10.1556/jfchem.2011.00008.
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 multi-gram scale using an epoxide opening/S(N)Ar cyclization protocol. Diversification of these sultam scaffolds was attained via a microwave-assisted intermolecular S(N)Ar reaction with a variety of amines. Overall, a facile, 2-step protocol generated a collection of benzothiaoxazepine-1,1'-dioxides possessing stereochemical complexity in rapid fashion, where all 8 stereoisomers were accessed from commercially available starting materials.
报道了用于高通量筛选化合物库富集的立体化学丰富的苯并噻二氮卓-1,1'-二氧化物的生成。利用微波辅助连续流动有机合成平台（MACOS），通过环氧化物开环/S(N)Ar环化方案，在多克规模上实现了核心苯并噻二氮卓-1,1'-二氧化物支架的放大合成。通过与多种胺的微波辅助分子间S(N)Ar反应实现了这些磺内酰胺支架的多样化。总体而言，一个简便的两步方案以快速的方式生成了一系列具有立体化学复杂性的苯并噻二氮卓-1,1'-二氧化物，所有8种立体异构体均可从市售起始原料获得。
