Steric-Hindrance Triggered Remote Lithiations of Bulky Silyl-Substituted Arenes

Article abstract of DOI:10.1055/s-0037-1611480

Functionalized arenes bearing two bulky triethylsilyl substituents were regioselectively lithiated at the 4-position (para position) by using a mixture of n BuLi and PMDTA (N, N, N ′, N ′′, N ′′-pentamethyldiethylenetriamine). The resulting aryllithium species, bearing sensitive functional groups such as amides or carbamates, reacted with a range of electrophiles leading to tri- and tetrasubstituted remote-functionalized products. This lithiation could be extended to 2,2′-bis(triethylsilyl)biphenyl, for which the favored metalation site was the one where steric interference of the silyl group could be avoided.

Full text of DOI:10.1055/s-0037-1611480

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–I
paper
A
en
A. B. Bellan, P. Knochel
Paper
Synthesis
Steric-Hindrance Triggered Remote Lithiations of Bulky
Silyl-Substituted Arenes
Andreas B. Bellan
FG
FG
FG
Et3Si
SiEt3
Et3Si
SiEt3
Et3Si
SiEt3
nBuLi•PMDTA
Paul Knochel*
0
0
0
0-0
0
0
1-7
9
1
3-
4
3
3
2
E-X
nhexane, –10 to 25 °C, 6 h
Department of Chemistry, Ludwig-Maximilians-Universität
München, Butenandtstr. 5–13, Haus F, 81377 München,
Germany
H
Li
E
16 examples, up to 59% yield
paul.knochel@cup.uni-muenchen.de
Y
Y
Y
Received: 14.03.2019
Et3Si
SiEt3
Et3Si
SiEt3
Et3Si
SiEt3
Accepted: 19.03.2019
Published online: 12.06.2019
DOI: 10.1055/s-0037-1611480; Art ID: ss-2019-t0179-op
Li-base
base-H
E-X
H
Li
E
1
2
3
Abstract Functionalized arenes bearing two bulky triethylsilyl substit-
uents were regioselectively lithiated at the 4-position (para position) by
using a mixture of nBuLi and PMDTA (N,N,N′,N′′,N′′-pentamethyldieth-
ylenetriamine). The resulting aryllithium species, bearing sensitive
functional groups such as amides or carbamates, reacted with a range
of electrophiles leading to tri- and tetrasubstituted remote-functional-
ized products. This lithiation could be extended to 2,2′-bis(triethylsi-
lyl)biphenyl, for which the favored metalation site was the one where
steric interference of the silyl group could be avoided.
O
SiEt3
OMe
O
NEt2
SiEt3
Et3Si
SiEt3
Et3Si
Et3Si
SiEt3
O
NEt2
SiEt3
H
SiEt3
Et3Si
1a
1c
1e
1b
1d
Scheme 1 Substrates of type 1 for remote lithiations leading to 5-lithi-
ated arenes 2 and subsequent quenching with electrophiles leading to
products of type 3
Key words arylsilanes, arene functionalization, lithiation, remote
metalation, steric hindrance
The directed functionalization of arenes via organome-
tallic intermediates is an essential method to prepare a
range of substituted aromatic target molecules.1 Especially
the directed lithiation of arenes via a precoordination by a
directing group pioneered by Snieckus has found wide-
spread applications.2 This proximity-induced metalation
has been especially useful for the ortho lithation of various
aromatic compounds. Schlosser has reported an alternative
approach for directed metalations, i.e. the steric hindrance
of substituents utilizing a buttress effect.3 Recently, we
have shown that 1,3-bis-silylated arenes were especially
well suited for remote lithiations at the 5-position.4 Herein,
we wish to report additional lithiations of 4-bis-silylated
substrates 1a–d, as well as a remote lithiation of bis-silylat-
ed biphenyl 1e (Scheme 1).
Bis-silylated arenes 1a–e were easily prepared by vari-
ous complementary methods. Thus, a mixture of 2,6-dibro-
moanisole (4) or 1,3-dibromobenzene (5) and Et3SiCl (2.5
equiv) was treated with nBuLi (2.2 equiv) at −78 °C in THF,
furnishing 1a and 1b in 80 and 97% yield, respectively
(Scheme 2). Bis-silylated carbamate (1c) and benzamide
(1d) were prepared by treating either phenyl diethylcarba-
mate (6) or N,N-diethylbenzamide (7) in the presence of
Et3SiCl (2.4 equiv) with TMPLi (2.2 equiv, TMP = 2,2,6,6-te-
X
X
Et3SiCl (2.5 equiv)
nBuLi (2.2 equiv)
Br
Br
Et3Si
SiEt3
THF, –78 °C, 2 h
1a,b
X = OMe, H
Y
Y
Et3SiCl (2.4 equiv)
TMPLi (2.2 equiv)
Et3Si
SiEt3
Due to the two bulky triethylsilyl groups of the arenes
of type 1, lithiation occurred only at the less sterically hin-
dered 5-position, leading to aryllithiums of type 2 which,
after quenching with electrophiles, led to functionalized
arenes of type 3.
THF, –78 °C, 2 h
1c,d
Y = OCONEt2, CONEt2
Scheme 2 Preparation of bis(triethylsilyl)arenes 1a–d via in situ silyl
chloride trapping reactions
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

B
A. B. Bellan, P. Knochel
Paper
Synthesis
tramethylpiperidyl)5 at −78 °C in THF furnishing the de-
sired carbamate 1c and amide 1d in 78% and 85% yield, re-
spectively.
with a ketone proceeded smoothly and afforded the tertiary
alcohol 3f in 44% yield (entry 6). Finally, reaction of 2a with
tert-butyl isocyanate gave amide 3g in 38% yield (entry 7).
Additionally, biphenyl 1e was prepared by the reaction
of 1,2-dibromobenzene (8) with nBuLi (2.1 equiv) in the
presence of an excess of Et3SiCl (2.5 equiv) in THF (−78 °C,
30 min), leading first to biphenyllithium 9, which, after a
second Br/Li exchange, furnished the bis(lithio)biphenyl 10.
An in situ quenching reaction with Et3SiCl furnished the de-
sired bis(silyl)biphenyl 1e in 37% yield (Scheme 3).
Table 1 Remote Lithiation of Anisole 1a, Leading to the Functionalized
Anisoles 3a–g
OMe
OMe
OMe
nBuLi (3.0 equiv)
PMDTA (3.0 equiv)
E-X
(3.5 equiv)
Et3Si
SiEt3
Et3Si
SiEt3
Et3Si
SiEt3
nhexane, 25 °C, 6 h
H
Li
E
3a–g
1a
2a
Br
Br
Entry
1
Electrophile
Me3SiCl
Product
3
Yield (%)a
39
Br
nBuLi
Li
OMe
Et3Si
Et3Si
Et3Si
Et3Si
SiEt3
8
9
3a
3b
3c
Br
Br
nBuLi
Li
Li
SiMe3
OMe
– LiBr
SiEt3
SiEt3
SiEt3
2
3
NFSI
40
Li
SiEt3
Et3SiCl (2.5 equiv)
THF, –78 °C, 30 min
nBuLi
9
F
Li
SiEt3
1e, 37%
OMe
10
Br2
51b
Scheme 3 Proposed mechanism for the formation of the bis(silyl)bi-
phenyl 1e from arene 8
Br
OMe
H
With the bis-silylated arenes 1a–e in hand, we exam-
ined the lithiation of 1a with various bases and found that
an excess of nBuLi (3.0 equiv) in combination with PMDTA
(N,N,N′,N′′,N′′-pentamethyldiethylenetriamine; 3.0 equiv) in
hexanes at 25 °C for 6 hours gave the best results.4 Longer
reaction times led to a partial decomposition of the aryllith-
ium intermediates 2. The large excess of nBuLi may be nec-
essary due to a competitive lithiation of the ligand PMDTA
by nBuLi.6
HO
C
H
O H
4
5
3d
3e
39
38
n
OH
OMe
Et3Si
SiEt3
O
H
NMe2
O
H
OMe
O
Et3Si
SiEt3
Thus, treatment of 2a with an excess of electrophile (E-
X; 3.5 equiv) regioselectively provides a range of 5-func-
tionalized products of type 3 (Table 1). As an example, the
addition of Me3SiCl furnished 2,4,6-trisilylated anisole 3a in
39% yield (entry 1). Electrophilic aryl fluorination at the 5-
position was possible by treating 2a with NFSI (N-fluoro-
benzenesulfonimide), affording fluoroarene 3b in 40% yield
(entry 2). The bromination of 2a was readily achieved after
a transmetalation to the corresponding zinc reagent by us-
ing ZnCl2 (3.0 equiv) and adding bromine in THF, leading to
6
3f
44
38
F
F
OH
OMe
Et3Si
SiEt3
N
C
7
3g
O
O
NHtBu
a Yields of isolated, analytically pure products.
b ZnCl2 (3.0 equiv) was added.
bromoarene 3c in 51% yield (entry 3).
