Highly Active Organocatalysts for Stereoselective Ring-Opening Polymerization of Racemic Lactide at Room Temperature

Abstract

Although significant advances have been achieved, highly stereocontrolled polymerization using organocatalysts is still a great challenge, such as ring-opening polymerization of racemic lactide (rac-LA) for the synthesis of stereoregular polylactide (PLA). In this context, a series of binary organocatalysts consisting of different phosphazenes (CTPB, C3N3-Me-P3, C3N3-Py-P3, t-BuP2, and t-BuP4) and achiral ureas (U1–U6) were applied for the stereocontrolled ROP of rac-LA under mild conditions. It is remarkable that C3N3-Py-P3/U4 with the compatible basicity/acidity showed both high activity (92% conversion within 10 min) and great stereoselectivity (P m = 0.92) at room temperature (20 °C), and the resultant stereoblock PLA had predictable molar mass, narrow distribution (Đ = 1.07), and high melting temperature (T m = 190 °C). Interactions involved among phosphazene, urea, and initiator were investigated by an in situ NMR technique. It was found that C3N3-Py-P3 reacted with benzyl alcohol (BnOH) to form a relatively loose ion pair in the presence of U4, which accounted for both high activity and stereoselectivity. Kinetics studies for different LA monomers at 20 °C showed k obs –1 (rac-LA) = 0.212 min–1, k obs –1 (D-LA) = 0.311 min–1, and k obs –1 (L-LA) = 0.317 min–1, indicative of the chain end control mechanism for stereocontrolled ROP.

Stereoselective ring‐opening polymerization ofrac‐lactide catalyzed by phenyl diphosphazene/urea binary catalytic system

“…First, achiral ureas with electron‐withdrawing substituents on the benzene rings ( U‐1 and U‐2 ) were combined with m ‐PDPB to evaluate the polymerization behavior of rac ‐LA (Table 1, runs 3–5). It has been reported that the addition of excess ureas could improve the solubility of the initiator/urea anion mixtures and a ratio of [urea] 0 /[base] 0 = 3/1 was generally adopted in the reported urea/base catalytic systems to ensure good solubility 40,51,52 . Therefore, a molar ratio of 1/3/1 between the base, the urea and the initiator was employed for the preliminary ROP experiments.…”

“…Newly designed chiral bifunctional squaramides could mediate the stereoselective ROP of rac ‐LA to prepare PLAs with P m up to 0.88 at 25°C 37 . Very recently, we found that phosphazene/urea with compatible basicity/acidity showed both high activity and great stereoselectivity ( P m = 0.92) toward the ROP of rac ‐LA at room temperature 40 . Although these progresses have been made, organocatalyzed stereoselective ROP of rac ‐LA under mild reaction conditions remains a challenge.…”

Structural Effect of Organic Catalytic Pairs Based on Chiral Amino(thio)ureas and Phosphazene Bases for the Isoselective Ring-Opening Polymerization of Racemic Lactide

“…, use of non-metallic catalysts for creation of C–C or C–X bonds with high stereoselectivity, has truly emerged in the early 2000s. − These developments, which were crowned in 2021 with the award of the Nobel Prize in Chemistry to McMillan and List, have led to organic catalysts constituting today the third pillar of catalysis, besides enzymes and metallic catalysts. − In contrast, adaptation of this concept in polymer synthesis, i.e. , stereoselective polymerization employing chiral organic catalysts, is more recent and remains underexplored. − In a more general way, organic catalysts, whether they are chiral or not, that can provide high stereoselectivity and high catalytic activity, in addition to operating under mild conditions, e.g., at room temperature or above, are rare. − Yet, the use of small organic molecules for organic catalysis of polymerization is now part of the methodological toolbox in macromolecular synthesis. − Depending on the structure of the organic catalyst, different mechanisms can operate, and this diversity of mechanistic pathways allows for improved polymerization rates, tuning of the selectivity, and rational design of a variety of polymer architectures. Organic catalysis of polymerization can offer other advantages over metal-catalyzed reactions, such as a reduced toxicity and cost, easier catalyst synthesis and storage, tolerance to functional groups, and operation at elevated temperatures and in a variety of solvents. − Recent years have witnessed new achievements at the crossroads between organocatalysis and macromolecular science, for instance, through the use of organic catalysts for photopolymerization or for controlled radical polymerization, for chemical recycling and upcycling of synthetic polymers, or for designing covalent adaptative networks …”

“…, made from the two LA monomer units of opposite configurations, may be obtained at lower cost by stereocontrolled ROP of rac -LA, leading to PLA-based materials of enhanced properties. , Since the 1990s, and until recent years, − the stereochemical control of the ROP of rac -LA has been intensively investigated using metal catalysts operating by a coordination–insertion mechanism. , As mentioned, however, specific design and/or storage of organometallic complexes can be demanding, in addition to their often-proven cytotoxicity. In that respect, organic catalysts have appeared as promising alternatives for the stereoselective ROP of rac -LA. − …”

Precision Synthesis of Polypeptides via Living Anionic Ring-Opening Polymerization of N-Carboxyanhydrides by Tri-thiourea Catalysts

“…Second, the stabilization of the carbamate anion propagating intermediate by tripodal tri-thiourea (TTU) via anion-binding interaction enables chain elongation to proceed in a synergistic decarboxylation fashion and avoids the formation of undesired highly basic −NH – propagating species, reducing the basicity and nucleophilicity of the anionic propagating species, thereby minimizing extensive side reactions and the “activated monomer” pathway. Third, the activation of tri-thiourea upon the NCA monomer through classical H-bonding − combined with propagation in a synergistic decarboxylation fashion can prevent inherent helix-induced self-acceleration in less-polar solvents, resulting in chain initiation rate at least comparable to that of propagation.…”