Abstract
Carbon–carbon (C–C) bonds form the backbone of many important molecules, including polymers, dyes and pharmaceutical agents. The development of new methods to create these essential connections in a rapid and practical fashion has been the focus of numerous organic chemists. This endeavour relies heavily on the ability to form C–C bonds in the presence of sensitive functional groups and congested structural environments. Here we report a chemical transformation that allows the facile construction of highly substituted and uniquely functionalized C–C bonds. Using a simple iron catalyst, an inexpensive silane and a benign solvent under ambient atmosphere, heteroatom-substituted olefins are easily reacted with electron-deficient olefins to create molecular architectures that were previously difficult or impossible to access. More than 60 examples are presented with a wide array of substrates, demonstrating the chemoselectivity and mildness of this simple reaction.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 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
References
Corey, E. J. & Cheng, X.-M. The Logic of Chemical Synthesis (Wiley, 1995)
Isayama, S. & Mukaiyama, T. A new method for the preparation of alcohols from olefins with molecular oxygen and phenylsilane by the use of bis(acetylacetonato)cobalt(II). Chem. Lett. 18, 1071–1074 (1989)
Kato, K. & Mukaiyama, T. Iron(III) complex catalyzed nitrosation of terminal and 1,2-disubstituted olefins with butyl nitrite and phenylsilane. Chem. Lett. 21, 1137–1140 (1992)
Waser, J., Gaspar, B., Nambu, H. & Carreira, E. M. Hydrazines and azides via the metal-catalyzed hydrohydrazination and hydroazidation of olefins. J. Am. Chem. Soc. 128, 11693–11712 (2006)
Leggans, E. K., Barker, T. J., Duncan, K. K. & Boger, D. L. Iron(III)/NaBH4-mediated additions to unactivated alkenes: synthesis of novel 20′-vinblastine analogues. Org. Lett. 14, 1428–1431 (2012)
Shigehisa, H., Aoki, T., Yamaguchi, S., Shimizu, N. & Hiroya, K. Hydroalkoxylation of unactivated olefins with carbon radicals and carbocation species as key intermediates. J. Am. Chem. Soc. 135, 10306–10309 (2013)
Shigehisa, H., Nishi, E., Fujisawa, M. & Hiroya, K. Cobalt-catalyzed hydrofluorination of unactivated olefins: a radical approach of fluorine transfer. Org. Lett. 15, 5158–5161 (2013)
Girijavallabhan, V., Alvarez, C. & Njoroge, F. G. Regioselective cobalt-catalyzed addition of sulfides to unactivated alkenes. J. Org. Chem. 76, 6442–6446 (2011)
Taniguchi, T., Goto, N., Nishibata, A. & Ishibashi, H. Iron-catalyzed redox radical cyclizations of 1,6-dienes and enynes. Org. Lett. 12, 112–115 (2010)
Wang, L. C. et al. Diastereoselective cycloreductions and cycloadditions catalyzed by Co(dpm)2-silane (dpm) 2,2,6,6-tetramethylheptane-3,5-dionate): mechanism and partitioning of hydrometallative versus anion radical pathways. J. Am. Chem. Soc. 124, 9448–9453 (2002)
Streuff, J. The electron-way: metal-catalyzed reductive umpolung reactions of saturated and α,β-unsaturated carbonyl derivatives. Synthesis 45, 281–307 (2013)
Zbieg, J. R., Yamaguchi, E., McInturff, E. L. & Krische, M. J. Enantioselective C–H crotylation of primary alcohols via hydrohydroxyalkylation of butadiene. Science 336, 324–327 (2012)
Lo, J. C., Yabe, Y. & Baran, P. S. A practical and catalytic reductive olefin coupling. J. Am. Chem. Soc. 136, 1304–1307 (2014)
Srikanth, G. S. C. & Castle, S. L. Advances in radical conjugate additions. Tetrahedron 61, 10377–10441 (2005)
Lackner, G. L., Quasdorf, K. W. & Overman, L. E. Direct construction of quaternary carbons from tertiary alcohols via photoredox-catalyzed fragmentation of tert-alkyl N-phthalimidoyl oxalates. J. Am. Chem. Soc. 135, 15342–15345 (2013)
