Gold-Catalyzed Chemoselective Couplings of Polyfluoroarenes with Aryl Germanes and Downstream Diversification

Article abstract of DOI:10.1021/jacs.0c02860

This report describes the chemoselective coupling of polyfluoroarenes with aryl germanes in the presence of aromatic C-I, C-Br, C-Cl, C-OTf, and C-SiMe₃ groups, as well as demonstrates the further downstream diversification to give richly functionalized and highly fluorinated polyarenes. The strategy relies on an in situ Umpolung of the F_nArH, followed by selective Au^(I)/Au^(III)-catalyzed coupling with electron-poor or-rich aryl germanes, even in the presence of challenging ortho-substituents, and widens the currently available coupling space in oxidative gold catalysis to previously inaccessible electron-poor/electron-poor biaryls.

Full text of DOI:10.1021/jacs.0c02860

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Communication
Gold-catalyzed Chemoselective Couplings of Polyfluoroarenes
with Aryl Germanes and Downstream Diversification
Amit Dahiya, Christoph Fricke, and Franziska Schoenebeck
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.0c02860 • Publication Date (Web): 05 Apr 2020
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Amit Dahiya†, Christoph Fricke† and Franziska Schoenebeck*
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
Supporting Information Placeholder
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(a) Attractive Strategy: Direct Arylation with FnAr-H
Challenges with Pd or Cu:
Abstract: This report describes the chemoselective coupling
For:
of polyfluoroarenes with aryl germanes in the presence of
aromatic C-I, C-Br, C-Cl, C-OTf and C-SiMe3 groups, as well as
demonstrates the further downstream diversification to give
Ref. 8,9
. unselective in X1 vs X2
richly functionalized and highly fluorinated polyarenes. The
strategy relies on an in situ Umpolung of the FnArH, followed
by selective Au(I)/Au(III)-catalyzed coupling with electron-
via:
Ref. 19,27
poor or -rich aryl germanes, even in the presence of
challenging ortho-substituents, and widens the currently
available coupling space in oxidative gold catalysis to
previously inaccessible electron-poor/electron-poor biaryls.
Challenge : SEAr as key step ⇒ electron-rich ArH needed
Owing to their unique electronic as well as solubility and
stability enhancing properties,1 polyfluorobiaryl motifs are
important building blocks in functional materials, organic
light emitting diodes (OLEDs),2 metal organic frameworks
(MOFs),3 batteries4 and photovoltaics.5 While they can in
principle be assembled via Pd-catalyzed cross coupling
strategies of the pre-functionalized arenes,6 especially owing
to recent advances by Carrow who developed an efficient
protocol to couple the notoriously unstable polyfluoroaryl
boronic acids with aryl diazonium salts,7 an alternative and
attractive strategy is the direct arylation with FnAr-H via C-H
activation,8,9 as it does not require pre-functionalization of
the polyfluoroarene.6-9
(b) This work: Orthogonal Construction of Biaryl, then Diversification
Access to: meta-biaryl
ortho substitution widened biaryl electronics
. Via:
. Coupling space in Au-catalysis:
electron-rich
Ar–H
Umpolung
Currently
possible
electron-poor
electron-rich
coupling
coupling
partner
THIS WORK
partner
FnAr–H
Priviliged reactivity
electron-poor
Figure 1. Overview of state of the art and this work.
In this context, we envisioned that a powerful approach to
diverse polyfluoroaryls would be to construct the
polyfluorobiaryl via C-H functionalization in the presence of
enabling functionality, which could then allow for further
downstream diversification, and as such unlock access to a
broad range of polyfluorobiaryl compounds that bear
functionalities which may be incompatible with the initial
biaryl formation. In this context, halogens (such as C-I or
C-Br) or orthogonal C-SiR3 groups would be appealing, as
their high (or orthogonal) reactivities in coupling processes
should outcompete potential side reactions with the
polyfluoroaryl motif in later diversifications.
