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Spiro-salen catalysts enable the chemical synthesis of stereoregular polyhydroxyalkanoates

Nature Catalysis volume 6, pages 720–728 (2023)Cite this article

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Abstract

Although bacterial stereoregular polyhydroxyalkanoates have attracted broad interest as sustainable materials, it remains a long-standing challenge to chemically synthesize stereoregular polyhydroxyalkanoates via the stereoselective ring-opening polymerization of four-membered lactones. Here we report the design and synthesis of a class of readily tunable spiro-salen yttrium complexes for stereoselective ring-opening polymerization of rac-β-butyrolactone. Ligand modification on this spiro-salen system allowed a switch from syndioselectivity to isoselectivity, producing syndiotactic poly(3-hydroxybutyrate) (probability of racemic linkages between monomer units up to 0.99) and isotactic poly(3-hydroxybutyrate) (probability of meso linkages between monomer units up to 0.95). A complete stereoselectivity switch between enantiopure and racemic catalysts was observed for the spiro-binaphthol-salen system. Incorporation of rac-β-valerolactone into poly(3-hydroxybutyrate) afforded stereoregular poly(3-hydroxybutyrate-co-3-hydroxyvalerate)s with high molecular weight and desirable material properties comparable to commercial material polyolefins. This spiro-salen ligand system provides a conceptual framework that could guide future stereoselective catalyst design efforts.

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Fig. 1: Salen ligand systems.
Fig. 2: Syndioselective ROP of rac-BBL by spiro-salen catalysts rac-Y5–Y7.
Fig. 3: Stereoselective polymerization.
Fig. 4: Stereoselectivity study for ROP of rac-BBL.
Fig. 5: Copolymerization study of rac-BBL and rac-BVL.

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Data availability

The data supporting the findings of this study are provided in the article and its Supplementary Information or are available from the corresponding author upon reasonable request. Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2206620 (rac-L6, structure shown in Supplementary Fig. 145), CCDC 2206621 (rac-L7, structure shown in Supplementary Fig. 146), CCDC 2206622 [(sS, aS)-L14, structure shown in Supplementary Fig. 147] and CCDC 2206623 (rac-Y7, structure shown in Fig. 2). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.

References

  1. Zhu, Y., Romain, C. & Williams, C. K. Sustainable polymers from renewable resources. Nature 540, 354–362 (2016).

    Article  CAS  PubMed  Google Scholar 

  2. MacLeod, M., Arp, H. P. H., Tekman, M. B. & Jahnke, A. The global threat from plastic pollution. Science 373, 61–65 (2021).

    Article  CAS  PubMed  Google Scholar 

  3. Law, K. L. & Narayan, R. Reducing environmental plastic pollution by designing polymer materials for managed end of life. Nat. Rev. Mater. 7, 104–116 (2022).

    Article  CAS  Google Scholar 

  4. Haque, F. M. et al. Defining the macromolecules of tomorrow through synergistic sustainable polymer research. Chem. Rev. 122, 6322–6373 (2022).

    Article  CAS  PubMed  Google Scholar 

  5. De Hoe, G. X., Şucu, T. & Shaver, M. P. Sustainability and polyesters: beyond metals and monomers to function and fate. Acc. Chem. Res. 55, 1514–1523 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Müller, H.-M. & Seebach, D. Poly(hydroxyalkanoates): a fifth class of physiologically important organic biopolymers? Angew. Chem. Int. Ed. 32, 477–502 (1993).

    Article  Google Scholar 

  7. Lenz, R. W. & Marchessault, R. H. Bacterial polyesters: biosynthesis, biodegradable plastics and biotechnology. Biomacromolecules 6, 1–8 (2005).

    Article  CAS  PubMed  Google Scholar 

  8. Chen, G.-Q. A microbial polyhydroxyalkanoates (PHA) based bio- and materials industry. Chem. Soc. Rev. 38, 2434–2446 (2009).

