A general ring-opening metathesis polymerization (ROMP) approach is proposed for integrating the science of combinatorial library synthesis with the science of high-throughput chemical library purification. Several new norbornene-based scaffolds amenable to ROMP techniques will be developed to aid in the generation and purification of combinatorial libraries. In our approach, the norbornenyl ring system is utilized as a general chemical tag for incorporation into a wide variety of reagents, scavenging agents, capturing agents for phase-trafficking, soluble supports, and photocleavable linkers. Two general strategies are being investigated: i) in situ ROM polymerization of norbornenyl-tagged monomers mediated by the Grubbs catalyst as an integrated and general purification operation, and ii) utilization of ROM polymerization to produce high-load functional oligomers with tunable solubility profiles that can be exploited in library production. The use of ROM polymerization offers several advantages, including i) selective timing of the ROMP event (in situ ROMP vs. preformed oligomers) tailored to meet the needs of each synthetic sequence, ii) control of bulk physical properties by judicious choice of polymerization conditions, iii) functional group compatibility, and iv) the ability to produce high-load soluble oligomers and polymers. The ultimate goal is the development of new ROMP phase-trafficking technologies for the generation of combinatorial libraries.
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