Thiourea (TU)/amine base cocatalysts are commonly employed for well-controlled, highly active “living” organocatalytic ring-opening polymerizations (ROPs) of cyclic esters and carbonates. In this work, several of the most active cocatalyst pairs are shown by 1H NMR binding studies to be highly associated in solution, dominating all other known noncovalent catalyst/reagent interactions during ROP. One strongly binding catalyst pair behaves kinetically as a unimolecular catalyst species. The high selectivity and activity exhibited by these ROP organocatalysts are attributed to the strong binding between the two cocatalysts, and the predictive utility of these binding parameters is applied for the discovery of a new, highly active cocatalyst pair.

The antibacterial compound, triclocarban (TCC), is shown to be a highly effective H-bond donating catalyst for ring-opening polymerization (ROP) when applied with an H-bond accepting base cocatalyst. These ROPs exhibit the characteristics of “living” polymerizations. TCC is shown to possess the high activity characteristic of urea (vs thiourea) H-bond donors. The urea class of H-bond donors is shown to remain highly active in H-bonding solvents, a trait that is not displayed by the corresponding thiourea H-bond donors. Two H-bond donating ureas that are electronically similar to TCC are evaluated for their efficacy in ROP, and a mechanism of action is proposed. This “off-the-shelf” H-bond donor is among the most active and most controlled organocatalysts for the ROP of lactones.

A cocatalyst system consisting of an alkylamine base and a bis(thiourea) featuring a linear alkane tether is shown to dramatically increase the rate of ring-opening polymerization (ROP) of L-lactide versus previously disclosed monothiourea H-bond donors. Rate acceleration occurs regardless of the identity of the alkylamine cocatalyst, and the ROP remains controlled yielding poly(lactide) with narrow molecular weight distributions, predictable molecular weights and high selectivity for monomer. This H-bond mediated ROP of L-lactide constitutes a rare, clear example of rate acceleration with bis(thiourea) H-bond donors versus monothioureas, and the bis(thiourea) is shown to remain highly active for ROP at fractional percent catalyst loadings. Activation at a single monomer ester by both thiourea moieties is implicated as the source of rate acceleration.

Thiourea/alkylamine cocatalysts have previously been shown to be effective systems for the ring-opening polymerization (ROP) of lactide, but an experimental explanation for the varied activity and selectivity of these structurally similar alkylamine cocatalysts combined with thiourea is elusive. In this work, several alkylamine bases are shown to be weakly associated with a thiourea cocatalyst in solution, and the nature of cocatalyst interactions vary with the identity of the alkylamine. Kinetic analyses of the organocatalytic ROP reactions reveal noninhibitory behavior in [alkylamine] and a new mode of activity for thiourea. Reactivity patterns are proposed based on computed cocatalyst geometries, and a new cocatalyst pair for the ROP of lactide is disclosed.

Organocatalysis is a powerful tool for polymer synthesis. It has been widely demonstrated that organocatalytic systems enable precise control over polymer microstructure, provide competitively fast reaction rates compared with metal-based catalysts, and effect a broad assortment of polymerization mechanisms. The added value of metal-free polymerizations is that they can be utilized in sensitive applications intolerant to the presence of residual metal-based catalysts. The initial focus of the present dissertation was placed on mechanistic studies in organocatalytic ring-opening polymerization (ROP) of cyclic esters alongside with subsequent development of new organocatalytic systems for ROP. ROPs of this kind can be mediated by a thiourea-based hydrogen-bond donating catalyst and a strong organic base. The two cocatalysts activate the monomer and initiator for the reaction to commence. The question is: how do the four species interact? The binding between thiourea and bases was investigated-an interaction that had not been previously considered. An array of binding constants between thiourea and various bases was obtained. Importantly, the binding constants proved to correlate with the δvalerolactone ROP rate depending upon the base used for the polymerization. The theory paved a way to the assessment of weaker bases in ROP. With the original theory working, a new goal was selected-to investigate the binding between thiourea and weak alkylamine bases. A range of binding constants was measured for various thiourea and alkylamine cocatalyst pairs. The correlation between the binding constants and the rate of L-lactide ROP was non-existent. However, enthalpy and entropy of cocatalyst binding were found to correlate with the L-lactide ROP rate. The more entropically favorable cocatalyst interactions yielded higher rates of L-lactide ROP. Additionally, the enthalpy and entropy of the thiourea-alkylamine binding exhibited enzyme-like compensation behavior similar enzyme-substrate analogues. Kinetic investigations demonstrated that thiourea-alkylamine mediated ROP of L-lactide exhibited a second-order rate dependence in thiourea. This observation prompted us to assess the effect of two thiourea motifs tethered in one molecule on the ROP rate. The new bis-thiourea catalyst provided exquisite control over ROP, yielded well-defined polymers (narrow polydispersities, predictable molecular weights), was able to polymerize a host of cyclic ester monomers, and brought a significant rate acceleration for polymerizations even at small catalyst loadings, compared with monothiourea catalyst. Seeking active and selective H-bonding catalysts, attention was attracted by the widely available triclocarban, formerly used as an antibacterial soap component. Triclocarban contains a urea functionality that renders the compound a potential H-bond donating catalyst. The examination of triclocarban as a ROP catalyst proved its efficiency for hydrogen-bonding ROP of a broad scope of monomers in different solvents. Having the ROP conditions opt...