Germylation of Arenes via Pd(I) Dimer Enabled Sulfonium Salt Functionalization

Article abstract of DOI:10.1021/acs.orglett.0c01609

While aryl germanes have recently found usage as coupling partners in powerful catalytic applications, the synthetic access to this promising functionality is currently limited. This report details the straightforward synthesis of functionalized aryl trie

Full text of DOI:10.1021/acs.orglett.0c01609

pubs.acs.org/OrgLett
Letter
Germylation of Arenes via Pd(I) Dimer Enabled Sulfonium Salt
Functionalization
Aymane Selmani, Avetik G. Gevondian, and Franziska Schoenebeck*
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ABSTRACT: While aryl germanes have recently found usage as
coupling partners in powerful catalytic applications, the synthetic
access to this promising functionality is currently limited. This
report details the straightforward synthesis of functionalized aryl
triethylgermanes via formal C−H functionalization. Building on the
concept of directing-group-free and site-selective C−H function-
alization of arenes to thianthrenium salt intermediates, we showcase their efficient couplings with triethylgermane (Et3Ge−H) at
room temperature, which was enabled by the air- and moisture-stable Pd(I) dimer, [Pd(μ-I)(PtBu3)]2. The method tolerates
numerous functional groups, including valuable (pseudo)halides.
hile organosilanes1 and -stannanes2 are ubiquitously
applied as coupling partners in metal-catalyzed cross-
W
coupling reactions,3 the corresponding organogermanes have
historically found only scarce usage in homogeneous catalysis.4
This is likely because of early reports that ascribed inferior
reactivity to organogermanes as compared to alternative
coupling partners.4 By contrast, very recently, our group
developed coupling methods based on Pd-nanoparticle and
Au(I)/Au(III) catalysis, which enabled the selective and
orthogonal functionalization of the organogermane in the
presence of silanes, boronic acids, or boronic ester groups as
well as a range of additional functionalities (see Figure 1).5 In
this context, the next frontier of applications of the robust and
nontoxic organogermanes in synthesis and catalysis will greatly
benefit from new and efficient strategies to install the R3Ge
functionality.
The current methodological repertoire largely relies on
prefunctionalized arenes, employing aryl (pseudo)halides that
are either converted to the corresponding ArMgX/Li, followed
by reaction with R3Ge electrophiles5,6 or coupled directly with
hydrogermane or digermane reagents (R3Ge)2 under Pd
catalysis4c,7 (see Figure 1). While the former method suffers
from the reactive nature of such organometallic reagents that
may limit functional group tolerance, the latter required
relatively high temperature or a significant excess of germane
or showed limited scope. There are only few examples of direct
C−H germylation under transition-metal catalysis;8 these
methods are characterized by the need for a directing group
(to yield predominantly ortho-functionalization),9 harsh
conditions (>100 °C), and limited functional group tolerance.
Clearly, a method that does not require prefunctionalized
arenes, but instead allows formal installation of the R3Ge
functionality selectively at Ar−H without the need for a
directing group or harsh conditions, would be greatly
empowering for this field of research.
Figure 1. Uses of aryl germanes and their current synthetic access
(top) and this work (bottom).
Received: May 11, 2020
https://dx.doi.org/10.1021/acs.orglett.0c01609
© XXXX American Chemical Society
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A

