Rapid synthesis of arylgold compounds using dielectric heating

Article abstract of DOI:10.1039/c2dt32129g

Dielectric heating has been successfully used in the preparation of a range of arylgold compounds. The approach is tolerant of a number of functional groups and rapidly generates the organometallic complexes in moderate to excellent yields.

Full text of DOI:10.1039/c2dt32129g

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Rapid synthesis of arylgold compounds using dielectric heating†
Heather K. Lenker,a Thomas G. Grayb and Robert A. Stockland Jr.*a
Received 21st August 2012, Accepted 14th September 2012
DOI: 10.1039/c2dt32129g
microwave assisted preparation of metal carbonyls could be
monitored using Raman spectroscopy.26
Dielectric heating has been successfully used in the prepa-
ration of a range of arylgold compounds. The approach is
tolerant of a number of functional groups and rapidly gener-
ates the organometallic complexes in moderate to excellent
yields.
ð1Þ
ð2Þ
Arylgold species are valuable compounds due to their appli-
cations as emissive materials,1,2 intermediates in organic trans-
formations,3,4 and metallodrug research.5,6 Recent work suggests
the use of (indolyl)gold(I) agents as potentiators of therapeutic
ionizing radiation.6b Furthermore, the ability of arylgold com-
pounds to readily transfer the aryl fragment to another metal
center has given rise to the use of arylgold complexes as trans-
metallating agents in palladium catalyzed cross-coupling reac-
tions.7,8 These organometallic complexes are commonly
prepared through the treatment of chlorogold precursors with
Grignard or organolithium reagents9,10 or tetraphenylborate.11
While often successful, this methodology suffers from signifi-
cant functional group intolerance.12 Recently, Gray and co-
workers have shown that the use of arylboronic acids or boronate
esters effectively arylates LAuX species (L = phosphine,
N-heterocyclic carbene; X = Br, Cl).13,14 This approach is attrac-
tive due to the mild reaction conditions and the wide range of
readily available arylboronic acids.
The use of dedicated microwave reactors for the synthesis
of organic compounds has rapidly expanded over the past
decade.15–18 However, the use of these reactors for the prep-
aration of organometallic compounds is comparatively rare.19–21
One of the earliest reports of organometallic synthesis using
dielectric heating focused on the preparation of rhodium
dimers.22 Recently, Navarro reported the microwave assisted syn-
thesis of (NHC)MCl (eqn (1); NHC = N-heterocyclic carbene;
M = Au, Cu, Ag) species,23 Carlsson reported the synthesis of
alkynylplatinum compounds using a focused microwave reactor
(eqn (2)),24 Kappe demonstrated that the synthesis of Grignard
reagents was significantly accelerated using a focused microwave
reactor,25 and elegant work by Leadbeater established that the
To determine if the preparation of arylgold compounds could
be aided through the use of dielectric heating, the arylation of
JohnPhosAuCl using phenylboronic acid was investigated as a
model system. The dialkylbiarylphosphine ligands were selected
for this investigation since they are often used to generate static
organogold complexes.27 The conventionally heated reactions
i
used PrOH as the solvent and Cs2CO3 as the base (50–60 °C,
i
24–60 h). Using this as a starting point, irradiating a PrOH
suspension of the reagents at 100 °C for 1 h resulted in the gen-
eration of a significant amount of metallic gold and an intractable
mixture of products. Lowering the temperature to 70 °C mini-
mized the generation of metallic gold, however, significant
amounts of free arene were still observed. After screening
several solvents, THF was selected as the solvent for these reac-
tions as its use afforded high yields of the arylgold compounds
and minimized the generation of the free arene. Further experi-
mentation determined that excellent yields of the arylgold com-
pound were obtained after only 20 minutes of irradiation.
Purification by column chromatography (basic alumina) afforded
high yields of JohnPhosAu(C6H5) (1).
After a successful system for the preparation of 1 was devised,
