Organic Ring-Opening Polymerization Catalysts: Reactivity Control by Balancing Acidity

Organocatalysts derived from thioureas and amines exhibit high functional group tolerance and extraordinary selectivities for ring-opening relative to chain transesterification. The modest activities of the thiourea/ amine catalysts prompted a detailed investigation of ureas and thiourea with organic bases for the ring-opening polymerization of lactones. An array of ureas or thioureas and organic bases were evaluated to assess the effect of the acidity of the urea (thiourea) and the basicity of the base cocatalyst on the activity for ring-opening polymerization. These studies reveal that for a given urea or thiourea stronger bases lead to faster rates. For a given base, the observed catalytic activity is highest when the acidity of the (thio)urea is closely matched with that of the B H+. For ureas and thioureas of comparable acidity, the urea/base catalyst systems are considerably more active than the corresponding thiourea/base systems. These results are consistent with two mechanisms: one mediated by deprotonated (thio)urea anions when (thio)ureas are combined with bases of sufficient basicity and one mediated by neutral (thio)ureas when the base is incapable of deprotonating the (thio)urea. Opposing trends in reactivity for (thio)urea anions and neutral (thio)ureas as a function of (thio)urea acidity lead to the maximal activity when the acidities of the (thio)ureas are closely matched with that of the protonated base (B-1-1+). These findings provide the basis for understanding the reactivity of ring-opening polymerization cocatalysts as well as guidelines for the rational design of other acid/base catalyst pairs.