Moreover, over-arylation may also occur if acidic sites
remain in the product (e.g. for tetrafluoroarene).8m Daugulis
showed that copper-catalysis circumvents over-arylation
and tolerates steric hindrance in the biaryl construction;
harsh reaction conditions (120°C) are required however and
site-selective couplings of competing halogen sites have not
been reported.8b,11 Moreover, none of these methods allow
for biaryl construction in the presence of C-iodine bonds,
which are receiving increasing interest in medicinal and
materials chemistry,12 owing to their halogen bonding
properties.13
However, while numerous protocols for polyfluoroarylation
of aryl halides via Pd-catalyzed C-H activation have appeared
since the pioneering work of Fagnou in 2006,8d site-selective
arylations in the presence of additional C-halogen sites are
rare and so far showcased only for specific substrates
(especially non-hindered 4-bromophenyl iodide).9 The
introduction of steric or electronic bias diminishes site-
selectivity.10 Indeed, to the best of our knowledge, there is no
report of coupling with ArFnH at a C-halogen bond that bears
an ortho-substituent in the presence of a competing C-
halogen coupling site. In fact, sterically hindered couplings
proceed best with aryl chlorides, which do not tolerate
additional C-halogen bonds.8j
By contrast, gold catalysis has emerged as a promising
strategy to build biaryls in the presence of C-halogen sites
(including C-I)14,15 via the direct oxidative coupling of arenes
(ArH) with aryl silanes,16 germanes,17 BPin18 or ArH.19,20
However, mechanistically, Au-catalyzed arylations involve as
key step an electrophilic aromatic substitution by the arene
(ArH) at an Au(III) intermediate.14,21,22 Consequently,there are
strict electronic requirements on the reaction partners –
Figure 1b illustrates the currently accessible coupling space,
consisting largely of electron-rich ArH and electron-
neutral/deficient coupling partners.21 In the context of
catalytic FnAr-functionalization, two elegant strategies have
been devised: Nevado showed that FnArBPin can be coupled
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under Au(I)/Au(III) catalysis with ArH at high temperature in
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the presence of C-I or C-Br, but requiring relatively electron-
rich arenes.18,23 More deficient ArH, such as e.g.
monofluoroarene, were unreactive. Larrosa elegantly
showed that FnAr-H in conjunction with silver can be coupled
with highly electron-rich arenes (Ar-H) directly (see Figure
1).19c The FnAr-H is converted to FnAr-Ag, which reacts at
Au(I) 19,24 Following oxidation to FnArAu(III), an electron-rich
.
ArH is then needed in the subsequent electrophilic aromatic
substitution. Both strategies therefore follow the currently
accessible electronic reactivity space (Figure 1), and offer a
regiochemical relationships of the biaryl in accord with
electrophilic aromatic substitution; there is hence limited
access to a meta-substitution-pattern.
We recently found that readily accessible and relatively
inexpensive aryl germanes react efficiently under Au(I)/Au(III)
catalysis with arenes.17,25 We therefore wondered whether
the high reactivity of aryl germanes especially in the
transmetalation at Au(III) might allow us to address the
polyfluoroaryl challenge and widen the currently accessible
coupling space. Building on the previous findings of FnArH
activation by the cooperative effects of silver salt and a gold
catalyst,19a,26 we initially investigated whether such an in situ
generated polyfluoroaryl-Au(III) intermediate would
subsequently react with an aryl germane to the
corresponding biaryl (Figure 2). Building on Larrosa’s
elegant work,19 we synthesized the aryl-Au(I) species 2 via the
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Figure 2. Stoichiometric tests of feasibility of elementary steps.
precedented Ag(I)-assisted C-H activation of C6F5H and
oxidized the resulting Au(I) with in situ formed hypervalent
iodine oxidant [formed from reaction of PhI(OAc)2 with
camphorsulfonic acid (CSA)] to yield Au(III) intermediate 3.18
We subsequently added 4-methoxyaryl germane to the
reaction mixture. Pleasingly, the corresponding biaryl
product 5 was obtained in 45% yield after 2 h at 70 °C.
Interestingly, our analogous test with ArSiMe3 showed no
conversion to the biaryl product in reaction with 3; the
organogermanes are hence privileged reaction partners in
this reactivity.
Table 1. Scope of silver assisted C–H functionalization.
Yields of isolated products are given (1H or 19F NMR quantification in parentheses). aReaction time: 120 h. bFormation of two
regioisomers, ratio given in parentheses. Determined by quantitative 19F NMR. cReaction temperature 100 °C.
