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

作者：Organ Michael G^*; Hanson Paul R; Rolfe Alan; Samarakoon Thiwanka B; Ullah Farman

来源：Journal of Flow Chemistry, 2011, 1(1): 32-U100.

DOI：10.1556/jfchem.2011.00008

• microwave-assisted
• continuous-flow organic synthesis (MACOS)
• Sultam
• SNAr
• diversity-oriented synthesis (DOS)
• high-throughput screening (HTS)

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.

• 出版日期2011-8