A para-hy-
droxymethylation was performed by treating 2a with an
excess of paraformaldehyde and acidic workup, which fur-
nished benzylic alcohol 3d in 39% yield (entry 4). Formyla-
tion of 2a was done by treating the aryllithium reagent with
dimethylformamide, leading to benzaldehyde 3e in 38%
yield (entry 5). The reaction of the para-lithiated anisole 2a
Interestingly, even the non-functionalized bis-silane 1b
was lithiated under our reaction conditions, regioselectively
affording meta-aryllithium 2b in ca. 60% yield. Quenching
with electrophiles such as pivaldehyde or iodine (after
transmetalation to the corresponding zinc reagent) gave the
expected products 3h and 3i in 58 and 43% yield, respec-
tively (Scheme 4).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

C
A. B. Bellan, P. Knochel
Paper
Synthesis
nBuLi (3.0 equiv)
PMDTA (3.0 equiv)
The lithiation of bis(silyl)biphenyl 1e was only partially
regioselective and produced an 86:14 mixture of two regio-
isomers. The major biphenyllithium species was metalated
at the para position relative to the bulky triethylsilyl group,
showing the steric hindrance of this silyl group compared
to the 2-(triethylsilyl)phenyl substituent. Reaction with
electrophiles such as dimethyl disulfide, allyl bromide, or
dimethylformamide provided the expected product mix-
tures 3n,3n′, 3o,3o′, and 3p,3p′ in good yields (Table 3, en-
tries 1–3).
E-X
(3.5 equiv)
Et3Si
SiEt3
Et3Si
SiEt3
Et3Si
SiEt3
nhexane, 25 °C, 6 h
H
Li
E
1b
2b
3h,i
Et3Si
SiEt3
Et3Si
SiEt3
I
HO
3h, 58%a
3i, 43%a,b
Scheme 4 Trifunctionalized benzenes 3h,i obtained after regioselec-
tive lithiation of benzene 1b and reaction with electrophiles. a Yield of
analytically pure, isolated product. b ZnCl2 (3.0 equiv) was added.
Table 3 Remote Lithiation of Biphenyl 1e, Leading to Product Mixtures
of Type 3n,n′–p,p′
We noticed that the introduction of a good coordination
function such as a carbamate (OCONEt2) or an amide
(CONEt2) gave the expected aryllithium species (2c and 2d)
in similar yields. The lithiated carbamate 2c displayed mod-
erate thermal stability and decomposed at 25 °C. Therefore,
the lithiation was performed at −10 °C instead of 25 °C as
usual (Table 2). Quenching of 2c and 2d with various elec-
trophiles provided the desired tetrasubstituted arenes 3j–
m in 34–46% yield (entries 1–4).
E-X
(3.5 equiv)
nBuLi (3.0 equiv)
PMDTA (3.0 equiv)
SiEt3
SiEt3
SiEt3
Li
E
nhexanes, 25 °C, 6 h
SiEt3
SiEt3
SiEt3
1e
2e
3n-p
Entry
Electrophile
Product, yield (%)
SMe
SMe
SiEt3
SiEt3
1
2
MeSSMe
SiEt3
SiEt3
3n′, 9a
Table 2 Remote Lithiation of the Functionalized Arenes 1c,d, Leading
to the Tetrasubstituted Silylated Arenes 3j–m
3n, 53a
SiEt3
Y
Y
Y
nBuLi (3.0 equiv)
PMDTA (3.0 equiv)
SiEt3
E-X
(3.5 equiv)
Et3Si
SiEt3
Et3Si
SiEt3
Et3Si
SiEt3
Br
SiEt3
nhexane, T, 6 h
SiEt3
3o′, 10b,c
H
Li
E
3o, 59a,b
1c,d
2c,d
3j–m
c: Y = OCONEt2
d: Y = CONEt2
O
H
O
SiEt3
H
SiEt3
O
3
Entry Substrate
Electrophile
Product
Temp Yield
(°C) (%)a
H
NMe2
SiEt3
SiEt3
3p′, 9c
3p, 57a
OCONEt2
SiEt3
OCONEt2
SiEt3
Et3Si
a Yield of isolated, analytically pure product.
Et3Si
O
b ZnCl2 (3.0 equiv) and CuCN·2LiCl (11 mol%) were added.
c Yield determined by GC and NMR analysis of crude mixtures.
1
2
–10 34
H
NMe2
O
H
1c
3j
In summary, we have reported a remote lithiation of
1,3-disilylsilanes and a related biphenyl by using two bulky
triethylsilyl groups, which hampered ortho and meta lithia-
tions. Further extensions of this type of steric-hindrance-
based regioselective metalations of arenes are currently in-
vestigated in our laboratories.
OCONEt2
Et3Si
SiEt3
O
Me
1c
–10 44
N
OMe
O
Ph
3k
CONEt2
CONEt2
SiEt3
Et3Si
SiEt3
Et3Si
3
4
Me3SiCl
PhSSPh
25 46
Unless stated otherwise, all reactions were carried out with magnetic
stirring and in flame-dried glassware under argon. Syringes which
were used to transfer anhydrous solvents or reagents were purged
with argon prior to use. Reactions were monitored by gas chromatog-
raphy or by thin-layer chromatography. TLC was performed using alu-
minum plates coated with SiO2 (Merck 60, F-254) and visualized by
UV radiation. Purification by column chromatography was performed
using silica gel 60 (40–63 mm, 230–400 mesh, ASTM from Merck).
For purification, an Agilent Technologies 1260 Infinity HPLC-System
was used, consisting of two prep-pumps (MeCN/H2O, no additives), a
SiMe3
1d
3l
CONEt2
Et3Si
SiEt3
1d
25 44
SPh
3m
a Yields of isolated, analytically pure products.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

D
A. B. Bellan, P. Knochel
Paper
Synthesis
MWD-detector (210 nm wavelength, 40 nm bandwidth, reference
wavelength 400 nm, reference bandwidth 100 nm) and a fraction col-
lector. Three different columns were used: (a) Kinetix EVO C18, 5 m
column (length: 150 mm, diameter: 10 mm), (b) Kinetix EVO C18, 5
m column (length: 150 mm, diameter: 21.2 mm), and (c) Waters
XBridge Prep C8, 5 m column (length: 150 mm, diameter: 30 mm).
Commercially available starting materials were used without further
purification unless stated otherwise. THF was continuously refluxed
and freshly distilled from sodium benzophenone. Commercially avail-
able Grignard reagents were titrated against iodine in THF prior to
use. Other Grignard reagents were prepared from the corresponding
bromides by insertion of magnesium in the presence of lithium chlo-
ride, and were titrated against iodine in THF prior to use. Yields refer
to isolated yields of compounds estimated to be >95% pure as deter-
mined by 1H NMR (25 °C) and capillary GC analysis. Melting points
were measured with a Büchi B-540 apparatus and are uncorrected. IR
spectra were recorded on a Perkin Elmer spectrum BX-59343 instru-
ment. For detection, a Smiths Detection DuraSamplIR II Diamond ATR
sensor was used. NMR spectra of samples in CDCl3 were recorded on a
Bruker Avance III HD 400 spectrometer. Mass spectra and high-reso-
lution mass spectra were recorded on Finnigan MAT 90 or Finnigan
MAT 95 instruments using electron ionization (EI).
halogenolysis) and extracted with EtOAc (3 × 20 mL). The combined
organic phases were washed with brine (20 mL), dried over MgSO4,
filtered, and concentrated in vacuo.
