Abstract
Carboazidation of olefins is an efficient process to convert hydrocarbons directly into nitrogen-containing molecules. Such chemicals find broad applications in medicine and material sciences. Despite the fast development of carboazidation reactions, asymmetric radical carboazidations are still elusive. Here, we report a radical asymmetric carboazidation of olefins via an iron-catalysed group transfer mechanism. The method affords valuable chiral halogenated organoazides from inexpensive industrial chemical feedstocks. This radical azidation reaction is supported by mechanistic studies and should inspire further development of enantioselective radical reactions.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Data availability
Data relating to the characterization data of materials and products, general methods, optimization studies, experimental procedures, mechanistic studies, mass spectrometry, high-performance liquid chromatography and NMR spectra, computational studies are available in the Supplementary Information. Crystallographic data for compounds L2Fe(OTf)2, 63, 72A and 72B are available free of charge from the Cambridge Crystallographic Data Centre (CCDC) under reference numbers 1938900, 1938899, 2003644 and 2015243, respectively.
References
Bräse, S. & Banert, K. (eds) Organic Azides: Syntheses and Applications (John Wiley & Sons, Ltd, 2009).
Sharma, A. & Hartwig, J. F. Metal-catalysed azidation of tertiary C–H bonds suitable for late-stage functionalization. Nature 517, 600–604 (2015).
Renaud, P., Ollivier, C. & Panchaud, P. Radical carboazidation of alkenes: an efficient tool for the preparation of pyrrolidinone derivatives. Angew. Chem. Int. Ed. 41, 3460–3462 (2002).
Wang, F., Qi, X., Liang, Z., Chen, P. & Liu, G. Copper-catalyzed intermolecular trifluoromethylazidation of alkenes: convenient access to CF3-containing alkyl azides. Angew. Chem. Int. Ed. 53, 1881–1886 (2014).
Dagousset, G., Carboni, A., Magnier, E. & Masson, G. Photoredox-induced three-component azido- and aminotrifluoromethylation of alkenes. Org. Lett. 16, 4340–4343 (2014).
Bunescu, A., Ha, T. M., Wang, Q. & Zhu, J. Copper-catalyzed three-component carboazidation of alkenes with acetonitrile and sodium azide. Angew. Chem. Int. Ed. 56, 10555–10558 (2017).
Geng, X., Lin, F., Wang, X. & Jiao, N. Azidofluoroalkylation of alkenes with simple fluoroalkyl iodides enabled by photoredox catalysis. Org. Lett. 19, 4738–4741 (2017).
Zhu, C.-L. et al. Iron(ii)-catalyzed azidotrifluoromethylation of olefins and N-heterocycles for expedient vicinal trifluoromethyl amine synthesis. ACS Catal. 8, 5032–5037 (2018).
Zhang, L. et al. (Salen)Mn(iii)-catalyzed chemoselective acylazidation of olefins. Chem. Sci. 9, 6085–6090 (2018).
Xiong, H. et al. Iron-catalyzed carboazidation of alkenes and alkynes. Nat. Commun. 10, 122 (2019).
Wu, K., Liang, Y. & Jiao, N. Azidation in the difunctionalization of olefins. Molecules 21, 352 (2016).
Jiang, H. & Studer, A. Intermolecular radical carboamination of alkenes. Chem. Soc. Rev. 49, 1790–1811 (2020).
Ge, L., Chiou, M.-F., Li, Y. & Bao, H. Radical azidation as a means of constructing C(sp3)-N3 bonds. Green Syn. Catal. https://doi.org/10.1016/j.gresc.2020.07.001 (2020).
Jacobsen, E. N. Asymmetric catalysis of epoxide ring-opening reactions. Acc. Chem. Res. 33, 421–431 (2000).
Ding, P.-G., Hu, X.-S., Zhou, F. & Zhou, J. Catalytic enantioselective synthesis of α-chiral azides. Org. Chem. Front. 5, 1542–1559 (2018).
Zhou, P. et al. Iron-catalyzed asymmetric haloazidation of alpha,beta-unsaturated ketones: construction of organic azides with two vicinal stereocenters. J. Am. Chem. Soc. 139, 13414–13419 (2017).
Seidl, F. J., Min, C., Lopez, J. A. & Burns, N. Z. Catalytic regio- and enantioselective haloazidation of allylic alcohols. J. Am. Chem. Soc. 140, 15646–15650 (2018).
