Angewandte
Chemie
DOI: 10.1002/anie.201402924
Gold-Catalyzed Cross-Coupling
Gold-Catalyzed Allylation of Aryl Boronic Acids: Accessing Cross-
Coupling Reactivity with Gold**
Mark D. Levin and F. Dean Toste*
3
2
a gold aryl species followed by sp2–sp3 reductive elimination
might prove achievable under the influence of a gold catalyst
(Scheme 1B).
À
Abstract: A sp –sp C C cross-coupling reaction catalyzed by
gold in the absence of a sacrificial oxidant is described. Vital to
the success of this method is the implementation of a bimetallic
catalyst bearing a bis(phosphino)amine ligand. A mechanistic
À
hypothesis is presented, and observable transmetalation, C Br
À
oxidative addition, and C C reductive elimination in a model
gold complex are shown. We expect that this method will serve
as a platform for the development of novel transformations
involving redox-active gold catalysts.
T
he air- and water-stability of gold catalysts, coupled with
their ability to promote complex transformations under mild
conditions has attracted considerable interest from the
academic community.[1] Despite the rapid pace of recent
developments, the majority of gold-catalyzed processes rely
on a select few reaction manifolds: 1) Lewis acid catalysis,
2) p-activation, and 3) the generation of carbenoid intermedi-
ates (Scheme 1A).[2] While these modes of reactivity have
yielded important catalytic methodologies of broad scope and
synthetic utility,[3] they are typified by catalytic cycles wherein
gold maintains a +1 oxidation state, in stark contrast to the 2-
electron redox cycles characteristic of late transition metal
catalysis.[4] Indeed, access to AuIII intermediates under
catalytic conditions typically requires strong F+ or I3+
oxidants.[5,6]
Despite this limitation, seminal work by Kochi and
Scheme 1. Reactivity in gold catalysis.
Schmidbaur has shown that AuI complexes oxidatively add
À
alkyl halides, and are further competent to undergo C C
reductive elimination, furnishing formally cross-coupled
products.[7] However, this mode of reactivity has not pre-
viously been realized in a catalytic fashion.
After examining several classes of aryl nucleophiles and
alkyl electrophiles, we found that allyl bromide and phenyl-
boronic acid produced allylbenzene and biphenyl as products
when Ph3PAuCl was used as a catalyst (Table 1, entry 1).
However, we were unable to substantially improve the yield
by implementing other traditional gold catalysts or by
increasing catalyst loading (entries 2–6, 11).
In seeking to improve the reaction, we were drawn to the
observation that closely linked bimetallic gold complexes
undergo accelerated oxidative addition, due to the formation
of AuII–AuII species (rather than discrete AuIII) upon oxida-
tion (Scheme 2).[10] While [dppm(AuCl)2] (dppm = bis(diphe-
nylphosphino)methane) showed considerable instability
under the reaction conditions, the bimetallic complex 1 pro-
duced the desired product in an improved 66% yield.[11]
Intriguingly, the analogous monometallic aminophos-
phine complex 2 afforded substantially lower yield (even at
10% loading), suggesting that the bimetallic catalyst archi-
tecture is responsible for the activity of 1, rather than the
electronic character of the aminophosphine ligand.[12] How-
ever, because monometallic complexes are capable of cata-
lyzing this transformation (albeit with lower efficiency), the
A possible barrier to the implementation of such a redox
cycle is the slow rate at which alkyl–alkyl reductive elimi-
nation occurs.[8] Nevertheless, we were encouraged by our
own recent observations that in contrast, aryl–aryl reductive
elimination from AuIII is remarkably fast.[9] As such, we
hypothesized that a process involving oxidative addition to
[*] M. D. Levin, Prof. Dr. F. D. Toste
Department of Chemistry, University of California, Berkeley
Berkeley, CA 94720 (USA)
E-mail: fdtoste@berkeley.edu
[**] We gratefully acknowledge NIHGMS (RO1 GM073932) for financial
support. M.D.L. thanks the NSF GRFP and ARCS foundation for
graduate research fellowships. We gratefully acknowledge Dr. Yi-
Ming Wang, Andrew V. Samant, and Dr. David A. Nagib for helpful
discussion, and Dr. Antonio DiPasquale for assistance with
collecting and analyzing crystallographic data. Prof. Neal P. Mankad
is thanked for initial investigations into the chemistry of 1 and 8.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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