Barton, D. H. R. & Crich, D. Formation of quaternary carbon centres from tertiary alcohols by free radical methods. Tetrahedron Lett. 26, 757–760 (1985)
Barton, D. H. R., Crich, D. & Kretzchmar, G. Formation of carbon-carbon bonds with radicals derived from the esters of thiohydroxamic acids. Tetrahedron Lett. 25, 1055–1058 (1984)
Iwasaki, K., Wan, K. W., Oppedisano, A., Crossley, S. W. M. & Shenvi, R. A. Simple, chemoselective hydrogenation with thermodynamic stereocontrol. J. Am. Chem. Soc. 136, 1300–1303 (2014)
King, S. M., Ma, X. & Herzon, S. B. A method for the selective hydrogenation of alkenyl halides to alkyl halides. J. Am. Chem. Soc. 136, 6884–6887 (2014)
Magnus, P., Waring, M. J. & Scott, D. A. Conjugate reduction of α,β-unsaturated ketones using an MnIII catalyst, phenylsilane and isopropyl alcohol. Tetrahedron Lett. 41, 9731–9733 (2000)
Zotto, C. D. et al. FeCl3-catalyzed addition of nitrogen and 1,3-dicarbonyl nucleophiles to olefins. J. Organomet. Chem. 696, 296–304 (2011)
Shigematsu, T., Matsui, M. & Utsunomiya, K. Gas chromatography of diisobutyrylmethane metal chelates. Bull. Inst. Chem. Res. Kyoto Univ. 46, 256–261 (1968)
Djerassi, C., Miramontes, L., Rosenkranz, G. & Sondheimer, F. Steroids. LIV. Synthesis of 19-nor-17α-ethynyltestosterone and 19-nor-17α-methyltestosterone. J. Am. Chem. Soc. 76, 4092–4094 (1954)
Juaristi, E., León-Romo, J. L., Reyes, A. & Escalante, J. Recent applications of α-phenylethylamine (α-PEA) in the preparation of enantiopure compounds. Part 3: α-PEA as chiral auxiliary. Part 4: α-PEA as chiral reagent in the stereodifferentiation of prochiral substrates. Tetrahedron Asymmetry 10, 2441–2495 (1999)
Mancilla, T. & Contreras, R. New bicyclic organylboronic esters derived from iminodiacetic acids. J. Organomet. Chem. 307, 1–6 (1986)
Gillis, E. P. & Burke, M. D. A simple and modular strategy for small molecule synthesis: iterative Suzuki−Miyaura coupling of B-protected haloboronic acid building blocks. J. Am. Chem. Soc. 129, 6716–6717 (2007)
Noguchi, H., Hojo, K. & Suginome, M. Boron-masking strategy for the synthesis of oligioarenes via iterative Suzuki–Miyaura coupling. J. Am. Chem. Soc. 129, 758–759 (2007)
Yamamoto, Y. & Maruyama, K. RCu̇BF3. 3. Conjugate addition to previously unreactive substituted enoate esters and enoic acids. J. Am. Chem. Soc. 100, 3240–3241 (1978)
Aurell, M. J., Domingo, L. R., Mestres, R., Muñoz, E. & Zaragová, R. J. Conjugate addition of organolithium reagents to α,β-unsaturated carboxylic acids. Tetrahedron 55, 815–830 (1999)
Hutchinson, D. K. & Fuchs, P. L. Amelioration of the conjugate addition chemistry of α-alkoxycopper reagents: application to the stereospecific synthesis of C-glycosides. J. Am. Chem. Soc. 109, 4930–4939 (1987)
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Vol. 44, Alcohol Drinking 71–99 (World Health Organization, 1988)
Kolb, H. C. & Sharpless, K. B. The growing impact of click chemistry on drug discovery. Drug Discov. Today 8, 1128–1137 (2003)
Chu, L., Ohta, C., Zuo, Z. & MacMillan, D. W. C. Carboxylic acids as a traceless activation group for conjugate additions: a three-step synthesis of (±)-pregabalin. J. Am. Chem. Soc. 136, 10886–10889 (2014)
Ishikawa, H. et al. Total synthesis of vinblastine, vincristine, related natural products, and key structural analogs. J. Am. Chem. Soc. 131, 4904–4916 (2009)
Bullock, R. M. & Samsel, E. G. Hydrogen atom transfer reactions of transition-metal hydrides. Kinetics and mechanism of the hydrogenation of α-cyclopropylstyrene by metal carbonyl hydrides. J. Am. Chem. Soc. 112, 6886–6898 (1990)
Matsuo, J. & Murakami, M. The Mukaiyama aldol reaction: 40 years of continuous development. Angew. Chem. Int. Edn 52, 9109–9118 (2013)
Stork, G., Brizzolara, A., Landesman, H., Szmuszkovicz, J. & Terrell, R. The enamine alkylation and acylation of carbonyl compounds. J. Am. Chem. Soc. 85, 207–222 (1963)