(2-Methoxy-1,3-phenylene)bis(triethylsilane) (1a)
According to GP1, 1,3-dibromo-2-methoxybenzene (5.04 g, 19 mmol)
and Et3SiCl (8.0 mL, 47.5 mmol) were dissolved in THF (40 mL). A
2.55 M solution of nBuLi in hexane (16.4 mL, 41.8 mmol) was slowly
added to the mixture at −78 °C. Purification of the crude product by
flash column chromatography (silica gel, isohexane) afforded the title
compound as a colorless oil.
Yield: 5.1 g (15 mmol, 80%).
IR (diamond-ATR, neat): 2951 (m), 2909 (w), 2874 (m), 1562 (w),
1457 (w), 1416 (w), 1370 (s), 1236 (w), 1209 (m), 1170 (vw), 1148
(vw), 1120 (w), 1076 (vw), 1014 (s), 1003 (s), 973 (w), 960 (w), 809
(w), 769 (vs), 717 (vs), 682 (m) cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.43 (d, J = 7.2 Hz, 2 H), 7.09 (t, J = 7.2
Hz, 1 H), 3.67 (s, 3 H), 1.03–0.76 (m, 30 H).
13C NMR (101 MHz, CDCl3):  = 172.33, 138.24, 128.64, 123.18, 63.65,
7.74, 4.27.
MS (EI, 70 eV): m/z (%) = 307 (5), 297 (25), 280 (14), 279 (100), 269
(12), 251 (89), 223 (71), 221 (17), 195 (47), 193 (23), 191 (12), 179
(14), 167 (27), 165 (24), 163 (17), 161 (30), 151 (22), 137 (19), 135
(13), 133 (46), 131 (18), 117 (65), 115 (12), 111 (11), 107 (14), 105
(15), 97 (12), 91 (13), 89 (84), 87 (27), 61 (26), 59 (13).
HRMS (EI): m/z calcd for C17H31O28Si2: 307.1913 [M – Et]•+; found:
307.1910.
o,o′-Bis-silylated Arenes 1 via In Situ Silylation of Dibromoarenes;
General Procedure 1 (GP1)
A dry and argon-flushed Schlenk flask, equipped with a magnetic
stirring bar and a septum, was charged with the appropriate dibro-
moarene (1.0 equiv) and Et3SiCl (2.5 equiv) in anhyd THF (0.5–1.0 M
solution). The resulting solution was cooled to −78 °C and nBuLi
(2.2 equiv) was added dropwise. The mixture was slowly warmed to
25 °C and subsequently quenched with sat. aq NH4Cl. The aqueous
phase was extracted with EtOAc (3 × 30 mL). The combined organic
phases were washed with brine (20 mL), dried over MgSO4, filtered,
and concentrated in vacuo.
1,3-Bis(triethylsilyl)benzene (1b)
According to GP1, 1,3-dibromobenzene (11.8 g, 50 mmol) and Et3SiCl
(21 mL, 125 mmol) were dissolved in THF (100 mL). A 2.55 M solution
of nBuLi in hexane (43.1mL, 110 mmol) was slowly added to the mix-
ture at −78 °C. Purification of the crude product by flash column chro-
matography (silica gel, isohexane) afforded the title compound as a
colorless oil.
o,o′-Bis-silylated Arenes 1 via In Situ Lithiation and Silylation Se-
quence; General Procedure 2 (GP2)
A dry and argon-flushed Schlenk flask, equipped with a magnetic
stirring bar and a septum, was charged with the appropriate arene
(1.0 equiv) and Et3SiCl (2.4 equiv) in anhyd THF (0.5–1.0 M solution).
The resulting solution was cooled to −78 °C and TMPLi (2.2 equiv)
was added dropwise. The mixture was allowed to warm to 25 °C and
was subsequently quenched with sat. aq NH4Cl. The aqueous phase
was extracted with EtOAc (3 × 30 mL). The combined organic phases
were washed with brine (20 mL), dried over MgSO4, filtered, and con-
centrated in vacuo.
Yield: 14.9 g (48.6 mmol, 97%).
IR (diamond-ATR, neat): 2952 (m), 2909 (w), 2874 (m), 1457 (w),
1415 (w), 1361 (w), 1236 (w), 1106 (m), 1002 (m), 972 (w), 778 (vs),
729 (s), 714 (vs), 685 (s).
1H NMR (400 MHz, CDCl3):  = 7.62 (dd, J = 2.2, 1.2 Hz, 1 H), 7.48 (dd,
J = 7.3, 1.3 Hz, 2 H), 7.32 (ddd, J = 7.7, 6.8, 0.7 Hz, 1 H), 1.01–0.94 (m,
18 H), 0.83–0.74 (m, 12 H).
13C NMR (101 MHz, CDCl3):  = 140.32, 136.27, 134.68, 127.05, 7.57,
3.56.
p-Substituted Arenes 3 from p-Lithiated Arenes 2, Obtained by Us-
ing nBuLi·PMDTA, Followed by Reaction with an Electrophile ;
General Procedure 3 (GP3)
MS (EI, 70 eV): m/z (%) = 306 (1), 278 (11), 277 (71), 249 (76), 221
(100), 217 (14), 189 (23), 165 (18), 163 (12), 161 (20), 137 (31), 135
(17), 135 (11), 133 (31), 131 (12), 115 (36), 107 (19), 105 (16), 96 (10),
87 (16).
A dry and argon-flushed flask, equipped with a magnetic stirring bar
and a septum, was charged with the appropriate bis-silylated arene 1
(1.0 equiv) in anhyd n-hexane (0.5 M solution), and PMDTA
(3.0 equiv) was added. The solution was stirred at 25 °C and nBuLi
(3.0 equiv) was added in one portion. After 6 h, the reaction mixture
was cooled to –20 °C and THF (1 mL) or a metal salt solution
(3.0 equiv) was added, immediately followed by the appropriate elec-
trophile (3.5 equiv). The reaction mixture was allowed to warm to
25 °C, quenched with a sat. aq NH4Cl solution (or sat. aq Na2S2O3 for
HRMS (EI): m/z calcd for C18H3428Si2: 306.2199 [M]•+; found: 306.2197.
2,6-Bis(triethylsilyl)phenyl Diethylcarbamate (1c)
According to GP2, phenyl diethylcarbamate (1.93 g, 10 mmol) and
Et3SiCl (4.2 mL, 25 mmol) were dissolved in THF (20 mL). TMPLi
(18.6 mL, 22 mmol) was slowly added to the mixture at −78 °C. Puri-
fication of the crude product by flash column chromatography (silica
gel, isohexane/EtOAc = 29:1) afforded the title compound as a color-
less oil.
Yield: 3.3 g (7.8 mmol, 78%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

E
A. B. Bellan, P. Knochel
Paper
Synthesis
IR (diamond-ATR, neat): 2952 (m), 2936 (w), 2909 (w), 2874 (m),
1714 (vs), 1573 (w), 1458 (w), 1422 (m), 1371 (s), 1350 (w), 1315
(vw), 1270 (vs), 1236 (w), 1211 (vw), 1178 (m), 1148 (vs), 1118 (s),
1070 (w), 1003 (s), 962 (m), 935 (w), 772 (s), 756 (m), 720 (vs), 684
[2-Methoxy-5-(trimethylsilyl)-1,3-phenylene]bis(triethylsilane)
(3a)
According to GP3, anisole derivative 1a (168 mg, 0.5 mmol) and PMD-
TA (0.31 mL, 1.5 mmol) were dissolved in n-hexane (1 mL). A 2.55 M
solution of nBuLi in hexane (0.59 mL, 1.5 mmol) was added and the
resulting solution was stirred for 6 h. Afterwards, the mixture was
cooled to –20 °C and THF (1 mL) was added, followed by Me3SiCl
(0.22 mL, 1.75 mmol). Purification of the crude product by flash col-
umn chromatography (silica gel, isohexane/EtOAc = 99:1) afforded
the title compound as a colorless oil.
(m) cm–1
.
1H NMR (599 MHz, CDCl3):  = 7.47 (d, J = 7.2 Hz, 2 H), 7.19 (t, J = 7.3
Hz, 1 H), 3.59 (q, J = 7.2 Hz, 2 H), 3.37 (q, J = 7.1 Hz, 2 H), 1.28 (t, J = 7.2
Hz, 3 H), 1.19 (t, J = 7.1 Hz, 3 H), 0.96–0.90 (m, 18 H), 0.78 (dtd, J = 8.5,
7.2, 3.8 Hz, 12 H).
