Article | Published:

Conversion of 1-alkenes into 1,4-diols through an auxiliary-mediated formal homoallylic C–H oxidation

Nature Chemistry volume 6, pages 122125 (2014) | Download Citation

Abstract

The ubiquitous nature of C–H bonds in organic molecules makes them attractive as a target for rapid complexity generation, but brings with it the problem of achieving selective reactions. In developing new methodologies for C–H functionalization, alkenes are an attractive starting material because of their abundance and low cost. Here we describe the conversion of 1-alkenes into 1,4-diols. The method involves the installation of a new Si,N-type chelating auxiliary group on the alkene followed by iridium-catalysed C–H silylation of an unactivated δ-C(sp3)–H bond to produce a silolane intermediate. Oxidation of the C–Si bonds affords a 1,4-diol. The method is demonstrated to have broad scope and good functional group compatibility by application to the selective 1,4-oxygenation of several natural products and derivatives.

  • Compound C24H40O

    3α-Methyl-24-nor-5β-chol-22-ene

  • Compound C14H25NSi

    2-((tert-Butyl(butyl)silyl)methyl)pyridine

  • Compound C16H40O2Si3

    1,5-Di-tert-butyl-3-butyl-1,1,5,5-tetramethyltrisiloxane

  • Compound C19H37NOSi2

    2-[(1-Butyl-3,3,3-triisopropyldisiloxanyl)methyl]pyridine

  • Compound C15H26Si

    Benzyl(tert-butyl)(butyl)silane

  • Compound C15H27NSi

    2-((tert-Butyl(butyl)silyl)methyl)-6-methylpyridine

  • Compound C15H27NSi

    2-((tert-Butyl(butyl)silyl)methyl)-4-methylpyridine

  • Compound C15H27NSi

    2-((tert-Butyl(butyl)silyl)methyl)-3-methylpyridine

  • Compound C15H27NSi

    2-(1-(tert-Butyl(butyl)silyl)ethyl)pyridine

  • Compound C13H24N2Si

    2-((tert-Butyl(butyl)silyl)methyl)pyrimidine

  • Compound C17H25NSi

    8-(tert-Butyl(butyl)silyl)quinolone

  • Compound C12H24N2Si

    2-((tert-Butyl(butyl)silyl)methyl)-1-methyl-1H-imidazole

  • Compound C14H25NSi

    2-((sec-Butyl(tert-butyl)silyl)methyl)pyridine

  • Compound C15H27NSi

    2-((tert-Butyl(pentyl)silyl)methyl)pyridine

  • Compound C16H29NSi

    2-((tert-Butyl(hexyl)silyl)methyl)pyridine

  • Compound C15H27NSi

    2-((sec-Butyl(tert-butyl)silyl)methyl)pyridine

  • Compound C18H33NSi

    2-((tert-Butyl(2-ethylhexyl)silyl)methyl)pyridine

  • Compound C15H27NSi

    2-((tert-Butyl(isopentyl)silyl)methyl)pyridine

  • Compound C20H37NSi

    2-((tert-Butyl(3,7-dimethyloctyl)silyl)methyl)pyridine

  • Compound C16H29NSi

    2-((tert-Butyl(3,3-dimethylbutyl)silyl)methyl)pyridine

  • Compound C19H33NSi

    2-((tert-Butyl((2,2-dimethylcyclohexyl)methyl)silyl)methyl)pyridine

  • Compound C22H31NSi

    2-((tert-Butyl(1-ethyl-1,2,3,4-tetrahydronaphthalen-2-yl)silyl)methyl)pyridine

  • Compound C22H33NSi

    2-((tert-Butyl(2-ethyl-4-phenylbutyl)silyl)methyl)pyridine

  • Compound C28H47NOSi2

    2-((tert-Butyl(4-(4-(tert-butyldimethylsilyloxy)phenyl)-2-ethylbutyl)silyl)methyl)pyridine

  • Compound C23H33NO2Si

    2-(((4-(Benzo[d][1,3]dioxol-5-yl)-2-ethylbutyl)(tert-butyl)silyl)methyl)pyridine

  • Compound C22H32FNSi

    2-((tert-Butyl(2-ethyl-4-(4-fluorophenyl)butyl)silyl)methyl)pyridine

  • Compound C22H32ClNSi

    2-((tert-Butyl(4-(4-chlorophenyl)-2-ethylbutyl)silyl)methyl)pyridine

  • Compound C22H32BrNSi

    2-(((4-(4-Bromophenyl)-2-ethylbutyl)(tert-butyl)silyl)methyl)pyridine

  • Compound C23H32F3NSi

    2-((tert-Butyl(2-ethyl-4-(4-(trifluoromethyl)phenyl)butyl)silyl)methyl)pyridine

  • Compound C31H52N2Si

    N-(4-(3-((tert-Butyl(pyridin-2-ylmethyl)silyl)methyl)pentyl)benzyl)-N-isobutyl-2-methylpropan-1-amine

  • Compound C21H29NSi

    2-((tert-Butyl(2-(1-phenylcyclopropyl)ethyl)silyl)methyl)pyridine

  • Compound C20H33NSi

    2-((tert-Butyl((3,3-dimethylbicyclo[2.2.1]heptan-2-yl)methyl)silyl)methyl)pyridine

