Norbornenyl-tagged reagents and soluble ROM polymers as tools for organic synthesis.

摘要

The use of ring-opening metathesis polymerization (ROMP) as a general purification tool for organic synthesis and library purification is described. Three general ROM polymer-based strategies have been utilized. The first scenario involves the in situ ROM polymerization of norbornenyl-tagged reagents. In one case, a tagged reagent was polymerized away from reaction by-products, following reaction with another component. The overall reaction product was then cleaved from the precipitated polymer and isolated in good yield and high purity. In a second approach, the norbornenyl tag was attached to a small molecule nucleophile that was used to scavenge excess electrophiles from the reaction mixture. When scavenging was complete, the newly tagged electrophiles and excess scavenger were polymerized away from the reaction products, which were isolated in high yield and purity.; In a second strategy, in situ ROM polymerization was used as a means of generating ROM polymers for subsequent use as soluble polymeric supports. Once formed, these supports can be isolated by precipitation away from the reaction by-products. The ROM polymer-supported scaffold was then modified in subsequent steps and isolated by precipitation from a suitable solvent. Following cleavage from the support, the fully modified scaffold was isolated by precipitating the support from methanol and filtering through a plug of silica gel.; In a final strategy, preformed ROM oligomers were utilized as soluble polymeric reagents. In one set of examples, a supported sulfonyl azide was employed as a diazo transfer agent. The resulting diazo compounds were isolated in high yield and purity, and free of sulfonamide by-products. In another set of examples, two ROM polymer-bound reagents were simultaneously used in a Mitsunobu reaction between an alcohol and an acid. The reaction products were purified by polymer precipitation and filtration through a plug of silica gel, and were isolated in good yield and free of phosphine oxide or hydrazine dicarboxylate by-products. A 31P NMR study was able to show that the polymeric phosphine and azodicarboxylate reagents are indeed interacting.