13C NMR (151 MHz, CDCl3):  = 161.68, 154.85, 137.60, 129.75,
Yield: 79 mg (0.19 mmol, 39%).
124.73, 40.78, 40.69, 13.94, 13.01, 7.59, 3.66.
IR (diamond-ATR, neat): 2951 (m), 2909 (w), 2874 (w), 1537 (w),
1457 (w), 1417 (vw), 1382 (m), 1247 (m), 1215 (w), 1107 (m), 1003
MS (EI, 70 eV): m/z (%) = 392 (80), 278 (32), 221 (14), 202 (14), 179
(12), 151 (30), 133 (16), 100 (100), 72 (63).
HRMS (EI): m/z calcd for C21H38NO228Si2: 392.2441 [M − Et]•+; found:
392.2442.
(m), 974 (vw), 869 (vs), 834 (vs), 782 (s), 718 (vs), 686 (s) cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.59 (s, 2 H), 3.69 (s, 3 H), 1.02–0.93
(m, 18 H), 0.91–0.81 (m, 12 H), 0.26 (s, 9 H).
N,N-Diethyl-2,6-bis(triethylsilyl)benzamide (1d)
13C NMR (101 MHz, CDCl3):  = 173.11, 143.56, 133.46, 127.52, 63.52,
7.79, 4.42, –0.78.
According to GP2, N,N-diethylbenzamide (3.36 g, 30 mmol) and Et3Si-
Cl (12.6 mL, 75 mmol) were dissolved in THF (60 mL). TMPLi (39 mL,
66 mmol) was slowly added to the mixture at −78 °C. Purification of
the crude product by flash column chromatography (silica gel, isohex-
ane/EtOAc = 19:1) afforded the title compound as a colorless solid.
MS (EI, 70 eV): m/z (%) = 393 (6), 369 (37), 352 (25), 351 (100), 341
(18), 323 (66), 295 (50), 267 (30), 265 (22), 249 (25), 247 (70), 239
(21), 235 (19), 221 (22), 219 (19), 207 (20), 193 (33), 191 (21), 179
(25), 163 (22), 161 (23), 117 (30), 89 (66), 87 (32), 73 (57), 61 (27), 59
(25).
HRMS (EI): m/z calcd for C26H41O28Si3: 393.2465 [M – Me]•+; found:
393.2457.
Yield: 10.3 g (25.5 mmol, 85%); mp 77.8–79.3 °C.
IR (diamond-ATR, neat): 2953 (s), 2908 (m), 2872 (s), 1627 (vs), 1456
(m), 1434 (m), 1380 (m), 1363 (m), 1280 (s), 1235 (m), 1219 (m),
1155 (w), 1124 (w), 1094 (m), 1062 (w), 1001 (vs), 962 (m), 872 (w),
795 (vs), 782 (vs), 720 (vs), 682 (s) cm–1
.
(5-Fluoro-2-methoxy-1,3-phenylene)bis(triethylsilane) (3b)
1H NMR (400 MHz, CDCl3):  = 7.53 (d, J = 7.5 Hz, 2 H), 7.28 (t, J = 7.4
Hz, 1 H), 3.54 (q, J = 7.2 Hz, 2 H), 2.99 (q, J = 7.2 Hz, 2 H), 1.27 (t, J = 7.2
Hz, 3 H), 1.00–0.62 (m, 33 H).
13C NMR (101 MHz, CDCl3):  = 172.39, 149.62, 136.05, 133.46,
125.94, 43.29, 38.71, 13.33, 12.89, 7.68, 3.92.
According to GP3, anisole derivative 1a (168 mg, 0.5 mmol) and PMD-
TA (0.31 mL, 1.5 mmol) were dissolved in n-hexane (1 mL). A 2.55 M
solution of nBuLi in hexane (0.59 mL, 1.5 mmol) was added and the
resulting solution was stirred for 6 h. Afterwards, the mixture was
cooled to –20 °C and THF (1 mL) was added, followed by NFSI
(582 mg, 1.75 mmol). Purification of the crude product by flash col-
umn chromatography (silica gel, isohexane/EtOAc = 19:1) afforded
the title compound as a colorless oil.
MS (EI, 70 eV): m/z (%) = 404 (1), 377 (31), 376 (100), 318 (19), 260
(21), 232 (16), 87 (19), 59 (16).
HRMS (EI): m/z calcd for C23H42NO28Si2: 404.2805 [M – H]•+; found:
404.2804.
Yield: 71 mg (0.20 mmol, 40%).
IR (diamond-ATR, neat): 2952 (m), 2909 (w), 2874 (m), 1572 (vw),
1457 (w), 1418 (vw), 1372 (vs), 1236 (w), 1200 (m), 1163 (w), 1003
2,2′-Bis(triethylsilyl)-1,1′-biphenyl (1e)
(s), 960 (w), 881 (w), 776 (s), 717 (vs) cm–1
.
According to GP1, 1,2-dibromobenzene (8; 7.08 g, 30 mmol) and
Et3SiCl (12.6 mL, 75 mmol) were dissolved in THF (60 mL). A 2.55 M
solution of nBuLi in hexane (25.9 mL, 66 mmol) was slowly added to
the mixture at –78 °C. Purification of the crude product by flash col-
umn chromatography (silica gel, isohexane) afforded the title com-
pound as a colorless solid.
1H NMR (400 MHz, CDCl3):  = 7.05 (d, J = 8.4 Hz, 2 H), 3.65 (s, 3 H),
0.95 (td, J = 7.1, 1.1 Hz, 18 H), 0.90–0.78 (m, 12 H).
13C NMR (101 MHz, CDCl3):  = 158.98 (d, J = 245.0 Hz), 138.24,
131.43 (d, J = 3.7 Hz), 123.72 (d, J = 20.7 Hz), 63.87, 7.63, 4.07.
19F NMR (377 MHz, CDCl3):  = –121.97 (t, J = 8.4 Hz).
Yield: 2.1 g (5.5 mmol, 37%); mp 89.9–91.4 °C.
MS (EI, 70 eV): m/z (%) = 325 (3), 297 (27), 269 (23), 241 (24), 213
(16), 211 (42), 197 (10), 189 (23), 185 (10), 183 (12), 169 (23), 163
(11), 155 (19), 153 (16), 151 (24), 149 (11), 133 (42), 131 (12), 125
(28), 123 (13), 117 (53), 115 (22), 109 (15), 107 (16), 93 (10), 91 (34),
89 (100), 87 (46), 77 (32), 75 (11), 61 (30), 59 (20).
HRMS (EI): m/z calcd for C17H30FO28Si2: 325.1819 [M – Et]•+; found:
325.1820.
IR (diamond-ATR, neat): 2952 (m), 2910 (w), 2872 (w), 1456 (w),
1416 (w), 1233 (w), 1121 (w), 1007 (w), 995 (m), 970 (w), 710 (vs),
675 (m) cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.58–7.53 (m, 2 H), 7.35–7.28 (m, 4 H),
7.15–7.10 (m, 2 H), 0.85–0.76 (m, 18 H), 0.59–0.31 (m, 12 H).
13C NMR (101 MHz, CDCl3):  = 151.09, 135.99, 135.40, 130.33,
127.61, 126.13, 7.73, 4.32.
(5-Bromo-2-methoxy-1,3-phenylene)bis(triethylsilane) (3c)
MS (EI, 70 eV): m/z (%) = 382 (1), 227 (15), 209 (60), 199 (17), 181
(53), 115 (62), 87 (100), 59 (30).
HRMS (EI): m/z calcd for C24H3828Si2: 382.2512 [M]•+; found: 382.2511.
According to GP3, anisole derivative 1a (168 mg, 0.5 mmol) and
PMDTA (0.31 mL, 1.5 mmol) were dissolved in n-hexane (1 mL). A
2.55 M solution of nBuLi in hexane (0.59 mL, 1.5 mmol) was added
and the resulting solution was stirred for 6 h. Afterwards, the mixture
was cooled to –20 °C and 1.0 M ZnCl2 in THF (1.5 mL, 1.5 mmol) was
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

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A. B. Bellan, P. Knochel
Paper
Synthesis
added, followed by a solution of Br2 (0.09 mL, 1.75 mmol) in THF
(1 mL). Purification of the crude product by flash column chromatog-
raphy (silica gel, isohexane/EtOAc = 99:1) afforded the title compound
as a colorless oil.
