Preparation and reactions of (1 H-tetrazol-5-yl)zinc pivalates

Article abstract of DOI:10.1055/s-0039-1691734

The preparation and reactivity of new solid heterocyclic organozinc reagents, namely N -protected (1 H -tetrazol-5-yl)zinc pivalates, as storable solids with appreciably air and moisture stability are reported. They are obtained in high yields from protected 1 H -tetrazoles by de-protonation using the mixed zinc-magnesium base TMPZnCl·Mg(OPiv) ₂(abbreviated as TMPZnOPiv; TMP = 2,2,6,6-tetramethylpiperidyl). Subsequent cross-couplings and copper-catalyzed electrophilic aminations using hydroxylamine benzoates give access to functionalized 1 H -tetrazoles while tolerating many functional groups.

Full text of DOI:10.1055/s-0039-1691734

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2020, 52, A–G
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C. P. Tüllmann et al.
Paper
Synthesis
Preparation and Reactions of (1H-Tetrazol-5-yl)zinc Pivalates
Carl Phillip Tüllmann
N
Sebastian Steiner
N
N
N
Paul Knochel*
0
0
0
0-0
0
0
1-7
9
1
3-
4
3
3
2
N
N
BzO
N
TMPZnOPiv
THF, 0 °C, 1 h
PMB
ZnOPiv
Department of Chemistry, Ludwig-Maximilian-University,
Butenandtstraße 5–13, 81377 Munich, Germany
Paul.Knochel@cup.uni-muenchen.de
PMB
Cu(OTf)2 (10 mol%)
THF, 25 °C, 2 h
N
N
N
PMB
N
N
N
N
N
N
N
N
N
Published as part of the Special Issue dedicated to Tomáš
Hudlický on the occasion of his 70th birthday
N
N
71%
ZnCl
·MgOPiv
Dedicated to Tomas Hudlicky for his 70th birthday.
Received: 24.01.2020
Accepted after revision: 04.02.2020
Published online: 20.02.2020
N
NH
N
DOI: 10.1055/s-0039-1691734; Art ID: ss-2020-t0053-op
N
NH
N
N
HO
O
Abstract The preparation and reactivity of new solid heterocyclic or-
ganozinc reagents, namely N-protected (1H-tetrazol-5-yl)zinc pivalates,
as storable solids with appreciably air and moisture stability are report-
ed. They are obtained in high yields from protected 1H-tetrazoles by de-
protonation using the mixed zinc–magnesium base TMPZnCl·Mg(OPiv)2
(abbreviated as TMPZnOPiv; TMP = 2,2,6,6-tetramethylpiperidyl). Sub-
sequent cross-couplings and copper-catalyzed electrophilic aminations
using hydroxylamine benzoates give access to functionalized 1H-tetra-
zoles while tolerating many functional groups.
N
Bu
N
N
N
N
OEt
HO
Cl
Candesartan
Losartan
Figure 1 Pharmaceuticals containing a 1H-tetrazole ring
Other methods include the reaction of triethoxymethane
with sodium azide and primary amines in acidic acid11a or a
three-component reaction of isocyanides, carbodiimides,
and trimethylsilyl azide.11b
Key words zinc, tetrazole, cross-coupling, amination, organozinc piv-
alates
The 1H-tetrazole scaffold is a popular building block in
pharmaceutical chemistry and materials science.1 It has
been used for many different purposes, for example, in li-
gands,2 explosives3 or propellants.4 5-Substituted 1H-tetra-
zoles play also an important role in medicinal chemistry
and biology.5–8 Based on steric and electrophilic consider-
ations, they are considered as non-classical isosteres or bio-
isosteres of the carboxylic acid moiety.5a Interestingly, they
possess very similar physicochemical and biological prop-
erties. Both are planar and acidic with a close pKa value (4.2
to 4.9) and thus, both are ionized at a physiological pH val-
ue of 7.4.5b Due to these useful pharmacological properties,
1H-tetrazoles have been incorporated in several target drug
molecules including anticancer6 or antiviral7 medications,
such as anti-HIV8 and others. Candesartan is a well-known
drug that is used for the treatment of hypertension and
heart failure. Losartan is mainly used to treat high blood
pressure (Figure 1).9,10
Until now, the usage of 1H-tetrazoles as nucleophilic re-
agents has been limited to lithium,12, tin,5 potassium, and
magnesium derivatives.13 Langille and co-workers have
achieved a zinc insertion in the 5-position and have used
the zincated tetrazole for a subsequent Negishi cross-
coupling.13
Recently, we have reported14 a new class of zinc organo-
metallics of the general formula RZnX·Mg(OPiv)2·nLiCl (ab-
breviated as RZnOPiv).15 The nature of R can be quite di-
verse: aryl,16 heteroaryl,17 benzyl,16c,18 alkynyl,19 ethynyl,20
allyl,21 and C-enolates.22 Due to the presence of Mg(OPiv)2,
these new zinc reagents show an enhanced air and mois-
ture stability.15
Herein, we wish to report the preparation and reactivity
of new organozinc pivalates, namely (1H-tetrazol-5-yl)zinc
pivalates 2a,b as storable solids with appreciably air and
moisture stability (91–92% activity as determined after 4 h
exposure to air; Table 1). They are obtained in quantitative
yields from the protected 1H-tetrazoles of type 1 by deprotona-
tion using the mixed zinc–magnesium base TMPZnCl·Mg(OPiv)2
(abbreviated as TMPZnOPiv; TMP = 2,2,6,6-tetramethyl-
5-Substituted-1H-tetrazoles were synthesized by a
number of methods. The most common way is via [3+2] di-
polar cycloaddition reactions between azides and nitriles.1
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
C. P. Tüllmann et al.
Paper
Synthesis
piperidyl)19a in THF at room temperature for 1 hour. After
solvent evaporation, 2a and 2b were obtained as white
powders in quantitative yields as indicated by titration with
iodine.23 The resulting powders can be handled for a short
time on the benchtop and retain more than 91% activity af-
ter an air exposure of 4 hours at 25 °C (Table 1).
