Efficient Solvent-Free Selective Monoalkylation of Arylacetonitriles
with Mono-, Bis-, and Tris-primary Alcohols
Catalyzed by a Cp*Ir Complex
Christian Lo¨fberg,† Ronald Grigg,*,† Mark A. Whittaker,† Ann Keep,‡ and Andrew Derrick§
Molecular, InnoVation, DiVersity, and Automated Synthesis (MIDAS) Centre, Department of Chemistry,
UniVersity of Leeds, LS2 9JT, United Kingdom, Johnson Matthey, Orchard Road, Royston, Hertz,
SG8 5HE, United Kingdom, and Pfizer, Ramsgate Road, Sandwich, Kent, CT13 9NJ, United Kingdom
ReceiVed May 31, 2006
Our objectives were to develop catalytic atom-economic processes accessing and/or incorporating versatile
functionality using aryl/heteroaryl acetonitriles as substrates. We report essentially solvent-free [Cp*IrCl2]2
catalyzed redox neutral processes whereby substituted acetonitriles react with primary alcohols to deliver
monosubstituted aryl/heteroaryl acetonitriles in excellent yield. We further demonstrate that such processes
can be achieved by conventional or microwave heating and that bis- and tris-primary alcohols are also
processed efficiently.
Introduction
of the alkylating agents, the concurrent formation of undesirable
waste salts, and the potential for dialkylated byproducts.7
The application of metal nucleophiles, catalytically generated
in situ, to C-C bond forming processes is a subject of continued
interest.1 The catalytic activation of arylacetonitriles as nucleo-
philes has been reported earlier by our group2 and by Murahashi
et al.3 The importance of R-alkylated nitriles lies in their
potential as versatile building blocks for the construction of
amides, carboxylic acids, ketones, heterocycles, and biologically
active compounds.4,5 Alkylated nitriles are traditionally syn-
thesized using stoichiometric amounts of inorganic bases and
alkyl halides.6 Major drawbacks with this method are the toxicity
Direct catalytic alkylation with alcohols is an attractive green
chemistry solution8 that generates only water as a byproduct.
Recently, Kaneda et al. reported a novel Ru-grafted hydrotalcite
(Ru/HT) possessing both active Ru4+ species and surface base
sites as a multifunctional heterogeneous catalyst for the mono-
alkylation of arylacetonitriles with alcohols.9 Using transfer
hydrogenation methodology, Cho et al. reported the direct
R-alkylation of ketones with alcohols, using a Ru catalyst, to
afford saturated alcohols via the R-alkylated ketone.10 The same
reaction can be performed in the presence of a sacrificial hydro-
† University of Leeds.
‡ Johnson Matthey.
§ Pfizer.
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10.1021/jo061113p CCC: $33.50 © 2006 American Chemical Society
Published on Web 09/09/2006
J. Org. Chem. 2006, 71, 8023-8027
8023