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Figure 3. Downstream derivatization of beneficial functional handles after gold catalyzed C-H functionalization with aryl germanes. For
experimental details, see Supporting Information. Reaction conditions: (a) ArSiMe3 (1 equiv.), N-iodosuccinimide (1.2 equiv.), pTsOH
(2 equiv.), CHCl3, rt, 12 h; (b) ArSiMe3 (1 equiv.), NOBF4 (2 equiv.), MeCN, rt, 20 min; (c) ArSiMe3 (1 equiv.), PhI(OCOCF3)2 (1.5 equiv.),
Pd(OAc)2 (5 mol%), AcOH, 80 °C, 17 h; (d) ArSi(Me)(OTMS)2 (1 equiv.), pyrrolidin-2-one (2 equiv.), Cu(OAc)2 (3 equiv.), Na2CO3 (2
equiv.), NaF (2 equiv.), DMSO, 80 °C, 12 h; (e) ArSiMe3 (1 equiv.), ArN2BF4 (2 equiv.), (Ph3P)AuCl (10 mol%), MeCN, blue LED, rt, 12 h;
(f) ArI (1 equiv.), PhMgBr (1.5 equiv.), [(PtBu3)Pd(I)(I)]2 (2.5 mol%), toluene, rt, 5 min; (g) ArI (1 equiv.), CuI (10 mol%),
(DMPU)2Zn(CF2H)2 (2 equiv.), DMPU, 120 °C, 20 h; (h) ArBr (1 equiv.), AlkZnCl∙LiCl (2 equiv.), [(PtBu3)Pd(I)(I)]2 (2.5 mol%), toluene, rt,
5 min; (i) ArBr (1 equiv.), PhMgBr (1.5 equiv.), [(PtBu3)Pd(I)(I)]2 (2.5 mol%), toluene, rt, 5 min.
We were therefore keen to explore whether a catalytic C-
H functionalization of polyfluoroarenes with aryl germanes
was also feasible, which requires the in situ generation of the
challenging in gold-catalysis, requiring extended reaction
times (for 2-F, 2-methyl or 2-OMs),16a or showing no
reactivity at all.30 Mechanistic investigations by Lloyd-Jones
and co-workers identified in this context that whilst ortho-
substituted aryl silanes are activated by gold, large ortho-
substituents must bear coordinating functionality in order
for subsequent reaction of the arene, and thus turnover, to
proceed.30
Pleasingly, with our method, where arene is already
installed on the Au intermediate (Figure 1b), ortho-
substitution was tolerated and hindered biaryls 21, 23 and
24 were efficiently prepared. Even the sterically demanding
2-isopropyl substituted aryl germane yielded the desired
product 24 in good yield.
Importantly, when we used instead trimethyl(p-
tolyl)silane under these conditions, in analogy to the above
stoichiometric experiments (Figure 2), no coupling occurred
under catalytic conditions either, highlighting the privileged
capability of the germane functionality to engage in this type
of Umpolung-enabled coupling process.
Given the lack of reactivity of aryl silanes, we next set out
to test whether we could tolerate silyl functionality in an
intramolecular competition with the germanium group. Such
intramolecular competitions and chemoselective trans-
formations tend to be challenging in gold-catalyzed C-H
functionalizations,owing to instabilities of the functionalities
towards the employed oxidants that may cause their
consumption in unproductive side-reactions.31 Nucleophilic
indole-type substrates are an exception, for which milder
oxidants can be employed and silyl or BPin groups in
intramolecular competitions are successfully tolerated.16b
We were able to fully selectively couple at the GeEt3-site
in 71% yield, while the SiMe3 functionality remained
untouched. As such, using the newly developed coupling with
aryl germanes, the polyfluoro biaryl motif can readily be
3
polyfluoroaryl silver species and its reaction with Au(I)
,
oxidation and transmetalation by ArGeR3.27 Following
explorations of different oxidants and silver sources, it was
found that Ag2O in conjunction with 1-pivaloyloxy-1,2-
benziodoxol-3(1H)-one (PBX) perform optimally and allow
for catalytic C-H functionalization of pentafluorobenzene,
used in excess (5 equiv.), with 4-methoxyaryl germane 4 to
biaryl 5 in excellent 79% yield.28,29
Encouraged by these findings, we subsequently explored
the scope of the C-H functionalization (see Table 1). To our
delight, several fluorinated (5-10) and heterocyclic
polyfluorinated arenes (11 and 12) were functionalized in
good to excellent yields.
