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A manganese catalyst for highly reactive yet chemoselective intramolecular C(sp3)–H amination

Nature Chemistry volume 7, pages 987994 (2015) | Download Citation

Abstract

C–H bond oxidation reactions underscore the existing paradigm wherein high reactivity and high selectivity are inversely correlated. The development of catalysts capable of oxidizing strong aliphatic C(sp3)–H bonds while displaying chemoselectivity (that is, tolerance of more oxidizable functionality) remains an unsolved problem. Here, we describe a catalyst, manganese tert-butylphthalocyanine [Mn(tBuPc)], that is an outlier to the reactivity–selectivity paradigm. It is unique in its capacity to functionalize all types of C(sp3)–H bond intramolecularly, while displaying excellent chemoselectivity in the presence of π functionality. Mechanistic studies indicate that [Mn(tBuPc)] transfers bound nitrenes to C(sp3)–H bonds via a pathway that lies between concerted C–H insertion, observed with reactive noble metals such as rhodium, and stepwise radical C–H abstraction/rebound, as observed with chemoselective base metals such as iron. Rather than achieving a blending of effects, [Mn(tBuPc)] aminates even 1° aliphatic and propargylic C–H bonds, demonstrating reactivity and selectivity unusual for previously known catalysts.

  • Compound C32H16ClFeN8

    iron(III) phthalocyanine chloride

  • Compound C32H16ClMnN8

    manganese(III) phthalocyanine chloride

  • Compound C48H48ClMnN8

    manganese(III) tert-butyl phthalocyanine chloride

  • Compound C10H23NO3S

    3,7-dimethyloctyl sulfamate

  • Compound C10H21NO3S

    4-methyl-4-(4-methylpentyl)-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C9H11NO3S

    4-phenyl-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C6H11NO3S

    (E)-4-(prop-1-en-1-yl)-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C6H13NO3S

    4-propyl-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C5H11NO3S

    5,5-dimethyl-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C14H16N2O5S

    2-((4,4-dimethyl-2,2-dioxido-1,2,3-oxathiazinan-6-yl)methyl)isoindoline-1,3-dione

  • Compound C23H33NO4SSi

    (-)-(R)-6-((S)-1-((tert-butyldiphenylsilyl)oxy)ethyl)-4,4-dimethyl-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C10H17NO3S

    (-)-(3R,4R,6R,7S)-3a,5,5-trimethylhexahydro-3H-4,6-methanobenzo[d][1,2,3]oxathiazole 2,2-dioxide

  • Compound C8H15NO3S

    3-oxa-2-thia-1-azaspiro[5.5]undecane 2,2-dioxide

  • Compound C10H19NO3S

    (+)-(4S,7R,8R)-4,4,7-trimethyloctahydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide

  • Compound C8H15NO5S

    methyl 4-(2,2-dioxido-1,2,3-oxathiazinan-4-yl)butanoate

  • Compound C14H21NO6S2

    4-(2,2-dioxido-1,2,3-oxathiazinan-4-yl)butyl 4-methylbenzenesulfonate

  • Compound C10H19NO3S

    6-(tert-butyl)-2-oxa-3-thia-4-azabicyclo[3.3.1]nonane 3,3-dioxide

  • Compound C10H17NO3S

    (+)-(7S,8aR)-9,9-dimethylhexahydro-5H-4a,7-methanobenzo[e][1,2,3]oxathiazine 2,2-dioxide

  • Compound C5H9NO3S

    4-cyclopropyl-1,2,3-oxathiazolidine 2,2-dioxide

  • Compound C5H9NO3S

    4-vinyl-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C8H13NO5S

    ethyl (E)-3-(2,2-dioxido-1,2,3-oxathiazinan-4-yl)acrylate

  • Compound C15H20N2O7S2

    methyl (E)-(3-(2,2-dioxido-1,2,3-oxathiazinan-4-yl)allyl)(tosyl)carbamate

  • Compound C7H11NO3S

    (±)-hexahydrobenzo[d][1,2,3]oxathiazine 2,2-dioxide

  • Compound C11H17NO3S

    4-((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)-1,2,3-oxathiazolidine 2,2-dioxide

  • Compound C10H11NO3S

    (E)-4-styryl-1,2,3-oxathiazolidine 2,2-dioxide

  • Compound C8H15NO3SSi

    4-((trimethylsilyl)ethynyl)-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C20H31NO7S2Si

    (-)-4-((4R,5S)-5-((tert-butyldimethylsilyl)oxy)-2,2-dioxido-1,2,3-oxathiazinan-4-yl)but-3-yn-1-yl 4-methylbenzenesulfonate

  • Compound C6H11NO5S

    (-)-(4R,7R)-6,6-dimethyltetrahydro-[1,3]dioxolo[4,5-d][1,2,3]oxathiazine 2,2-dioxide

  • Compound C9H11NO3S

    4,4-dimethyl-3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide

  • Compound C14H19NO6S

    tert-butyl (4,4-dimethyl-2,2-dioxido-3,4-dihydrobenzo[e][1,2,3]oxathiazin-7-yl) carbonate

  • Compound C9H10BrNO3S

    4-(4-bromophenyl)-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C10H10F3NO3S

    4-(4-(trifluoromethyl)phenyl)-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C12H15NO5S

    ethyl-4-phenyl-1,2,3-oxathiazinane-6-carboxylate 2,2-dioxide

  • Compound C10H13NO3S

    trans-5-methyl-4-phenyl-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C11H15NO3S

