Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - DUAL-PHOSCAT (Multi-functional DUAL PHOSphorus-based organoCATalysts for stereoselective ring-opening polymerisation)

Teaser

Summary of the context and overall objectives of the project:Aliphatic polyesters are a highly important class of biodegradable polymers on account of their controllable materials and degradation properties that enable their use in applications as varied as commodity plastics...

Summary

Summary of the context and overall objectives of the project:
Aliphatic polyesters are a highly important class of biodegradable polymers on account of their controllable materials and degradation properties that enable their use in applications as varied as commodity plastics (such as in packaging or fibers) or as speciality plastics (e.g. in biomedical devices). The micro and macro-structure of a polymer define the physical properties and potential applications. Thus, the synthesis of such macromolecules must be controlled to obtained materials with predictable and desired properties. The ring-opening polymerisation (ROP) of cyclic (di)esters in the presence of a catalyst/initiator (Cat/I) system readily enables the synthesis of polyesters with well-defined structure. The ROP of LA has been studied extensively, largely as a consequence of the production of lactide (LA) from renewable resources and the widespread study of polylactide (PLA) materials across a wide range of application areas. However, challenges still remain in which targeted catalyst design presents the most favourable solutions.
Achieving stereocontrol in polymerisation of chiral monomers has been one of the most important goals since the early 90’s. Apart from the exciting challenge of accomplishing the perfect control in enantioselective reactions, another important aspect has also stimulated this field: the properties of the polymer are highly dependent on the microstructure of the macromolecule and controlling the stereoselectivity gives access to materials with precise and finely-tuned properties for specific applications. Numerous efficient organometallic initiators have been reported for the stereoselective ring-opening polymerization of cyclic esters but most of them are air and moisture sensitive compounds and should be used under strictly air and water free conditions that is an important drawback to their industrial applications.
Organocatalysts have emerged as a viable alternative to organometallic initiators in ROP processes. These catalysts result in polymers that are free of residual metal contaminates as desired for specific biomedical or microelectronic applications. To date there are very few reports of stereocontrolled organocatalytic ROP under practical conditions (room temperature or above, in bulk etc.). To advance the field, new tuneable chiral organocatalysts are required. The project will pave the way in the design of tunable polymerisation organocatalysts for the preparation of polymers with controlled tacticity such as polylactide. The research project proposed to develop chiral tunable phosphorus-based organocatalysts possessing chiral functionalities such as thioureas for dual activation of both the monomer(s) and the initiator, to overcome these challenges.

Work performed

Work performed from the beginning to the end of the project and main results achieved:
Based on previous reports, different types of dual organocatalyst were proposed: phosphines, amines for polymer growing chain-end activation and thioureas for lactide monomer activation as well as self-assembled phosphate-ammonium organocatalysts. Chiral catalysts were preferred to achieve stereocontrolled ROP and kinetic resolution of rac-LA.
The different components for the preparation of the dual organocatalysts were either synthesized, purified and characterized or bought from chemical suppliers. Numerous organocatalytic systems were tested for the stereocontrolled ROP of rac-LA under different reaction conditions (solvent, temperature, etc.) to identify promising combinations and pursue the design and optimisation of the organocatalysts. Surprisingly, in our hands, phosphines showed almost no activity for ROP of rac-lactide even in the presence of a cocatalyst at high temperature and the ammonium phosphate salt didn’t work at all in LA ROP even in bulk melt lactide. Due to the lack of reactivity of the different catalyst systems based on phosphine/thiourea and phosphate ammonium, we envisaged the design of the dual catalysts starting from chiral amines and chiral thioureas.
As an alternative to commercially available Takemoto’s catalyst (TUC) we reported recently in collaboration with Taton’s group, we designed a library of amines and thioureas varying the steric and electronic parameters of the catalysts for optimisation. We could obtain highly isotactic polylactide with a calculated probability of creating a meso enchainment Pm up to 0.87. Surprisingly, the PLAs with calculated Pm ranging from 0.79 to 0.87 showed unexpected melting temperature (Tm) trend; in fact, some PLAs having a calculated Pm of 0.85 showed no Tm on the contrary to less isotactic PLAs. This could be explained by the formation and polymerisation of meso-lactide affecting the tacticity of the polymer and the length of the isotactic blocks. On the other hand, the accuracy of the method used to determine the tacticity of the PLA either by 1H homonuclear decoupling or 13C quantitative NMR spectroscopy could also be questioned when applying site-control statistics or chain-end control statistics to catalytic systems that could combine both mechanism of stereocontrol. Those results highlighted the fact that the Tm of the PLA determined by differential scanning calorimetry (DSC) remains always necessary to support the calculated Pm.
Gratifyingly, the different amine/thiourea catalysts developed for the project produced highly isotactic polylactide (Pm up to 0.87) with high melting temperature (Tm up to 174 ºC; enthalpy of fusion ΔHm up to 20 J.g-1) in a controlled manner. The polymerisation is fast for a chiral catalyst taking into account that the conversion of the unpreferred monomer enantiomer is usually much slower; 100eq. of rac-LA are converted in 18 h at room temperature. The enantioselectivity factors s (kfast/kslow) achieved (up to 6.2) are high and were supported by the high Pm and Tm observed for the polylactide obtained.

Final results

Progress beyond the state of the art and expected potential impact:
The developed organocatalysts enabled advances in the preparation of isotactic metal-free PLA. In fact, highly isotactic semi-crystalline PLA showing high melting temperature could be obtained from rac-lactide. The catalysts are easily accessible synthetically and could selectively polymerise D or L-lactide depending on the chirality of the selected catalyst system.
We could also highlight catalyst structure/stereoselectivity relationship for further development and optimisation of highly isoselective catalysts; we observed the enantioselection to be dictated by the thiourea chirality indifferently of the chirality of the amines; using (R)-thioureas polymerises L-lactide faster and vice-versa for instance. The steric bulk of the amine was also shown to be very important in achieving the high enantioselectivity as other common smaller (chiral) amines combined with chiral thioureas gave almost no enantioselectivity, even if the synthesized chiral amine is not able to enantioselectively activate the chiral growing chain-end. This can be easily explained by the fact that lactide is a much bigger chiral molecule than the polymer chain-end, a chiral lactic ester R-O(C=O)-CH(CH3)-OH.
Those results will open new avenues and will undoubtedly be very useful to the development of organocatalysts for sterecontrolled ROP of rac-lactide and also more generally to the ROP of chiral monomers.