Highly Selective O-Phenylene Bisurea Catalysts for ROP: Stabilization of Oxyanion Transition State by a Semiflexible Hydrogen Bond Pocket.

Organocatalyzed ring-opening polymerization (ROP) is a versatile technique for synthesizing biodegradable polymers, including polyesters and polycarbonates. We introduce o-phenylene bisurea (OPBU) (di)anions as a novel class of organocatalysts that are fast, easily tunable, mildly basic, and exceptionally selective. These catalysts surpass previous generations, such as thiourea, urea, and TBD, in selectivity (kp/ktr) by 8 to 120 times. OPBU catalysts facilitate the ROP of various monomers, achieving high conversions (>95%) in seconds to minutes, producing polymers with precise molecular weights and very low dispersities (D ≈ 1.01). This performance nearly matches the ideal distribution expected from living polymerization (Poisson distribution). Density functional theory (DFT) calculations reveal that the catalysts stabilize the oxyanion transition state via a hydrogen bond pocket similar to the "oxyanion hole" in enzymatic catalysis. Both experimental and theoretical analyses highlight the critical role of the semirigid o-phenylene linker in creating a hydrogen bond pocket that is tight yet flexible enough to accommodate the oxyanion transition state effectively. These new insights have provided a new class of organic catalysts whose accessibility, moderate basicity, excellent solubility, and unparalleled selectivity and tunability open up new opportunities for controlled polymer synthesis.

Ring-Opening Polymerization of Cyclic Esters and Carbonates with (Thio)urea/Cyclopropenimine Organocatalytic Systems.

Organocatalyzed ring-opening polymerization is a powerful tool for the synthesis of a variety of functional, readily degradable polyesters and polycarbonates. We report the use of (thio)ureas in combination with cyclopropenimine bases as a unique catalyst for the polymerization of cyclic esters and carbonates with a large span of reactivities. Methodologies of exceptionally effective and selective cocatalyst combinations were devised to produce polyesters and polycarbonates with narrow dispersities (D = 1.01-1.10). Correlations of the pKa of the various ureas and cyclopropenimine bases revealed the critical importance of matching the pKa of the two cocatalysts to achieve the most efficient polymerization conditions. It was found that promoting strong H-bonding interactions with a noncompetitive organic solvent, such as CH2Cl2, enabled greatly increased polymerization rates. The stereoselective polymerization of rac-lactide afforded stereoblock poly(lactides) that crystallize as stereocomplexes, as confirmed by wide-angle X-ray scattering.

Accelerating the end-to-end production of cyclic phosphate monomers with modular flow chemistry.

The biocompatibility, tunable degradability and broad functionalities of polyphosphoesters and their potential for biomedical applications have stimulated a renewed interest from Chemistry, Medicinal Chemistry and Polymer Sciences. Commercial applications of polyphosphoesters as biomaterials are still hampered because of the time and resource-intensive sourcing of their corresponding monomers, in addition to the corrosive and sensitive nature of their intermediates and by-products. Here, we present a groundbreaking challenge for sourcing the corresponding cyclic phosphate monomers by a different approach. This approach relies on the use of continuous flow technologies to intensify the end-to-end preparation of cyclic phosphate monomers with a semi-continuous modular flow platform. The applied flow technology mitigates both safety and instability issues related to the more classical production of cyclic phosphate monomers. The first flow module allows safe synthesis of a library of cyclic chlorophosphite building blocks and features in-line 31P NMR real-time monitoring. After optimization on the microfluidic scale, this first module is successfully transposed toward mesofluidic scale with a daily throughput of 1.88 kg. Downstream of the first module, a second module is present, allowing the quantitative conversion of cyclic chlorophosphites with molecular oxygen toward chlorophosphate derivatives within seconds. The two modules are concatenable with a downstream semi-batch quench of intermediate chlorophosphate with alcohols, hence affording the corresponding cyclic phosphate monomers. Such a continuous flow setup provides considerable unprecedented advantages to safely and efficiently synthesize a library of versatile high value-added cyclic phosphate monomers at large scale. These freshly produced monomers can be successfully (co)polymerized, using either batch or flow protocols, into well-defined polyphosphoesters with assessed thermal properties and cytotoxicity.

Sustaining the Transition from a Petrobased to a Biobased Chemical Industry with Flow Chemistry.

In the current context of transitioning to more sustainable chemical processes, the upgrading of biobased platform molecules (i.e., the chemical transformation of widely available low molecular weight entities from biomass) is attracting significant attention, in particular when combined with enabling continuous flow conditions. The success of this combination is largely due to the ability to explore new process conditions and the perspective of facilitating seamless scalability while maintaining a small overall footprint. This review considers representative continuous flow processes which utilize a selection of currently popular platform molecules that target industrially relevant building blocks, including (a) commodity chemicals, (b) specialty and fine chemicals, and (c) fuels and fuel additives.