13C NMR (101 MHz, CDCl3):  = 192.17, 177.39, 140.63, 131.53,
130.08, 63.55, 7.73, 7.65, 4.00.
MS (EI, 70 eV): m/z (%) = 335 (26), 325 (46), 307 (100), 297 (39), 279
(75), 277 (12), 269 (25), 267 (13), 251 (55), 249 (20), 241 (22), 223
(44), 221 (15), 213 (12), 207 (13), 195 (28), 193 (24), 191 (17), 183
(20), 179 (36), 165 (52), 163 (15), 161 (24), 149 (16), 145 (14), 135
(14), 117 (41), 107 (16), 91 (23), 89 (79), 87 (24), 61 (34), 59 (18).
Yield: 106 mg (0.26 mmol, 51%).
IR (diamond-ATR, neat): 2952 (m), 2909 (w), 2874 (m), 1456 (w),
1417 (vw), 1368 (s), 1238 (w), 1207 (m), 1114 (s), 1003 (s), 973 (w),
882 (w), 772 (s), 721 (vs), 683 (m) cm–1
.
HRMS (EI): m/z calcd for C18H31O228Si2: 335.1863 [M – Et]•+; found:
335.1855.
1H NMR (400 MHz, CDCl3):  = 7.45 (s, 2 H), 3.65 (s, 3 H), 0.99–0.89
(m, 18 H), 0.89–0.78 (m, 12 H).
13C NMR (101 MHz, CDCl3):  = 171.03, 140.33, 132.39, 117.83, 63.73,
7.64, 4.07.
Cyclopropyl(4-fluorophenyl)[4-methoxy-3,5-bis(triethylsilyl)phe-
nyl]methanol (3f)
According to GP3, anisole derivative 1a (168 mg, 0.5 mmol) and PMD-
TA (0.31 mL, 1.5 mmol) were dissolved in n-hexane (1 mL). A 2.55 M
solution of nBuLi in hexane (0.59 mL, 1.5 mmol) was added and the
resulting solution was stirred for 6 h. Afterwards, the mixture was
cooled to –20 °C and THF (1 mL) was added, followed by cyclopropyl
4-fluorophenyl ketone (0.25 mL, 1.75 mmol). Purification of the
crude product by flash column chromatography (silica gel, isohex-
ane/EtOAc = 19:1) afforded the title compound as a slightly yellow oil.
MS (EI, 70 eV): m/z (%) = 414 (2), 360 (15), 359 (60), 358 (15), 357
(55), 331 (28), 329 (30), 303 (10), 301 (15), 273 (11), 244 (10), 165
(12), 151 (11), 150 (12), 118 (13), 117 (100), 115 (22), 89 (32), 87 (24),
61 (15), 59 (19), 57 (15), 55 (11), 43 (69).
HRMS (EI): m/z calcd for C19H3579BrO28Si2: 414.1410 [M]•+; found:
414.1407.
[4-Methoxy-3,5-bis(triethylsilyl)phenyl]methanol (3d)
Yield: 110 mg (0.22 mmol, 44%).
According to GP3, anisole derivative 1a (168 mg, 0.5 mmol) and PMD-
TA (0.31 mL, 1.5 mmol) were dissolved in n-hexane (1 mL). A 2.55 M
solution of nBuLi in hexane (0.59 mL, 1.5 mmol) was added and the
resulting solution was stirred for 6 h. Afterwards, the mixture was
cooled to –20 °C and THF (1 mL) was added, followed by paraformal-
dehyde (53 mg, 1.75 mmol). Purification of the crude product by flash
column chromatography (silica gel, isohexane/EtOAc = 19:1) afforded
the title compound as a colorless oil.
IR (diamond-ATR, neat): 2951 (m), 2909 (w), 2874 (m), 1603 (vw),
1553 (vw), 1506 (m), 1457 (w), 1418 (w), 1379 (m), 1314 (vw), 1221
(s), 1158 (w), 1107 (s), 1002 (vs), 898 (w), 839 (m), 777 (s), 719 (vs),
684 (m) cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.46 (s, 2 H), 7.41–7.35 (m, 2 H), 7.02–
6.92 (m, 2 H), 3.67 (s, 3 H), 1.87 (d, J = 0.8 Hz, 1 H), 1.56 (tt, J = 8.2, 5.5
Hz, 1 H), 0.94–0.87 (m, 18 H), 0.84–0.75 (m, 12 H), 0.69–0.61 (m, 1 H),
0.58–0.39 (m, 3 H).
13C NMR (101 MHz, CDCl3):  = 171.46, 161.84 (d, J = 245.0 Hz),
143.50 (d, J = 3.1 Hz), 140.58, 137.11, 128.57 (d, J = 8.3 Hz), 127.89,
114.51 (d, J = 21.0 Hz), 63.57, 21.98, 7.70, 4.28, 2.38, 1.40.
Yield: 72 mg (0.20 mmol, 39%).
IR (diamond-ATR, neat): 3299 (br vw), 2951 (m), 2909 (w), 2873 (m),
1557 (w), 1456 (w), 1417 (w), 1376 (s), 1210 (s), 1108 (m), 1003 (vs),
917 (vw), 889 (vw), 780 (s), 717 (vs), 685 (s) cm–1
.
19F NMR (377 MHz, CDCl3):  = –116.49 to –116.64 (m).
1H NMR (400 MHz, CDCl3):  = 7.40 (s, 2 H), 4.64 (s, 2 H), 3.67 (s, 3 H),
MS (EI, 70 eV): m/z (%) = 482 (1), 443 (15), 254 (13), 252 (14), 249
(12), 225 (17), 209 (12), 207 (39), 203 (14), 202 (19), 196 (13), 189
(10), 183 (12), 165 (11), 123 (100), 117 (30), 115 (12), 109 (25), 107
(20), 105 (11), 103 (24), 89 (78), 87 (76), 77 (12), 75 (37), 61 (39), 59
(54).
HRMS (EI): m/z calcd for C29H43FO28Si2: 482.2836 [M – H2O]•+; found:
482.2829.
1.63 (s, 1 H), 0.99–0.92 (m, 18 H), 0.90–0.80 (m, 12 H).
13C NMR (101 MHz, CDCl3):  = 172.06, 137.38, 135.00, 129.01, 65.72,
63.64, 7.74, 4.22.
MS (EI, 70 eV): m/z (%) = 366 (1), 310 (21), 309 (69), 281 (23), 253
(12), 205 (15), 203 (45), 117 (13), 89 (14), 87 (12), 85 (15), 71 (22), 61
(14), 59 (12), 57 (33), 45 (15), 43 (100).
HRMS (EI): m/z calcd for C20H38O228Si2: 366.2410 [M]•+; found:
366.2398.
N-tert-Butyl-4-methoxy-3,5-bis(triethylsilyl)benzamide (3g)
According to GP3, anisole derivative 1a (168 mg, 0.5 mmol) and PMD-
TA (0.31 mL, 1.5 mmol) were dissolved in n-hexane (1 mL). A 2.55 M
solution of nBuLi in hexane (0.59 mL, 1.5 mmol) was added and the
resulting solution was stirred for 6 h. Afterwards, the mixture was
cooled to –20 °C and THF (1 mL) was added, followed by tert-butyl
isocyanate (0.20 mL, 1.75 mmol). Purification of the crude product by
flash column chromatography (silica gel, isohexane/EtOAc = 9:1) af-
forded the title compound as a colorless solid.
4-Methoxy-3,5-bis(triethylsilyl)benzaldehyde (3e)
According to GP3, anisole derivative 1a (168 mg, 0.5 mmol) and PMD-
TA (0.31 mL, 1.5 mmol) were dissolved in n-hexane (1 mL). A 2.55 M
solution of nBuLi in hexane (0.59 mL, 1.5 mmol) was added and the
resulting solution was stirred for 6 h. Afterwards, the mixture was
cooled to –20 °C and THF (1 mL) was added, followed by dimethylfor-
mamide (0.14 mL, 1.75 mmol). Purification of the crude product by
flash column chromatography (silica gel, isohexane/EtOAc = 19:1) af-
forded the title compound as a colorless oil.
Yield: 83 mg (0.19 mmol, 38%); mp 56.4–58.2 °C.