Table 2 (continued)
Entry Aryl bromide 3
Product 4a
O
tBuHN
O
Br
2
PMB
tBuHN
N
3b
Table 1 Activity of (1H-Tetrazol-5-yl)zinc Pivalates 2a,b after Exposure
N
N
N
to Air at 25 °Ca
4b: 67%
OHC
H
PG
PivOZn
PG
TMPZnOPiv
N
N
N
N
N
N
THF, RT, 0 °C, 1 h
N
N
PMB
OHC
Br
3
4
5
6
7
N
1a,b
2a,b
3c
N
N
N
Entry
Time (h)
2a (PG = Bn)
2b (PG = PMB)
4c: 82%
EtO2C
1
2
3
4
0
1
2
4
100%
96%
93%
91%
100%
97%
95%
92%
EtO2C
Br
PMB
N
3d
N
N
N
a Activity determined by titration with iodine.23
4d: 58%
NC
Furthermore, we have examined the reactivity of these
new solid (1H-tetrazol-5-yl)zinc pivalates 2a,b in Negishi
cross-coupling reactions24 with various aryl halides using
the more air stable tetrazole 2b. The screening of several
palladium catalysts showed that the Buchwald ligand,
SPhos25 (10 mol%), gave the best results in combination
with Pd(OAc)2 (5 mol%). Under these conditions, a range of
(hetero)aryl bromides of type 3 underwent smooth Negishi
cross-couplings, producing arylated tetrazoles of type 4 in
58–90% yield (Table 2). Remarkably, a variety of sensitive
functional groups, such as an amide (Table 2, entry 2), an
aldehyde (entry 3), an ester (entry 4), a nitrile (entry 5), ei-
ther a protected or unprotected amine (entries 6, 7), and an
unprotected indole (entry 8) were tolerated in these cross-
couplings reactions.
PMB
NC
Br
N
3e
N
N
N
4e: 65%
Me2N
PMB
Me2N
Br
N
3f
N
N
N
4f: 74%
H2N
H2N
PMB
Br
N
3g
N
N
N
Table 2 Negishi Cross-Coupling of (1H-Tetrazol-5-yl)zinc Pivalate 2b
with Aryl Bromides 3
4g: 68%
HN
R
PivOZn
PMB
Pd(OAc)2 (5 mol%)
SPhos (10 mol%)
PMB
Br
Br
N
HN
PMB
8
N
R
+
N
N
N
N
N
THF, 40 °C, 12 h
N
3h
N
N
N
4
N
2b
3
4h: 62%
aYield of isolated product.
Entry
Aryl bromide 3
Product 4a
PivOZn
Bn
PivOZn
PMB
N
N
Next, we have examined the debenzylation of several
previously obtained arylated tetrazoles of type 4. The use of
ammonium formate with palladium on charcoal (5 mol%) in
iPrOH/H2O (1:1) at 60 °C for 24 hours proved to be an excellent
N
N
N
N
1
N
N
2a
2b
3a
4a: 90%
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C. P. Tüllmann et al.
Paper
Synthesis
Table 3 Debenzylation of Arylated 1H-Tetrazoles 4
After evaporation of the solvent, the products were ob-
tained as white powders showing enhanced air and mois-
ture stability. These reagents underwent Negishi cross-cou-
plings with various bromides. Several obtained products
were successfully debenzylated using ammonium formate
with palladium on charcoal. The copper-catalyzed amina-
tion with hydroxylamine benzoates, gave access to substi-
tuted tetrazoles while tolerating several functional groups.
Further scope extensions are currently explored in our lab-
oratories.
R
R
H
PMB
HCO2NH4, Pd/C
N
N
iPrOH/H2O, 60 °C, 24 h
N
N
N
N
N
N
4
5
5
R
Yield (%)
5a
5b
5c
5d
OMe
CF3
95
93
88
92
CO2Et
NMe2
All reactions were carried out under an argon atmosphere in flame-
dried glassware. Syringes which were used to transfer anhydrous sol-
vents or reagents were purged with argon prior to use. THF was con-
tinuously refluxed and freshly distilled from sodium benzophenone
ketyl under N2 and stored over molecular sieves. EtOAc was purchased
from Sigma-Aldrich with a purity of 99% and used without distillation
or drying prior to use. Yields refer to isolated yields of compounds es-
timated to be >95% pure as determined by 1H NMR spectroscopy
(25 °C) and capillary GC-analyses. Column chromatography was per-
formed using SiO2 (0.040–0.063 mm, 230–400 mesh ASTM) from
Merck. Melting points were measured using a Büchi B-540 apparatus
and are uncorrected. NMR spectra were recorded in CDCl3 or DMSO-
d6 and chemical shifts are reported in parts per million (ppm). Stan-
dard abbreviations were used to denote signal coupling . Mass spectra
and high-resolution mass spectra (HRMS) were recorded using elec-
tron ionization (EI), except otherwise noted. GCs were recorded on
machines of the types Hewlett-Packard 6890 or 5890 Series II (Hewl-
ett Packard, 5% phenylmethylpolysiloxane; length: 10 m, diameter:
0.25 mm; film thickness: 0.25 m).
choice,26 providing the desired unprotected 1H-tetrazoles
of type 5 in 88–95% yield (Table 3).
In addition, the metalated tetrazole 2b underwent a
copper-catalyzed electrophilic amination using N-hydrox-
ylamine benzoates.27 Thus, tetrazole 2b was aminated with
hydroxylamine benzoates of type 6 in the presence of cop-
per(II) triflate (10 mol%) in THF at 25 °C for 2 hours leading
to different 5-amino-1H-tetrazoles of type 6 in 71–93%
yield (Scheme 1). Hydroxylamine benzoates derived from
biologically active molecules such as nicotinic acid 7a or
sertraline 7d28 were functionalized using this method.
In summary, we have achieved the metalation and func-
tionalization of 1H-tetrazoles 2a and 2b in 5-position utilizing
the sterically hindered TMP-zinc base TMPZnCl·Mg(OPiv)2.
The metalations were performed under mild conditions.
Stability Studies of Zinc Reagents in Air
To evaluate the stability of organozinc reagents in air, accurately
weighed aliquots of the solid material were placed in open Schlenk
flasks at 25 °C. After exposure to air for a given time, the flask was
closed, evacuated, filled with argon, and the contents were dissolved
in THF. The resulting solution was titrated against I2 and the mea-
sured concentration was compared to the one before the exposure to
air.23
R1
PivOZn
PMB
R2
PMB
N
R1
R2
Cu(OTf)2 (10 mol%)
THF, 25 °C, 2 h
N
N
BzO
N
+
N
N
N
N
N
N
2b
6
7
N
TMPZnCl·Mg(OPiv)2 (TMPZnOPiv)21
A dry and argon-flushed Schlenk flask equipped with a magnetic stir-
rer and a septum was charged with THF (10 mL). Subsequently,
2,2,6,6-tetramethylpiperidine (3.56 mL, 21 mmol, 1.05 equiv) was
dissolved and a solution of benzylmagnesium chloride in THF (10 mL,
2 M, 20 mmol, 1.00 equiv) was added dropwise. The solution was
stirred overnight at 40 °C. Then, Zn(OPiv)2 (5.34 g, 20 mmol, 1.0
equiv) was added in portions and the suspension was stirred at RT for
20 min. TMPZnOPiv was obtained as a brownish liquid in quantitative
yield and was titrated with benzoic acid using 4-(phenylazo)diphe-
nylamine as indicator.