    Article  CAS  PubMed  Google Scholar 

  9. Muhammadi, S., Afzal, M. & Hameed, S. Bacterial polyhydroxyalkanoates-eco-friendly next generation plastic: production, biocompatibility, biodegradation, physical properties and applications. Green. Chem. Lett.Rev. 8, 56–77 (2015).

    Article  Google Scholar 

  10. Rehm, B. H. A. Bacterial polymers: biosynthesis, modifications and applications. Nat. Rev. Microbiol. 8, 578–592 (2010).

    Article  CAS  PubMed  Google Scholar 

  11. Barouti, G., Jaffredo, C. G. & Guillaume, S. M. Advances in drug-delivery systems based on synthetic poly(hydroxybutyrate) (co)polymers. Prog. Polym. Sci. 73, 1–31 (2017).

    Article  CAS  Google Scholar 

  12. Hazer, B. & Steinbüchel, A. Increased diversification of polyhydroxyalkanoates by modification reactions for industrial and medical applications. Appl. Microbiol. Biotechnol. 74, 1–12 (2007).

    Article  CAS  PubMed  Google Scholar 

  13. Laycock, B., Halley, P., Pratt, S., Werker, A. & Lant, P. The chemomechanical properties of microbial polyhydroxyalkanoates. Prog. Polym. Sci. 38, 536–583 (2013).

    Article  CAS  Google Scholar 

  14. Worch, J. C. et al. Stereochemical enhancement of polymer properties. Nat. Rev. Chem. 3, 514–535 (2019).

    Article  CAS  Google Scholar 

  15. Choi, S. Y. et al. Microbial polyhydroxyalkanoates and nonnatural polyesters. Adv. Mater. 32, 1907138 (2020).

    Article  CAS  Google Scholar 

  16. Możejko-Ciesielska, J. & Kiewisz, R. Bacterial polyhydroxyalkanoates: Still fabulous? Microbiol. Res. 192, 271–282 (2016).

    Article  PubMed  Google Scholar 

  17. Inoue, S., Tomoi, Y., Tsuruta, T. & Furukawa, J. Organometallic-catalyzed polymerization of propiolactone. Makromol. Chem. 48, 229–233 (1961).

    Article  CAS  Google Scholar 

  18. Westlie, A. H., Quinn, E. C., Parker, C. R. & Chen, E. Y.-X. Synthetic biodegradable polyhydroxyalkanoates (PHAs): recent advances and future challenges. Prog. Polym. Sci. 134, 101608 (2022).

    Article  CAS  Google Scholar 

  19. Amgoune, A., Thomas, C. M., Ilinca, S., Roisnel, T. & Carpentier, J. F. Highly active, productive, and syndiospecific yttrium initiators for the polymerization of racemic β-butyrolactone. Angew. Chem. Int. Ed. 45, 2782–2784 (2006).

    Article  CAS  Google Scholar 

  20. Ajellal, N. et al. Syndiotactic-enriched poly(3-hydroxybutyrate)s via stereoselective ring-opening polymerization of racemic β-butyrolactone with discrete yttrium catalysts. Macromolecules 42, 987–993 (2009).

    Article  CAS  Google Scholar 

  21. Ajellal, N. et al. Polymerization of racemic β-butyrolactone using supported catalysts: a simple access to isotactic polymers. Chem. Commun. 46, 1032–1034 (2010).

    Article  CAS  Google Scholar 

  22. Dong, X. & Robinson, J. R. The role of neutral donor ligands in the isoselective ring-opening polymerization of rac-β-butyrolactone. Chem. Sci. 11, 8184–8195 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dong, X., Brown, A. M., Woodside, A. J. & Robinson, J. R. N-oxides amplify catalyst reactivity and isoselectivity in the ring-opening polymerization of rac-β-butyrolactone. Chem. Commun. 58, 2854–2857 (2022).

    Article  CAS  Google Scholar 

  24. Haslböck, M. et al. Mechanical and thermal properties of mixed-tacticity polyhydroxybutyrates and their association with iso- and atactic chain segment length distributions. Macromolecules 52, 5407–5418 (2019).

