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Iridium-catalysed asymmetric hydrogenation of allylic alcohols via dynamic kinetic resolution

Abstract

Dynamic kinetic resolutions (DKRs) allow for the conversion of both enantiomers of starting material into a single enantiomer of product, hence avoiding the 50% yield limit observed in traditional kinetic resolutions. Transition-metal-catalysed variants have become an important and useful method in asymmetric synthesis. Here we report an asymmetric hydrogenation of allylic alcohols using an Ir–N,P-ligand complex via DKR. In contrast to the many DKRs involving carbonyl reduction, this methodology allows for DKR during alkene reduction. Mechanistic studies support the hypothesis that racemization of the substrate is achieved by cleavage and reforming of the oxygen–carbon bond. Under the cooperative dynamic kinetic asymmetric hydrogenation, a broad range of chiral alcohols containing two stereogenic centres were produced with excellent diastereoselectivities (up to 95:5) and enantioselectivities (up to 99%).

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Fig. 1: DKR using catalysts and enzymes.
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References

  1. Peschiulli, A., Procuranti, B., O’Connor, C. J. & Connon, S. J. Synergistic organocatalysis in the kinetic resolution of secondary thiols with concomitant desymmetrization of an anhydride. Nat. Chem. 2, 380–384 (2010).

    Article  CAS  PubMed  Google Scholar 

  2. Binanzer, M., Hsieh, S.-Y. & Bode, J. W. Catalytic kinetic resolution of cyclic secondary amines. J. Am. Chem. Soc. 133, 19698–19701 (2011).

    Article  CAS  PubMed  Google Scholar 

  3. Taylor, J. E., Bull, S. D. & Williams, J. M. J. Amidines, isothioureas, and guanidines as nucleophilic catalysts. Chem. Soc. Rev. 41, 2109–2121 (2012).

    Article  CAS  PubMed  Google Scholar 

  4. Noyori, R. et al. Stereoselective hydrogenation via dynamic kinetic resolution. J. Am. Chem. Soc. 111, 9134–9135 (1989).

    Article  CAS  Google Scholar 

  5. Huerta, F. F., Minidis, A. B. E. & Bäckvall, J.-E. Racemisation in asymmetric synthesis. Dynamic kinetic resolution and related processes in enzyme and metal catalysis. Chem. Soc. Rev. 30, 321–331 (2001).

    Article  CAS  Google Scholar 

  6. Ebbers, E. J., Ariaans, G. J. A., Houbiers, J. P. M., Bruggink, A. & Zwanenburg, B. Controlled racemization of optically active organic compounds: prospects for asymmetric transformation. Tetrahedron 53, 9417–9476 (1997).

    Article  CAS  Google Scholar 

  7. Hussain, I. & Bäckvall, J.-E. in Enzyme Catalysis in Organic Synthesis (eds Drauz, K., Gröger, H. and May, O.)1777–1806 (Wiley-VCH, Weinheim, 2012)..

  8. Rachwalski, M., Vermue, N. & Rutjes, F. P. J. T. Recent advances in enzymatic and chemical deracemisation of racemic compounds. Chem. Soc. Rev. 42, 9268–9282 (2013).

    Article  CAS  PubMed  Google Scholar 

  9. Pellissier, H. Recent developments in organocatalytic dynamic kinetic resolution. Tetrahedron 72, 3133–3150 (2016).

    Article  CAS  Google Scholar 

  10. Ikariya, T., Murata, K. & Noyori, R. Bifunctional transition metal-based molecular catalysts for asymmetric syntheses. Org. Biomol. Chem. 4, 393–406 (2006).

    Article  CAS  PubMed  Google Scholar 

  11. Steward, K. M., Gentry, E. C. & Johnson, J. S. Dynamic kinetic resolution of α-keto esters via asymmetric transfer hydrogenation. J. Am. Chem. Soc. 134, 7329–7332 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ahn, Y., Ko, S.-B., Kim, M.-J. & Park, J. Racemization catalysts for the dynamic kinetic resolution of alcohols and amines. Coord. Chem. Rev. 252, 647–658 (2008).