IR (diamond-ATR, neat): 3318 (vw), 2953 (m), 2909 (w), 2874 (w),
1634 (m), 1573 (w), 1532 (m), 1448 (w), 1365 (m), 1313 (m), 1211
Yield: 69 mg (0.19 mmol, 38%).
(s), 1165 (vw), 1104 (m), 1003 (s), 908 (m), 785 (w), 729 (vs) cm–1
.
IR (diamond-ATR, neat): 2952 (m), 2909 (w), 2874 (m), 1698 (s), 1571
(w), 1554 (w), 1456 (w), 1417 (w), 1380 (w), 1358 (m), 1212 (s), 1101
1H NMR (400 MHz, CDCl3):  = 7.74 (s, 2 H), 5.82 (s, 1 H), 3.68 (s, 3 H),
1.47 (s, 9 H), 0.98–0.90 (m, 18 H), 0.90–0.80 (m, 12 H).
13C NMR (101 MHz, CDCl3):  = 174.68, 167.57, 136.90, 130.72,
129.16, 63.58, 51.61, 29.06, 7.69, 4.12.
(s), 1003 (vs), 926 (m), 782 (m), 721 (vs), 684 (m) cm–1
.
1H NMR (400 MHz, CDCl3):  = 9.96 (s, 1 H), 7.94 (s, 2 H), 3.74 (s, 3 H),
0.98–0.83 (m, 30 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

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A. B. Bellan, P. Knochel
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Synthesis
MS (EI, 70 eV): m/z (%) = 434 (1), 406 (19), 380 (13), 379 (32), 378
(100), 351 (16), 350 (53), 322 (12), 318 (10), 294 (10), 217 (14), 89
(12), 87 (11), 57 (24), 43 (17).
HRMS (EI): m/z calcd for C24H44NO228Si2: 434.2911 [M – H]•+; found:
4-Formyl-2,6-bis(triethylsilyl)phenyl Diethylcarbamate (3j)
According to GP3, carbamate 1c (177 mg, 0.42 mmol) and PMDTA
(0.26 mL, 1.26 mmol) were dissolved in n-hexane (1 mL) and cooled
to –10 °C. A 2.55 M solution of nBuLi in hexane (0.50 mL, 1.26 mmol)
was added and the resulting solution was stirred for 6 h at –10 °C. Af-
terwards, the mixture was cooled to –20 °C and THF (1 mL) was add-
ed, followed by dimethylformamide (0.11 mL, 1.47 mmol). Purifica-
tion of the crude product by flash column chromatography (silica gel,
isohexane/EtOAc = 19:1) afforded the title compound as a slight yel-
low oil.
434.2899.
1-[3,5-Bis(triethylsilyl)phenyl]-2,2-dimethylpropan-1-ol (3h)
According to GP3, arene 1b (307 mg, 1.0 mmol) and PMDTA (0.63 mL,
3.0 mmol) were dissolved in n-hexane (2 mL). A 2.55 M solution of
nBuLi in hexane (1.18 mL, 3.0 mmol) was added and the resulting
solution was stirred for 6 h. Afterwards, the mixture was cooled to –
20 °C and THF (2 mL) was added, followed by trimethylacetaldehyde
(0.38 mL, 3.5 mmol). Purification of the crude product by flash col-
umn chromatography (silica gel, isohexane/EtOAc = 19:1) afforded
the title compound as a colorless oil.
Yield: 65 mg (0.14 mmol, 34%).
IR (diamond-ATR, neat): 2952 (w), 2909 (w), 2874 (w), 1716 (s), 1696
(s), 1564 (w), 1457 (w), 1424 (m), 1380 (m), 1363 (m), 1272 (s), 1221
(m), 1178 (m), 1145 (vs), 1100 (s), 1003 (s), 961 (m), 936 (m), 807
(w), 784 (m), 726 (vs), 671 (m) cm–1
.
1H NMR (599 MHz, CDCl3):  = 10.00 (s, 1 H), 7.97 (s, 2 H), 3.58 (q, J =
7.2 Hz, 2 H), 3.37 (q, J = 7.1 Hz, 2 H), 1.29 (t, J = 7.2 Hz, 3 H), 1.19 (t, J =
7.1 Hz, 3 H), 0.96–0.90 (m, 18 H), 0.88–0.76 (m, 12 H).
Yield: 228 mg (0.58 mmol, 58%).
IR (diamond-ATR, neat): 3455 (vw), 2952 (m), 2908 (w), 2874 (m),
1737 (vw), 1458 (w), 1416 (w), 1363 (w), 1235 (w), 1143 (w), 1055
(w), 1005 (s), 973 (w), 863 (vw), 801 (s), 719 (vs), 678 (s) cm–1
.
13C NMR (151 MHz, CDCl3):  = 192.09, 166.35, 154.02, 139.49,
1H NMR (400 MHz, CDCl3):  = 7.55 (t, J = 1.2 Hz, 1 H), 7.44 (d, J = 1.2
Hz, 2 H), 4.42 (s, 1 H), 2.00 (s, 1 H), 1.03–0.98 (m, 18 H), 0.94 (s, 9 H),
0.87–0.78 (m, 12 H).
132.61, 131.55, 40.82, 40.69, 13.73, 12.78, 7.34, 3.35.
MS (EI, 70 eV): m/z (%) = 448 (1), 422 (18), 421 (55), 420 (40), 179
(11), 168 (12), 100 (100), 72 (23).
13C NMR (101 MHz, CDCl3):  = 140.08, 139.40, 135.27, 133.98, 82.90,
HRMS (EI): m/z calcd for C24H42NO328Si2: 448.2703 [M – H]•+; found:
35.80, 26.08, 7.55, 3.58.
448.2693.
MS (EI, 70 eV): m/z (%) = 374 (8), 345 (30), 335 (34), 317 (40), 289
(51), 260 (16), 258 (13), 231 (47), 205 (17), 203 (82), 201 (19), 189
(13), 175 (100), 173 (39), 163 (13), 159 (14), 151 (31), 147 (13), 145
(41), 144 (18), 143 (16), 141 (19), 133 (30), 131 (24), 129 (34), 128
(32), 123 (38), 115 (22), 105 (15), 103 (23), 87 (68), 75 (17), 59 (45).
HRMS (EI): m/z calcd for C23H4228Si2: 374.2825 [M – H2O]•+; found:
374.2822.
4-Benzoyl-2,6-bis(triethylsilyl)phenyl Diethylcarbamate (3k)
According to GP3, carbamate 1c (211 mg, 0.5 mmol) and PMDTA
(0.31 mL, 1.5 mmol) were dissolved in n-hexane (1 mL) and cooled to
–10 °C. A 2.55 M solution of nBuLi in hexane (0.59 mL, 1.5 mmol) was
added and the resulting solution was stirred for 6 h at –10 °C. After-
wards, the mixture was cooled to –20 °C and THF (1 mL) was added,
followed by N-methoxy-N-methylbenzamide (0.27 mL, 1.75 mmol).
Purification of the crude product by flash column chromatography
(silica gel, isohexane/EtOAc = 19:1) afforded the title compound as a
slight yellow oil.
(5-Iodo-1,3-phenylene)bis(triethylsilane) (3i)
According to GP3, arene 1b (153 mg, 0.5 mmol) and PMDTA (0.31 mL,
1.5 mmol) were dissolved in n-hexane (1 mL). A 2.55 M solution of
nBuLi in hexane (0.59 mL, 1.5 mmol) was added and the resulting
solution was stirred for 6 h. Afterwards, the mixture was cooled to –
20 °C and 1.0 M ZnCl2 in THF (1.5 mL, 1.5 mmol) was added, followed
by a solution of I2 (444 mg, 1.75 mmol) in THF (1 mL). Purification of
the crude product by flash column chromatography (silica gel, isohex-
ane/EtOAc = 99:1) afforded the title compound as a colorless oil.
Yield: 116 mg (0.22 mmol, 44%).
