Published on Web 11/11/2005
Scope and Mechanistic Study of the Ruthenium-Catalyzed
ortho-C-H Bond Activation and Cyclization Reactions of
Arylamines with Terminal Alkynes
Chae S. Yi* and Sang Young Yun
Contribution from the Department of Chemistry, Marquette UniVersity,
Milwaukee, Wisconsin 53201-1881
Received August 16, 2005; E-mail: chae.yi@marquette.edu
Abstract: The cationic ruthenium hydride complex [(PCy3)2(CO)(CH3CN)2RuH]+BF4 was found to be a
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highly effective catalyst for the C-H bond activation reaction of arylamines and terminal alkynes. The
regioselective catalytic synthesis of substituted quinoline and quinoxaline derivatives was achieved from
the ortho-C-H bond activation reaction of arylamines and terminal alkynes by using the catalyst Ru3-
(CO)12/HBF4‚OEt2. The normal isotope effect (kCH/kCD ) 2.5) was observed for the reaction of C6H5NH2
and C6D5NH2 with propyne. A highly negative Hammett value (F ) -4.4) was obtained from the correlation
of the relative rates from a series of meta-substituted anilines, m-XC6H4NH2, with σp in the presence of
Ru3(CO)12/HBF4‚OEt2 (3 mol % Ru, 1:3 molar ratio). The deuterium labeling studies from the reactions of
both indoline and acyclic arylamines with DCtCPh showed that the alkyne C-H bond activation step is
reversible. The crossover experiment from the reaction of 1-(2-amino-1-phenyl)pyrrole with DCtCPh and
HCtCC6H4-p-OMe led to preferential deuterium incorporation to the phenyl-substituted quinoline product.
A mechanism involving rate-determining ortho-C-H bond activation and intramolecular C-N bond formation
steps via an unsaturated cationic ruthenium acetylide complex has been proposed.
important polycyclic alkaloids.5 Both intermolecular6 and in-
tramolecular7 oxidative C-H bond activation reactions of indole
Introduction
Considerable research has been directed to the development
of catalytic C-H bond activation methods which are applicable
to the synthesis of biologically important quinolines, indoles,
and related nitrogen heterocyclic compounds.1 In part due to
their innate ability for functional group tolerance, late-transition-
metal catalysts have been found to be suitable for directing
regio- and chemoselective C-H bond activation reactions of
nitrogen compounds. For example, Rh and Ir catalysts have been
successfully utilized for highly regioselective sp2 C-H bond
activation reactions of benzimidazole and related nitrogen
heterocyclic compounds2 and sp3 C-H bond insertion reactions
of amine compounds.3 Chelation control methodology has been
shown to be particularly effective for mediating regioselective
C-H bond activation reactions of nitrogen compounds,4 and
has recently been utilized for the synthesis of pharmaceutically
and pyridine derivatives have recently been achieved by using
Pd, Pt, and Cu catalysts. A remarkably selective catalytic sp3
C-H bond oxidative amination method has been successfully
applied to the synthesis of amino acid derivatives.8
Inspired by recent reports on the unusual reactivity of late-
metal amido complexes,9 we have begun to explore the catalytic
activity of well-defined ruthenium amido complexes for N-H
and other unreactive bond activation reactions.10 We recently
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J. AM. CHEM. SOC. 2005, 127, 17000-17006
10.1021/ja055608s CCC: $30.25 © 2005 American Chemical Society