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Alkane desaturation by concerted double hydrogen atom transfer to benzyne.

Niu D, Willoughby PH, Woods BP, Baire B, Hoye TR - Nature (2013)

Bottom Line: 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).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 substrates.Computational studies indicate a preferred geometry with eclipsed vicinal C-H bonds in the alkane donor.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA.

ABSTRACT
The removal of two vicinal hydrogen atoms from an alkane to produce an alkene is a challenge for synthetic chemists. In nature, desaturases and acetylenases are adept at achieving this essential oxidative functionalization reaction, for example during the biosynthesis of unsaturated fatty acids, eicosanoids, gibberellins and carotenoids. 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 substrates. 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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Dihydrogen transfer between arynes and cyclic hydrocarbonsa. Relative efficiency (% yield and krel vs. cyclopentane) of various hydrocarbon (and cyclic ether) 2H-donors for the reduction of aryne13 to arene14. For tabular inset notes a-f see Supplementary Information. b, A representative No-D 1H NMR22 spectrum [this of the reaction solution arising from heating 12 (at 10 mM) in a 1.5:1 molar ratio of cyclopentane:cyclooctane at 95 °C]; thisshows the overall efficiency of the reaction and validates the krel value (1:2.6) obtained as described above. c, Computed TS geometries and ΔG‡ for transfer of two hydrogen atoms to benzyne (3) from cyclopentane (15a) and cyclohexane (15b). d, Reduced benzenoid products 16a-g generated by heating the triyne precursor in cyclooctane under the indicated conditions (starting substrate concentration of 10mM).
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Figure 3: Dihydrogen transfer between arynes and cyclic hydrocarbonsa. Relative efficiency (% yield and krel vs. cyclopentane) of various hydrocarbon (and cyclic ether) 2H-donors for the reduction of aryne13 to arene14. For tabular inset notes a-f see Supplementary Information. b, A representative No-D 1H NMR22 spectrum [this of the reaction solution arising from heating 12 (at 10 mM) in a 1.5:1 molar ratio of cyclopentane:cyclooctane at 95 °C]; thisshows the overall efficiency of the reaction and validates the krel value (1:2.6) obtained as described above. c, Computed TS geometries and ΔG‡ for transfer of two hydrogen atoms to benzyne (3) from cyclopentane (15a) and cyclohexane (15b). d, Reduced benzenoid products 16a-g generated by heating the triyne precursor in cyclooctane under the indicated conditions (starting substrate concentration of 10mM).

Mentions: We now report a double hydrogen atom (2H) transfer reaction in which a HDDA-generated benzyne simultaneously accepts two vicinal hydrogen atoms from a suitable alkane 2H-donor (H–Csp3Csp3–H). This gives the corresponding (oxidized) alkene and (reduced) benzenoid products. For example, when we heated triyne 8 in cyclooctane to 85 °C, the only isolated product (89%) was the reduced fluorenone derivative 10-h2 (Fig. 2a). Using 1H NMR spectroscopy, we observed that a comparable amount of cyclooctene had been formed via desaturation15 (see Fig. 3b). The only well-characterized example of benzyne reduction via the net addition of two hydrogen atoms is the work of Sterenberg and coworkers in which a benzyne intermediate derived from a bis-diyne-bridged, dinuclear metal complex was reduced to the arene16. They demonstrated that the solvent (THF) was the source of the hydrogen (and, in the case of THF-d8, deuterium17) atoms that appeared in the reduced benzenoid product. When we heated substrate 8 in THF-h8, 10-h2 was the only product isolated (75%, Fig. 2a). Similarly, when 8 was heated in THF-d8, the dideuterated analog 10-d2 (MS and 1H NMR) was the only isolated product.


Alkane desaturation by concerted double hydrogen atom transfer to benzyne.

Niu D, Willoughby PH, Woods BP, Baire B, Hoye TR - Nature (2013)

Dihydrogen transfer between arynes and cyclic hydrocarbonsa. Relative efficiency (% yield and krel vs. cyclopentane) of various hydrocarbon (and cyclic ether) 2H-donors for the reduction of aryne13 to arene14. For tabular inset notes a-f see Supplementary Information. b, A representative No-D 1H NMR22 spectrum [this of the reaction solution arising from heating 12 (at 10 mM) in a 1.5:1 molar ratio of cyclopentane:cyclooctane at 95 °C]; thisshows the overall efficiency of the reaction and validates the krel value (1:2.6) obtained as described above. c, Computed TS geometries and ΔG‡ for transfer of two hydrogen atoms to benzyne (3) from cyclopentane (15a) and cyclohexane (15b). d, Reduced benzenoid products 16a-g generated by heating the triyne precursor in cyclooctane under the indicated conditions (starting substrate concentration of 10mM).
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getmorefigures.php?uid=PMC3818522&req=5

Figure 3: Dihydrogen transfer between arynes and cyclic hydrocarbonsa. Relative efficiency (% yield and krel vs. cyclopentane) of various hydrocarbon (and cyclic ether) 2H-donors for the reduction of aryne13 to arene14. For tabular inset notes a-f see Supplementary Information. b, A representative No-D 1H NMR22 spectrum [this of the reaction solution arising from heating 12 (at 10 mM) in a 1.5:1 molar ratio of cyclopentane:cyclooctane at 95 °C]; thisshows the overall efficiency of the reaction and validates the krel value (1:2.6) obtained as described above. c, Computed TS geometries and ΔG‡ for transfer of two hydrogen atoms to benzyne (3) from cyclopentane (15a) and cyclohexane (15b). d, Reduced benzenoid products 16a-g generated by heating the triyne precursor in cyclooctane under the indicated conditions (starting substrate concentration of 10mM).
Mentions: We now report a double hydrogen atom (2H) transfer reaction in which a HDDA-generated benzyne simultaneously accepts two vicinal hydrogen atoms from a suitable alkane 2H-donor (H–Csp3Csp3–H). This gives the corresponding (oxidized) alkene and (reduced) benzenoid products. For example, when we heated triyne 8 in cyclooctane to 85 °C, the only isolated product (89%) was the reduced fluorenone derivative 10-h2 (Fig. 2a). Using 1H NMR spectroscopy, we observed that a comparable amount of cyclooctene had been formed via desaturation15 (see Fig. 3b). The only well-characterized example of benzyne reduction via the net addition of two hydrogen atoms is the work of Sterenberg and coworkers in which a benzyne intermediate derived from a bis-diyne-bridged, dinuclear metal complex was reduced to the arene16. They demonstrated that the solvent (THF) was the source of the hydrogen (and, in the case of THF-d8, deuterium17) atoms that appeared in the reduced benzenoid product. When we heated substrate 8 in THF-h8, 10-h2 was the only product isolated (75%, Fig. 2a). Similarly, when 8 was heated in THF-d8, the dideuterated analog 10-d2 (MS and 1H NMR) was the only isolated product.

Bottom Line: 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).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 substrates.Computational studies indicate a preferred geometry with eclipsed vicinal C-H bonds in the alkane donor.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA.

ABSTRACT
The removal of two vicinal hydrogen atoms from an alkane to produce an alkene is a challenge for synthetic chemists. In nature, desaturases and acetylenases are adept at achieving this essential oxidative functionalization reaction, for example during the biosynthesis of unsaturated fatty acids, eicosanoids, gibberellins and carotenoids. 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 substrates. 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.

Show MeSH
Related in: MedlinePlus