    Article  CAS  Google Scholar 

  13. Stürmer, R. Enzymes and transition metal complexes in tandem—a new concept for dynamic kinetic resolution. Angew. Chem. Int. Ed. Engl. 36, 1173–1174 (1997).

    Article  Google Scholar 

  14. Shvo, Y., Czarkie, D., Rahamim, Y. & Chodosh, D. F. A new group of ruthenium complexes: structure and catalysis. J. Am. Chem. Soc. 108, 7400–7402 (1986).

    Article  CAS  Google Scholar 

  15. Dinh, P. M., Howarth, J. A., Hudnott, A. R., Williams, J. M. J. & Harris, W. Catalytic racemization of alcohols: applications to enzymic resolution reactions. Tetrahedron Lett. 37, 7623–7626 (1996).

    Article  CAS  Google Scholar 

  16. Larsson, A. L. E., Persson, B. A. & Bäckvall, J.-E. Enzymic resolution of alcohols coupled with ruthenium-catalyzed racemization of the substrate alcohol. Angew. Chem. Int. Ed. Engl. 36, 1211–1212 (1997).

    Article  CAS  Google Scholar 

  17. Ohkuma, T., Ishii, D., Takeno, H. & Noyori, R. Asymmetric hydrogenation of amino ketones using chiral RuCl2(diphosphine)(1,2-diamine) complexes. J. Am. Chem. Soc. 122, 6510–6511 (2000).

    Article  CAS  Google Scholar 

  18. Xie, J.-H., Zhou, Z.-T., Kong, W.-L. & Zhou, Q.-L. Ru-catalyzed asymmetric hydrogenation of racemic aldehydes via dynamic kinetic resolution: efficient synthesis of optically active primary alcohols. J. Am. Chem. Soc. 129, 1868–1869 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Xie, J.-H. et al. Highly enantioselective and diastereoselective synthesis of chiral amino alcohols by ruthenium-catalyzed asymmetric hydrogenation of α-amino aliphatic ketones. J. Am. Chem. Soc. 131, 4222–4223 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. Liu, C., Xie, J.-H., Li, Y.-L., Chen, J.-Q. & Zhou, Q.-L. Asymmetric hydrogenation of α,α′-disubstituted cycloketones through dynamic kinetic resolution: an efficient construction of chiral diols with three contiguous stereocenters. Angew. Chem. Int. Ed. Engl. 52, 593–596 (2013).

    Article  CAS  PubMed  Google Scholar 

  21. Liu, S., Xie, J.-H., Wang, L.-X. & Zhou, Q.-L. Dynamic kinetic resolution allows a highly enantioselective synthesis of cis-α-aminocycloalkanols by ruthenium-catalyzed asymmetric hydrogenation. Angew. Chem. Int. Ed. Engl. 46, 7506–7508 (2007).

    Article  CAS  PubMed  Google Scholar 

  22. Hamada, Y. Diastereo- and enantioselective anti-selective hydrogenation of alpha-amino-beta-keto ester hydrochlorides and related compounds using transition-metal-chiral-bisphosphine catalysts. Chem. Rec. 14, 235–250 (2014).

    Article  CAS  PubMed  Google Scholar 

  23. Tao, X., Li, W., Li, X., Xie, X. & Zhang, Z. Diastereo- and enantioselective asymmetric hydrogenation of alpha-amido-beta-keto phosphonates via dynamic kinetic resolution. Org. Lett. 15, 72–75 (2013).

    Article  CAS  PubMed  Google Scholar 

  24. Ding, Z., Yang, J., Wang, T., Shen, Z. & Zhang, Y. Dynamic kinetic resolution of beta-keto sulfones via asymmetric transfer hydrogenation. Chem. Commun. 571–573 (2009).

  25. Lin, H. et al. Enantioselective approach to (−)-hamigeran B and (−)-4-bromohamigeran B via catalytic asymmetric hydrogenation of racemic ketone to assemble the chiral core framework. Org. Lett. 18, 1434–1437 (2016).

    Article  CAS  PubMed  Google Scholar 

  26. Shi, L. et al. Enantioselective iridium-catalyzed hydrogenation of 3,4-disubstituted isoquinolines. Angew. Chem. Int. Ed. Engl. 51, 8286–8289 (2012).