IR (diamond-ATR, neat): 2952 (w), 2909 (w), 2874 (w), 1715 (s), 1657
(m), 1568 (vw), 1457 (w), 1426 (w), 1375 (m), 1315 (w), 1267 (vs),
1219 (w), 1183 (m), 1146 (vs), 1099 (s), 1002 (s), 967 (s), 852 (vw),
778 (s), 728 (s), 712 (vs), 691 (s) cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.92 (s, 2 H), 7.85–7.80 (m, 2 H), 7.61–
7.55 (m, 1 H), 7.50–7.44 (m, 2 H), 3.60 (q, J = 7.2 Hz, 2 H), 3.39 (q, J =
7.1 Hz, 2 H), 1.29 (t, J = 7.2 Hz, 3 H), 1.21 (t, J = 7.1 Hz, 3 H), 0.98–0.88
(m, 18 H), 0.85–0.75 (m, 12 H).
13C NMR (101 MHz, CDCl3):  = 196.63, 164.95, 154.36, 139.81,
137.95, 133.71, 132.40, 130.47, 130.21, 128.27, 40.93, 40.82, 13.87,
12.94, 7.50, 3.54.
Yield: 93 mg (22 mmol, 43%).
IR (diamond-ATR, neat): 2952 (m), 2908 (w), 2873 (m), 1529 (w),
1457 (w), 1414 (w), 1367 (w), 1235 (w), 1135 (s), 1099 (m), 1003 (s),
972 (w), 860 (w), 787 (vs), 716 (vs), 687 (vs) cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.77 (d, J = 1.0 Hz, 2 H), 7.53 (t, J = 1.1
Hz, 1 H), 1.01–0.93 (m, 18 H), 0.83–0.74 (m, 12 H).
13C NMR (101 MHz, CDCl3):  = 143.00, 140.27, 138.84, 96.88, 7.46,
3.40.
MS (EI, 70 eV): m/z (%) = 496 (19), 255 (17), 207 (35), 105 (12), 100
(100), 72 (55).
HRMS (EI): m/z calcd for C28H42NO328Si2: 496.2703 [M – Et]•+; found:
496.2703.
MS (EI, 70 eV): m/z (%) = 432 (11), 405 (10), 404 (29), 403 (100), 376
(16), 375 (53), 348 (12), 347 (48), 173 (12), 159 (18), 145 (14), 87 (15),
59 (13), 43 (42).
N,N-Diethyl-2,6-bis(triethylsilyl)-4-(trimethylsilyl)benzamide (3l)
HRMS (EI): m/z calcd for
C
18H33I28Si2: 432.1165 [M]•+; found:
According to GP3, benzamide 1d (203 mg, 0.5 mmol) and PMDTA
(0.31 mL, 1.5 mmol) were dissolved in n-hexane (1 mL). A 2.55 M
solution of nBuLi in hexane (0.59 mL, 1.5 mmol) was added and the
resulting solution was stirred for 6 h. Afterwards, the mixture was
cooled to –20 °C and THF (1 mL) was added, followed by Me3SiCl
432.1165.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

H
A. B. Bellan, P. Knochel
Paper
Synthesis
(0.22 mL, 1.75 mmol). Purification of the crude product by flash col-
umn chromatography (silica gel, isohexane) afforded the title com-
pound as a colorless solid.
IR (diamond-ATR, neat): 2951 (w), 2908 (w), 2872 (w), 1573 (w),
1455 (w), 1420 (w), 1239 (w), 1086 (w), 1055 (w), 1003 (m), 966 (w),
821 (w), 769 (m), 715 (vs), 685 (m) cm–1
.
Yield: 110 mg (0.23 mmol, 46%); mp 67.6–69.2 °C.
1H NMR (400 MHz, CDCl3):  = 7.58–7.54 (m, 1 H), 7.45 (d, J = 7.9 Hz, 1
H), 7.36–7.27 (m, 2 H), 7.20 (dd, J = 8.0, 2.0 Hz, 1 H), 7.14–7.10 (m, 1
H), 6.99 (d, J = 2.0 Hz, 1 H), 2.47 (s, 3 H), 0.87–0.75 (m, 18 H), 0.61–
0.28 (m, 12 H).
13C NMR (101 MHz, CDCl3):  = 151.51, 150.59, 138.10, 135.95,
135.80, 135.49, 132.00, 130.18, 127.71, 127.68, 126.31, 123.70, 15.07,
7.75, 7.69, 4.39, 4.29.
IR (diamond-ATR, neat): 2951 (s), 2909 (w), 2872 (m), 1622 (s), 1473
(w), 1456 (w), 1426 (m), 1379 (w), 1286 (m), 1248 (m), 1069 (w),
1002 (m), 881 (w), 851 (vs), 800 (m), 766 (w), 726 (vs), 689 (m) cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.66 (s, 2 H), 3.54 (q, J = 7.2 Hz, 2 H),
3.00 (q, J = 7.2 Hz, 2 H), 1.26 (t, J = 7.2 Hz, 3 H), 0.97 (t, J = 7.2 Hz, 3 H),
0.96–0.64 (m, 30 H), 0.27 (s, 9 H).
MS (EI, 70 eV): m/z (%) = 428 (1), 413 (19), 285 (11), 273 (18), 255
(40), 245 (11), 227 (25), 165 (13), 115 (33), 105 (13), 87 (100), 59 (36).
13C NMR (101 MHz, CDCl3):  = 172.46, 149.82, 141.05, 136.61,
131.84, 43.31, 38.63, 13.36, 12.90, 7.73, 4.05, –1.04.
HRMS (EI): m/z calcd for
C
25H40S28Si2: 428.2389 [M]•+; found:
MS (EI, 70 eV): m/z (%) = 476 (1), 450 (15), 449 (37), 448 (100), 43
(17).
428.2382.
HRMS (EI): m/z calcd for C26H50NO28Si3: 476.3200 [M – H]•+; found:
476.3202.
Compound 3n′
Yield: 17 mg (0.04 mmol, 9%); colorless solid; mp 71.3–73.7 °C.
IR (diamond-ATR, neat): 2949 (m), 2930 (w), 2906 (w), 2870 (w),
1585 (vw), 1453 (w), 1418 (w), 1375 (vw), 1360 (w), 1320 (vw), 1234
(w), 1149 (vw), 1121 (w), 1108 (w), 1091 (w), 1012 (m), 996 (w), 973
(w), 948 (vw), 833 (w), 810 (vw), 769 (w), 751 (w), 728 (vs), 716 (vs),
N,N-Diethyl-4-(phenylthio)-2,6-bis(triethylsilyl)benzamide (3m)
According to GP3, benzamide 1d (203 mg, 0.5 mmol) and PMDTA
(0.31 mL, 1.5 mmol) were dissolved in n-hexane (1 mL). A 2.55 M
solution of nBuLi in hexane (0.59 mL, 1.5 mmol) was added and the
resulting solution was stirred for 6 h. Afterwards, the mixture was
cooled to –20 °C and THF (1 mL) was added, followed by diphenyl di-
sulfide (382 mg, 1.75 mmol). Purification of the crude product by
flash column chromatography (silica gel, isohexane) afforded the title
compound as an orange oil.
680 (m), 667 (m) cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.56–7.52 (m, 1 H), 7.45 (d, J = 2.1 Hz, 1
H), 7.34–7.27 (m, 2 H), 7.21 (dd, J = 8.0, 2.1 Hz, 1 H), 7.10–7.07 (m, 1
H), 7.05 (d, J = 8.0 Hz, 1 H), 2.53 (s, 3 H), 0.80 (td, J = 7.9, 1.7 Hz, 18 H),
0.57–0.31 (m, 12 H).
Yield: 112 mg (0.22 mmol, 44%).
13C NMR (101 MHz, CDCl3):  = 150.43, 148.20, 136.96, 136.11,
135.91, 135.48, 133.96, 130.84, 130.46, 127.68, 126.23, 126.17, 16.57,
7.74, 7.73, 4.40, 4.29.
IR (diamond-ATR, neat): 2951 (m), 2908 (w), 2873 (m), 1632 (s), 1545
(w), 1473 (w), 1457 (m), 1423 (m), 1378 (w), 1280 (m), 1222 (w),
1124 (m), 1067 (w), 1001 (s), 872 (w), 793 (vs), 722 (vs), 688 (vs) cm–1
.
MS (EI, 70 eV): m/z (%) = 428 (18), 400 (29), 227 (11), 115 (69), 88
(12), 87 (63), 70 (11), 61 (20), 59 (26), 45 (15), 43 (100).