Li, X., Qi, X., Hou, C., Chen, P. & Liu, G. Palladium(ii)-catalyzed enantioselective azidation of unactivated alkenes. Angew. Chem. Int. Ed. 59, 17239–17244 (2020).
Liu, C., Wang, X., Li, Z., Cui, L. & Li, C. Silver-catalyzed decarboxylative radical azidation of aliphatic carboxylic acids in aqueous solution. J. Am. Chem. Soc. 137, 9820–9823 (2015).
Krasutsky, A. P., Kuehl, C. J. & Zhdankin, V. V. Direct azidation of adamantane and norbornane by stable azidoiodinanes. Synlett 1995, 1081–1082 (1995).
Magnus, P., Lacour, J., Evans, P. A., Roe, M. B. & Hulme, C. hypervalent iodine chemistry: new oxidation reactions using the iodosylbenzene−trimethylsilyl azide reagent combination. direct α- and β-azido functionalization of triisopropylsilyl enol ethers. J. Am. Chem. Soc. 118, 3406–3418 (1996).
Huang, X., Bergsten, T. M. & Groves, J. T. Manganese-catalyzed late-stage aliphatic C–H azidation. J. Am. Chem. Soc. 137, 5300–5303 (2015).
Chiou, M. F., Xiong, H., Li, Y., Bao, H. & Zhang, X. Revealing the iron-catalyzed beta-methyl scission of tert-butoxyl radicals via the mechanistic studies of carboazidation of alkenes. Molecules 25, 1224 (2020).
Sibi, M. P., Manyem, S. & Zimmerman, J. Enantioselective radical processes. Chem. Rev. 103, 3263–3296 (2003).
Wang, K. & Kong, W. Recent advances in transition metal-catalyzed asymmetric radical reactions. Chin. J. Chem. 36, 247–256 (2018).
Wang, F., Chen, P. & Liu, G. Copper-catalyzed radical relay for asymmetric radical transformations. Acc. Chem. Res. 51, 2036–2046 (2018).
Huang, X. & Meggers, E. Asymmetric photocatalysis with bis-cyclometalated rhodium complexes. Acc. Chem. Res. 52, 833–847 (2019).
Yang, D., Zheng, B.-F., Gao, Q., Gu, S. & Zhu, N.-Y. Enantioselective PhSe-group-transfer tandem radical cyclization reactions catalyzed by a chiral Lewis acid. Angew. Chem. Int. Ed. 45, 255–258 (2005).
Beeson, T. D., Mastracchio, A., Hong, J. B., Ashton, K. & Macmillan, D. W. Enantioselective organocatalysis using SOMO activation. Science 316, 582–585 (2007).
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).
Zhu, R. & Buchwald, S. L. Enantioselective functionalization of radical intermediates in redox catalysis: copper-catalyzed asymmetric oxytrifluoromethylation of alkenes. Angew. Chem. Int. Ed. 52, 12655–12658 (2013).
Rono, L. J., Yayla, H. G., Wang, D. Y., Armstrong, M. F. & Knowles, R. R. Enantioselective photoredox catalysis enabled by proton-coupled electron transfer: development of an asymmetric aza-pinacol cyclization. J. Am. Chem. Soc. 135, 17735–17738 (2013).
Hashimoto, T., Kawamata, Y. & Maruoka, K. An organic thiyl radical catalyst for enantioselective cyclization. Nat. Chem. 6, 702–705 (2014).
Ruiz Espelt, L., McPherson, I. S., Wiensch, E. M. & Yoon, T. P. Enantioselective conjugate additions of alpha-amino radicals via cooperative photoredox and Lewis acid catalysis. J. Am. Chem. Soc. 137, 2452–2455 (2015).
Murphy, J. J., Bastida, D., Paria, S., Fagnoni, M. & Melchiorre, P. Asymmetric catalytic formation of quaternary carbons by iminium ion trapping of radicals. Nature 532, 218–222 (2016).
Jiang, H., Lang, K., Lu, H., Wojtas, L. & Zhang, X. P. Asymmetric radical bicyclization of allyl azidoformates via cobalt(ii)-based metalloradical catalysis. J. Am. Chem. Soc. 139, 9164–9167 (2017).
Poremba, K. E., Kadunce, N. T., Suzuki, N., Cherney, A. H. & Reisman, S. E. Nickel-catalyzed asymmetric reductive cross-coupling to access 1,1-diarylalkanes. J. Am. Chem. Soc. 139, 5684–5687 (2017).