N
N
N
O
N
N
N
N
N
OEt
N
N
PMB
N
N
PMB
7a 93%
7b 71%
Cl
Cl
F
Ph
PMB
N
Me
N
N
N
F
O
N
N
PMB
N
N
Metalation of Tetrazoles Using TMPZnOPiv and Subsequent
Negishi Cross-Coupling with Aryl Halides; 1-(4-Methoxybenzyl)-5-
(4-methoxyphenyl)-1H-tetrazole (4a); Typical Procedure (TP1)
N
N
7c 73%
7d 85%
A dry and argon-flushed flask equipped with a magnetic stirrer and a
septum was charged with THF. Subsequently, 1-(4-methoxybenzyl)-
1H-tetrazole (1b; 95 mg, 0.6 mmol, 1.2 equiv) was dissolved and
TMPZnOPiv (1.25 mmol, 2.5 equiv) was added dropwise while cooling
Scheme 1 Amination of (1H-tetrazol-5-yl)zinc pivalate 2b using
hydroxylamine benzoates in the presence of catalytic amounts of
Cu(OTf)2
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

D
C. P. Tüllmann et al.
Paper
Synthesis
with an ice-bath. The solution was stirred for 1 h and allowed to
warm to RT. Then, 1-bromo-4-methoxybenzene (3a; 93.5 mg, 0.5
mmol), Pd(OAc)2 (4 mg, 0.025 mmol, 5 mol%), and SPhos (20 mg, 0.05
mmol, 10 mol%) were added and the mixture was stirred overnight at
45 °C. The suspension was quenched with sat. aq NH4Cl and extracted
with EtOAc (3 × 15 mL). The combined organic layers were dried
(MgSO4) and the solvent was evaporated in vacuo. The product was
purified by flash column chromatography (isohexane/EtOAc 9:1 + 5%
Et3N) and obtained as a white solid; yield: 133 mg (90%, 0.45 mmol);
mp 118–120 °C.
ed. After stirring the reaction mixture for 1–2 h at 0 °C, the solvent
was removed in vacuo (at least 6 h) and the dried solid 2a was ob-
tained as a fine powder in quantitative yield.
[1-(4-Methoxybenzyl)-1H-tetrazol-5-yl]zinc Pivalate (2b)
A dry and argon-flushed Schlenk-flask equipped with a magnetic stir-
ring bar and a septum was charged with the 1-(4-methoxybenzyl)-
1H-tetrazole (1b; 0.95 g, 5.0 mmol). TMPZnOPiv (0.6 M in THF, 6.0
mmol) was added. After stirring the reaction mixture for 1–2 h at
0 °C, the solvent was removed in vacuo (at least 6 h) and the dried sol-
id 2b was obtained as a fine powder in quantitative yield.
For spectral data, see below.
Deprotection of Aryltetrazoles Using Ammonium Formate; Gen-
eral Procedure 1 (GP1)
1-(4-Methoxybenzyl)-5-(4-methoxyphenyl)-1H-tetrazole (4a)
Compound 4a was prepared from 1b and 3a as described in TP1.
A pressure resistant flask equipped with a cover and a magnetic stir-
rer was charged with H2O and iPrOH in equal ratio. Subsequently, the
protected aryltetrazole of type 4 (0.2 mmol, 1.0 equiv) was suspend-
ed and Pd/C (50 mg, 0.05 mmol, 5 mol%) and ammonium formate
(198 mg, 3.15 mmol, 15 equiv) were added. The reaction mixture was
stirred overnight at 65 °C. The suspension was filtered through Celite
and washed with iPrOH. The filtrate was extracted with DCM (3 ×)
and the combined organic layers were dried (MgSO4). The solvent was
evaporated in vacuo. The residue was purified via column chromatog-
raphy to afford the desired product.
IR (Diamond-ATR, neat): 3072 (w), 2929 (s), 2842 (w), 1601(s), 1449
(w), 1294 (vw), 1163 cm–1 (w).
1H NMR (400 MHz, CDCl3):  = 7.50–7.44 (m, 2 H), 7.07–6.99 (m, 2 H),
6.98–6.89 (m, 2 H), 6.83–6.75 (m, 2 H), 5.47 (s, 2 H), 3.80 (s, 3 H), 3.72
(s, 3 H).
13C NMR (100 MHz, CDCl3):  = 161.9, 154.6, 134.1, 130.4, 129.2,
129.0, 128.7, 127.9, 127.4, 127.1, 115.7, 114.7, 55.5, 51.3, 27.1, 26.7.
MS (EI, 70 eV): m/z (%) = 296 (4), 121 (100), 97 (12), 85 (13), 71 (17),
57 (24), 43 (21).
HRMS (EI): m/z calcd for [C16H16N4O2]: 296.1273; found: 296.1268
Amination of Tetrazoles Using TMPZnOPiv and Amine Benzoate;
Ethyl 1-[1-(4-Methoxybenzyl)-1H-tetrazol-5-yl]piperidine-3-car-
boxylate (7a); Typical Procedure (TP2)
(M+).
The 1H data are in accordance with those reported in the literature.29
1-(4-Methoxybenzyl)-1H-tetrazole (1b; 0.5 mmol, 95 mg) was dis-
solved in THF (1.5 mL) and cooled to 0 °C. TMPZnOPiv solution (1
mmol, 2.0 equiv) was slowly added to the stirred solution. A dry, ar-
gon flushed Schlenk flask equipped with magnetic stirring bar and
septum was charged with 1-(benzoyloxy)piperidine-3-carboxylate
(6a; 138 mg, 0.5 mmol, 1.0 equiv), Cu(OTf)2 (36 mg, 0.1 mmol,
20 mol%), and THF (2.0 mL). To a vigorously stirred solution of the lat-
ter was added slowly the above prepared solution of the zinc pivalate
species. After 2 h, the mixture was quenched with sat. aq NH4Cl (15
mL), extracted with DCM (3 × 15 mL) and dried (MgSO4). The desired
product was obtained after column chromatography (silica gel, iso-
hexane/EtOAc 1:1); colorless solid; yield: 163 mg (0.475 mmol, 93%);
mp 172–175 °C.
