.
Angewandte
Communications
PdI Catalysts
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Highly Efficient C SeCF3 Coupling of Aryl Iodides Enabled by an
Air-Stable Dinuclear PdI Catalyst**
Marialuisa Aufiero, Theresa Sperger, Althea S.-K. Tsang, and Franziska Schoenebeck*
Abstract: Building on our recent disclosure of catalysis at
dinuclear PdI sites, we herein report the application of this
concept to the realization of the first catalytic method to
convert aryl iodides into the corresponding ArSeCF3 com-
ity which in turn are of relevance to numerous branches of
chemistry.[7] In this context, the trifluoromethylselenide group
(SeCF3) is a promising target for agrochemical and pharma-
ceutical research as it features several important properties
that control membrane permeability and bioavailability.[8]
Although excess selenium is toxic to humans because it
replaces sulfur in several metabolic processes without mim-
icking its function,[9] at lower (subtoxic) doses selenium is an
essential nutrient to humans and other living systems.[10]
Moreover, it has recently stimulated increasing attention
because of its therapeutic and preventive effects against
several kinds of cancer, in particular prostate and colorectal
cancer.[11] Straightforward access to fluorinated analogues, in
particular ArSeCF3 compounds may hence enable various
avenues in chemical and biomedical research.
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pounds. Highly efficient C SeCF3 coupling of a range of aryl
iodides was achieved, enabled by an air-, moisture-, and
thermally stable dinuclear PdI catalyst. The novel SeCF3-
bridged dinuclear PdI complex 3 was isolated, studied for its
catalytic competence and shown to be recoverable. Exper-
imental and computational data are presented in support of
dinuclear PdI catalysis.
W
hile nature makes use of the synergistic interplay of two
(or more) metals in many metalloenzymes,[1] the field of
homogeneous cross-coupling catalysis is dominated by the
reactivity of mononuclear metal complexes, in particular well-
defined Pd(0) complexes.[2] Dinuclear PdI-PdI complexes have
been known for the past 70 years,[3] but their application in
catalysis has been primarily limited to being labile off-cycle
precursors to the active Pd(0) complexes.[4] In contrast our
group recently established that more robust dinuclear PdI
complexes that are less prone to the release of Pd(0) may
function directly as catalysts in cross-coupling of aryl halides
by alternative coupling cycles.[5,6] In this context we recently
succeeded in the catalytic I/Br halogen exchange[5a,b] and the
trifluoromethylthiolation of aryl halides,[5c] employing the
iodine-bridged PdI-dimer 1. Notable practical advantages of
this concept are the air-stability of 1 and the straightforward
recoverability of the dinuclear entity after reaction comple-
tion, avoiding the handling of sensitive Pd(0) complexes or
ligands. Building on this work, we herein report the first
catalytic method to synthesize ArSeCF3 compounds.
However, the synthetic access to this class of compounds
is limited, relying on indirect synthetic approaches[12] which
often have a small substrate scope or which require the
employment of stoichiometric amounts of metal salts.[13] To
date, no direct catalytic route to aryltrifluoromethyl selenides
exists. While palladium-catalyzed cross coupling is arguably
the method of choice to install carbon–heteroatom bonds in
a catalytic fashion, little progress has been made in the Pd-
catalyzed synthesis of ArSeR[14] where R = CF3 and also more
generally (i.e. for R ¼ CF3). The current state of the art relies
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on a Stille approach with the use of Bu3Sn SePh as coupling
partner.[15] This approach would generate stoichiometric
amounts of potentially toxic stannane by-products, thus our
objective was instead to develop an operationally simple and
general method that minimizes the generation of waste.
Ideally, this involves convenient and air-stable reagents.
Following our detailed fundamental studies, we recently
succeeded in a highly efficient cross-coupling reaction trig-
gered by a dinuclear PdI complex.[5] Our mechanistic data of
this coupling process were consistent with the mechanism
presented in Figure 1. Key to effective catalysis is that the
The embedding of fluorine into organic molecules sig-
nificantly alters their physical properties. These include
conformational, solubility, lipophilicity, and metabolic stabil-
[*] M. Aufiero, T. Sperger, Dr. A. S.-K. Tsang, Prof. Dr. F. Schoenebeck
Institute of Organic Chemistry
RWTH Aachen University
Landoltweg 1, 52074 Aachen (Germany)
E-mail: franziska.schoenebeck@rwth-aachen.de
M. Aufiero
ETH Zürich, Laboratory for Organic Chemistry
Vladimir-Prelog-Weg 3, 8093 Zürich (Switzerland)
[**] We thank the RWTH Aachen, the MIWF NRW, ETH Zürich
(studentship to M.A.) and Evonik (doctoral scholarship to T.S.) for
funding. We are grateful to the Small Molecule Crystallography
Center at ETH for analysis of 3, and I. A. Sanhueza for LogP values.
Supporting information for this article is available on the WWW
Figure 1. Anticipated PdI-dimer catalyzed C–SeCF3 coupling.
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ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 10322 –10326