Kern, N., Plesniak, M. P., McDouall, J. J. W. & Procter, D. J. Enantioselective cyclizations and cyclization cascades of samarium ketyl radicals. Nat. Chem. 9, 1198–1204 (2017).
Yin, Y. et al. Conjugate addition-enantioselective protonation of N-aryl glycines to alpha-branched 2-vinylazaarenes via cooperative photoredox and asymmetric catalysis. J. Am. Chem. Soc. 140, 6083–6087 (2018).
Proctor, R. S. J., Davis, H. J. & Phipps, R. J. Catalytic enantioselective Minisci-type addition to heteroarenes. Science 360, 419–422 (2018).
Li, J. et al. Formal enantioconvergent substitution of alkyl halides via catalytic asymmetric photoredox radical coupling. Nat. Commun. 9, 2445 (2018).
Wang, Z., Yin, H. & Fu, G. C. Catalytic enantioconvergent coupling of secondary and tertiary electrophiles with olefins. Nature 563, 379–383 (2018).
Dong, X. Y. et al. A general asymmetric copper-catalysed Sonogashira C(sp(3))-C(sp) coupling. Nat. Chem. 11, 1158–1166 (2019).
Biegasiewicz, K. F. et al. Photoexcitation of flavoenzymes enables a stereoselective radical cyclization. Science 364, 1166–1169 (2019).
Zheng, D. & Studer, A. Asymmetric synthesis of heterocyclic gamma-amino-acid and diamine derivatives by three-component radical cascade reactions. Angew. Chem. Int. Ed. 58, 15803–15807 (2019).
Goswami, M. & de Bruin, B. Metal-catalysed azidation of organic molecules. Eur. J. Org. Chem. 2017, 1152–1176 (2017).
Huang, X. & Groves, J. T. Taming azide radicals for catalytic C–H azidation. ACS Catal. 6, 751–759 (2015).
Sibi, M. P. & Patil, K. Enantioselective H-atom transfer reactions: a new methodology for the synthesis of beta2-amino acids. Angew. Chem. Int. Ed. 43, 1235–1238 (2004).
Aechtner, T., Dressel, M. & Bach, T. Hydrogen bond mediated enantioselectivity of radical reactions. Angew. Chem. Int. Ed. 43, 5849–5851 (2004).
Zhu, S., Ruppel, J. V., Lu, H., Wojtas, L. & Zhang, X. P. Cobalt-catalyzed asymmetric cyclopropanation with diazosulfones: rigidification and polarization of ligand chiral environment via hydrogen bonding and cyclization. J. Am. Chem. Soc. 130, 5042–5043 (2008).
Jin, L. M. et al. Effective synthesis of chiral N-fluoroaryl aziridines through enantioselective aziridination of alkenes with fluoroaryl azides. Angew. Chem. Int. Ed. 52, 5309–5313 (2013).
Chen, B., Fang, C., Liu, P. & Ready, J. M. Rhodium-catalyzed enantioselective radical addition of CX4 reagents to olefins. Angew. Chem. Int. Ed. 56, 8780–8784 (2017).
Liang, Y., Wei, J., Qiu, X. & Jiao, N. Homogeneous oxygenase catalysis. Chem. Rev. 118, 4912–4945 (2018).
Milan, M., Bietti, M. & Costas, M. Enantioselective aliphatic C–H bond oxidation catalyzed by bioinspired complexes. Chem. Commun. 54, 9559–9570 (2018).
Wu, W. et al. Trifluoroacetic anhydride promoted copper(I)-catalyzed interrupted click reaction: from 1,2,3-triazoles to 3-trifluoromethyl-substituted 1,2,4-triazinones. Angew. Chem. Int. Ed. 56, 10476–10480 (2017).
Åhman, J., Birch, M., Haycock-Lewandowski, S. J., Long, J. & Wilder, A. Process research and scale-up of a commercialisable route to maraviroc (UK-427,857), a CCR-5 receptor antagonist. Org. Process Res. Dev. 12, 1104–1113 (2008).
Kanemasa, S. et al. Cationic aqua complexes of the C2-symmetrictrans-chelating ligand (R,R)-4,6-dibenzofurandiyl-2,2‘-bis(4-phenyloxazoline). Absolute chiral induction in Diels–Alder reactions catalyzed by water-tolerant enantiopure Lewis acids. J. Org. Chem. 62, 6454–6455 (1997).
