Asymmetric photoredox transition-metal catalysis activated by visible light

ABSTRACT Asymmetric catalysis is seen as one of the most economical strategies to satisfy the growing demand for enantiomerically pure small molecules in the fine chemical and pharmaceutical

industries1. And visible light has been recognized as an environmentally friendly and sustainable form of energy for triggering chemical transformations and catalytic chemical

processes2,3,4,5. For these reasons, visible-light-driven catalytic asymmetric chemistry is a subject of enormous current interest2,3,4,5. Photoredox catalysis provides the opportunity to

generate highly reactive radical ion intermediates with often unusual or unconventional reactivities under surprisingly mild reaction conditions6. In such systems, photoactivated sensitizers

initiate a single electron transfer from (or to) a closed-shell organic molecule to produce radical cations or radical anions whose reactivities are then exploited for interesting or

unusual chemical transformations. However, the high reactivity of photoexcited substrates, intermediate radical ions or radicals, and the low activation barriers for follow-up reactions

provide significant hurdles for the development of efficient catalytic photochemical processes that work under stereochemical control and provide chiral molecules in an asymmetric fashion7.

Here we report a highly efficient asymmetric catalyst that uses visible light for the necessary molecular activation, thereby combining asymmetric catalysis and photocatalysis. We show that

a chiral iridium complex can serve as a sensitizer for photoredox catalysis and at the same time provide very effective asymmetric induction for the enantioselective alkylation of 2-acyl

imidazoles. This new asymmetric photoredox catalyst, in which the metal centre simultaneously serves as the exclusive source of chirality, the catalytically active Lewis acid centre, and the

photoredox centre, offers new opportunities for the ‘green’ synthesis of non-racemic chiral molecules. Access through your institution Buy or subscribe This is a preview of subscription

content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 51 print issues and online access $199.00 per year only $3.90 per issue

Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL

ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS ASYMMETRIC PHOTOREDOX CATALYTIC FORMAL DE

MAYO REACTION ENABLED BY SENSITIZATION-INITIATED ELECTRON TRANSFER Article 02 April 2024 LIGHT-ENABLED DERACEMIZATION OF CYCLOPROPANES BY AL-SALEN PHOTOCATALYSIS Article Open access 23

August 2023 DICARBOXYLATION OF ALKENES, ALLENES AND (HETERO)ARENES WITH CO2 VIA VISIBLE-LIGHT PHOTOREDOX CATALYSIS Article 15 April 2021 REFERENCES * Walsh, P. J. & Kozlowski, M. C.

_Fundamentals of Asymmetric Catalysis_ (University Science Books, 2009) Google Scholar  * Zeitler, K. Photoredox catalysis with visible light. _Angew. Chem. Int. Edn_ 48, 9785–9789 (2009)

Article  CAS  Google Scholar  * Narayanam, J. M. R. & Stephenson, C. R. J. Visible light photoredox catalysis: applications in organic synthesis. _Chem. Soc. Rev._ 40, 102–113 (2011)

Article  CAS  Google Scholar  * Prier, C. K., Rankic, D. A. & MacMillan, D. W. C. Visible light photoredox catalysis with transition metal complexes: applications in organic synthesis.

_Chem. Rev._ 113, 5322–5363 (2013) Article  CAS  Google Scholar  * Schultz, D. M. & Yoon, T. P. Solar synthesis: prospects in visible light photocatalysis. _Science_ 343, 1239176 (2014)

Article  Google Scholar  * Schmittel, M. & Burghart, A. Understanding reactivity patterns of radical cations. _Angew. Chem. Int. Edn Engl._ 36, 2550–2589 (1997) Article  Google Scholar 

* Curran, D. P., Porter, N. A. & Giese, B. _Stereochemistry of Radical Reactions: Concepts, Guidelines, and Synthetic Applications_ (VCH, 1996) Google Scholar  * Hopkinson, M. N., Sahoo,

B., Li, J.-L. & Glorius, F. Dual catalysis sees the light: combining photoredox with organo-, acid, and transition-metal catalysis. _Chem. Eur. J._ 20, 3874–3886 (2014) Article  CAS 

Google Scholar  * Nicewicz, D. A. & MacMillan, D. W. C. Merging photoredox catalysis with organocatalysis: the direct asymmetric alkylation of aldehydes. _Science_ 322, 77–80 (2008)

Article  ADS  CAS  Google Scholar  * Shih, H.-W., Vander Wal, M. N., Grange, R. L. & MacMillan, D. W. C. Enantioselective α-benzylation of aldehydes via photoredox organocatalysis. _J.

