Alkane desaturation by concerted double hydrogen atom transfer to benzyne

Abstract

The removal of two vicinal hydrogen atoms from an alkane to produce an alkene is a challenge for synthetic chemists1,2. In nature, desaturases and acetylenases are adept at achieving this essential oxidative functionalization reaction, for example during the biosynthesis of unsaturated fatty acids3, eicosanoids, gibberellins4 and carotenoids5. Alkane-to-alkene conversion almost always involves one or more chemical intermediates in a multistep reaction pathway; these may be either isolable species (such as alcohols or alkyl halides) or reactive intermediates (such as carbocations, alkyl radicals, or σ-alkyl-metal species). Here we report a desaturation reaction of simple, unactivated alkanes that is mechanistically unique. We show that benzynes are capable of the concerted removal of two vicinal hydrogen atoms from a hydrocarbon. The discovery of this exothermic, net redox process was enabled by the simple thermal generation of reactive benzyne intermediates through the hexadehydro-Diels–Alder cycloisomerization reaction of triyne substrates6. We are not aware of any single-step, bimolecular reaction in which two hydrogen atoms are simultaneously transferred from a saturated alkane. Computational studies indicate a preferred geometry with eclipsed vicinal C–H bonds in the alkane donor.

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Figure 1: Introduction and background.
Figure 2: Both hydrogen atoms come from the same donor molecule.
Figure 3: Dihydrogen transfer between arynes and cyclic hydrocarbons.

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Acknowledgements

We thank C. J. Cramer for helpful discussions about the computational studies. D.N. and P.H.W. thank the University of Minnesota Graduate School Doctoral Dissertation Fellowship and National Science Foundation Graduate Research Fellowship program, respectively. Financial support from the National Institute of General Medical Sciences (GM65597) and the National Cancer Institute (CA76497) of the US Department of Health and Human Services is acknowledged. Portions of this work were performed with hardware and software resources available through the University of Minnesota Supercomputing Institute (MSI).

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D.N. made the initial key observations and performed most of the scope studies. P.H.W. performed most of the mechanistic studies. B.P.W. and B.B. also performed aspects of the experimental work. All authors interpreted the data and wrote the manuscript.

Corresponding author

Correspondence to Thomas R. Hoye.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains General Experimental Protocols; Preparation procedures and Characterization data for all new compounds; Computational details for double hydrogen atom transfer reactions; Supplementary References and Copies of 1H and 13C NMR spectra of all new compounds (see Contents list for details). (PDF 4471 kb)

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Niu, D., Willoughby, P., Woods, B. et al. Alkane desaturation by concerted double hydrogen atom transfer to benzyne. Nature 501, 531–534 (2013). https://doi.org/10.1038/nature12492

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