Miyaura, N. & Suzuki, A. Palladium-catalyzed cross-coupling reactions of organoboron compounds. Chem. Rev. 95, 2457–2483 (1995)
Jana, R., Pathak, T. P. & Sigman, M. S. Advances in transition metal (Pd,Ni,Fe)-catalyzed cross-coupling reactions using alkyl-organometallics as reaction partners. Chem. Rev. 111, 1417–1492 (2011)
Dubbaka, S. R. & Vogel, P. Organosulfur compounds: electrophilic reagents in transition-metal-catalyzed carbon–carbon bond-forming reactions. Angew. Chem. Int. Edn 44, 7674–7684 (2005)
Blumenkopf, T. A. & Overman, L. E. Vinylsilane- and alkynylsilane-terminated cyclization reactions. Chem. Rev. 86, 857–873 (1986)
Nakao, Y. & Hiyama, T. Silicon-based cross-coupling reaction: an environmentally benign version. Chem. Soc. Rev. 40, 4893–4901 (2011)
Diederich F., Stang P. J., eds. Metal-catalyzed Cross-coupling Reactions (Wiley-VCH, 1998)
Seebach, D. Methods of reactivity umpolung. Angew. Chem. Int. Edn Engl. 18, 239–258 (1979)
Gao, X., Soo, S. K. & Krische, M. J. Total synthesis of 6-deoxyerythronolide B via C−C bond-forming transfer hydrogenation. J. Am. Chem. Soc. 135, 4223–4226 (2013)
Werner, E. W., Mei, T.-S., Burckle, A. J. & Sigman, M. S. Enantioselective Heck arylations of acyclic alkenyl alcohols using a redox-relay strategy. Science 338, 1455–1458 (2012)
Meek, S. J., O’Brien, R. V., Llaveria, J., Schrock, R. J. & Hoveyda, A. H. Catalytic Z-selective olefin cross-metathesis for natural product synthesis. Nature 471, 461–466 (2011)
Acknowledgements
Financial support for this work was provided by NIH/NIGMS (GM-097444). The National Science Foundation supported a predoctoral fellowship for J.C.L.; the Shanghai Institute of Organic Chemistry, Zhejiang Medicine Co. and Pharmaron supported a postdoctoral fellowship for J.G.; and the Japan Society for the Promotion of Science supported a postdoctoral fellowship for Y.Y. We are grateful to D.-H. Huang and L. Pasternack (TSRI) for assistance with NMR spectroscopy, and A. L. Rheingold and C. E. Moore (UCSD) for X-ray crystallographic analysis. We thank R. A. Shenvi (TSRI) and Y. Ji (TSRI) for discussions.
Author information
Authors and Affiliations
Contributions
J.C.L. and P.S.B. conceived the work; J.C.L. conducted initial feasibility studies; J.C.L., J.G., Y.Y., C.-M.P. and P.S.B. designed the experiments and analysed the data; J.C.L., J.G., Y.Y. and C.-M.P. performed the experiments; and J.C.L. and P.S.B. wrote the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Additional information
Crystallographic data for the structure of Fe(dibm)3 (5) is available free of charge from the Cambridge Crystallographic Data Centre under deposition number CCDC 1022625.
Supplementary information
Supplementary Information
This file contains Supplementary Text and Data, Supplementary Tables 1-2, Supplementary Figures 1-30 and Supplementary References. (PDF 16782 kb)
Rights and permissions
About this article
Cite this article
Lo, J., Gui, J., Yabe, Y. et al. Functionalized olefin cross-coupling to construct carbon–carbon bonds. Nature 516, 343–348 (2014). https://doi.org/10.1038/nature14006
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nature14006
This article is cited by
-
Selective dimerization of terminal alkenes to form alkyl–alkyl products
Nature Synthesis (2023)
-
Nickel-catalysed hydrodimerization of unactivated terminal alkenes
Nature Synthesis (2023)
-
Iron-catalysed reductive cross-coupling of glycosyl radicals for the stereoselective synthesis of C-glycosides
Nature Synthesis (2022)
-
Total synthesis of nine longiborneol sesquiterpenoids using a functionalized camphor strategy
Nature Chemistry (2022)
-
Copper-catalysed asymmetric reductive cross-coupling of prochiral alkenes
Nature Communications (2022)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.