Am. Chem. Soc._ 132, 13600–13603 (2010) Article  CAS  Google Scholar  * Neumann, M., Füldner, S., König, B. & Zeitler, K. Metal-free, cooperative asymmetric organophotoredox catalysis

with visible light. _Angew. Chem. Int. Edn_ 50, 951–954 (2011) Article  CAS  Google Scholar  * Cherevatskaya, M. et al. Visible-light-promoted stereoselective alkylation by combining

heterogeneous photocatalysis with organocatalysis. _Angew. Chem. Int. Edn_ 51, 4062–4066 (2012) Article  CAS  Google Scholar  * Nagib, D. A., Scott, M. E. & MacMillan, D. W. C.

Enantioselective α-trifluoromethylation of aldehydes via photoredox organocatalysis. _J. Am. Chem. Soc._ 131, 10875–10877 (2009) Article  CAS  Google Scholar  * DiRocco, D. A. & Rovis,

T. Catalytic asymmetric _α_-acylation of tertiary amines mediated by a dual catalysis mode: N-heterocyclic carbene and photoredox catalysis. _J. Am. Chem. Soc._ 134, 8094–8097 (2012) Article

  CAS  Google Scholar  * Tarantino, K. T., Liu, P. & Knowles, R. R. Catalytic ketyl-olefin cyclizations enabled by proton-coupled electron transfer. _J. Am. Chem. Soc._ 135, 10022–10025

(2013) Article  CAS  Google Scholar  * Du, J., Skubi, K. L., Schultz, D. M. & Yoon, T. P. A dual-catalysis approach to enantioselective [2 + 2] photocycloadditions using visible light.

_Science_ 344, 392–396 (2014) Article  ADS  CAS  Google Scholar  * Bergonzini, G., Schindler, C. S., Wallentin, C.-J., Jacobsen, E. N. & Stephenson, C. R. J. Photoredox activation and

anion binding catalysis in the dual catalytic enantioselective synthesis of β-amino esters. _Chem. Sci._ 5, 112–116 (2013) Article  Google Scholar  * Bauer, A., Westkämper, F., Grimme, S.

& Bach, T. Catalytic enantioselective reactions driven by photoinduced electron transfer. _Nature_ 436, 1139–1140 (2005) Article  ADS  CAS  Google Scholar  * Müller, C., Bauer, A. &

Bach, T. Light-driven enantioselective organocatalysis. _Angew. Chem. Int. Edn_ 48, 6640–6642 (2009) Article  Google Scholar  * Brimioulle, R. & Bach, T. Enantioselective Lewis acid

catalysis of intramolecular enone [2+2] photocycloaddition reactions. _Science_ 342, 840–843 (2013) Article  ADS  CAS  Google Scholar  * Alonso, R. & Bach, T. A chiral thioxanthone as an

organocatalyst for enantioselective [2+2] photocycloaddition reactions induced by visible light. _Angew. Chem. Int. Edn_ 53, 4368–4371 (2014) Article  CAS  Google Scholar  * Arceo, E.,

Jurberg, I. D., Álvarez-Fernández, A. & Melchiorre, P. Photochemical activity of a key donor–acceptor complex can drive stereoselective catalytic α-alkylation of aldehydes. _Nature

Chem._ 5, 750–756 (2013) Article  ADS  CAS  Google Scholar  * Huo, H., Fu, C., Harms, K. & Meggers, E. Asymmetric catalysis with substitutionally labile yet stereochemically stable

chiral-at-metal iridium(III) complex. _J. Am. Chem. Soc._ 136, 2990–2993 (2014) Article  CAS  Google Scholar  * Fontecave, M., Hamelin, O. & Ménage, S. Chiral-at-metal complexes as

asymmetric catalysts. _Top. Organomet. Chem._ 15, 271–288 (2005) Article  CAS  Google Scholar  * Bauer, E. B. Chiral-at-metal complexes and their catalytic applications in organic synthesis.