N-(tert-Butyl)-4-[1-(4-methoxybenzyl)-1H-tetrazol-5-yl]ben-
zamide (4b)
Compound 4b was prepared according to TP1 using 4-bromo-N-(tert-
butyl)benzamide (3b; 128 mg, 0.5 mmol, 1.0 equiv) as electrophile.
The product was purified by flash column chromatography
(isohexane/EtOAc 2:1 + 5% Et3N); yield: 122 mg (0.335 mmol, 67%);
white solid; mp 120–125 °C.
IR (Diamond-ATR, neat): 3418 (w), 2965 (m), 2361 (w), 1590 (s), 1420
(s), 1278 (s), 1023 (s), 720 cm–1 (s).
1H NMR (400 MHz, CDCl3):  = 7.81 (d, J = 8.4 Hz, 2 H), 7.57 (d, J = 8.4
Hz, 2 H), 7.04 (d, J = 8.7 Hz, 2 H), 6.81 (d, J = 8.7 Hz, 2 H), 6.27 (s, 1 H),
5.50 (s, 2 H), 3.74 (s, 3 H), 1.45 (s, 9 H).
For spectral data, see below.
13C NMR (101 MHz, CDCl3):  = 165.7, 160.1, 153.9, 138.6, 129.2,
128.9, 127.7, 126.4, 125.7, 114.7, 55.5, 52.2, 51.3, 28.9.
Protected 1H-Tetrazoles
1H-tetrazoles 1a,b were prepared according to the literature.13
MS (EI, 70 eV): m/z (%) = 365 (16), 293 (10), 122 (7), 121 (100).
HRMS (EI): m/z calcd for [C20H23N5O2]: 365.1852; found: 365.1846
The respective benzylamine (100 mmol, 1.0 equiv), triethyl orthofor-
mate (23.68 g, 160 mmol, 1.60 equiv), and NaN3 (9.75 g, 150 mmol,
1.50 equiv) were suspended in AcOH (100 mL) and stirred at 85 °C for
12 h. The mixture was cooled to RT and the solvents were evaporated
in vacuo. The residue was diluted with H2O and extracted with EtOAc
(2 ×). The combined organic layers were washed with 1 M aq HCl,
H2O, sat. aq NaHCO3, and brine. Subsequently, they were dried
(MgSO4) and the solvent was evaporated in vacuo. The residue was
purified by flash chromatography (silica gel, isohexane/EtOAc 1:1).
(M+).
4-[1-(4-Methoxybenzyl)-1H-tetrazol-5-yl]benzaldehyde (4c)
Compound 4c was prepared according to TP1 using 4-bromobenzal-
dehyde (3c; 93 mg, 0.5 mmol, 1.0 equiv) as electrophile. The product
was purified by flash column chromatography (isohexane/EtOAc 2:1 +
5% Et3N); yield: 120 mg (0.41 mmol, 82%); colorless oil.
IR (Diamond-ATR, neat): 2961 (w), 1714 (m), 1513 (s), 1253 (vs),
1246 (s), 1178 (s), 1028 (s), 687 cm–1 (s).
1H NMR (400 MHz, CDCl3):  = 10.04 (s, 1 H), 8.06–7.84 (m, 2 H), 7.84–
7.60 (m, 2 H), 7.06–6.95 (m, 2 H), 6.89–6.68 (m, 2 H), 5.52 (s, 2 H),
3.73 (s, 3 H).
(1-Benzyl-1H-tetrazol-5-yl)zinc Pivalate (2a)
A dry and argon-flushed Schlenk-flask equipped with a magnetic stir-
ring bar and a septum was charged with the 1-benzyl-1H-tetrazole
(1a; 0.8 g, 5.0 mmol). TMPZnOPiv (0.6 M in THF, 6.0 mmol) was add-
13C NMR (101 MHz, CDCl3):  = 165.5, 159.9, 153.8, 133.0, 130.2,
127.9, 125.5, 114.6, 61.6, 55.3, 51.3, 14.3.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

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C. P. Tüllmann et al.
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Synthesis
MS (70 eV, EI): m/z (%) = 294 (5), 238 (14), 207 (3), 122 (9), 121 (110),
91 (6), 77 (5).
HRMS (EI): m/z calcd for [C17H19N5O]: 309.3730; found: 309.1579
(M+).
HRMS (EI): m/z calcd for [C16H14N4O2]: 294.1117; found: 294.1111
(M+).
4-[1-(4-Methoxybenzyl)-1H-tetrazol-5-yl]aniline (4g)
Compoun 4g was prepared according to TP1 using 4-bromoaniline
(3g; 86 mg, 0.5 mmol, 1.0 equiv) as electrophile. The product was pu-
rified by flash column chromatography (isohexane/EtOAc 1:2 + 5%
Et3N); yield: 95 mg (0.34 mmol, 68%); colorless solid; mp 118–120 °C.
Ethyl 4-[1-(4-Methoxybenzyl)-1H-tetrazol-5-yl]benzoate (4d)
Compound 4d was prepared according to TP1 using ethyl 4-bromo-
benzoate (3d; 106 mg, 0.5 mmol, 1.0 equiv) as electrophile. The prod-
uct was purified by flash column chromatography (isohexane/EtOAc
2:1 + 5% Et3N); yield: 98 mg (0.29 mmol, 58%); colorless solid; mp
110–114 °C.
IR (Diamond-ATR, neat): 2924 (m), 1612 (vs), 1514 (s), 1492 (s), 1252
(m), 847 (m), 776 (vs), 742 (s).
1H NMR (400 MHz, CDCl3):  = 7.40 (d, J = 8.6 Hz, 2 H), 7.11 (d, J = 8.7
Hz, 2 H), 6.86 (d, J = 8.7 Hz, 2 H), 6.72 (d, J = 8.6 Hz, 2 H), 5.52 (s, 2 H),
4.06 (s, 2 H), 3.78 (s, 3 H).
IR (Diamond-ATR, neat): 3087 (w), 1538 (m), 1137 (m), 769 (m), 730
(vs), 655 cm–1 (s).