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Letter
In this context, we were inspired by the recent reports by the
groups of Lewis,10 Procter,11 and Ritter12 who demonstrated
the elegant concept of first installing a sulfonium salt by formal
C−H functionalization of alkenes or aromatics, followed by
Scheme 1. Pd-Catalyzed Germylation of Aryl
Tetrafluorothianthrenium Salts
a
+
further C−SR2 derivatizations (see Figure 1). Ritter’s
thianthrenium approach is especially appealing for its exquisite
site-selectivity in aromatic C−H functionalization to C−
12a
+
SR2 . However, while C−C, C−halogen, C−SR, C−BPin,
C−N, C−O, and C−PR3 bond formations via indirectly
synthesized13 or C−H-functionalized C−SR2 salts10−12 have
+
been showcased,14 there is no report of the corresponding
Csp2−GeR3 bond formation. With a view toward widening the
accessibility of the R3Ge functionality in organic molecules, we
recently set out to investigate the feasibility of a C−H
germylation via this concept.
Following the C−H thianthrenation of fluorobenzene with
(tetrafluoro)thianthrene S-oxide,12a we set out to investigate its
germylation using triethylgermane (Et3Ge−H) and different
palladium catalysts (see Table 1). We observed that those Pd
Table 1. Evaluation of Pd Complexes in the Germylation of
a
an Aryl Thianthrenium Salt
b
entry
1
2
[Pd]/ligand
yield of 1 (%)
Pd2(dba)3/Xantphos
Pd(OAc)2/PPh3
Pd(PPh3)2Cl2
22
0
0
14
0
82
c
3
4
5
Pd(dppf)Cl2
[Pd(PtBu3)]2
d
6
[Pd(μ-I)PtBu3]2
a
Reaction conditions: aryl thianthrenium salt (1.0 equiv), Et3GeH
(1.2 equiv), DABCO (3 equiv), [Pd] cat. (10 mol % Pd), ligand (10
b
mol %), DCE, rt, 15 h. Yields determined by quantitative 19F NMR
analysis of the crude reaction mixture using 1,4-difluorobenzene as
c
d
internal standard. PPh3 (17 mol %). DCM was used instead of DCE
a
Reaction conditions: aryl tetrafluorothianthrenium salt (0.30 mmol,
1.0 equiv), Et3GeH (0.36 mmol, 1.2 equiv), DABCO (0.90 mmol, 3.0
equiv), PdI dimer (15 μmol, 5 mol %), DCM (3 mL), rt, 15 h.
(75% of 1 was formed in DCE).
b
Isolated yields are shown. Yields determined by quantitative 1H
catalysts that have previously been reported to efficiently
transform thianthrenium salts to various functionalities12a did
not give rise to efficient C−GeEt3 bond formation; either no or
only little of the desired aryl germane was obtained, regardless
whether Pd(0) or Pd(II) (pre)catalysts were employed (entries
1−5). In contrast, the air-stable Pd(I) dimer [Pd(μ-
I)(PtBu3)]2, which we previously utilized for a wide range of
catalytic transformations,15 efficiently afforded (4-
fluorophenyl)triethylgermane 1 in 82% yield at room temper-
ature in dichloromethane in conjunction with the base
DABCO (entry 6).
With the reaction conditions in hand, we next examined the
wider scope of the methodology (Scheme 1). Pleasingly, the
protocol proved to be effective for a wide range of compounds,
tolerating electron-donating, electron-withdrawing, or no
substituents (2). Various aniline derivatives reacted smoothly
with triethylgermane to afford the corresponding p-arylger-
manes in moderate to high yields (3−7). Moreover, several
anisole-containing germanes could be synthesized. The
NMR analysis of the crude reaction mixture using mesitylene as
internal standard.
method shows a high functional group tolerance since
phenoxy, carbonyl, amide, nitro, nitrile, and chloride
substituents are tolerated in the germylation. These function-
alities are of utmost value for further derivatizations.
Additionally, the triethylgermanium moiety can be selectively
installed to a wide range of hetero- or polycyclic scaffolds that
are present in various natural products and bioactive
compounds, such as xanthone (13), chromanone (14), 1-
tetralone (15), and pyridine (16). However, in the case of the
electronically and sterically less distinct isochromane, a mixture
of isomers was obtained during thianthrenation, resulting in
the same ratio of isomers of the corresponding aryl germanes
(17). In a few cases, reduction of the aryl tetrafluorothian-
threnium salt was observed during germylation, leading to the
recovery of initial arene substrate. This competing side process
B
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Notes
was also reported previously for metal-catalyzed germyla-
tion7b,c and silylation7b,16 reactions.
The authors declare no competing financial interest.
Synthetic access to halogenated aryl germanes would be
especially appealing, as these compounds would be ideal
platforms for selective and modular derivatizations in the
context of cross-coupling catalysis (see Figure 1). We therefore
initially evaluated the relative reactivity of (pseudo)halides in
germylation as compared to the reactivity of tetrafluorothian-
threnium salt. While the aryl iodide afforded the germylated
arene in 37% yield under these conditions, the corresponding
aryl bromide and triflate gave only traces of the germylated
products (≤4%). As such, the selective germylation of a
thianthrenium-derived (pseudo)halogenated arene appears
feasible. Indeed, when we tested the intramolecular competi-
tion of C−SR2+ versus C−X (X = I, Br, OTf), we succeeded in
ACKNOWLEDGMENTS
■
We thank the RWTH Aachen University and the European
Research Council for funding.
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ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c01609.
1
Experimental procedures, characterization data, and H
and 13C NMR spectra of the new compounds (PDF)
̂
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AUTHOR INFORMATION
Corresponding Author
■
Franziska Schoenebeck − Institute of Organic Chemistry,
RWTH Aachen University, 52074 Aachen, Germany;
orcid.org/0000-0003-0047-0929;
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Email: franziska.schoenebeck@rwth-aachen.de
Authors
Aymane Selmani − Institute of Organic Chemistry, RWTH
Aachen University, 52074 Aachen, Germany
Avetik G. Gevondian − Institute of Organic Chemistry, RWTH
Aachen University, 52074 Aachen, Germany
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c01609
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