    Article  Google Scholar 

  25. Dunn, E. W. & Coates, G. W. Carbonylative polymerization of propylene oxide: a multicatalytic approach to the synthesis of poly(3-hydroxybutyrate). J. Am. Chem. Soc. 132, 11412–11413 (2010).

    Article  CAS  PubMed  Google Scholar 

  26. Yang, J.-C., Yang, J., Li, W.-B., Lu, X.-B. & Liu, Y. Carbonylative polymerization of epoxides mediated by tri-metallic complexes: a dual catalysis strategy for synthesis of biodegradable polyhydroxyalkanoates. Angew. Chem. Int. Ed. 61, e202116208 (2022).

    Article  CAS  Google Scholar 

  27. Tang, X. & Chen, E. Y.-X. Chemical synthesis of perfectly isotactic and high melting bacterial poly(3-hydroxybutyrate) from bio-sourced racemic cyclic diolide. Nat. Commun. 9, 2345 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Tang, X., Westlie, A. H., Watson, E. M. & Chen, E. Y.-X. Stereosequenced crystalline polyhydroxyalkanoates from diastereomeric monomer mixtures. Science 366, 754–758 (2019).

    Article  CAS  PubMed  Google Scholar 

  29. Cozzi, P. G. Metal–salen Schiff base complexes in catalysis: practical aspects. Chem. Soc. Rev. 33, 410–421 (2004).

    Article  CAS  PubMed  Google Scholar 

  30. Shaw, S. & White, J. D. Asymmetric catalysis using chiral salen–metal complexes: recent advances. Chem. Rev. 119, 9381–9426 (2019).

    Article  CAS  PubMed  Google Scholar 

  31. Zhong, Z., Dijkstra, P. J. & Feijen, J. [(salen)Al]-mediated, controlled and stereoselective ring-opening polymerization of lactide in solution and without solvent: synthesis of highly isotactic polylactide stereocopolymers from racemic d,l-lactide. Angew. Chem. Int. Ed. 41, 4510–4513 (2002).

    Article  CAS  Google Scholar 

  32. Longo, J. M., Sanford, M. J. & Coates, G. W. Ring-opening copolymerization of epoxides and cyclic anhydrides with discrete metal complexes: structure–property relationships. Chem. Rev. 116, 15167–15197 (2016).

    Article  CAS  PubMed  Google Scholar 

  33. Darensbourg, D. J. Making plastics from carbon dioxide: salen metal complexes as catalysts for the production of polycarbonates from epoxides and CO2. Chem. Rev. 107, 2388–2410 (2007).

    Article  CAS  PubMed  Google Scholar 

  34. Tschan, M. J.-L., Gauvin, R. M. & Thomas, C. M. Controlling polymer stereochemistry in ring-opening polymerization: a decade of advances shaping the future of biodegradable polyesters. Chem. Soc. Rev. 50, 13587–13608 (2021).

    Article  CAS  PubMed  Google Scholar 

  35. Plajer, A. J. & Williams, C. K. Heterocycle/heteroallene ring-opening copolymerization: selective catalysis delivering alternating copolymers. Angew. Chem. Int. Ed. 61, e202104495 (2022).

    Article  CAS  Google Scholar 

  36. Liao, X., Su, Y. & Tang, X. Stereoselective synthesis of biodegradable polymers by salen-type metal catalysts. Sci. China Chem. 65, 2096–2121 (2022).

    Article  CAS  Google Scholar 

  37. Zintl, M. et al. Variably isotactic poly(hydroxybutyrate) from racemic β-butyrolactone: microstructure control by achiral chromium(III) salophen complexes. Angew. Chem. Int. Ed. 47, 3458–3460 (2008).

    Article  CAS  Google Scholar 

  38. Pang, X. et al. Breaking the paradox between catalytic activity and stereoselectivity: rac-lactide polymerization by trinuclear salen–al complexes. Macromolecules 51, 906–913 (2018).

    Article  CAS  Google Scholar 

  39. Majerska, K. & Duda, A. Stereocontrolled polymerization of racemic lactide with chiral initiator: combining stereoelection and chiral ligand-exchange mechanism. J. Am. Chem. Soc. 126, 1026–1027 (2004).

