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

Abstract

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.

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Correspondence to Michael G. Organ.

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Organ, M.G., Hanson, P.R., Rolfe, A. et al. Accessing Stereochemically Rich Sultams via Microwave-assisted, Continuous-flow Organic Synthesis (MACOS) Scale-out. J Flow Chem 1, 32–39 (2011). https://doi.org/10.1556/jfchem.2011.00008

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  • DOI: https://doi.org/10.1556/jfchem.2011.00008

Keywords

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