Electricity-driven asymmetric Lewis acid catalysis

Abstract

Catalytic asymmetric electrosynthesis combines the unique features of an electrochemical addition or removal of electrons with the catalytic asymmetric synthesis of enantioenriched molecules. However, identifying suitable catalysts that are compatible with electrochemical conditions and provide a high stereocontrol is a formidable challenge. Here we introduce a versatile electricity-driven chiral Lewis acid catalysis for the oxidative cross-coupling of 2-acyl imidazoles with silyl enol ethers. Powered by an electric current, this work provides a sustainable avenue to synthetically useful non-racemic 1,4-dicarbonyls, which include products that bear all-carbon quaternary stereocentres. A chiral-at-metal rhodium catalyst activates a substrate towards anodic oxidation by raising the highest occupied molecular orbital on enolate formation, which enables mild redox conditions, high chemo- and enantioselectivities (up to >99% enantiomeric excess) and a broad substrate scope. This work demonstrates the potential of combining asymmetric Lewis acid catalysis with electrochemistry and we anticipate that it will spur the further development of catalytic asymmetric electrosynthesis.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Strategies for electrochemical asymmetric catalysis with anodic processes.
Fig. 2: Substrate scope for the generation of tertiary carbon stereocentres.
Fig. 3: Products with all-carbon quaternary stereocentres.
Fig. 4: Mechanistic investigations.
Fig. 5

Data availability

The X-ray crystallographic coordinates for the structures of Λ-Rh2, 3g, 6n and Rh2-1a reported in this article have been deposited at the Cambridge Crystallographic Data Centre (CCDC) under deposition numbers CCDC 1866726, 1866727, 1868792 and 1866728, respectively. The data can be obtained free of charge from the CCDC via https://www.ccdc.cam.ac.uk/structures/. All other data are available from the authors upon reasonable request.

References

  1. 1.

    Degner, D. in Electrochemistry III (ed. Steckchan, E.) 1–95 (Springer, Berlin, 1988).

  2. 2.

    Yoshida, J., Kataoka, K., Horcajada, R. & Nagaki, A. Modern strategies in electroorganic synthesis. Chem. Rev. 108, 2265–2299 (2008).

    CAS  Article  Google Scholar 

  3. 3.

    Yan, M., Kawamata, Y. & Baran, P. S. Synthetic organic electrochemical methods since 2000: on the verge of a renaissance. Chem. Rev. 117, 13230–13319 (2017).

    CAS  Article  Google Scholar 

  4. 4.

    Moeller, K. D. Using physical organic chemistry to shape the course of electrochemical reactions. Chem. Rev. 118, 4817–4833 (2018).

    CAS  Article  Google Scholar 

  5. 5.

    Nutting, J. E., Rafiee, M. & Stahl, S. S. Tetramethylpiperidine N-oxyl (TEMPO), phthalimide N-oxyl (PINO), and related N-oxyl species: electrochemical properties and their use in electrocatalytic reactions. Chem. Rev. 118, 4834–4885 (2018).

    CAS  Article  Google Scholar 

  6. 6.

    Sauer, G. S. & Lin, S. An electrocatalytic approach to the radical difunctionalization of alkenes. ACS Catal. 8, 5175–5187 (2018).

    CAS  Article  Google Scholar 

  7. 7.

    Sauermann, N., Meyer, T. H., Qiu, Y. & Ackermann, L. Electrocatalytic C–H activation. ACS Catal. 8, 7086–7103 (2018).

    CAS  Article  Google Scholar 

  8. 8.

    Trost, B. M. Asymmetric catalysis: an enabling science. Proc. Natl Acad. Sci. USA 101, 5348–5355 (2004).

    CAS  Article  Google Scholar 

  9. 9.

    Walsh, P. J. & Kozlowski, M. C. Fundamentals of Asymmetric Catalysis (University Science Books, Herndon, 2009).

  10. 10.

    Klotz-Berendes, B., Schäfer, H. J., Grehl, M. & Fröhlich, R. Diastereoselective coupling of anodically generated radicals bearing chiral amide groups. Angew. Chem. Int. Ed. Engl. 34, 189–191 (1995).

    CAS  Article  Google Scholar 

  11. 11.

    Kise, N., Ozaki, H., Moriyama, N., Kitagishi, Y. & Ueda, N. Electroreductive intramolecular coupling of chiral α-imino esters: stereoselective synthesis of mixed ketals of cis-2,4-disubstituted azetidine-3-ones. J. Am. Chem. Soc. 125, 11591–11596 (2003).