    Article  CAS  PubMed  Google Scholar 

  40. Ovitt, T. M. & Coates, G. W. Stereoselective ring-opening polymerization of meso-lactide: synthesis of syndiotactic poly(lactic acid). J. Am. Chem. Soc. 121, 4072–4073 (1999).

    Article  CAS  Google Scholar 

  41. Ovitt, T. M. & Coates, G. W. Stereochemistry of lactide polymerization with chiral catalysts: new opportunities for stereocontrol using polymer exchange mechanisms. J. Am. Chem. Soc. 124, 1316–1326 (2002).

    Article  CAS  PubMed  Google Scholar 

  42. Pappalardo, D., Bruno, M., Lamberti, M. & Pellecchia, C. Ring-opening polymerization of racemic β-butyrolactone promoted by salan- and salen-type yttrium amido complexes. Macromol. Chem. Phys. 214, 1965–1972 (2013).

    Article  CAS  Google Scholar 

  43. Zhang, Y.-Z., Zhu, S.-F., Wang, L.-X. & Zhou, Q.-L. Copper-catalyzed highly enantioselective carbenoid insertion into Si−H bonds. Angew. Chem. Int. Ed. 47, 8496–8498 (2008).

    Article  CAS  Google Scholar 

  44. Ding, K., Han, Z. & Wang, Z. Spiro skeletons: a class of privileged structure for chiral ligand design. Chem. Asian J. 4, 32–41 (2009).

    Article  CAS  PubMed  Google Scholar 

  45. Zhu, S.-F. & Zhou, Q.-L. in Privileged Chiral Ligands and Catalysts (ed. Zhou, Q.-L.) Ch. 4 (Wiley-VCH, 2011); https://doi.org/10.1002/9783527635207.ch4

  46. Zhang, F.-H., Zhang, F.-J., Li, M.-L., Xie, J.-H. & Zhou, Q.-L. Enantioselective hydrogenation of dialkyl ketones. Nat. Catal. 3, 621–627 (2020).

    Article  CAS  Google Scholar 

  47. Xie, J.-H., Liu, X.-Y., Xie, J.-B., Wang, L.-X. & Zhou, Q.-L. An additional coordination group leads to extremely efficient chiral iridium catalysts for asymmetric hydrogenation of ketones. Angew. Chem. Int. Ed. 50, 7329–7332 (2011).

    Article  CAS  Google Scholar 

  48. O’Shaughnessy, P. N., Knight, P. D., Morton, C., Gillespie, K. M. & Scott, P. Chiral-at-metal organolanthanides: enantioselective aminoalkene hydroamination/cyclisation with non-cyclopentadienyls. Chem. Commun. 1770–1771 (2003).

  49. Mulzer, M., Ellis, W. C., Lobkovsky, E. B. & Coates, G. W. Enantioenriched β-lactone and aldol-type products from regiodivergent carbonylation of racemic cis-epoxides. Chem. Sci. 5, 1928–1933 (2014).

    Article  CAS  Google Scholar 

  50. Press, K., Goldberg, I. & Kol, M. Mechanistic insight into the stereochemical control of lactide polymerization by salan–aluminum catalysts. Angew. Chem. Int. Ed. 54, 14858–14861 (2015).

    Article  CAS  Google Scholar 

  51. Hador, R. et al. The dual-stereocontrol mechanism: heteroselective polymerization of rac-lactide and syndioselective polymerization of meso-lactide by chiral aluminum salan catalysts. Angew. Chem. Int. Ed. 58, 14679–14685 (2019).

    Article  CAS  Google Scholar 

  52. Peterson, A. et al. Defining stereochemistry in the polymerization of lactide by aluminum catalysts: insights into the dual-stereocontrol mechanism. J. Am. Chem. Soc. 144, 20047–20055 (2022).

    Article  CAS  PubMed  Google Scholar 

  53. Irie, R., Uchida, T. & Matsumoto, K. Katsuki catalysts for asymmetric oxidation: design concepts, serendipities for breakthroughs, and applications. Chem. Lett. 44, 1268–1283 (2015).

