One-Pot Preparation of Stable Organoboronate Reagents for the Functionalization of Unsaturated Four- and Five-Membered Carbo and Heterocycles

Article abstract of DOI:10.1055/s-0036-1592004

Combining a facile preparation of organoboronates with their remarkable stability and functional group tolerance allows for the straightforward synthesis of four- and five-membered carbo- and heterocycles. While most strategies rely on the ex situ preparation of boronic acids as isolated intermediates, we demonstrate that in situ transmetalation of sensitive organometallics with boron alkoxides can lead to great stabilization of such species at room temperature. A considerable extension of the library of unsaturated strained structures is achieved through these sequences, expanding the potential applicability of such unusual building blocks.

Full text of DOI:10.1055/s-0036-1592004

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–L
special topic
A
en
A. N. Baumann et al.
Special Topic
Synthesis
One-Pot Preparation of Stable Organoboronate Reagents for
the Functionalization of Unsaturated Four- and Five-Membered
Carbo- and Heterocycles
Andreas N. Baumann‡
Michael Eisold‡
Arif Music‡
R
R
I
Het
Dorian Didier*
0
0
0
0
0-
0
0
2
6-
3
5
8
1-
4
8
5
rt stable intermediates
versatile
One-Pot
metalation
in situ transmetalation
cross-coupling
high yielding
high functional group tolerance
sophisticated strained systems
University Ludwig-Maximilians, Department of Chemistry
and Pharmacy, Butenandtstraße 5-13, 81377 Munich,
Germany
R
R
I
Het
dorian.didier@cup.uni-muenchen.de
NBoc
NBoc
‡ These authors contributed equally to this work.
R
R
H
Het
Published as part of the Special Topic Modern Coupling
Approaches and their Strategic Applications in Synthesis
Received: 23.02.2018
Accepted after revision: 03.04.2018
Published online: 14.05.2018
to the targeted compounds, avoiding an extra purification
of intermediate boronic acids. Taking into account the re-
cent work of Buchwald and co-workers on direct cross-cou-
pling of lithium organoboronates,8 Miyaura et al. on base-
free coupling of triolborates,9 Cammidge on coupling of ex
situ generated trihydroxyborates,10 and Knochel’s group on
the in situ generation of magnesium bis-organoborinates,11
we designed different strategies in which the cross-cou-
pling reaction would be relayed by the in situ formation of a
stable intermediate boron species. Our first objective was to
demonstrate the long-term stability of such strained organo-
boron derivatives over time, opening the strategy to reagent
storage; secondly, we aimed to explore the scope and lim-
itations of the method to complete a large library of new
building blocks, being hitherto difficult to access.
DOI: 10.1055/s-0036-1592004; Art ID: ss-2018-c0107-st
Abstract Combining a facile preparation of organoboronates with
their remarkable stability and functional group tolerance allows for the
straightforward synthesis of four- and five-membered carbo- and hetero-
cycles. While most strategies rely on the ex situ preparation of boronic
acids as isolated intermediates, we demonstrate that in situ transmeta-
lation of sensitive organometallics with boron alkoxides can lead to
great stabilization of such species at room temperature. A considerable
extension of the library of unsaturated strained structures is achieved
through these sequences, expanding the potential applicability of such
unusual building blocks.
Key words cyclobutenes, cyclopentenes, azetines, organoboronates,
one-pot sequences
Cyclobutene and cyclopentene iodides 1a,b were readily
prepared from procedures originally described by Negishi
et al. involving π-cyclization of gem-bismetalated alkenes,12
which we recently applied to the synthesis of alkylidene-
cyclobutanes and fused four-membered rings.13 Halogen–
lithium exchanges on 1a and 1b were performed employing
n-BuLi in diethyl ether at –78 °C (as THF led to further al-
kylation of the newly formed cycloalkenyllithium) and the
corresponding cycloalkenyl-boronates A and B were gener-
ated by addition of B(Oi-Pr)3 in THF (Scheme 1).
Azetinyllithium reagents were generated by α-lithiation
of in situ formed azetines 2 using s-BuLi in the presence of
TMEDA in THF at –78 °C,14 and subsequently trapped with
boron isopropoxide to give C.15
Organoboronates A, B and C were then stored either in
solution or neat at –20 °C or room temperature before being
engaged in Suzuki cross-couplings (Scheme 2).
The transition-metal-catalyzed cross-couplings of organo-
boronic acids with organic halides, a process developed by
Suzuki et al.,1 has become one of the most powerful tools
for the creation of C–C bonds.2 Both simplicity and func-
tional group tolerance have made it a privileged method3
for assembling complex structures in many fields of chem-
istry such as drug discovery,4 materials science,5 chemosen-
sors6 and total synthesis.7 Spurred on by the particular sta-
bility of organoboron species, we took on the challenge of
generalizing the access to classes of molecules that have
been scarcely reported: strained cyclobutenes, cyclo-
pentenes and 2-azetines. Due to their commercial availabil-
ity, organoboronic acids are employed as stable substrates
for numerous cross-coupling reactions. For more elaborated
scaffolds however, tailor-made boronic acids must be pre-
pared ex situ in order to be engaged in a subsequent reac-
tion through a two-step process. For the sake of step-econ-
omy, we needed to develop a more straightforward access
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

