Synthesis of functionalizable and degradable polymers by ring-opening metathesis polymerization.

A valuable approach for creating synthetic polymers is the ring-opening metathesis polymerization (ROMP). Welldefined metal carbene catalysts have been devised that afford control over the polymer chain length and architecture. In addition, ruthenium carbene initiators have been developed with excellent air stability and functional group tolerance. These catalysts enable the synthesis of polymers with a range of functionality, thereby providing access to polymers for diverse applications. Extant polymers from ROMP, like the majority of synthetic polymers, are nondegradable. They therefore lead to the accumulation of waste. A functional and degradable polymer from ROMP would allow the synthetically useful traits of ROMP reactions to be combined with the growing need for new degradable polymer scaffolds. To date, efforts to prepare degradable materials by using ROMP have afforded polymers that are either functional or partially hydrolyzable, but not both (Figure 1). For example, cargo can be attached through a linker such that it can be released from the polymer backbone by photolysis or hydrolysis in acid. Still, the polymeric backbone persists. Alternatively, partially degradable polymers have been generated. A block copolymer can be generated from a modifiable monomer and a sacrificial dioxepine or dithiepine monomer. In this scenario, one block is composed of a nonhydrolyzable backbone and the degradable block contains acid-labile acetals or thioacetals that can be cleaved by hydrogenation. Polymers of this type only undergo partial degradation, as one block persists. The current state-of-the-art therefore demands a compromise between generating polymers that can be customized and polymers that can be easily degraded. Applying ROMP to synthesize a modifiable homopolymer with a degradable backbone requires a monomer with three important attributes. First, it must be a strained cyclic or bicyclic olefin, so that it undergoes polymerization. Second, it must contain core functionality that gives rise to a polymer that can be degraded. Third, a means to append desired functionality onto the monomer or polymer is needed to enable polymer diversification. Monomers with all of these attributes have been elusive. Many strained olefinic heterocycles spontaneously aromatize. In addition, attempts to incorporate handles for diversification can further increase monomer instability. Thus, traditional monomers used in ROMP cannot be simply modified to instill polymer degradability. We sought a new class of monomers that would give rise to degradable materials. The generation of substrates with an 8oxo-2-azabicylo[3.2.1]oct-6-en-3-one framework through a novel aza-[4+3] cycloaddition was recently reported (Scheme 1A). We postulated that this bicyclic oxazinone would be a substrate for ROMP. Calculations suggest that this framework has a ring strain of 13.4 kcalmol , which is comparable to that of trans-cyclooctene (a monomer that has favorable kinetics of polymerization in ROMP). Reports of successful ring-opening cross metathesis on architecturally analogous 8-oxo-bicyclo[3.2.1.]oct-6-en-3-ones provided additional impetus. Significantly, if the bicyclic oxazinone serves as a monomer in ROMP, the resulting framework should be both acid and base labile (Scheme 1B). Moreover, we postulated that we could modify this core monomer at a site distal to the polymerizable moieties and bridgehead carbon atoms. Thus, without destabilizing the heterocycle, we could tailor the properties of the resulting materials. Despite our optimism that bicyclic oxazinones would serve as monomers, we had concerns that polymerization would yield highly oxygenated polymer products that would facilitate backbiting. Our initial results confirmed our suspicions. The reaction of 3a using Grubbs second generation catalyst (8) in chloroform afforded polymer 4a (Table 1, entry 1), but we observed a concomitant increase Figure 1. Strategies to synthesize functionalizable and degradable ROMP polymers: A) ligand attachment through a cleavable linker, B) copolymerization with a sacrificial monomer, and C) homopolymerization of a functionalizable, heterocyclic oxazinone.