1H NMR (599 MHz, CDCl3):  = 7.42 (d, J = 0.8 Hz, 2 H), 7.35–7.28 (m, 4
H), 7.27–7.23 (m, 1 H), 3.52 (q, J = 7.2 Hz, 2 H), 3.00 (q, J = 7.2 Hz, 2 H),
1.25 (td, J = 7.3, 0.7 Hz, 3 H), 0.96 (t, J = 7.3 Hz, 3 H), 0.88–0.60 (m, 30
H).
HRMS (EI): m/z calcd for
C
25H40S28Si2: 428.2389 [M]•+; found:
428.2380.
13C NMR (151 MHz, CDCl3):  = 171.98, 148.03, 137.72, 135.38,
135.08, 133.77, 131.38, 129.32, 127.30, 43.29, 38.75, 13.32, 12.81,
7.58, 3.75.
[5-Allyl-1,1′-biphenyl-2,2′-diyl]bis(triethylsilane) (3o)
According to GP3, biphenyl 1e (172 mg, 0.45 mmol) and PMDTA
(0.28 mL, 1.35 mmol) were dissolved in n-hexane (1 mL). A 2.55 M
solution of nBuLi in hexane (0.53 mL, 1.35 mmol) was added and the
resulting solution was stirred for 6 h. Afterwards, the mixture was
cooled to –20 °C and 1.0 M ZnCl2 in THF (1.5 mL, 1.5 mmol) and
CuCN•2LiCl (0.05 mL, 0.05 mmol, 0.11 equiv) were added, followed by
allyl bromide (0.14 mL, 1.58 mmol). Purification of the crude product
by flash column chromatography (silica gel, isohexane) afforded a
MS (EI, 70 eV): m/z (%) = 512 (1), 486 (10), 485 (38), 484 (100), 368
(13), 340 (16), 225 (16), 213 (15), 207 (34), 109 (13), 87 (23), 75 (12),
59 (24).
HRMS (EI): m/z calcd for C29H46NOS28Si2: 512.2839 [M – H]•+; found:
512.2836.
mixture of the regioisomers as
(0.31 mmol, 69%). The mixture was further purified by HPLC and the
major regioisomer was isolated as a colorless oil.
a colorless oil; yield: 131 mg
[5-(Methylthio)-1,1′-biphenyl-2,2′-diyl]bis(triethylsilane) (3n)
and [4-(Methylthio)-1,1′-biphenyl-2,2′-diyl]bis(triethylsilane)
(3n′)
Yield: 112 mg (0.27 mmol, 59%).
According to GP3, biphenyl 1e (172 mg, 0.45 mmol) and PMDTA
(0.28 mL, 1.35 mmol) were dissolved in n-hexane (1 mL). A 2.55 M
solution of nBuLi in hexane (0.53 mL, 1.35 mmol) was added and the
resulting solution was stirred for 6 h. Afterwards, the mixture was
cooled to –20 °C and THF (1 mL) was added, followed by dimethyl di-
sulfide (0.14 mL, 1.58 mmol). Purification of the crude product by
flash column chromatography (silica gel, isohexane) afforded a mix-
ture of the regioisomers as a colorless oil; yield: 120 mg (0.28 mmol,
62%). The mixture of regioisomers was further purified by HPLC
yielding 3n (53%) as a colorless oil and 3n′ (9%) as a colorless solid.
IR (diamond-ATR, neat): 2951 (w), 2908 (w), 2873 (w), 1458 (w),
1415 (w), 1235 (vw), 1094 (w), 1003 (m), 973 (vw), 913 (w), 770 (w),
711 (vs), 677 (m) cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.60–7.55 (m, 1 H), 7.51 (d, J = 7.7 Hz, 1
H), 7.36–7.29 (m, 2 H), 7.20–7.12 (m, 2 H), 6.99 (d, J = 1.9 Hz, 1 H),
6.14–5.90 (m, 1 H), 5.17–5.04 (m, 2 H), 3.43–3.38 (m, 2 H), 0.82 (td, J =
7.9, 1.2 Hz, 18 H), 0.64–0.26 (m, 12 H).
13C NMR (101 MHz, CDCl3):  = 151.24, 151.16, 139.40, 137.20,
135.95, 135.66, 135.44, 133.21, 130.75, 130.29, 127.58, 126.41,
126.08, 116.11, 40.26, 7.74, 7.73, 4.36, 4.32.
Compound 3n
Yield: 102 mg (0.24 mmol, 53%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

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A. B. Bellan, P. Knochel
Paper
Synthesis
MS (EI, 70 eV): m/z (%) = 422 (1), 306 (10), 267 (45), 250 (16), 249
(100), 239 (14), 221 (38), 217 (12), 115 (40), 105 (14), 87 (98), 59 (36).
Funding Information
We thank the Deutsche Forschungsgemeinschaft (DFG) for financial
support. We thank Albemarle (Frankfurt, Germany) for the generous
gift of chemicals.()
HRMS (EI): m/z calcd for C27H4228Si2: 422.2825 [M]•+; found: 422.2819.
2′,6-Bis(triethylsilyl)-1,1′-biphenyl-3-carbaldehyde (3p)
According to GP3, biphenyl 1e (172 mg, 0.45 mmol) and PMDTA
(0.28 mL, 1.35 mmol) were dissolved in n-hexane (1 mL). A 2.55 M
solution of nBuLi in hexane (0.53 mL, 1.35 mmol) was added and the
resulting solution was stirred for 6 h. Afterwards, the mixture was
cooled to –20 °C and THF (1 mL) was added, followed by dimethylfor-
mamide (0.12 mL, 1.58 mmol). Purification of the crude product by
flash column chromatography (silica gel, isohexane) afforded a mix-
ture of the regioisomers as a yellow oil; yield: 122 mg (0.30 mmol,
67%).The mixture was further purified by HPLC and the major regio-
isomer was isolated as a yellow oil.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611480.
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References
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J. E.; Williams, R. M., Ed.; Pergamon: Oxford, 2002. (b) Mongin,
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D.; Chevallier, F.; Mongin, F.; Gros, P. C. Chem. Rev. 2014, 114,
1207.
Yield: 106 mg (0.26 mmol, 57%).
IR (diamond-ATR, neat): 2952 (w), 2909 (w), 2873 (w), 1701 (s), 1457
(w), 1416 (vw), 1376 (w), 1237 (w), 1174 (w), 1121 (vw), 1091 (vw),
1003 (m), 962 (vw), 706 (vs) cm–1
.
(2) (a) Beak, P.; Snieckus, V. Acc. Chem. Res. 1982, 15, 306. (b) Ray,
D. R.; Song, Z.; Smith, S. G.; Beak, P. J. Am. Chem. Soc. 1988, 110,
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E.; Mongin, F.; Schlosser, M. Eur. J. Org. Chem. 2007, 669.
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(5) (a) Frischmuth, A.; Fernández, M.; Barl, N. M.; Achrainer, F.;
Zipse, H.; Berionni, G.; Mayr, H.; Karaghiosoff, K.; Knochel, P.
Angew. Chem. Int. Ed. 2014, 53, 7928. (b) Ketels, M.; Ziegler, D.
S.; Knochel, P. Synlett 2017, 28, 2817.
1H NMR (400 MHz, CDCl3):  = 10.02 (s, 1 H), 7.82 (dd, J = 7.7, 1.7 Hz, 1
H), 7.74 (d, J = 7.7 Hz, 1 H), 7.62–7.57 (m, 2 H), 7.34 (pd, J = 7.4, 1.6 Hz,
2 H), 7.12–7.07 (m, 1 H), 0.80 (td, J = 7.9, 3.7 Hz, 18 H), 0.59–0.27 (m,
12 H).
13C NMR (101 MHz, CDCl3):  = 192.70, 151.93, 149.60, 145.16,
136.11, 136.08, 135.70, 135.30, 131.16, 130.16, 127.87, 126.73,
126.67, 7.69, 7.64, 4.46, 4.17.
MS (EI, 70 eV): m/z (%) = 410 (1), 381 (13), 209 (20), 115 (21), 105
(14), 87 (100), 59 (43).
HRMS (EI): m/z calcd for
C
25H38O28Si: 410.2461 [M]•+; found:
410.2461.
(6) (a) Schakel, M.; Aarnts, M. P.; Klumpp, G. W. Recl. Trav. Chim.
Pays-Bas 1990, 109, 305. (b) Strohmann, C.; Gessner, V. H.
Angew. Chem. Int. Ed. 2007, 46, 4566.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I