Notably, tri-, tetra- and pentafluoroarenes were
successfully coupled, tolerating C-I or the pyridyl nitrogen on
the polyfluoroaryl motif. Even trimethoxy- or naphthyl-
substituted scaffolds yielded the desired biaryls in good
yields (8 and 10), although such compounds previously
resulted in poor mass balances when employed as aryl
germanes (or aryl silanes) in previous Au-catalyzed C-H
functionalizations.16a,17 Importantly, also electron-deficient
aryl germanes coupled to the corresponding biaryl motifs
13-20 (& 22) allowing the installation of the crucial halogen
handle for later diversification and unlocking for the first
time access to the electronic space of electron-deficient/
electron-deficient
functionalization.
biaryls
via
gold-catalyzed
C-H
Notably, meta-substitution was also successfully
synthesized (22), which is not accessible via the established
electrophilic aromatic-type reactivity in gold catalysis.
We next investigated whether ortho-substituents can also be
tolerated in the coupling process, which have been
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Property of Perfluorinated Phenylene Dendrimers. J. Am. Chem. Soc.
2000, 122, 1832-1833.
constructed in the presence of SiMe3 and/or highly reactive
halogen handles (C-I, C-Br, C-Cl). Figure 3 demonstrates a
number of examples (13, 15, 27 and 28).
1
2
3
(2)
Tsuzuki, T.; Shirasawa, N.; Suzuki, T.; Tokito, S. Color
Tunable Organic Light-Emitting Diodes Using Pentafluorophenyl-
Substituted Iridium Complexes. Adv. Mater. 2003, 15, 1455-1458.
Clearly, the tolerance of these synthetic handles in the
coupling process will only be of value if their further
functionalization is possible in the presence of the
polyfluoroaryl motif. We envisioned that a very rapid
coupling method might outcompete C-F activation even for
the most nucleophilic coupling partners, such as Grignard
reagents. Indeed, using our previously developed Pd(I) dimer
enabled methodology,10,32 we were able to selectively and
quantitatively alkylate and/or arylate the C-I and C-Br sites
at room temperature in less than 5 min in the presence of
oxygen using the air-stable Pd(I) dimer (see Figure 3,
compounds 33, 35 and 36).33 Similarly, the SiMe3
functionality was readily halogenated, nitrosylated and
acetoxylated,34,35 to give compounds 13, 29 and 30 in high
yields. Light-activated arylation of SiMe331 was also efficient.
The C-I bond serves as key site for the pharmaceutically and
agrochemically important difluoromethylation.36 Notably,
we also found that aside from SiMe3, Si(Me)(OTMS)2 can also
be tolerated in the gold-catalyzed polyfluoroarylation. The
latter silane has previously been employed in efficient
aminations,37 which was effective in our hands also to give
31. Given that coordinating groups, such as -NH2 or -OH,
impede the coupling38 (mirroring challenges in the area of
gold catalysis more generally)39,40 their later introduction via
C-halogen or C-[Si] diversifications is advantageous.
In conclusion, we have developed a robust, general and
chemoselective gold catalyzed C-H functionalization of
polyfluoroarenes with aryl germanes. The strategy relies on
an Umpolung approach to activate the polyfluoroarene
which enables the privileged coupling with aryl germanes in
the presence of C-I, C-Br, C-Cl, C-OTf and C-SiMe3
functionalities, tolerating even highly challenging ortho
substitution, and allowing also the synthesis of meta-
connected biaryls as well as previously inaccessible electron-
poor/electron-poor biaryls. Straightforward downstream
diversification to functionalized polyfluoroarene motifs was
also demonstrated.
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* E-mail: franziska.schoenebeck@rwth-aachen.de
† These authors contributed equally.
The authors declare no competing financial interest.
Experimental procedures and characterization data of
compounds. The Supporting Information is available free of
charge on the ACS Publications website.