    Article  Google Scholar 

  54. Cheng, J. K., Xiang, S.-H., Li, S., Ye, L. & Tan, B. Recent advances in catalytic asymmetric construction of atropisomers. Chem. Rev. 121, 4805–4902 (2021).

    Article  CAS  PubMed  Google Scholar 

  55. Lu, X.-B., Ren, W.-M. & Wu, G.-P. CO2 copolymers from epoxides: catalyst activity, product selectivity, and stereochemistry control. Acc. Chem. Res. 45, 1721–1735 (2012).

    Article  CAS  PubMed  Google Scholar 

  56. Tanahashi, N. & Doi, Y. Thermal properties and stereoregularity of poly(3-hydroxybutyrate) prepared from optically active β-butyrolactone with a zinc-based catalyst. Macromolecules 24, 5732–5733 (1991).

    Article  CAS  Google Scholar 

  57. Policastro, G., Panico, A. & Fabbricino, M. Improving biological production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) co-polymer: a critical review. Rev. Environ. Sci. Biotechnol. 20, 479–513 (2021).

    Article  CAS  Google Scholar 

  58. Bloembergen, S., Holden, D. A., Bluhm, T. L., Hamer, G. K. & Marchessault, R. H. Isodimorphism in synthetic poly (β-hydroxybutyrate-co-β-hydroxyvalerate): stereoregular copolyesters from racemic β-lactones. Macromolecules 22, 1663–1669 (1989).

    Article  CAS  Google Scholar 

  59. Chudnovsky, A. & Sehanobish, K. in Handbook of Industrial Polyethylene and Technology (eds Spalding, M. A. & Chatterjee, A. M.) Ch. 9 (Scrivener, 2017); https://doi.org/10.1002/9781119159797.ch9

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Acknowledgements

This work was supported by the National Key R&D Program of China (2021YFA1501700), the National Natural Science Foundation of China (22071163 and U19A2095), the ‘1000-Youth Talents Program’, the Fundamental Research Funds for the Central Universities (YJ201924) and the State Key Laboratory of Polymer Materials Engineering (sklpme2020-3-15). We thank M. Yang and Y. Zhou from the College of Chemistry, Sichuan University, for single-crystal X-ray diffraction analysis. We thank D. Deng from the College of Chemistry, Sichuan University, for NMR testing.

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Authors and Affiliations

  1. National Engineering Laboratory of Eco-Friendly Polymeric Materials (Sichuan), College of Chemistry, Sichuan University, Chengdu, People’s Republic of China

    Hao-Yi Huang, Wei Xiong, Yu-Ting Huang, Kun Li, Zhongzheng Cai & Jian-Bo Zhu

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Contributions

J.-B.Z. conceived the project and directed the research. H.-Y.H. designed and conducted experiments related to polymer synthesis and characterizations. H.-Y.H., W.X., Y.-T.H. and K.L. designed and conducted catalyst synthesis. Z.C., H.-Y.H. and J.-B.Z. wrote the initial paper and all authors contributed to the revised paper.

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Correspondence to Jian-Bo Zhu.

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Competing interests

J.-B.Z., H.-Y.H. and Z.C. are inventors on China patent application 202110887204.1, submitted by Sichuan University, which covers the design and synthesis of spiro-salen complexes and their catalytic polymerization. The other authors declare no competing interests.

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Nature Catalysis thanks Claudio Pellecchia and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–229, Discussion and Tables 1–24.

Supplementary Data 1

CIF file for rac-L6.

Supplementary Data 2

CIF file for rac-L7.

Supplementary Data 3

CIF file for (sS, aS)-L14.

Supplementary Data 4

CIF file for rac-Y7.

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Huang, HY., Xiong, W., Huang, YT. et al. Spiro-salen catalysts enable the chemical synthesis of stereoregular polyhydroxyalkanoates. Nat Catal 6, 720–728 (2023). https://doi.org/10.1038/s41929-023-01001-7

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