    Article  CAS  PubMed  Google Scholar 

  27. Cram, D. J. & Kopecky, K. R. Studies in stereochemistry. XXX. Models for steric control of asymmetric induction. J. Am. Chem. Soc. 81, 2748–2755 (1959).

    Article  CAS  Google Scholar 

  28. Reetz, M. T. Chelate- or nonchelate control in addition reactions of chiral α- and β-alkoxycarbonyl compounds. Angew. Chem. 96, 542–555 (1984).

    Article  CAS  Google Scholar 

  29. Akashi, M., Arai, N., Inoue, T. & Ohkuma, T. Catalyst-controlled diastereoselection in the hydrogenation of heterocycloalkyl ketones. Adv. Synth. Catal. 353, 1955–1960 (2011).

    Article  CAS  Google Scholar 

  30. Verendel, J. J., Pamies, O., Dieguez, M. & Andersson, P. G. Asymmetric hydrogenation of olefins using chiral Crabtree-type catalysts: scope and limitations. Chem. Rev. 114, 2130–2169 (2014).

    Article  CAS  PubMed  Google Scholar 

  31. Stork, G. & Kahne, D. E. Stereocontrol in homogeneous catalytic-hydrogenation via hydroxyl group coordination. J. Am. Chem. Soc. 105, 1072–1073 (1983).

    Article  CAS  Google Scholar 

  32. Zhou, J. G. et al. Asymmetric hydrogenation routes to deoxypolyketide chirons. Chem. Eur. J. 13, 7162–7170 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Bernasconi, M., Ramella, V., Tosatti, P. & Pfaltz, A. Iridium- catalyzed asymmetric hydrogenation of 3,3-disubstituted allylic alcohols in ethereal solvents. Chem. Eur. J. 20, 2440–2444 (2014).

    Article  CAS  PubMed  Google Scholar 

  34. Crabtree, R. H. & Davis, M. W. Directing effects in homogeneous hydrogenation with [Ir(cod)(PCy3)(py)]PF6. J. Org. Chem. 51, 2655–2661 (1986).

    Article  CAS  Google Scholar 

  35. Akai, S. et al. One-pot synthesis of optically active allyl esters via lipase–vanadium combo catalysis. Org. Lett. 12, 4900–4903 (2010).

    Article  CAS  PubMed  Google Scholar 

  36. Egi, M. et al. A mesoporous-silica-immobilized oxovanadium cocatalyst for the lipase-catalyzed dynamic kinetic resolution of racemic alcohols. Angew. Chem. Int. Ed. Engl. 52, 3654–3658 (2013).

    Article  CAS  PubMed  Google Scholar 

  37. Abate, A. et al. Chirality and fragrance chemistry: stereoisomers of the commercial chiral odorants muguesia and pamplefleur. J. Org. Chem. 70, 1281–1290 (2005).

    Article  CAS  PubMed  Google Scholar 

  38. Gualandi, A., Emma, M. G., Giacoboni, J., Mengozzi, L. & Cozzi, P. G. A highly stereoselective organocatalytic approach to lilial and muguesia. Synlett 24, 449–452 (2013).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The Swedish Research Council (VR) and Stiftelsen Olle Engkvist Byggmästare supported this work. J.L. thanks the Guangzhou Elite Scholarship Council for the PhD fellowship and Thishana Singh, School of Chemistry and Physics, University of Kwazulu-Natal, South Africa for proofreading and editing the manuscript.

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P.G.A. conceived and designed the experiments. J.L., S.K., J.Y. and J.-Q.L. performed experiments and prepared the Supplementary Information. P.G.A. and J.L. wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Pher G. Andersson.

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Supplementary Methods, Supplementary Figures 1–60, Supplementary References

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Liu, J., Krajangsri, S., Yang, J. et al. Iridium-catalysed asymmetric hydrogenation of allylic alcohols via dynamic kinetic resolution. Nat Catal 1, 438–443 (2018). https://doi.org/10.1038/s41929-018-0070-0

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