    CAS  Article  Google Scholar 

  12. 12.

    Kise, N., Hamada, Y. & Sakurai, T. Electroreductive coupling of optically active α,β-unsaturated carbonyl compounds with diaryl ketones: asymmetric synthesis of 4,5,5-trisubstituted γ-butyrolactones. Org. Lett. 16, 3348–3351 (2014).

    CAS  Article  Google Scholar 

  13. 13.

    Cao, Z.-Y. & Zhou, J. in Multicatalyst System in Asymmetric Catalysis (ed. Zhou, J.) 475–500 (John Wiley & Sons, Hoboken, 2014).

  14. 14.

    Hammerich, O. & Speiser, B. Organic Electrochemistry 5th edn (CRC Press, Boca Raton, 2016).

    Google Scholar 

  15. 15.

    Page, P. C. B. et al. Enantioselective organocatalytic epoxidation driven by electrochemically generated percarbonate and persulfate. Adv. Synth. Catal. 350, 1149–1154 (2008).

    CAS  Article  Google Scholar 

  16. 16.

    Jensen, K. L., Franke, P. T., Nielsen, L. T., Daasbjerg, K. & Jørgensen, K. A. Anodic oxidation and organocatalysis: direct regio- and stereoselective access to meta-substituted anilines by α-arylation of aldehydes. Angew. Chem. Int. Ed. 49, 129–133 (2010).

    CAS  Article  Google Scholar 

  17. 17.

    Fu, N., Li, L., Yang, Q. & Luo, S. Catalytic asymmetric electrochemical oxidative coupling of tertiary amines with simple ketones. Org. Lett. 19, 2122–2125 (2017).

    CAS  Article  Google Scholar 

  18. 18.

    Kashiwagi, Y.et al. Enantioselective electrocatalytic oxidation of racemic amines using a chiral 1-azaspiro[5.5]undecane N-oxyl radical. Chem. Commun. 1983–1984 (1999)

  19. 19.

    Kashiwagi, Y. et al. Asymmetric electrochemical lactonization of diols on a chiral 1-azaspiro[5.5]undecane N-oxyl radical mediator-modified graphite felt electrode. Chem. Commun. 114–115 (2003).

  20. 20.

    Moutet, J.-C., Duboc-Toia, C., Ménage, S. & Tingry, S. A Chiral poly(2,2′-bipyridyl rhodium(iii) complex) film electrode for asymmetric induction in electrosynthesis. Adv. Mater. 10, 665–667 (1999).

    Article  Google Scholar 

  21. 21.

    Moutet, J.-C. et al. Heterogeneous and homogeneous asymmetric electrocatalytic hydrogenation with rhodium(iii) complexes containing chiral polypyridyl ligands. New J. Chem. 23, 939–944 (1999).

    CAS  Article  Google Scholar 

  22. 22.

    Franco, D., Riahi, A., Hénin, F., Muzart, J. & Duñach, E. Electrochemical reduction of a racemic allyl β-keto ester catalyzed by nickel complexes: asymmetric induction. Eur. J. Org. Chem. 2257–2259 (2002)

  23. 23.

    Francke, R. & Little, R. D. Redox catalysis in organic electrosynthesis: basic principles and recent developments. Chem. Soc. Rev. 43, 2492–2521 (2014).

    CAS  Article  Google Scholar 

  24. 24.

    Torii, S., Liu, P., Bhuvaneswari, N., Amatore, C. & Jutand, A. Chemical and electrochemical asymmetric dihydroxylation of olefins in I2−K2CO3−K2OsO2(OH)4 and I2−K3PO4/K2HPO4−K2OsO2(OH)4 systems with Sharpless’ ligand. J. Org. Chem. 61, 3055–3060 (1996).

    CAS  Article  Google Scholar 

  25. 25.

    Nguyen, B. H., Redden, A. & Moeller, K. D. Sunlight, electrochemistry, and sustainable oxidation reactions. Green Chem. 16, 69–72 (2014).

    CAS  Article  Google Scholar 

  26. 26.

    Tanaka, H., Kuroboshi, M., Takeda, H., Kanda, H. & Torii, S. Electrochemical asymmetric epoxidation of olefins by using an optically active Mn–salen complex. J. Electroanal. Chem. 507, 75–81 (2001).

    CAS  Article  Google Scholar 

  27. 27.