_Chem. Soc. Rev._ 41, 3153–3167 (2012) Article  CAS  Google Scholar  * Evans, D. A., Downey, C. W. & Hubbs, J. L. Ni(II) bis(oxazoline)-catalyzed enantioselective syn aldol reactions of

_N_-propionylthiazolidinethiones in the presence of silyl triflates. _J. Am. Chem. Soc._ 125, 8706–8707 (2003) Article  CAS  Google Scholar  * Sato, H. & Yamagishi, A. Application of

the ΔΛ isomerism of octahedral metal complexes as a chiral source in photochemistry. _J. Photochem. Photobiol. C_ 8, 67–84 (2007) Article  CAS  Google Scholar  * Herrmann, A. T., Smith, L.

L. & Zakarian, A. A simple method for asymmetric trifluoromethylation of _N_-acyl oxazolidinones via Ru-catalyzed radical addition to zirconium enolates. _J. Am. Chem. Soc._ 134,

6976–6979 (2012) Article  CAS  Google Scholar  * Studer, A. & Curran, D. P. The electron is a catalyst. _Nature Chem._ 6, 765–773 (2014) Article  ADS  CAS  Google Scholar  * Andrieux, C.

P., Le Gorande, A. & Savéant, J. M. Electron transfer and bond breaking. Examples of passage from a sequential to a concerted mechanism in the electrochemical reductive cleavage of

arylmethyl halides. _J. Am. Chem. Soc._ 114, 6892–6904 (1992) Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We acknowledge funding from the German Research Foundation

(ME 1805/4-1). H.H. thanks the China Scholarship Council for a stipend. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße,

35043 Marburg, Germany, Haohua Huo, Xiaodong Shen, Chuanyong Wang, Lilu Zhang, Philipp Röse, Klaus Harms, Michael Marsch, Gerhard Hilt & Eric Meggers * College of Chemistry and Chemical

Engineering, Xiamen University, Xiamen 361005, China, Liang-An Chen & Eric Meggers Authors * Haohua Huo View author publications You can also search for this author inPubMed Google

Scholar * Xiaodong Shen View author publications You can also search for this author inPubMed Google Scholar * Chuanyong Wang View author publications You can also search for this author

inPubMed Google Scholar * Lilu Zhang View author publications You can also search for this author inPubMed Google Scholar * Philipp Röse View author publications You can also search for this

author inPubMed Google Scholar * Liang-An Chen View author publications You can also search for this author inPubMed Google Scholar * Klaus Harms View author publications You can also

search for this author inPubMed Google Scholar * Michael Marsch View author publications You can also search for this author inPubMed Google Scholar * Gerhard Hilt View author publications

You can also search for this author inPubMed Google Scholar * Eric Meggers View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS E.M. conceived

and coordinated the project and wrote the Letter. E.M. and H.H. designed the experiments. H.H. carried out the majority of the experiments. X.S. synthesized the new catalyst Λ-IR2. C.W.

contributed to the synthesis of substrates. L.Z. contributed to the synthesis and crystallization of iridium complexes. L.-A.C. provided insights into iridium enolate chemistry. P.R.

performed and analysed the cyclic voltammetry under supervision of G.H. The X-ray crystallographic studies were performed by K.H. and M.M. CORRESPONDING AUTHOR Correspondence to Eric

Meggers. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. ADDITIONAL INFORMATION The X-ray crystallographic coordinates for structures of the

iridium complex Λ-IR2, substrate coordinated iridium complex I and the iridium enolate complex II have been deposited at the Cambridge Crystallographic Data Centre (CCDC) under deposition

numbers CCDC 1014509, 1014510 and 1014876, respectively. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION This file contains Supplementary Figures 1-7, Supplementary Table 1,

Supplementary Methods and Supplementary References. (PDF 4767 kb) POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR FIG. 2 POWERPOINT SLIDE FOR FIG. 3 POWERPOINT SLIDE FOR

FIG. 4 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Huo, H., Shen, X., Wang, C. _et al._ Asymmetric photoredox transition-metal catalysis activated by

visible light. _Nature_ 515, 100–103 (2014). https://doi.org/10.1038/nature13892 Download citation * Received: 04 August 2014 * Accepted: 23 September 2014 * Published: 05 November 2014 *

Issue Date: 06 November 2014 * DOI: https://doi.org/10.1038/nature13892 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link

Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative