Angewandte
Chemie
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Catalytic C H amination is an attractive strategy to prepare
promise of C H amination. A recent report of N-alkylcarba-
[1–3]
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C N bonds without the need for a pre-functionalized site.
zole formation by Pd-catalyzed intramolecular C H amina-
This approach offers substantial opportunities to streamline
chemical syntheses by decreasing the number of functional-
group manipulations such as “hydroxyl to amine”.[4] An
appealing feature of this and related catalytic C H function-
alization reactions is that protection steps may not be
required for these transformations—the relative inertness of
tion of biphenylamines is a notable exception.[15]
We recently described the isolation of the b-diketiminato
dicopper nitrene [{(Cl2NN)Cu}2(m-NAd)] from reaction of
[{(Cl2NN)Cu}2(benzene)] with the organoazide N3Ad
(Scheme 1; Ad = 1-adamantyl).[16] This species reacts readily
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the C H bond insulates it from many traditional functional
group modifications.[3,5] The ability to directly effect the C H
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to C N transformation without the need to isolate, purify, and
transform oxidized precursors promises reduced cost, energy
consumption, and environmental impact.
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There are a growing number of C H amination catalysts
3
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that allow for sp -C N bond formation compatible with
multistep syntheses of complex molecules.[1,3,5,6] While typi-
cally based on expensive metals like Rh[7] and Ru,[8] catalysts
employing base metals such as Fe,[9] Co,[10] and Cu[11,12] have
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Scheme 1. Nitrene-based stoichiometric and catalytic C H amination.
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been successfully demonstrated. Existing C H amination
methods typically employ nitrogen sources bearing powerful
electron-withdrawing groups such as H2NSO2R or
H2NC(O)OR along with oxidants such as PhI(OAc)2 capable
of generating sulfonylnitrene (N-SO2R) or carbamoylnitrene
(N-C(O)OR) intermediates in the presence of a transition
metal catalyst; in some cases simple organic amides
H2NC(O)R may be employed.[12] Complementary approaches
with hydrocarbons to formally insert the nitrene moiety NAd
3
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into sp -hybridized C H bonds under both stoichiometric and
catalytic conditions. We were eager to examine the related
copper(II) amide [(Cl2NN)Cu-NHAd] as a potential inter-
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mediate formed by H-atom abstraction (HAA) of a C H
bond by
a
terminal copper–nitrene intermediate
[16,17]
=
[(Cl2NN)Cu NR].
For instance, the b-diketiminato
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=
inlcude Pd-based allylic C H amination with HNTs-
nickel nitrene [(Me3NN)Ni NAd] reacts with 1,4-cyclohex-
(COOMe) (Ts = tosyl)[13] or Cu-based benzylic and allylic
amination with HNMe(SO2Ph).[14] In most circumstances use
of these methods in complex molecule synthesis requires
N-based deprotection of the activating group followed by
refunctionalization, thus detracting from the atom-economic
adiene by HAA to give [(Me3NN)Ni-NHAd].[18]
Herein we describe synthetic studies that target a
copper(II) amide intermediate in C H amination
reveal a bifunctional role for [(Cl2NN)Cu-NHAd] in stoi-
chiometric C H functionalization and result in a new system
[19,20]
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which
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for catalytic intermolecular C H amination with simple,
unactivated alkylamines.[21] Since N-based activating groups
are not required, the method promises broader amine
[*] S. Wiese, Dr. Y. M. Badiei, R. T. Gephart, Dr. M. S. Varonka,
Dr. M. M. Melzer, Prof. T. H. Warren
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substrate scope than found in known C H amination systems.
Department of Chemistry, Georgetown University
Box 571227, Washington, DC 20057-1227 (USA)
Fax: (+1)202-687-6209
Addition of Li(Cl2NN) to anhydrous CuCl2 gives the
dinuclear b-diketiminato copper(II) chloride [{(Cl2NN)Cu}2-
(m-Cl)2] (1) in 79% yield as green crystals.[22] Reaction of 1
with LiNHAd in Et2O at ꢀ358C immediately produces a deep
purple solution from which the corresponding copper(II)
amide [(Cl2NN)Cu-NHAd] (2) may be isolated as thermally
sensitive purple crystals from pentane in 50–70% yield
(Scheme 2).
E-mail: thw@georgetown.edu
Prof. T. R. Cundari
Department of Chemistry
Center for Advanced Scientific Computing and Modeling (CASCaM)
University of North Texas, Denton, TX 78203 (USA)
E-mail: t@unt.edu
Dr. S. Mossin,[+] Prof. Dr. K. Meyer
Department of Chemistry and Pharmacy
Friedrich-Alexander-University Erlangen-Nꢀrnberg
Egerlandstrasse 1, 91058 Erlangen (Germany)
The X-ray structure of 2 exhibits a three-coordinate
copper center with a short Cu Namido bond of 1.839(9) ꢀ
(Scheme 2 and Figure S33 in the Supporting Information).
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[+] Current address: Centre for Catalysis and Sustainable Chemistry
Department of Chemistry, Technical University of Denmark
2800 Kgs Lyngby (Denmark)
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The Cu Namido bond is similar to that in the recently reported
b-diketiminato copper(II) amide [(Me2NN)Cu-NPh2]
(1.841(6) ꢀ)[19] and shorter than in the three-coordinate
k -[{Ph2B(CH2PtBu)2}Cu-N(p-tolyl)2] (Cu N 1.906(2) ꢀ)
2
[23]
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[**] The authors acknowledge funding from the National Science
Foundation (CHE-0716304 to T.H.W.; CHE-0701247 and CHE-
0741936 to T.R.C), the Deutsche Forschungsgemeinschaft (SFB
583), the Alexander von Humboldt Foundation (re-invitation award
to T.H.W.), and the Chemical Computing Group (MOE software to
T.R.C.). Y.M.B. thanks Georgetown University for a Dissertation
Fellowship and M.M.M. is grateful to the Luce Foundation for a pre-
doctoral fellowship.
which was described as a copper(I)–aminyl radical com-
plex.[24] The X-ray structure of 2 is distinct from that of the
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simple amine adduct [(Cl2NN)Cu(NH2Ad)] (Cu Namine
1.970(2) ꢀ; Cu-N-C 117.69(11)8; Figure S34).
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Copper amide 2 is reactive towards benzylic C H bonds
at room temperature (Scheme 2). Reaction of 2 equivalents
of 2 with ethylbenzene or indane (100 equiv in heptane) at
room temperature for 24 h results in formation of PhCH-
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2010, 49, 8850 –8855
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
8851