We thank the RWTH Aachen University and the European
Research Council for funding.
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5581. (b) Cambeiro, X. C.; Boorman, T. C.; Lu, P.; Larrosa, I. Redox-
Controlled Selectivity of C-H Activation in the Oxidative Cross-
Coupling of Arenes. Angew. Chem. Int. Ed. 2013, 52, 1781-1784. (c)
Cambeiro, X. C.; Ahlsten, N.; Larrosa, I. Au-Catalyzed Cross-Coupling
of Arenes Via Double C-H Activation. J. Am. Chem. Soc. 2015, 137,
15636-15639.
Transmetalation
and
Ligand-Accelerated
Highly
Selective
Monoarylation. ACS Catal. 2017, 7, 7421-7430. For Ru catalysis: (o)
Simonetti, M.; Perry, G. J.; Cambeiro, X. C.; Julia-Hernandez, F.;
Arokianathar, J. N.; Larrosa, I. Ru-Catalyzed C-H Arylation of
Fluoroarenes with Aryl Halides. J. Am. Chem. Soc. 2016, 138, 3596-
3606. For photoredox-catalyzed: (p) Meyer, A. U.; Slanina, T.; Yao, C.-
J.; König, B. Metal-Free Perfluoroarylation by Visible Light Photoredox
Catalysis. ACS Catal. 2015, 6, 369-375.
(20)
Kang, L. J.; Xing, L.; Luscombe, C. K. Exploration and
9
Development of Gold- and Silver-Catalyzed Cross Dehydrogenative
Coupling toward Donor–Acceptor π-Conjugated Polymer Synthesis.
Polymer Chemistry 2019, 10, 486-493.
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(21)
Ball, L. T.; Lloyd-Jones, G. C.; Russell, C. A. Gold-Catalyzed
(9)
Few chemoselective couplings with ArFnH in the presence of
Oxidative Coupling of Arylsilanes and Arenes: Origin of Selectivity and
Improved Precatalyst. J. Am. Chem. Soc. 2014, 136, 254-264.
competing C-halogen bonds have been reported in scope studies, see: (a)
Rene, O.; Fagnou, K. Room-Temperature Direct Arylation of
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2116-2119. (b) Chen, F.; Min, Q. Q.; Zhang, X. Pd-Catalyzed Direct
Arylation of Polyfluoroarenes on Water under Mild Conditions Using
PPh3 Ligand. J. Org. Chem. 2012, 77, 2992-2998. (c) Fan, H.; Shang, Y.;
Su, W. Palladium-Catalyzed Direct Arylation of Polyfluoroarenes with
Organosilicon Reagents. Eur. J. Org. Chem. 2014, 2014, 3323-3327. (d)
Xu, S.; Wu, G.; Ye, F.; Wang, X.; Li, H.; Zhao, X.; Zhang, Y.; Wang, J.
Copper(I)-Catalyzed Alkylation of Polyfluoroarenes through Direct C-H
Bond Functionalization. Angew. Chem. Int. Ed. 2015, 54, 4669-4672.
(22)
For early examples of catalytic methods involving C-H
activation at Au(III), see: (a) Brand, J. P.; Charpentier, J.; Waser, J. Direct
Alkynylation of Indole and Pyrrole Heterocycles. Angew. Chem., Int. Ed.
2009, 48, 9346-9349. (b) De Haro, T.; Nevado, C. Gold-Catalyzed
Ethynylation of Arenes. J. Am. Chem. Soc. 2010, 132, 1512-1513. (c)
Brand, J. P.; Waser, J. Direct Alkynylation of Thiophenes: Cooperative
Activation of TIPS–EBX with Gold and Brønsted Acids. Angew. Chem.,
Int. Ed. 2010, 49, 7304-7307. C-H arylation with arylboronic acids: (d)
Wu, Q.; Du, C.; Huang, Y.; Liu, X.; Long, Z.; Song, F.; You, J.
Stoichiometric to Catalytic Reactivity of the Aryl Cycloaurated Species
with Arylboronic Acids: Insight into the Mechanism of Gold-Catalyzed
Oxidative C(sp2)–H Arylation. Chem. Sci. 2015, 6, 288-293.