    5,5-dimethyl-4-phenyl-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C14H16N2O5S2

    6-methyl-4-(1-(phenylsulfonyl)-1H-pyrrol-3-yl)-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C18H18N2O5S2

    6-methyl-4-(1-(phenylsulfonyl)-1H-indol-3-yl)-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C12H14N2O5S

    3-(4-(2,2-dioxido-1,2,3-oxathiazinan-4-yl)phenyl)oxazolidin-2-one

  • Compound C11H11N3O4S

    4-(4-(1,3,4-oxadiazol-2-yl)phenyl)-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C18H16N2O4S

    4-(4,5-diphenyloxazol-2-yl)-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C10H21NO3S

    (E)-2-methylnon-7-en-4-yl sulfamate

  • Compound C13H21NO3S

    5-methyl-1-phenylhexan-3-yl sulfamate

  • Compound C12H25NO3SSi

    2-methyl-8-(trimethylsilyl)oct-7-yn-4-yl sulfamate

  • Compound C9H21NO3S

    2-methyloctan-4-yl sulfamate

  • Compound C9H12DNO3S

    3-phenylpropyl-3-d sulfamate

  • Compound C9H13NO3S

    3-phenylpropyl sulfamate

  • Compound C9H11D2NO3S

    3-phenylpropyl-3,3-d2 sulfamate

  • Compound C6H13NO3S

    (Z)-hex-4-en-1-yl sulfamate

  • Compound C6H15NO3S

    (R)-3-methylpentyl sulfamate

  • Compound C6H13NO3S

    (+)-(R)-4-ethyl-4-methyl-1,2,3-oxathiazinane 2,2-dioxide

  • Compound C16H23NO8S

    (+)-tetrahydropicrotoxin-3-(2,2-dioxido-1,2,3-oxathiazinan-3-yl)-15-methyl ester

  • Compound C21H31NO4S

    (-)-3,4-(2,2-dioxido-1,2,3-oxathiazinan-3-yl)-pregnenolone

  • Compound C29H47NO3S

    (-)-3,4-(2,2-dioxido-1,2,3-oxathiazinan-3-yl)-stigmasterol

  • Compound C28H33N3O7S

    (-)-12-sulfamoyloxy-(N-nitroisoindolyl)dihydroabietylamine

  • Compound C28H31N3O7S

    (-)-12,15-(2,2-dioxido-1,2,3-oxathiazinan-3-yl)-(N-nitroisoindolyl)dihydroabietylamine

  • Compound C20H33NO4S

    (-)-18-sulfamoyloxy-13-methyl-17-norkauran-16-one

  • Compound C20H31NO4S

    (-)-3,18-(2,2-dioxido-1,2,3-oxathiazinan-3-yl)-13-methyl-17-norkauran-16-one

  • Compound C28H38N4O3

    (-)-3-(benzylcarbamoyl)-18-azido-13-methyl-17-norkauran-16-one

  • Compound C30H41NO5

    (-)-3-(benzylcarbamoyl)-18-acetoxy-13-methyl-17-norkauran-16-one

  • Compound C31H51NO5S

    (+)-3-(sulfamoyloxy) betulinic acid methyl ester

  • Compound C31H49NO5S

    (-)-3,23-(2,2-dioxido-1,2,3-oxathiazinan-3-yl)-24-methyl betulinic acid methyl ester

  • Compound C24H37NO9S

    (+)-(7S)-sulfamoyloxy-dihydropleuromutilone acetate

  • Compound C24H35NO9S

    (-)-7,16-(2,2-dioxido-1,2,3-oxathiazinan-3-yl)-dihydropleuromutilone acetate

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Acknowledgements

Financial support for this work was provided by the NIH/NIGMS (GM112492). S.M.P. was a NSF Graduate Research Fellow, J.R.G is a NSF Graduate Research Fellow and a Springborn Graduate Fellow, J.P.Z. is a R.C. Fuson graduate fellow, and S.M.M. is a UIUC Summer Undergraduate Research Fellow. The authors thank Bristol-Myers-Squibb for generous support with an unrestricted ‘Freedom to Discover’ grant to M.C.W. and acknowledge J.M. Howell, J.R. Clark and C.C. Pattillo for checking our experimental procedure. The authors thank J. Bertke and D. Gray for crystallographic analysis of compound 56, L. Zhu for assistance with NMR data analysis, and D. Loudermilk for creative graphic assistance.

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Author notes

    • Shauna M. Paradine
    •  & Jennifer R. Griffin

    These authors contributed equally to this work

    • Shauna M. Paradine

    Harvard University, Cambridge, Massachusetts, USA

Affiliations

  1. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA

    • Shauna M. Paradine
    • , Jennifer R. Griffin
    • , Jinpeng Zhao
    • , Aaron L. Petronico
    • , Shannon M. Miller
    •  & M. Christina White

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Contributions

S.M.P., J.R.G., J.P.Z., A.L.P. and S.M.M. conducted the experiments and analysed the data. S.M.P., J.R.G. and M.C.W. conceived and designed the project, analysed the data and prepared the manuscript.

Competing interests

The University of Illinois has filed a patent application on the [Mn(tBuPc)] catalyst for general C–H functionalizations. The [Mn(tBuPc)] catalyst (prod # 799688) will be offered by Aldrich through a licence from the University of Illinois.

Corresponding author

Correspondence to M. Christina White.

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    Crystallographic data for compound 56

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https://doi.org/10.1038/nchem.2366

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