Abstract
Terminal, monosubstituted alkenes are ideal prospective starting materials for organic synthesis because they are manufactured on very large scales and can be functionalized via a broad range of chemical transformations. Alkenes also have the attractive feature of being stable in the presence of many acids, bases, oxidants and reductants. In spite of these attributes, relatively few catalytic enantioselective transformations have been developed that transform aliphatic α-olefins into chiral products with an enantiomeric excess greater then 90 per cent. With the exception of site-controlled isotactic polymerization of α-olefins1, none of these catalytic enantioselective processes results in chain-extending carbon–carbon bond formation to the terminal carbon2,3,4,5,6. Here we describe a strategy that directly addresses this gap in synthetic methodology, and present a single-flask, catalytic enantioselective conversion of terminal alkenes into a number of chiral products. These reactions are facilitated by a neighbouring functional group that accelerates palladium-catalysed cross-coupling of 1,2-bis(boronates) relative to non-functionalized alkyl boronate analogues. In tandem with enantioselective diboration, this reactivity feature transforms alkene starting materials into a diverse array of chiral products. We note that the tandem diboration/cross-coupling reaction generally provides products in high yield and high selectivity (>95:5 enantiomer ratio), uses low loadings (1–2 mol per cent) of commercially available catalysts and reagents, offers an expansive substrate scope, and can address a broad range of alcohol and amine synthesis targets, many of which cannot be easily addressed with current technology.
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
Resconi, L., Cavallo, L., Fait, A. & Piemontesi, F. Selectivity in propene polymerization with metallocene catalysts. Chem. Rev. 100, 1253–1345 (2000)
Subbarayan, V., Ruppel, J. V., Zhu, S., Perman, J. A. & Zhang, X. P. Highly asymmetric cobalt-catalyzed aziridination of alkenes with trichloroethoxysulfonyl azide (TcesN3). Chem. Commun. 4266–4268 (2009)
Uozumi, Y. & Hayashi, T. Catalytic asymmetric synthesis of optically active 2-alkanols via hydrosilylation of 1-alkenes with a chiral monophosphine-palladium catalyst. J. Am. Chem. Soc. 113, 9887–9888 (1991)
Lo, M. M.-C. & Fu, G. C. A new class of planar−chiral ligands: synthesis of a C2-symmetric bisazaferrocene and its application in the enantioselective Cu(I)-catalyzed cyclopropanation of olefins. J. Am. Chem. Soc. 120, 10270–10271 (1998)
Becker, H. & Sharpless, K. B. A new ligand class for the asymmetric dihydroxylation of olefins. Angew. Chem. Int. Edn Engl. 35, 448–451 (1996)
Noonan, G. M., Fuentes, J. A., Cobley, C. J. & Clarke, M. L. An asymmetric hydroformylation catalyst that delivers branched aldehydes from alkyl alkenes. Angew. Chem. Int. Edn Engl. 51, 2477–2480 (2012)
Coombs, J. R., Haefner, F., Kliman, L. T. & Morken, J. P. Scope and mechanism of the Pt-catalyzed enantioselective diboration of monosubstituted alkenes. J. Am. Chem. Soc. 135, 11222–11231 (2013)
Miller, S. P., Morgan, J. B., Nepveux, F. J. & Morken, J. P. Catalytic asymmetric carbohydroxylation of alkenes by a tandem diboration/Suzuki cross-coupling/oxidation reaction. Org. Lett. 6, 131–133 (2004)
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)
Lee, Y., Jang, H. & Hoveyda, A. H. Vicinal diboronates in high enantiomeric purity through tandem site-selective NHC-Cu-catalyzed boron-copper additions to terminal alkynes. J. Am. Chem. Soc. 131, 18234–18235 (2009)
Carrow, B. P. & Hartwig, J. F. Distinguishing between pathways for transmetallation in Suzuki-Miyaura reactions. J. Am. Chem. Soc. 133, 2116–2119 (2011)
Amatore, C., Jutand, A. & Le Duc, G. Kinetic data for the transmetalation/reductive elimination in palladium-catalyzed Suzuki–Miyaura reactions: unexpected triple role of hydroxide ions used as base. Chemistry 17, 2492–2503 (2011)
Matos, K. & Soderquist, J. A. Alkylboranes in the Suzuki-Miyaura coupling: stereochemical and mechanistic studies. J. Org. Chem. 63, 461–470 (1998)