(10) For a discussion, see: Kalvet, I.; Magnin, G.; Schoenebeck, F. Rapid
Room-Temperature, Chemoselective Csp2-Csp2 Coupling of
Poly(Pseudo)Halogenated Arenes Enabled by Palladium(I) Catalysis in
Air. Angew. Chem. Int. Ed. 2017, 56, 1581-1585.
(23)
Interestingly, when the corresponding FnAr silanes or
germanes are used instead of FnArBPin, no coupling is seen. See
Supporting Information for details.
(11)
For example, 2-iodo-4-bromo-toluene is unreactive in a state-
of-the-art Pd-catalyzed C-H functionalization and in Cu-catalyzed
protocol resulted in the formation of an unseparable product mixture (see
supporting information for details on our tests).
(24)
For an example of silver-free C-H activation of
polyfluoroarene, see: Gaillard, S.; Slawin, A. M.; Nolan, S. P. A N-
heterocyclic Carbenegold Hydroxide Complex: A Golden Synthon.
Chem. Commun. 2010, 46, 2742-2744.
(12)
Tepper, R.; Schubert, U. S. Halogen Bonding in Solution:
Anion Recognition, Templated Self‐Assembly, and Organocatalysis.
Angew. Chem. Int. Ed. 2018, 57, 6004.
(25)
The aryl germanes can be made by analogy to silanes, e.g. by
reaction of aryl Grignard reagents with R3GeCl. The cost of Et3GeCl is
35 $/gram.
(13)
For examples, see: (a) Hardegger, L. A.; Kuhn, B.; Spinnler,
B.; Anselm, L.; Ecabert, R.; Stihle, M.; Gsell, B.; Thoma, R.; Diez, J.;
Benz, J.; Plancher, J. M.; Hartmann, G.; Banner, D. W.; Haap, W.;
Diederich, F. Systematic Investigation of Halogen Bonding in Protein–
Ligand Interactions. Angew. Chem. Int. Ed. 2011, 50, 314-318. (b)
Wilcken, R.; Liu, X.; Zimmermann, M. O.; Rutherford, T. J.; Fersht, A.
R.; Joerger, A. C.; Boeckler, F. M. Halogen-Enriched Fragment Libraries
as Leads for Drug Rescue of Mutant p53. J. Am. Chem. Soc. 2012, 134,
6810-6818.
(26)
For detailed investigation of the mechanism, see: (a) Li, W.;
Yuan, D.; Wang, G.; Zhao, Y.; Xie, J.; Li, S.; Zhu, C. Cooperative Au/Ag
Dual-Catalyzed Cross-Dehydrogenative Biaryl Coupling: Reaction
Development and Mechanistic Insight. J. Am. Chem. Soc. 2019, 141,
3187-3197. (b) Liu, J. R.; Duan, Y. Q.; Zhang, S. Q.; Zhu, L. J.; Jiang,
Y. Y.; Bi, S.; Hong, X. C–H Acidity and Arene Nucleophilicity as
Orthogonal Control of Chemoselectivity in Dual C–H Bond Activation.
Org. Lett. 2019, 21, 2360-2364.
(14)
For early work in gold catalyzed coupling strategies tolerating
(27)
For discussion of silver mediated Umpolung strategies of
halide sites, see: (a) Kar, A.; Mangu, N.; Kaiser, H. M.; Beller, M.; Tse,
M. K. A General Gold-Catalyzed Direct Oxidative Coupling of Non-
Activated Arenes. Chem. Commun. 2008, 386-388. (b) Kar, A.; Mangu,
N.; Kaiser, H. M.; Tse, M. K. Gold-Catalyzed Direct Oxidative Coupling
Reactions of Non-Activated Arenes. J. Organomet. Chem. 2009, 694,
524-537.
FnC6H in Pd-catalyzed cross couplings, see: (a) He, C.-Y.; Min, Q.-Q.;
Zhang, X. Palladium-Catalyzed Aerobic Dehydrogenative Cross-
Coupling of Polyfluoroarenes with Thiophenes: Facile Access to
Polyfluoroarene–Thiophene Structure. Organometallics 2011, 31, 1335-
1340. (b) Li, H.; Liu, J.; Sun, C. L.; Li, B. J.; Shi, Z. J. Palladium-
Catalyzed Cross-Coupling of Polyfluoroarenes with Simple Arenes. Org.