Deng, Q. H., Bleith, T., Wadepohl, H. & Gade, L. H. Enantioselective iron-catalyzed azidation of beta-keto esters and oxindoles. J. Am. Chem. Soc. 135, 5356–5359 (2013).
Bauer, I. & Knölker, H.-J. Iron catalysis in organic synthesis. Chem. Rev. 115, 3170–3387 (2015).
Contreras-Garcia, J. et al. NCIPLOT: a program for plotting non-covalent interaction regions. J. Chem. Theor. Comput. 7, 625–632 (2011).
Lee, C., Yang, W. & Parr, R. G. Development of the Colle–Salvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B. 37, 785–789 (1988).
Becke, A. D. Density‐functional thermochemistry. III. The role of exact exchange. J. Chem. Phys. 98, 5648–5652 (1993).
Grimme, S., Antony, J., Ehrlich, S. & Krieg, H. A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H–Pu. J. Chem. Phys. 132, 154104 (2010).
Grimme, S., Ehrlich, S. & Goerigk, L. Effect of the damping function in dispersion corrected density functional theory. J. Comput. Chem. 32, 1456–1465 (2011).
Weigend, F. Accurate Coulomb-fitting basis sets for H to Rn. Phys. Chem. Chem. Phys. 8, 1057–1065 (2006).
Weigend, F. & Ahlrichs, R. Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: design and assessment of accuracy. Phys. Chem. Chem. Phys. 7, 3297–3305 (2005).
Marenich, A. V., Cramer, C. J. & Truhlar, D. G. Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J. Phys. Chem. B. 113, 6378–6396 (2009).
Frisch, M. J. et al. Gaussian 09, Revision D.01 (Gaussian Inc., 2013).
Johnson, E. R. et al. Revealing noncovalent interactions. J. Am. Chem. Soc. 132, 6498–6506 (2010).
Acknowledgements
We thank K. Ding and X.L. Hou from Shanghai Institute of Organic Chemistry, A. Studer from University of Münster, X. Wang from Lanzhou University, W. Xie from Northwest A&F University and W. Su from our institute for inspiring discussions, D. Yuan and X. Jiang from our institute for X-ray crystallography analysis. We thank G.W.A. Milne for his writing suggestions. Supported by the National Key R&D Programme of China (grant no. 2017YFA0700103), the NSFC (grant nos. 21672213, 21871258 and 21922112), the Strategic Priority Research Programme of the Chinese Academy of Sciences (grant no. XDB20000000), the Haixi Institute of CAS (grant no. CXZX-2017-P01), the Innovative Research Teams Programme II of Fujian Normal University in China (grant no. IRTL1703), the Shenzhen STIC (grant no. JCYJ20170412150343516) and the Shenzhen San-Ming Project (grant no. SZSM201809085).
Author information
Authors and Affiliations
Contributions
H.B. directed the investigations and prepared the manuscript. L.G., H.Z., W.J., C.Y., X.L., X. Zhu and H.X. performed the synthetic experiments and analysed the experimental data. X. Zhang directed the calculation study and M.-F.C. completed the theoretical calculations. H.J. conducted the mass spectra studies, L.S. did the non-covalent bond interaction analysis. Y.L. double checked the data in the Supplementary Information. L.G., H.Z. and M.-F.C. contributed equally.
Corresponding authors
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 Tables 1–4, Methods, Discussion, Figs. 1–8 and references.
Supplementary Data
44 coordinate of optimized structures file as text.
Supplementary Data 1
X-ray crystal structure of iron catalyst A, L2Fe(OTf)2.
Supplementary Data 2
X-ray crystal structure of product 72B.
Supplementary Data 3
X-ray crystal structure of product 72A.
Supplementary Data 4
X-ray crystal structure of product 63.
Rights and permissions
About this article
Cite this article
Ge, L., Zhou, H., Chiou, MF. et al. Iron-catalysed asymmetric carboazidation of styrenes. Nat Catal 4, 28–35 (2021). https://doi.org/10.1038/s41929-020-00551-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41929-020-00551-4
This article is cited by
-
Asymmetric 1,2-oxidative alkylation of conjugated dienes via aliphatic C–H bond activation
Nature Synthesis (2022)
-
Nickel-catalysed asymmetric hydrogenation of oximes
Nature Chemistry (2022)
-
Palladium-catalyzed asymmetric allylic 4-pyridinylation via electroreductive substitution reaction
Nature Communications (2022)
-
Asymmetric radical carboesterification of dienes
Nature Communications (2021)