1H NMR (400 MHz, CDCl3):  = 8.37–8.12 (m, 2 H), 7.72–7.63 (m, 2 H),
7.13–7.05 (m, 2 H), 6.89–6.81 (m, 2 H), 5.57 (s, 2 H), 4.43 (q, J = 7.2 Hz,
2 H), 3.79 (s, 3 H), 1.43 (t, J = 7.2 Hz, 3 H).
13C NMR (101 MHz, CDCl3):  = 159.8, 154.8, 149.4, 130.3, 128.8,
126.3, 115.0, 114.9, 112.8, 55.5, 50.9.
MS (EI, 70 eV): m/z (%) = 281 (8), 225 (9), 210 (18), 122 (11), 121
(100), 78 (16), 77 (19).
13C NMR (101 MHz, CDCl3):  = 165.5, 160.0, 153.8, 133.0, 130.2,
128.8, 127.9, 125.5, 114.6, 61.6, 55.4, 51.3, 14.3.
HRMS (EI): m/z calcd for [C15H15N5O]: 281.1277; found: 281.1268
MS (70 eV, EI): m/z (%) = 338 (13), 277 (72), 183 (17), 121 (100), 91
(M+).
(44), 71 (39), 57 (52).
5-[1-(4-Methoxybenzyl)-1H-tetrazol-5-yl]-1H-indole (4h)
HRMS (EI): m/z calcd for [C18H18N4O3]: 338.1373; found: 338.1367
(M+).
Compound 4h was prepared according to TP1 using 5-bromo-1H-in-
dole (3h; 98 mg, 0.5 mmol, 1.0 equiv) as electrophile. The product
was purified by flash column chromatography (isohexane/EtOAc 1:2 +
5% Et3N); yield: 94 mg (0.32 mmol, 62%); colorless solid; mp 115–
118 °C.
5-(4-Cyanophenyl)-1-(4-methoxybenzyl)-1H-tetrazole (4e)
Compound 4e was prepared according to TP1 using 4-bromobenzoni-
trile (3e; 92 mg, 0.5 mmol, 1.0 equiv) as electrophile. The product was
purified by flash column chromatography (isohexane/EtOAc 2:1 + 5%
Et3N); yield: 93 mg (0.32 mmol, 65%); colorless solid; mp 106–108 °C.
IR (Diamond-ATR, neat): 2925 (m), 1515 (vs), 1458 (s), 1252 (vs),
1178 (m), 821 (m), 770 (m), 655 cm–1 (s).
IR (Diamond-ATR, neat): 2934 (w), 2214 (w), 1611 (s), 1250 (vs), 1031
(s), 848 (s), 655 cm–1 (s).
1H NMR (400 MHz, CDCl3):  = 7.74 (d, J = 8.4 Hz, 2 H), 7.70–7.60 (m, 2
H), 7.04–6.96 (m, 2 H), 6.82–6.78 (m, 2 H), 5.51 (s, 3 H), 3.73 (s, 3 H).
13C NMR (101 MHz, CDCl3):  = 160.1, 153.0, 132.8, 129.6, 128.6,
1H NMR (400 MHz, CDCl3):  = 9.36 (s, 1 H), 7.86–7.84 (m, 1 H), 7.51–
7.47 (m, 1 H), 7.36 (dd, J = 8.5, 1.7 Hz, 1 H), 7.33–7.30 (m, 1 H), 7.13 (d,
J = 8.7 Hz, 2 H), 6.84 (d, J = 8.7 Hz, 2 H), 6.60–6.55 (m, 1 H), 5.56 (s, 2
H), 3.77 (s, 3 H).
13C NMR (101 MHz, CDCl3):  = 159.7, 156.0, 137.2, 129.0, 128.0,
126.4, 126.3, 122.2, 122.0, 114.5, 114.4, 112.2, 103.1, 55.3, 50.9.
128.3, 125.2, 117.5, 115.2, 114.7, 55.3, 51.4.
MS (EI, 70 eV): m/z (%) = 305 (18), 249 (8), 234 (7), 122 (8), 121 (100),
78 (6), 77 (7).
MS (70 eV, EI): m/z (%) = 291 (6), 235 (10), 121 (100), 78 (14), 77 (13),
71 (11), 57 (19), 55 (11), 43 (16).
HRMS (EI): m/z calcd for [C17H15N5O]: 305.1277; found: 305.1268
HRMS (EI): m/z calcd for [C16H13N5O]: 291.1120; found: 291.1136
(M+).
(M+).
5-(4-Methoxyphenyl)-1H-tetrazole (5a)
4-[1-(4-Methoxybenzyl)-1H-tetrazol-5-yl]-N,N-dimethylaniline
According to GP1, 1-(4-methoxybenzyl)-5-(4-methoxyphenyl)-1H-
tetrazole (4a; 75 mg, 0.25 mmol, 1.0 equiv) was suspended in H2O
(2 mL) and iPrOH (2 mL). Subsequently, Pd/C (53 mg, 0.50 mmol, 5%)
and ammonium formate (209 mg, 3.75 mmol, 15 equiv) were added
and the mixture was stirred overnight at 65 °C. The crude product
was purified twice by column chromatography (silica gel,
DCM/MeOH 4:1); yield: 41 mg (0.24 mmol, 95%); colorless solid; mp
218–220 °C.
(4f)
Compound 4f was prepared according to TP1 using 4-bromo-N,N-di-
methylaniline (3f; 100 mg, 0.5 mmol, 1.0 equiv) as electrophile. The
product was purified by flash column chromatography (isohex-
ane/EtOAc 2:1 + 5% Et3N); yield: 114 mg (0.37 mmol, 74%); colorless
solid; mp 120–122 °C.
IR (Diamond-ATR, neat): 2938 (w), 2839 (w), 1514 (vs), 1251 (vs),
1178 (s), 1028 (s), 840 (s), 687 cm–1 (s).
1H NMR (400 MHz, CDCl3):  = 7.51 (d, J = 9.0 Hz, 2 H), 7.14 (d, J = 8.7
Hz, 2 H), 6.87 (d, J = 8.7 Hz, 2 H), 6.73 (d, J = 8.9 Hz, 2 H), 5.55 (s, 2 H),
3.79 (s, 3 H), 3.04 (s, 6 H).
13C NMR (100 MHz, CDCl3):  = 159.7, 154.9, 152.0, 129.9, 128.6,
126.5, 114.5, 111.8, 110.1, 55.4, 50.8, 40.1.
IR (Diamond-ATR, neat): 2842 (w), 1611 (s), 1499 (s), 1259 (s), 1020
(s), 832 (vs), 750 (vs), 655 cm–1 (s).