Lett. 2011, 13, 276-279 (c) Lee, S. Y.; Hartwig, J. F. Palladium-
Catalyzed, Site-Selective Direct Allylation of Aryl C–H Bonds by Silver-
Mediated C–H Activation: A Synthetic and Mechanistic Investigation. J.
Am. Chem. Soc. 2016, 138, 15278-15284. (d) M. D. Lotz, J. F.; Camasso,
N. M.; Canty, A. J.; Sanford, M. S. Role of Silver Salts in Palladium-
Catalyzed Arene and Heteroarene C–H Functionalization Reactions.
Organometallics 2016, 36, 165-171. (e) Whitaker, D.; Bures, J.; Larrosa,
I. Ag(I)-Catalyzed C–H Activation: The Role of the Ag(I) Salt in Pd/Ag-
Mediated C–H Arylation of Electron-Deficient Arenes. J. Am. Chem.
Soc. 2016, 138, 8384-8387.
(15)
For literature on gold-catalyzed activation of aryl halides, see:
(a) Livendahl, M.; Goehry, C.; Maseras, F.; Echavarren, A. M. Rationale
for the Sluggish Oxidative Addition of Aryl Halides to Au(I). Chem.
Commun. 2014, 50, 1533-1536. (b) Guenther, J.; MalletLadeira, S.;
Estevez, L.; Miqueu, K.; Amgoune, A.; Bourissou, D. Activation of Aryl
Halides at Gold(I): Practical Synthesis of (P,C) Cyclometalated Gold(III)
Complexes. J. Am. Chem. Soc. 2014, 136, 1778-1781. (c) Joost, M.;
Zeineddine, A.; Estevez, L.; Mallet-Ladeira, S.; Miqueu, K.; Amgoune,
A.; Bourissou, D. Facile Oxidative Addition of Aryl Iodides to Gold(I)
by Ligand Design: Bending Turns on Reactivity. J. Am. Chem. Soc. 2014,
136, 14654-14657.
(28)
We systematically ommitted (Ph3P)AuCl and Ag2O in
(16)
(a) Ball, L. T.; Lloyd-Jones, G. C.; Russell, C. A. Gold-
separate reactions and only observed productive coupling to the desired
product when all componens were present. With Pd2dba3 instead of
(Ph3P)AuCl, no product formation occured, however several
sideproducts were formed. This suggests that Pd nanoparticles can be
ruled out as the catalytically active species. Under Pd nanoparticle
conditions in conjunction with silver salts, aryl germanes can be
efficiently coupled with aryl iodides, see: Fricke, C.; Sherborne, G. J.;
Funes-Ardoiz, I.; Senol, E.; Guven, S.; Schoenebeck, F. Orthogonal
Nanoparticle Catalysis with Organogermanes. Angew. Chem. Int. Ed.
2019, 58, 17788-17795.
Catalyzed Direct Arylation. Science 2012, 337, 1644-1648. (b)
Cresswell, A. J.; Lloyd-Jones, G. C. Room-Temperature Gold-Catalysed
Arylation of Heteroarenes: Complementarity to Palladium Catalysis.
Chem. Eur. J. 2016, 22, 12641-12645. (c) Corrie, T. J.; Ball, L. T.;
Russell, C. A.; Lloyd-Jones, G. C. Au-Catalyzed Biaryl Coupling to
Generate 5- to 9-Membered Rings: Turnover-Limiting Reductive
Elimination Versus Pi-Complexation. J. Am. Chem. Soc. 2017, 139, 245-
254.
(17)
Fricke, C.; Dahiya, A.; Reid, W. B.; Schoenebeck, F. Gold-
Catalyzed C–H Functionalization with Aryl Germanes. ACS Catal. 2019,
9, 9231-9236.
(29)
The C-H fucntionalization only proceeds with (Ph3P)AuCl;
(tht)AuBr3 as gold pre-catalyst did not result in any product formation.