the chemistry was extended to a range of arylboronic acids
(Table 1). For most examples, using the conditions developed
for the synthesis of 1 afforded high yields of the new arylgold
compounds (70 °C, 30 min). The metallation reaction was not
sensitive to electronic manipulation of the aryl boronic acid as
both electron withdrawing and electron donating groups were
well tolerated. Furthermore, heteroaryl groups were also readily
added to the metal center. The successful use of benzothio-
phene-2-boronic acid (Table 1: compounds 5, 19) in this chem-
istry is particularly noteworthy as α-heteroatom substituted
arylboronic acids are prone to protodeboronation reactions when
used as transmetallating agents.7
aDepartment of Chemistry, Bucknell University, 701 Moore Ave.,
Lewisburg, PA, USA. E-mail: rstockla@bucknell.edu;
Fax: +1 570-577-1739; Tel: +1 570-577-1665
bDepartment of Chemistry, Case Western Reserve University, 10900
Euclid Avenue, Cleveland, Ohio 44106-7078, USA.
Arylation reactions using substrates with ortho-substituents
are often low yielding and prone to the generation of secondary
products. The microwave assisted chemistry described herein
was quite tolerant of a single group in the ortho position
E-mail: tgray@case.edu; Fax: +1 216-368-3006; Tel: +1 216-368-0991
†Electronic supplementary information (ESI) available: Synthetic pro-
cedures and NMR spectra for all arylgold compounds. See DOI:
10.1039/c2dt32129g
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Table 1 Preparation of arylgold compoundsa,c
ligand project over the gold center and effectively block access
to a portion of the metal. Despite the increased steric hindrance,
the arylation reactions involving the bulkier BuXPhos ligand
t
generated high yields of the arylgold compounds after only
30 minutes of irradiation at 70 °C. The reactions using tBuXPhos
also showed great tolerance to variations in the electronics and
the presence of heteroaryl groups. The aryl boronic acids bearing
single ortho-substituents were well tolerated, and the transfer of
mesityl groups or 9-bromoanthracene required slightly longer
reaction times and the use of iPrOH as the solvent.
In summary, the use of microwave irradiation to assist in the
preparation of arylgold compounds has been established. In most
cases, excellent yields of the organometallic compounds were
observed after only 30 minutes of irradiation.
The authors thank the National Science Foundation (grant
CHE-1057659 to T. G. G.) and for the funds to purchase the
NMR spectrometer (CHE-0521108), the Petroleum Research
Fund (51819-UR1 to R. A. S.), Bucknell University for a
Scadden Research Fellowship (R. A. S.) and an Undergraduate
Research Fellowship (H. K. L.). The authors thank Professor
David Rovnyak for helpful discussions.
Notes and references
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t
a Reaction conditions: JohnPhosAuCl (0.19 mmol) or BuXPhosAuCl
(0.15 mmol), ArB(OH)2 (2 equiv), Cs2CO3 (2 equiv), 1.5 mL THF or
iPrOH (for 10, 13, 24, 27), 70 °C, 30 min, focused microwave reactor.
b 90 min. c Isolated yields. JohnPhos = di(tert-butyl)(1,1′-biphenyl-2-yl)-
t
phosphine; BuXPhos = di-tert-butyl(2′,4′,6′-triisopropylbiphenyl-2-yl)-
phosphine. MWI = microwave irradiation.
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(Table 1, compounds 4 and 18); however, adding a second ortho
substituent resulted in lower yields of the arylgold compounds.
Following the progress of the reactions by 31P NMR revealed
incomplete consumption of JohnPhosAuCl. To circumvent this
issue, the battery of solvents and reaction conditions were
rescreened using the bulky arylboronic acids in order to find a
successful match. It was found that changing the solvent to
iPrOH and increasing the reaction time to 90 minutes consumed
the starting material (Table 1: compounds 10, 13, 24, 27). The
drawback to the use of PrOH as the solvent was the generation
of the free arene. This secondary product was separated by
column chromatography or extraction with hexane.
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tBuXPhosAuCl was used as the gold precursor. The bulky iso-
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