1H NMR (400 MHz, DMSO-d6):  = 7.98 (d, J = 8.8 Hz, 2 H), 7.09 (d, J =
8.7 Hz, 2 H), 6.37 (s, 1 H), 3.81 (s, 3 H).
13C NMR (101 MHz, DMSO-d6):  = 161.0, 155.6, 128.4, 117.6, 114.7,
55.4.
MS (EI, 70 eV): m/z (%) = 309 (20), 281 (10), 253 (17), 252 (16), 145
(12), 132 (25), 121 (100), 78 (14), 77 (13).
MS (EI, 70 eV): m/z (%) = 176 (20), 148 (33), 134 (16), 133 (100), 105
(19), 103 (17), 90 (21), 57 (13), 44 (79), 43 (48).
HRMS (EI): m/z calcd for [C8H8N4O]: 176.0698; found: 176.0687 (M+).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

F
C. P. Tüllmann et al.
Paper
Synthesis
5-[4-(Trifluoromethyl)phenyl]-1H-tetrazole (5b)
Ethyl 1-[1-(4-Methoxybenzyl)-1H-tetrazol-5-yl]piperidine-3-car-
boxylate (7a)
According to GP1, 1-(4-methoxybenzyl)-5-[4-(trifluoromethyl)phe-
nyl]-1H-tetrazole (4i; 64 mg, 0.21 mmol, 1.0 equiv) was suspended in
H2O (2 mL) and iPrOH (2 mL). Subsequently, Pd/C (50 mg, 0.05 mmol,
5 mol%) and ammonium formate (198 mg, 3.15 mmol, 15 equiv) were
added and the mixture was stirred overnight at 65 °C. The crude
product was purified twice by column chromatography (silica gel,
DCM/MeOH 10:1); yield: 42 mg (0.19 mmol, 93%); colorless solid; mp
202–205 °C.
Compound 7a was prepared from 6a as described in TP2.
IR (Diamond-ATR, neat): 2116 (m), 1977 (s), 1725 (m), 1663 (vw),
1252 (w), 1109 (w), 887 (m), 758 cm–1 (m).
1H NMR (400 MHz, DMSO-d6):  = 7.18–7.08 (m, 2 H), 6.94–6.80 (m, 2
H), 5.41 (s, 2 H), 4.10–3.92 (m, 2 H), 3.70 (s, 3 H), 3.44 (dd, J = 12.6, 3.8
Hz, 1 H), 3.29 (s, 1 H), 3.17 (dd, J = 12.6, 8.6 Hz, 1 H), 3.01 (ddd, J =
12.5, 9.3, 3.2 Hz, 1 H), 2.61 (dq, J = 8.5, 4.2 Hz, 1 H), 1.88–1.77 (m, 1 H),
1.72–1.57 (m, 2 H), 1.51 (qt, J = 9.7, 5.1 Hz, 1 H), 1.11 (t, J = 7.1 Hz, 3
H).
IR (Diamond-ATR, neat): 2927 (w), 1455 (s), 1323 (vs), 1123 (s), 1067
(vs), 1013 (s), 849 (s), 729 (s), 655 cm–1 (s).
1H NMR (400 MHz, DMSO-d6):  = 8.18 (d, J = 8.0 Hz, 1 H), 7.76 (d, J =
13C NMR (101 MHz DMSO-d6):  = 172.9, 159.5, 158.7, 130.3, 129.2,
127.0, 114.6, 60.6, 55.6, 51.5, 50.1, 49.8, 26.1, 23.4, 14.4.
8.1 Hz, 1 H).
13C NMR (101 MHz DMSO-d6):  = 136.1, 128.1, 127.7, 126.7, 126.3,
125.88 (q, J = 3.9 Hz).
MS (EI, 70 eV): m/z (%) = 345(1), 317 (11), 156 (14), 122 (10), 121
(100), 92, (2),78 (4), 76 (4).
MS (EI, 70 eV): m/z (%) = 214 (11), 186 (82), 171 (100), 152 (38), 121
(51), 102 (13), 50 (10).
HRMS (EI): m/z calcd for [C8H5F3N4]: 214.0466; found: 214.0443 (M+).
HRMS (EI): m/z calcd for [C17H23N5O3]: 345.1801; found: 345.1803
(M+).
2-{4-[1-(4-methoxybenzyl)-1H-tetrazol-5-yl]piperazin-1-yl}py-
Ethyl 4-(1H-Tetrazol-5-yl)benzoate (5c)
rimidine (7b)
According to GP1, ethyl 4-[1-(4-methoxybenzyl)-1H-tetrazol-5-
yl]benzoate (4d; 114 mg, 0.33 mmol, 1.0 equiv) was suspended in
H2O (2 mL) and iPrOH (2 mL). Subsequently, Pd/C (16 mg, 0.26 mmol,
5 mol%) and ammonium formate (316 mg, 1.04 mmol, 15 equiv) were
added and the mixture was stirred overnight at 65 °C. The crude
product was purified twice by column chromatography (silica gel,
DCM/MeOH 10:1); yield: 64 mg (0.294 mmol, 88%); colorless solid;
mp 220–224 °C.
Compound 7b was prepared according to TP2 using 4-(pyrimidin-2-
yl)piperazin-1-yl benzoate (6b; 142 mg, 0.5 mmol, 1.0 equiv) as elec-
trophile. The desired product was obtained after column chromatog-
raphy (silica gel, isohexane/EtOAc 2:1); yield: 115 mg (0.34 mmol,
71%); colorless solid; mp 175–177 °C.
IR (Diamond-ATR, neat): 2868 (w), 2167 (w), 1586 (s), 1315 (w), 1250
(vs), 1176 (s), 957 (s), 816 cm–1 (vs).
1H NMR (400 MHz, DMSO-d6):  = 8.35 (d, J = 4.7 Hz, 2 H), 7.27–7.13
(m, 2 H), 6.98–6.78 (m, 2 H), 6.63 (t, J = 4.7 Hz, 1 H), 5.47 (s, 2 H),
3.88–3.74 (m, 4 H), 3.70 (s, 3 H), 3.38–3.21 (m, 4 H).
13C NMR (101 MHz DMSO-d6):  = 161.5, 159.5, 158.5, 158.4, 129.5,
126.9, 114.7, 111.0, 55.6, 50.1, 49.3, 43.1.
IR (Diamond-ATR, neat): 2968 (m), 1502 (m), 1401 (s), 1275 (s), 994
(s), 729 (s), 847 (m), 679 (m), 655 cm–1 (s).