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(30)
Robinson, M. P.; Lloyd-Jones, G. C. Au-Catalyzed Oxidative
(36)
Catalyzed
Serizawa, H.; Ishii, K.; Aikawa, K.; Mikami, K. Copper-
Difluoromethylation of Aryl Iodides with
Arylation: Chelation-Induced Turnover of Ortho-Substituted
1
2
3
4
5
6
7
8
Arylsilanes. ACS Catal. 2018, 8, 7484-7488.
(Difluoromethyl)Zinc Reagent. Org. Lett. 2016, 18, 3686-3689.
(31)
An alternative startegy to circumvent the oxidant is using aryl
(37) Morstein, J.; Kalkman, E. D.; Bold, C.; Cheng, C.; Hartwig,
J. F. Copper-Mediated C-N Coupling of Arylsilanes with Nitrogen
Nucleophiles. Org. Lett. 2016, 18, 5244-5247.
diazonium salts, which allow for chemoselective couplings, see: Xie, J.;
Sekine, K.; Witzel, S.; Kramer, P.; Rudolph, M.; Rominger, F.; Hashmi,
A. S. K. Light‐Induced Gold‐Catalyzed Hiyama Arylation: A Coupling
Access to Biarylboronates. Angew. Chem. Int. Ed. 2018, 57, 16648-
16653.
(38) When we assessed the effect of the additives phenol and aniline in
the coupling of phenyl germane, the coupling product was no longer
formed and the phenyl germane fully recovered. Heterocyclic germanes
(we tested furane-, pyridine-. isoxazole- derived germanes) did not give
rise to coupling.
(32)
(a) Aufiero, M.; Scattolin, T.; Proutiere, F.; Schoenebeck, F.
Catalyst,
Air-Stable Dinuclear Iodine-Bridged Pd(I) Complex
-
Precursor, or Parasite? The Additive Decides. Systematic Nucleophile-
Activity Study and Application as Precatalyst in Cross-Coupling.
Organometallics 2015, 34, 5191-5195. (b) Kalvet, I.; Sperger, T.;
Scattolin, T.; Magnin, G.; Schoenebeck, F. Palladium(I) Dimer Enabled
Extremely Rapid and Chemoselective Alkylation of Aryl Bromides over
Triflates and Chlorides in Air. Angew. Chem. Int. Ed. 2017, 56, 7078-
7082.
(39)
For reviews, see: (a) Hopkinson, M. N.; Gee, A. D.;
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Gouverneur, V. AuI/AuIII Catalysis: An Alternative Approach for C-C
Oxidative Coupling. Chem. Eur. J. 2011, 17, 8248-8262. (b) Nevado, C.;
deꢀHaro, T. On Gold-Mediated C-H Activation Processes. Synthesis
2011, 2530-2539.
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(40)
For discussion of importance of gold catalysis in Csp2-Csp2
cross coupling reactions, see: (a) Joost, M.; Amgoune, A.; Bourissou, D.
Reactivity of Gold Complexes Towards Elementary Organometallic
Reactions. Angew. Chem. Int. Ed. 2015, 54, 15022-15045. (b)
Echavarren, A. M.; Hashmi, A. S. K.; Toste, F. D. Gold Catalysis -
Steadily Increasing in Importance. Adv. Synth. Catal. 2016, 358, 1347.
(c) Pflasterer, D.; Hashmi, A. S. Gold Catalysis in Total Synthesis -
Recent Achievements. Chem. Soc. Rev. 2016, 45, 1331-1367. (d)
Furstner, A. Gold Catalysis for Heterocyclic Chemistry: a Representative
Case Study on Pyrone Natural Products. Angew. Chem. Int. Ed. 2018, 57,
4215-4233.
(33)
precautions. For details, see ref. 10 and ref. 32.
(34) Gondo, K.; Oyamada, J.; Kitamura, T. Palladium-Catalyzed
Desilylative Acyloxylation of Silicon-Carbon Bonds on
The reaction is performed open to air without special
(Trimethylsilyl)Arenes: Synthesis of Phenol Derivatives from
Trimethylsilylarenes. Org. Lett. 2015, 17, 4778-4781.
(35)
Kohlmeyer, C.; Kluppel, M.; Hilt, G. Synthesis of
Nitrosobenzene Derivatives Via Nitrosodesilylation Reaction. J. Org.
Chem. 2018, 83, 3915-3920.
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