Stereoregular Isotactic Poly(mandelic acid) via Organocatalytic Ring-Opening Polymerization of a Cyclic O-carboxyanhydride**

Poly(mandelic acid), PMA, is an aryl analogue of poly(lactic acid), PLA, and a biodegradable analogue of polystyrene. Preparation of stereoregular PMA is reported for the first time in this work using a pyridine-mandelic acid adduct (Py·MA) as an organocatalyst for the ring-opening polymerisation (ROP) of the cyclic O-carboxyanhydride, manOCA. Polymers with narrow polydispersity index and excellent molecular weight control were prepared at ambient temperature. These highly isotactic chiral polymers exhibit glass transition temperature (Tg) enhancement of 15 ̊C compared to the racemic polymer, suggesting potential future application as high performance commodity and biomedical materials. Degradable polymers based on biorenewable resources are desirable alternatives to common commodity polymers. The environmental persistence and dependence on fossil-based resources of the latter are increasingly viewed as unsustainable. Polylactide (PLA) is a thermoplastic aliphatic polyester derived from lactic acid that is perhaps the most widely studied degradable and renewable polymer. PLA is commercially available for packaging and fibre applications via solvent-free ring-opening polymerization (ROP) of lactide, (Scheme 1). In recent years, the drive to achieve enhanced physical and mechanical properties such as impact and heat resistance for such applications of PLA has led to detailed mechanistic understanding and prompted the development of a wide range of single-site metal alkoxides and organocatalytic bases for the well-controlled and stereoselective ROP of lactide.. Despite these impressive advances, major challenges remain. For example, the glass transition temperature (Tg) of PLA remains low (typically 30-60 ̊C) due to the inherently flexible polymer backbone. This low heat resistance limits the range of applications for which PLA-based materials are applicable. Recently, in an intriguing report, Baker et al. demonstrated the first synthesis of high molecular weight poly(mandelic acid), PMA, via the tin-catalyzed ROP of mandelide, the cyclic dimer of mandelic acid (an aryl analogue of lactide) (Scheme 1). They demonstrated that polymandelide shares many physical and mechanical properties with polystyrene, including a high Tg (95-100 ̊C) while, in common with PLA, it is available from renewable resources and is degradable. However, the synthesis of mandelide requires extended reaction times, high-boiling solvents and results in poor to moderate yields of poorly soluble monomers. Furthermore, relative to lactide, decreased reactivity of mandelide, coupled with its increased C-H acidity makes racemization of the monomer during polymerization unavoidable, meaning that only atactic material is available via this route (Scheme 1). Scheme 1. Metaland organo-catalysed ring-opening polymerization to isotactic poly-L-(lactic acid) (PLLA) and atactic poly(mandelic acid) (PMA) from: (i) L-lactide (commercial process); (ii) L-lacOCA (ref 14); (iii) , Lmandelide (ref 13); and (iv) L-manOCA (this work). Building on these intriguing results, and the elegant demonstration of controlled synthesis of PLA via the Ocarboxyanhydride (OCA) activated monomer, L-lacOCA by Bourrisou and others, we reasoned that an organocatalytic approach to ROP of an activated mandelic acid monomer, manOCA might promote controlled polymerization under sufficiently mild conditions to prevent racemization and yield stereoregular isotactic PMA (Scheme 1). Herein, we report the successful application of this strategy to achieve, for the first time, the synthesis and unambiguous characterization of high molecular weight isotactic PMA via a new organocatalytic adduct. The enantiomerically pure activated monomer manOCA was prepared in good yield by modification of a literature procedure (Supporting Information, SI). Initial investigations of polymerization of manOCA focused on pyridine-based catalysts and initiators which have proved effective for well-controlled organocatalytic ROP of lacOCA and related monomers. A [*] Antoine Buchard, David R. Carbery,* Matthew G. Davidson,* Petya K. Ivanova, Ben J. Jeffery, Gabriele I. Kociok-Köhn and John P. Lowe Department of Chemistry and Centre for Sustainable Chemical Technologies University of Bath Bath, BA2 7AY, United Kingdom Fax: (+)44 01225 386231 E-mail: [email protected], [email protected] [**] We thank Sue and Roger Whorrod, the UK Engineering and Physical Sciences Research Council (EPSRC) (EP/J005118/1), the University of Bath and Johnson Matthey for financial support. Supporting information for this article is given via a link at the end of the document