Aliphatic polyesters and polycarbonates are a class of biorenewable, biocompatible, and biodegradable materials. One of the most powerful methods for accessing these materials is the ring-opening polymerization (ROP) of cyclic monomers. Here we report that the deprotonation of ureas generates a class of versatile catalysts that are simultaneously fast and selective for the living ring-opening polymerization of several common monomers, including lactide, δ-valerolactone, ε-caprolactone, a cyclic carbonate, and a cyclic phosphoester. Spanning several orders of magnitude, the reactivities of several diaryl urea anions correlated to the electron-withdrawing substituents on the aryl rings. With the appropriate urea anions, the polymerizations reached high conversions (∼90%) at room temperature within seconds (1-12 s), yielding polymers with narrow molecular weight distributions (Đ = 1.06 to 1.14). These versatile catalysts are simple to prepare, easy to use, and exhibit a range of activities that can be tuned for the optimal performance of a broad range of monomers.

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–H+). 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.

The critical role of composition, architecture, molecular weight, and molecular weight distribution on the functional properties of macromolecular materials underscores the need for reproducible, robust, scalable, and programmable synthetic methods to generate macromolecules that span a systematic and wide range of structure−property space. Herein, we describe the marriage of tunable and highly active organic catalysts with programmed continuous-flow reactors to rapidly generate libraries of polyester and polycarbonate homopolymers and block copolymers with exquisite efficiency and control. Under continuous-flow conditions, highly controlled polymerizations occur with residence times as low as 6 ms (TOF = 24 000 000 h −1 ) and can be readily scaled-up to generate polymers at a rate of tens of grams per minute. We describe an in-flow catalyst switch strategy to enable the rapid generation of block copolymer libraries (100 distinct polymers in 9 min) from monomers with drastically different reactivity profiles.

The controlled anionic ring-opening polymerization of lactones and siloxanes is carried out in continuous-flow reactors. Anionic ring-opening polymerization of cyclic esters with strong, soluble bases such as potassium tert-butoxide (KOtBu) is typically performed as batch reactions, leading to broad dispersity and poor control over the molecular weight (M n) mainly because of transesterification reactions. Although reactions with strong bases give rise to “uncontrolled” polymerizations, a variety of transition metal-based and organocatalysts have been developed with the goal of reliably controlling the dispersity and M n. Herein, we show that the rapid mixing and short residence times accessible with a continuous-flow apparatus can enable the controlled polymerization of low-reactivity monomers such as δ-valerolactone and ε-caprolactone on millisecond time scales using a base [such as KOtBu or potassium bis­(trimethylsilyl)­amide (KHMDS)] in conjunction with a primary alcohol. These reactions exhibit characteristics capable of producing narrow dispersity with predictable molecular weights and can rapidly generate well-defined block copolymers with residence times below 0.1 s.

A new organocatalyst for the ring-opening polymerization of lactones has been identified. Under the tested conditions, the anions of 2,2′-bisindole promote fast, living polymerizations (as short as 10 ms) which are selective for chain elongation over transesterification (Đ ≤ 1.1). While structurally related to (thio)­urea anion catalysts, anions of 2,2′-bisindole activate the monomer via the counterion rather than through hydrogen bonding. This new activation motif enables modulation of the polymerization rate by 2 orders of magnitude by changing the counterion.