1H NMR (400 MHz, DMSO-d6):  = 8.18–8.03 (m, 2 H), 8.03–7.84 (m, 2
H), 4.32 (q, J = 7.1 Hz, 2 H), 1.34 (t, J = 7.1 Hz, 3 H).
13C NMR (101 MHz DMSO-d6):  = 165.7, 130.4, 127.3, 61.4, 55.4, 45.8,
14.6, 8.9.
MS (EI, 70 eV): m/z (%) 352 (13), 148 (11), 136 (10), 134 (39), 122 (26),
121 (100), 80 (25), 77 (12), 44 (28).
MS (EI, 70 eV): m/z (%) = 218 (64), 202 (100), 175 (44), 147 (54), 129
(18), 102 (19), 87 (11).
HRMS (EI): m/z calcd for [C17H20N8O]: 352.1760; found: 352.1755
(M+).
HRMS (EI): m/z calcd for [C10H10N4O2]: 218.0804; found: 218.1051
(M+).
N-[(1R,4R)-4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-
1-yl]-1-(4-methoxybenzyl)-N-methyl-1H-tetrazol-5-amine (7c)
N,N-Dimethyl-4-(1H-tetrazol-5-yl)aniline (5d)
Compound 7c was prepared according to TP2 using O-benzoyl-N-
[(1R,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl]-
N-methylhydroxylamine (6c; 213mg, 0.5 mmol, 1.0 equiv) as electro-
phile. The desired product was obtained after column chromatogra-
phy (silica gel, isohexane/EtOAc 1:1); yield: 180 mg (0.37 mmol, 73%);
colorless solid; mp 155–160 °C.
According to GP1, 4-[1-(4-methoxybenzyl)-1H-tetrazol-5-yl]-N,N-di-
methylaniline (4f; 103 mg, 0.33 mmol, 1.0 equiv) was suspended in
H2O (2 mL) and iPrOH (2 mL). Subsequently, Pd/C (70 mg, 0.66 mmol,
5 mol%) and ammonium formate (340 mg, 5.00 mmol, 15 equiv) were
added and the mixture was stirred overnight at 65 °C. The crude
product was purified twice by column chromatography (silica gel,
DCM/MeOH 10:1); yield: 57 mg (0.31 mmol, 92%); colorless solid; mp
218–220 °C.
IR (Diamond-ATR, neat): 2938 (w), 1514 (s), 1249 (s), 1178 (m), 1027
(vs), 820 (s), 738 cm–1 (s).
1H NMR (400 MHz, DMSO-d6):  = 7.34 (d, J = 8.2 Hz, 1 H), 7.23 –7.14
(m, 2 H), 7.13–7.07 (m, 2 H), 7.07–6.99 (m, 2 H), 6.96 (dd, J = 7.0, 2.1
Hz, 1 H), 6.94–6.88 (m, 2 H), 6.81 (dd, J = 8.3, 2.1 Hz, 1 H), 5.62 (d, J =
16.1 Hz, 1 H), 5.38 (d, J = 16.1 Hz, 1 H), 5.05 (dd, J = 9.9, 6.7 Hz, 1 H),
4.15 (dd, J = 5.8, 2.8 Hz, 1 H), 3.84 (s, 3 H), 2.78 (s, 3 H), 2.18–2.03 (m,
1 H), 2.02–1.89 (m, 1 H), 1.86–1.69 (m, 2 H).
13C NMR (101 MHz DMSO-d6):  = 159.8, 158.8, 146.8, 138.3, 135.4,
132.3, 130.9, 130.6, 130.1, 128.1, 128.0, 127.8, 127.5, 127.3, 126.4,
114.6, 60.4, 60.2, 55.4, 50.8, 42.9, 33.1, 29.8, 27.0, 23.8.
IR (Diamond-ATR, neat): 2926 (w), 2531 (w), 2133 (w), 1407 (m),
1206 (m), 944 (m), 749 (s), 655 cm–1 (s).
1H NMR (400 MHz, DMSO-d6):  = 7.85 (d, J = 8.9 Hz, 2 H), 6.86 (d, J =
8.9 Hz, 2 H), 3.00 (s, 6 H).
13C NMR (101 MHz DMSO-d6):  = 155.4, 152.4, 128.6, 128.4, 112.4,
110.8.
MS (EI, 70 eV): m/z (%) = 189 (66), 161 (65), 160 (100), 147 (11), 146
(40), 145 (50), 132 (11), 118 (12), 80 (10).
HRMS (EI): m/z calcd for [C9H11N5]: 189.1014; found: 189.1011 (M+).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

G
C. P. Tüllmann et al.
Paper
Synthesis
MS (EI, 70 eV): m/z (%) = 493 (4), 273 (8), 271 (12), 201 (12), 159 (20),
129 (13), 121 (100), 43 (10).
(6) De Souza, A. O.; Pedrosa, M. T.; Alderete, J. B.; Cruz, A. F.; Prado,
M. A.; Alves, R. B.; Silva, C. L. Pharmazie 2005, 60, 396.
(7) Vieira, E.; Huwyler, J.; Jolidon, S.; Knoflach, F.; Mutel, V.;
Wichmann, J. Bioorg. Med. Chem. Lett. 2005, 15, 4628.
(8) Gagnon, A.; Landry, S.; Coulombe, R.; Jakalian, A.; Guse, I.;
Thavonekham, B.; Bonneau, P. R.; Yoakim, C.; Simoneau, B.
Bioorg. Med. Chem. Lett. 2009, 19, 1199.
(9) Aureggi, V.; Sedelmeier, G. Angew. Chem. Int. Ed. 2007, 46, 8440.
(10) Alonen, A.; Jansson, J.; Kallonen, S.; Kiriazis, A.; Aitio, O.; Finel,
M.; Kostiainen, R. Bioorg. Chem. 2008, 36, 148.
HRMS (EI): m/z calcd for [C26H25Cl2N5O]: 493.1436; found: 493.1431
(M+).
(2,6-Difluorophenyl)[4-(3-{[1-(4-methoxybenzyl)-1H-tetrazol-5-
yl](phenethyl)amino}propyl)phenyl]methanone (7d)
Compound 7d was prepared according to TP2 using (4-{3-[(benzoyl-
oxy)(phenethyl)amino]propyl}phenyl)(2,6-difluorophenyl)metha-
none (6d; 250 mg, 0.5 mmol, 1.0 equiv) as electrophile. The desired
product was obtained after column chromatography (silica gel, iso-
hexane/EtOAc 1:1); yield: 240 mg (0.425 mmol, 85%); colorless solid;
mp 184–185 °C.