    Chen, B.-L. et al. Asymmetric electrocarboxylation of 1-phenylethyl chloride catalyzed by electrogenerated chiral [Coi(salen)] complex. Electrochem. Commun. 42, 55–59 (2014).

    Article  Google Scholar 

  28. 28.

    Yuan, R., Watanabe, S., Kuwabata, S. & Yoneyama, H. Asymmetric electroreduction of ketone and aldehyde derivatives to the corresponding alcohols using alcohol dehydrogenase as an electrocatalyst. J. Org. Chem. 62, 2494–2499 (1997).

    CAS  Article  Google Scholar 

  29. 29.

    Kawabata, S., Iwata, N. & Yoneyama, H. Asymmetric electrosynthesis of amino acid using an electrode modified with amino acid oxidase and electron mediator. Chem. Lett. 29, 110–111 (2000).

    Article  Google Scholar 

  30. 30.

    Hollmann, F., Hofstetter, K., Habicher, T., Hauer, B. & Schmid, A. Direct electrochemical regeneration of monooxygenase subunits for biocatalytic asymmetric epoxidation. J. Am. Chem. Soc. 127, 6540–6541 (2005).

    CAS  Article  Google Scholar 

  31. 31.

    Höllrigl, V., Otto, K. & Schmid, A. Electroenzymatic asymmetric reduction of rac‐3‐methylcyclohexanone to (1S,3S)‐3‐methylcyclohexanol in organic/aqueous media catalyzed by a thermophilic alcohol dehydrogenase. Adv. Synth. Catal. 349, 1337–1340 (2007).

    Article  Google Scholar 

  32. 32.

    Bui, N.-N., Ho, X.-H., Mho, S.-i. & Jang, H.-Y. Organocatalyzed α-oxyamination of aldehydes using anodic oxidation. Eur. J. Org. Chem. 5309–5312 (2009)

  33. 33.

    Ho, X.-H., Mho, S.-i., Kang, H. & Jang, H.-Y. Electro-organocatalysis: enantioselective α-alkylation of aldehydes. Eur. J. Org. Chem. 4436–4441 (2010)

  34. 34.

    DeMartino, M. P., Chen, K. & Baran, P. S. Intermolecular enolate heterocoupling: scope, mechanism, and application. J. Am. Chem. Soc. 130, 11546–11560 (2008).

    CAS  Article  Google Scholar 

  35. 35.

    Tang, S., Liu, Y. & Lei, A. Electrochemical oxidative cross-coupling with hydrogen evolution: a green and sustainable way for bond formation. Chem 4, 27–45 (2018).

    CAS  Article  Google Scholar 

  36. 36.

    Zhu, L. et al. Catalytic asymmetric oxidative enamine transformations. ACS Catal. 8, 5466–5484 (2018).

    CAS  Article  Google Scholar 

  37. 37.

    Næsborg, L. et al. Direct enantio‐ and diastereoselective oxidative homo‐coupling of aldehydes. Chem. Eur. J. 24, 14844–14848 (2018).

    Article  Google Scholar 

  38. 38.

    Jang, H.-Y., Hong, J.-B. & MacMillan, D. W. C. Enantioselective organocatalytic singly occupied molecular orbital activation: the enantioselective α-enolation of aldehydes. J. Am. Chem. Soc. 129, 7004–7005 (2007).

    CAS  Article  Google Scholar 

  39. 39.

    Tisovský, P., Mečiarová, M. & Šebesta, R. Asymmetric organocatalytic SOMO reactions of enol silanes and silyl ketene (thio)acetals. Org. Biomol. Chem. 12, 9446–9452 (2014).

    Article  Google Scholar 

  40. 40.

    Zhang, L. & Meggers, E. Steering asymmetric Lewis acid catalysis exclusively with octahedral metal-centered chirality. Acc. Chem. Res. 50, 320–330 (2017).

    CAS  Article  Google Scholar 

  41. 41.

    Horn, E. J. et al. Scalable and sustainable electrochemical allylic C–H oxidation. Nature 533, 77–81 (2016).

    CAS  Article  Google Scholar 

  42. 42.

    Badalyan, A. & Stahl, S. S. Cooperative electrocatalytic alcohol oxidation with electron–proton-transfer mediators. Nature 535, 406–410 (2016).

    CAS  Article  Google Scholar 

  43. 43.

    Fu, N., Sauer, G. S., Saha, A., Loo, A. & Lin, S. Metal-catalyzed electrochemical diazidation of alkenes. Science 357, 575–579 (2017).