  • Compound C21H35NSi

    2-((tert-Butyl((1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)methyl)silyl)methyl)pyridine

  • Compound C34H57NOSi

    2-((tert-Butyl((R)-3-((3R,5R,8R,9S,10S,13R,14S,17R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)butyl)silyl)methyl)pyridine

  • Compound C14H23NSi

    2-((1-tert-Butylsilolan-1-yl)methyl)pyridine

  • Compound C15H25NSi

    2-((1-tert-Butyl-2-methylsilolan-1-yl)methyl)pyridine

  • Compound C18H31NSi

    2-((1-tert-Butyl-3-butylsilolan-1-yl)methyl)pyridine

  • Compound C15H25NSi

    2-((1-tert-Butyl-3-methylsilolan-1-yl)methyl)pyridine

  • Compound C20H35NSi

    2-((1-tert-Butyl-3-(4-methylpentyl)silolan-1-yl)methyl)pyridine

  • Compound C16H27NSi

    2-((1-tert-Butyl-3,3-dimethylsilolan-1-yl)methyl)pyridine

  • Compound C19H31NSi

    2-((2-tert-Butyl-3a-methyloctahydro-1H-benzo[c]silol-2-yl)methyl)pyridine

  • Compound C22H29NSi

    2-(((3S,3aR,9bR)-3-(tert-Butyl)-2,3,3a,4,5,9b-hexahydro-1H-naphtho[2,1-b]silol-3-yl)methyl)pyridine

  • Compound C22H31NSi

    2-((1-tert-Butyl-3-phenethylsilolan-1-yl)methyl)pyridine

  • Compound C28H45NOSi2

    2-((1-tert-Butyl-3-(4-(tert-butyldimethylsilyloxy)phenethyl)silolan-1-yl)methyl)pyridine

  • Compound C23H31NO2Si

    2-((3-(2-(Benzo[d][1,3]dioxol-5-yl)ethyl)-1-tert-butylsilolan-1-yl)methyl)pyridine

  • Compound C22H30FNSi

    2-((1-tert-Butyl-3-(4-fluorophenethyl)silolan-1-yl)methyl)pyridine

  • Compound C22H30ClNSi

    2-((1-tert-Butyl-3-(4-chlorophenethyl)silolan-1-yl)methyl)pyridine

  • Compound C22H30BrNSi

    2-((1-tert-Butyl-3-(4-bromophenethyl)silolan-1-yl)methyl)pyridine

  • Compound C23H30F3NSi

    2-((1-tert-Butyl-3-(4-trifluoromethyl)silolan-1-yl)methyl)pyridine

  • Compound C31H50N2Si

    N-(4-(2-((1-tert-Butyl-1-(pyridin-2-ylmethyl)silolan-3-yl)ethyl)benzyl)-N-isobutyl-2-methylpropan-1-amine

  • Compound C21H27NSi

    2-((2-tert-Butyl-5-phenyl-2-silabicyclo[3.1.0]hexan-2-yl)methyl)pyridine

  • Compound C20H31NSi

    2-[(2-tert-Butyl-3a-methyloctahydro-1H-4,7-methano-2-benzosilol-2-yl)methyl]pyridine

  • Compound C21H33NSi

    2-[(2-tert-Butyl-3a-methyloctahydro-1H-4,7-methano-2-benzosilol-2-yl)methyl]pyridine

  • Compound C34H55NOSi

    2-(((1R,3R)-1-tert-Butyl-3-((3R,5R,8R,9S,10S,13S,14S,17R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)silolan-1-yl)methyl)pyridine

  • Compound C12H22O4

    2-Butylbutane-1,4-diyl diacetate

  • Compound C13H22O4

    (1-Methylcyclohexane-1,2-diyl)dimethanediyl diacetate

  • Compound C16H20O4

    2-((1R(S),2R(S))-2-Acetoxy-1,2,3,4-tetrahydronaphthalen-1-yl)ethyl acetate

  • Compound C14H22O4

    [(1S(R),2S(R),3R(S),4R(S))-2-Methylbicyclo[2.2.1]heptane-2,3-diyl]di(methylene) diacetate

  • Compound C15H24O4

    [(1R,2R,4R)-7,7-Dimethylbicyclo[2.2.1]heptane-1,2-diyl]di(methylene) diacetate

  • Compound C28H46O5

    (R)-2-((3R,5R,8R,9S,10S,13S,14S,17R)-3-Methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)butane-1,4-diyl diacetate

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Acknowledgements

The support of the National Institute of Health (GM-64444) and the National Science Foundation (CHE-1112055) is gratefully acknowledged.

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Affiliations

  1. Department of Chemistry, University of Illinois at Chicago, 845 West Taylor St, Room 4500, Chicago, Illinois 60607, USA

    • Nugzar Ghavtadze
    • , Ferdinand S. Melkonyan
    • , Anton V. Gulevich
    • , Chunhui Huang
    •  & Vladimir Gevorgyan

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Contributions

N.G., F.S.M. and A.V.G. contributed equally to this work. N.G., F.S.M. and A.V.G. designed and performed the experiments and wrote the manuscript. C.H. performed the experiments at an early stage of the project. All authors participated in the discussion of the results. V.G. conceived and guided the research.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Vladimir Gevorgyan.

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DOI

https://doi.org/10.1038/nchem.1841

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