ROMP-Facilitated Methodologies and Automated Library Development of Thiadiazepin-1,1-dioxide-4-ones

Abstract

The use of ring-opening metathesis polymerization (ROMP) for polymer-assisted solution phase (PASP) synthesis is described herein. Multiple ROMP-based strategies will be discussed in the scope of this dissertation. These include the development and application of a multifaceted oligomeric phosphate as a facilitated leaving group in both SN2 and SN2´ processes, as well as an in-situ generated sequestration reagent. We also investigate the use of ROMP in an atom-economical approach to generate a diverse collection of cyclic sulfonamides (sultams) whereby a vanishing support protocol imparts a traceless, chromatography-free synthesis of these motifs. Also highlighted within is the ability to use ROMP technology to aid in the development of higher-loading magnetic nanoparticles for the purpose of supported catalysis. These cobalt-based ROMPgel nanoparticles were subsequently doped with Pd and demonstrated for use in several Suzuki-Miyaura coupling reactions. The nanoparticles were conveniently reclaimed via external magnetic field and recycled for later use. Lastly, we present the design, validation, and completion of a 225-member library of thiadiazepin-1,1-dioxide-4-ones using both solution- and polymer-assisted solution phase protocols. The library was validated and conducted on an automated parallel synthesis platform in which a facile, two-step diversity-rendering sequence was performed.