    CAS  Article  Google Scholar 

  44. 44.

    Möckel, R. et al. Electrochemical synthesis of aryl iodides by anodic iododesilylation. Angew. Chem. Int. Ed. 57, 442–445 (2017).

    Article  Google Scholar 

  45. 45.

    Gieshoff, T., Kehl, A., Schollmeyer, D., Moeller, K. D. & Waldvogel, S. R. Insights into the mechanism of anodic N–N bond formation by dehydrogenative coupling. J. Am. Chem. Soc. 139, 12317–12324 (2017).

    CAS  Article  Google Scholar 

  46. 46.

    Xiong, P., Xu, H.-H., Song, J. & Xu, H.-C. Electrochemical difluoromethylarylation of alkynes. J. Am. Chem. Soc. 140, 2460–2464 (2018).

    CAS  Article  Google Scholar 

  47. 47.

    Yang, Q.-L. et al. Copper-catalyzed electrochemical C–H amination of arenes with secondary amines. J. Am. Chem. Soc. 140, 11487–11494 (2018).

    CAS  Article  Google Scholar 

  48. 48.

    Huo, H. et al. Asymmetric photoredox transition-metal catalysis activated by visible light. Nature 515, 100–103 (2014).

    CAS  Article  Google Scholar 

  49. 49.

    Yan, M., Kawamata, Y. & Baran, P. S. Synthetic organic electrochemistry: calling all engineers. Angew. Chem. Int. Ed. 57, 4149–4155 (2017).

    Article  Google Scholar 

  50. 50.

    Ma, J., Zhang, X., Huang, X., Luo, S. & Meggers, E. Preparation of chiral-at-metal catalysts and their use in asymmetric photoredox chemistry. Nat. Protoc. 13, 605–632 (2018).

    CAS  Article  Google Scholar 

  51. 51.

    König, B. Chemical Photocatalysis (De Gruyter, Berlin 2013).

    Google Scholar 

  52. 52.

    Kärkäs, M. D., Porco, J. A. & Stephenson, C. R. J. Photochemical approaches to complex chemotypes: applications in natural product synthesis. Chem. Rev. 116, 9683–9747 (2016).

    Article  Google Scholar 

  53. 53.

    Romero, N. A. & Nicewicz, D. A. Organic photoredox catalysis. Chem. Rev. 116, 10075–10166 (2016).

    CAS  Article  Google Scholar 

  54. 54.

    Twilton, J. et al. The merger of transition metal and photocatalysis. Nat. Rev. Chem. 1, 0052 (2017).

    CAS  Article  Google Scholar 

  55. 55.

    Tan, Y., Yuan, W., Gong, L. & Meggers, E. Aerobic asymmetric dehydrogenative cross-coupling between two –H groups catalyzed by a chiral-at-metal rhodium complex. Angew. Chem. Int. Ed. 54, 13045–13048 (2015).

    CAS  Article  Google Scholar 

  56. 56.

    Evans, D. A., Fandrick, K. R., Song, H.-J., Scheidt, K. A. & Xu, R. Enantioselective Friedel-Crafts alkylations catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes. J. Am. Chem. Soc. 129, 10029–10041 (2007).

    CAS  Article  Google Scholar 

  57. 57.

    Fu, N., Sauer, G. S. & Lin, S. A general, electrocatalytic approach to the synthesis of vicinal diamines. Nat. Protoc. 13, 1725–1743 (2018).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We are grateful for funding from the Deutsche Forschungsgemeinschaft (grant no. ME 1805/13-1).

Author information

Affiliations

Authors

Contributions

E.M. coordinated the project. E.M. and X.H. conceived the project, designed the experiments and wrote the manuscript. X.H. carried out the majority of the synthetic experiments. Q.Z. and J.L. synthesized and characterized Rh2. K.H. collected the crystallographic data, and solved and refined the X-ray crystal structures.

Corresponding author

Correspondence to Eric Meggers.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Methods, Supplementary Figures 1–41, Supplementary References

Compound Λ-Rh2

Crystallographic Data for Compound Λ-Rh2

Compound 3g

Crystallographic Data for Compound 3g

Compound 6n

Crystallographic Data for Compound 6n

Compound Rh2-1a

Crystallographic Data for Compound Rh2-1a

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Huang, X., Zhang, Q., Lin, J. et al. Electricity-driven asymmetric Lewis acid catalysis. Nat Catal 2, 34–40 (2019). https://doi.org/10.1038/s41929-018-0198-y

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing