ROMP-Derived Alkylating Reagents and Scavengers: Application in Library Development and Sequestration

Abstract

The overarching goal of this dissertation is the development and utilization of (ring-opening metathesis polymerization) ROMP-derived high load phosphorus- and sulfur-based soluble, silica and magnetic alkylating reagents and scavengers. Chapter one begins with a brief introduction of solid phase and solution phase organic synthesis, and next describes the advances in soluble-, silica- and magnetic-immobilized reagents, with a few applications in flow chemistry. Chapter one also outlines the advances in ROMP technology for the synthesis of polymeric soluble, silica and magnetic materials for use as reagents, scavengers and catalysts. Chapter 2 begins with a brief review of immobilized alkylating reagents and next describes the development and utilization of soluble high load ROMP-derived oligomeric triazole phosphates (OTPn) for the efficient (triazolyl)methylation of nucleophilic species in purification free protocols. Chapter 2 finishes with a description of library efforts using a purification-free route that combines MACOS scale-out and ROMP-derived oligomeric triazole phosphates (OTPn) for the generation of a 106-member library of triazole-containing benzothiaoxazepine-1,1-dioxides. In Chapter 3, the first section describes the use of ROMP technology to aid in the development of high-load hybrid silica oligomeric phosphates based alkylating reagents, and their applications for facile benzylation and (triazolyl)methylating of N-, O- and S-containing nucleophilic species. The surface initiated ROMP reaction of Nb-tagged silica particles and functionalized Nb-tagged monomers efficiently yields high-load, hybrid Si-ROMP benzylating (Si-OBP) and (triazolyl)methylating (Si-OTP) reagents. The second section, describes the application of the developed silica-immobilized alkylating reagents in one-pot sequential protocols for diversification of benzothiaoxazepine-1,1-dioxides analogues. The last section of Chapter 3 outlines the synthesis of high-load, hybrid silica-immobilized heterocyclic benzyl phosphate (Si−OHBP) and triazolyl phosphate (Si−OHTP) alkylating reagents for efficient hetero-benzylation and hetero-(triazolyl)methylation and their application in purification-free protocols, which diversify various nucleophilic species. Chapter 4 describes the development and utilization of recyclable magnetic ROMP-derived alkylating reagents and scavengers, immobilized on Co/C magnetic nanoparticles via surface-initiated ROM polymerization. The first section 4.1 outlines the development and application of a high-load magnetic Co/C ROMP-derived oligomeric benzenesulfonate ester Co/C-OBSEn, as an efficient methylating reagent for a variety of carboxylic acids. In addition, an in situ method of methylation/alkylation was developed using Co/C benzenesulfonyl chloride Co/C-OBSCn and corresponding ROH. The desired alkylated products were isolated by simple magnetic decantation and filtration and the spent byproduct magnetic benzenesulfonic acid Co/C-OBSAn was successfully recycled and re-used up to ten times without considerable loss of magnetic material. Section 4.2 details the synthesis and utilization of high-load hybrid magnetic oligomeric phosphonyl dichloride Co/C-OPCn as an efficient scavenger of amines. The magnetic Co/C-OPCn scavenger is employed in amide formations, sulfonylations and urea formations using a variety of amines (used in excess). The coupling products were isolated by simple magnetic decantation and filtrations of reaction mixture. The spent magnetic scavenger was easily isolated by external magnetic decantation and its regeneration is in progress.