(11) (a) Habibi, D.; Nasrollahzadeh, M.; Mehrabi, L.; Mostafaee, S.
Monatsh. Chem. 2013, 144, 725. (b) Kazemizadeh, A. R.;
Hajaliakbari, N.; Hajian, R.; Shajari, N.; Ramazania, A. Helv. Chim.
Acta 2012, 95, 594.
IR (Diamond-ATR, neat): 2919 (w), 1672 (s), 1623 (s), 1464 (vs), 1279
(s), 1252 (s), 1006 (s), 931 (s), 792 cm–1 (s).
(12) Satoh, Y.; Moliterni, J. Synlett 1998, 528.
(13) Wiedemann, S. H.; Bio, M. M.; Brown, L. M.; Hansen, K. B.;
Langillle, N. F. Synlett 2012, 23, 2231.
(14) (a) Chen, Y.-H.; Ellwart, M.; Malakhov, V.; Knochel, P. Synthesis
2017, 49, 3215. (b) Manolikakes, S. M.; Ellwart, M.; Stathakis, C.
I.; Knochel, P. Chem. Eur. J. 2014, 20, 12289.
1H NMR (400 MHz, DMSO-d6):  = 7.85–7.74 (m, 2 H), 7.48 (tt, J = 8.5,
6.3 Hz, 1 H), 7.28–7.19 (m, 3 H), 7.19–7.13 (m, 2 H), 7.09–6.98 (m, 4
H), 7.00–6.91 (m, 2 H), 6.88–6.81 (m, 2 H), 5.17 (s, 2 H), 3.77 (s, 3 H),
3.50–3.36 (m, 2 H), 3.31–3.20 (m, 2 H), 2.73 (dd, J = 8.5, 6.5 Hz, 2 H),
2.50 (t, J = 7.7 Hz, 2 H), 1.90–1.71 (m, 2 H).
13C NMR (101 MHz DMSO-d6):  = 188.4, 161.0, 161.0, 159.7, 158.5,
158.5, 157.6, 148.3, 138.2, 135.0, 132.0, 131.9, 131.8, 130.0, 128.7,
128.7, 128.6, 128.2, 126.6, 125.9, 114.4, 112.1, 112.0, 111.9, 111.8,
111.8, 55.3, 53.6, 51.4, 50.0, 33.8, 32.9, 28.5.
(15) Hernán-Gómez, A.; Herd, E.; Hevia, E.; Kennedy, A. R.; Knochel,
P.; Koszinowski, K.; Manolikakes, S. M.; Mulvey, R. E.;
Schnegelsberg, C. Angew. Chem. Int. Ed. 2014, 53, 2706.
(16) (a) Bernhardt, S.; Manolikakes, G.; Kunz, T.; Knochel, P. Angew.
Chem. Int. Ed. 2011, 50, 9205. (b) Stathakis, C. I.; Bernhardt, S.;
Quint, V.; Knochel, P. Angew. Chem. Int. Ed. 2012, 51, 9428.
(c) Greshock, T. J.; Moore, K. P.; McClain, R. T.; Bellomo, A.;
Chung, C. K.; Dreher, S. D.; Kutchikian, P. S.; Peng, Z.; Davies, I.
W.; Vachal, P.; Ellwart, M.; Manolikakes, S. M.; Knochel, P.;
Natermet, P. G. Angew. Chem. Int. Ed. 2016, 55, 13714.
(d) Hammann, J. M.; Lutter, F. H.; Haas, D.; Knochel, P. Angew.
Chem. Int. Ed. 2017, 56, 1082.
(17) (a) Stathakis, C.; Manolikakes, S. M.; Knochel, P. Org. Lett. 2013,
15, 1302. (b) Colombe, J. R.; Bernhardt, S.; Stathakis, C.;
Buchwald, S. L.; Knochel, P. Org. Lett. 2013, 15, 5754.
(18) Chen, Y.-H.; Graßl, S.; Knochel, P. Angew. Chem. Int. Ed. 2018, 57,
1108.
MS (EI, 70 eV): m/z (%) = 567 (2), 476 (17), 313 (5), 232 (26), 141 (17),
122 (10), 121 (100), 105 (10).
HRMS (EI): m/z calcd for [C33H31F2N5O2]: 567.2446; found: 567.2468.
Funding Information
We thank the Deutsche Forschungsgemeinschaft (DFG) for financial
support.
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(19) (a) Chen, Y.-H.; Tüllmann, C. P.; Ellwart, M.; Knochel, P. Angew.
Chem. Int. Ed. 2017, 56, 9236. (b) Hammann, J. M.; Thomas, L.;
Chen, Y.-H.; Haas, D.; Knochel, P. Org. Lett. 2017, 19, 3847.
(20) Tüllmann, C. P.; Chen, Y.-H.; Schuster, R. J.; Knochel, P. Org. Lett.
2018, 15, 4601.
(21) Ellwart, M.; Knochel, P. Angew. Chem. Int. Ed. 2015, 54, 10662.
(22) Chen, Y.-H.; Ellwart, M.; Toupalas, G.; Ebe, Y.; Knochel, P. Angew.
Chem. Int. Ed. 2017, 56, 4612.
(23) Krasovskiy, A.; Knochel, P. Synthesis 2006, 890.
(24) (a) King, A. O.; Okukado, N. O.; Negishi, E.-i. J. Chem. Soc., Chem.
Commun. 1977, 683. (b) Negishi, E.-i.; Anastasia, L. Chem. Rev.
2003, 103, 1979. (c) Negishi, E.-i.; Wang, G.; Rao, H.; Xu, Z. J. Org.
Chem. 2010, 75, 3151.
(25) Barder, I. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S. L. J. Am.
Chem. Soc. 2005, 13, 4685.
(26) Seki, M. Synthesis 2014, 46, 3240.
(27) (a) Berman, A. M.; Johnson, J. S. J. Am. Chem. Soc. 2004, 126,
5680. (b) McDonald, S. L.; Hendrick, C. E.; Wang, Q. Angew.
Chem. Int. Ed. 2014, 53, 4667.
(28) Obach, R. S.; Cox, L. M.; Tremaine, L. M. Drug Metabol. Disp.
2006, 33, 262.
Acknowledgment
We thank Albemarle (Germany) for the generous gift of chemicals.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1691734.
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