Sato, M., Miyaura, N. & Suzuki, A. Cross-coupling reaction of alkyl- or arylboronic acid esters with organic halides induced by thallium(I) salts and palladium catalyst. Chem. Lett. 18, 1405–1408 (1989)
Zou, G. & Falck, J. R. Suzuki-Miyaura cross coupling of lithium n-alkylborates. Tetrahedr. Lett. 42, 5817–5819 (2001)
Christmann, U. & Vilar, R. Monoligated palladium species as catalysts in cross-coupling reactions. Angew. Chem. Int. Edn Engl. 44, 366–374 (2005)
Yang, C.-T. et al. Alkylboronic esters from copper-catalyzed borylation of primary and secondary alkyl halides and pseudohalides. Angew. Chem. Int. Edn Engl. 51, 528–532 (2012)
Charles, M. D., Schultz, P. & Buchwald, S. L. Efficient Pd-catalyzed amination of heteroaryl halides. Org. Lett. 7, 3965–3968 (2005)
Sandrock, D. L., Jean-Gérard, L., Chen, C., Dreher, S. D. & Molander, G. A. Stereospecific cross-coupling of secondary alkyl β-trifluoroboratoamides. J. Am. Chem. Soc. 132, 17108–17110 (2010)
Endo, K., Ohkubo, T., Hirokami, M. & Shibata, T. Chemoselective and regiospecific Suzuki coupling on a multisubstituted sp3 carbon in 1,1-diborylalkanes at room temperature. J. Am. Chem. Soc. 132, 11033–11035 (2010)
Ridgway, B. H. & Woerpel, K. A. Transmetalation of alkylboranes to palladium in the Suzuki coupling reaction proceeds with retention of stereochemistry. J. Org. Chem. 63, 458–460 (1998)
Yus, M., González-Gómez, J. C. & Foubelo, F. Catalytic enantioselective allylation of carbonyl compounds and imines. Chem. Rev. 111, 7774–7854 (2011)
Silverio, D. L. et al. Simple organic molecules as catalysts for enantioselective synthesis of amines and alcohols. Nature 494, 216–221 (2013)
Nogrady T., Weaver D. F., eds. Medicinal Chemistry: A Molecular and Biochemistry Approach Ch. 4 193–309 (Oxford, 2005)
Mlynarski, S. N., Karns, A. S. & Morken, J. P. Direct stereospecific amination of alkyl and aryl pinacol boronates. J. Am. Chem. Soc. 134, 16449–16451 (2012)
Sadhu, K. M. & Matteson, D. S. (Chloromethyl)lithium: efficient generation and capture by boronic esters and a simple preparation of diisopropyl (chloromethyl)boronate. Organometallics 4, 1687–1689 (1985)
Himmele, W. & Pommer, E.-H. 3-Phenylpropylamines: a new class of systemic fungicides. Angew. Chem. Int. Edn Engl. 19, 184–189 (1980)
Itoh, T., Chika, J., Takagi, Y. & Nishiyama, S. An efficient enantioselective total synthesis of antitumor lignans: synthesis of enantiomerically pure 4-hydroxyalkanenitriles via an enzymatic reaction. J. Org. Chem. 58, 5717–5723 (1993)
Silverman, R. B. & Andruszkiewicz, R. Gamma amino butyric acid analogs and optical isomers. US Patent 6,197,819 B1 (2001)
Acknowledgements
This research was supported by the US National Institutes of Health, Institute of General Medical Sciences (grant GM-59417). S.N.M. and C.H.S. were supported by John LaMattina graduate fellowships. We thank Allychem for providing B2(pin)2.
Author information
Authors and Affiliations
Contributions
S.N.M. and C.H.S. developed the procedure for the DCC reaction and collected the data in Figs 2b and 4. S.N.M. conducted the studies in Figs 5 and 6 and conducted the isotope labelling experiment in Fig. 3. J.P.M. conceived and designed the studies, planned the research and wrote the manuscript with assistance from C.H.S.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Information
This file contains Supplementary Text and Data – see contents page for details. (PDF 5776 kb)
Rights and permissions
About this article
Cite this article
Mlynarski, S., Schuster, C. & Morken, J. Asymmetric synthesis from terminal alkenes by cascades of diboration and cross-coupling. Nature 505, 386–390 (2014). https://doi.org/10.1038/nature12781
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nature12781
This article is cited by
-
Programmable late-stage functionalization of bridge-substituted bicyclo[1.1.1]pentane bis-boronates
Nature Chemistry (2024)
-
Enantioselective C–C cross-coupling of unactivated alkenes
Nature Catalysis (2023)
-
Automated iterative Csp3–C bond formation
Nature (2022)
-
Cobalt-catalyzed deoxygenative triborylation of allylic ethers to access 1,1,3-triborylalkanes
Nature Communications (2020)
-
Site-selective alkene borylation enabled by synergistic hydrometallation and borometallation
Nature Catalysis (2020)
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.