Rate Accelerated Organocatalytic Ring-Opening Polymerization of l-Lactide via the Application of a Bis(thiourea) H-bond Donating Cocatalyst

Abstract

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.

Solvent‐free ring‐opening polymerization of lactones with hydrogen‐bonding bisurea catalyst

“…Four bisurea catalysts were prepared by the reaction between 3,5‐bis(trifluoromethyl)phenyl isocyanate and the corresponding bisamines. This approach was inspired by the use of monourea or bis(thio)urea catalysts in small molecule transformations . Neutral bisureas were readily prepared in one step from the commercially available isocyanates and bisamines at room temperature .…”

“…Here, a synergistic catalytic mechanism was proposed, in which the bisurea activated the carbonyl group of monomer and MTBD facilitated the nucleophilic attack of the initiating/propagating alcohol by hydrogen bonding (Scheme ) . Kiesewetter expounded that (thio)urea/MTBD mediated ROP of VL proceeded through one of two mechanisms, (thio)‐imidate mechanism and classic H‐bond mediated mechanism.…”

“…Under the conditions of solvent‐free ROP, the bisurea/MTBD may perform a classic H‐bond mediated ROP mechanism. The catalytic effect of bis(thio)urea connected by flexible groups proceeded through an activated‐urea mechanism, in which one urea moiety activated the other urea with increased electrophilicity and subsequently activated the monomer . However, in our bisurea system, the intramolecular H‐bonding in enhancing the catalytic performances may be not possible because bisurea was connected by rigid groups.…”

“…Compared to the bifunctional catalysts, the advantage of hydrogen bond donor (HBD) in cooperation with a hydrogen bond acceptor (HBA) is a straightforward synthetic access from the commercial compounds. Kiesewetter and coworkers reported that the HBDs—urea and thiourea stand out among the controlled ROP of lactones, because of their precise controls for polymerization over transesterification . The urea HBD has better activity and controllability than the thiourea in the ROP of lactones (lactide excluded).…”

“…Based on the previous work, the multi(thio)urea catalysts studied by Kiesewetter are connected by flexible groups, and the activation mechanism is activated‐urea or dual‐urea activation that all between intramolecular hydrogen bonding . We put forward an assumption that the catalytic performances of HBD with essential rigid groups enhance the activity by intermolecular hydrogen bonding.…”