B
A. N. Baumann et al.
Special Topic
Synthesis
n-BuLi
Et2O, –78 °C
30 min
s-BuLi, TMEDA
THF, –78 °C
30 min
NBoc
B(Oi-Pr)3
NBoc
n
n
B
B
Li
Li
R1
Me
1a,b
I
R1
Me
B(Oi-Pr)3
B(Oi-Pr)3
THF, –78 °C
to rt, 30 min
B(Oi-Pr)3
–78 °C to rt
30 min
2
A (n = 1)
B (n = 2)
C
stability tests - organoboronate reagents
NBoc
Me
B(Oi-Pr)3
Me
B(Oi-Pr)3
R1
B(Oi-Pr)3
stored at room temperature or –20 °C in THF or neat
Scheme 1 Organoboronate synthesis through Li/I exchange–transmetalation or α-lithiation–transmetalation
Cyclobutenyl- and cyclopentenylboronates A and B
were coupled with 1-iodo-3-nitrobenzene as a test partner.
From freshly prepared solutions, both products 3a16 and 4a
were obtained in excellent yields (96%). Keeping solutions
at –20 °C showed constancy in reactivity, delivering 3a in
94% yield after seven weeks and 4a (81%) after three weeks.
Diverse conditions were evaluated for storage of azetinyl-
boronates C. When kept in an open flask, the yields de-
creased drastically after only one week of storage, and a fast
decrease in reactivity was also observed on storing C in
solution at room temperature. However, reproducible re-
sults were obtained when the boronate salts were kept ei-
ther in solution at –20 °C (as for A and B), or neat at room
temperature. Products 5a were isolated in constant, reason-
able yields (up to 70% after fifteen weeks). Stock solutions
of azetinylboronate reagents were prepared and further
used in cross-coupling reactions after different storage
times at room temperature. In some cases (5b, 5c and 5e),
the salts gave reproducible yields after one or ten weeks of
storage, showing the great potential of such reagents as
building blocks. In some other cases (5d), the solution
showed a rapid decrease of reactivity, furnishing only a 47%
yield of the desired product.
Having established the stability of strained organoboro-
nates, we next investigated the scope of the transformation
toward a new library of cyclobutenes. The protocol of
Scheme 1 was used to generate in situ the cyclobutenylbor-
onate A, which was then engaged directly in cross-coupling
reactions in the presence of Pd(dppf)Cl2·CH2Cl2 (Scheme 3).
Aromatic and heteroaromatic iodides bearing ketone, ester,
nitro or amide moieties led to the expected arylcy-
clobutenes 3b–g in moderate to good yields (51 to 82%). In-
terestingly, an unprotected phenol and a benzoic acid fur-
nished the desired products 3h and 3i in excellent yields of
80% and 96%, respectively. Not only iodides, but bromides
could be engaged as cross-coupling partners with similar
efficacy, furnishing 3j–n with up to 95% yield and with ex-
ceptional functional group tolerance (SF5, NH2, OH). Alter-
natively, an aryl triflate gave a similar result (3q, 96%) while
aryl chlorides showed decreased efficiency (3o,p, 23 to
66%).
R2X
(i-PrO)3B
R1
R2
R1
Pd
Y
Y
n
n
Pd(dppf)Cl2
(4 mol%)
freshly prepared: 96%
freshly prepared: 96%
kept in solution at –20 °C
kept in solution at –20 °C
Me
Me
t = 3 weeks: 84%
t = 7 weeks: 94%
t = 1 week: 85%
t = 3 weeks: 81%
3a
4a
O2N
O2N
kept in solution at –20 °C
kept in solution at rt
t = 1 week: 68%
t = 5 weeks: 73%
t = 10 weeks: 71%
t = 15 weeks: 62%
t = 1 week: 74%
t = 5 weeks: 62%
t = 10 weeks: 37%
t = 15 weeks: 21%
NBoc
Ph
NO2
kept neat at rt
kept in an open flask
5a
t = 1 week: 72%
t = 5 weeks: 79%
t = 10 weeks: 71%
t = 15 weeks: 70%
t = 1 week: 56%
t = 5 weeks: 31%
t = 10 weeks: 8%
t = 15 weeks: 0%
freshly prepared: 74%
NBoc
NBoc
freshly prepared: 77%
freshly prepared: 73%
kept in solution at rt
kept in solution at rt
N
Ph
5c
Ph
5b
t = 1 week: 71%
t = 1 week: 83%
Ac
freshly prepared: 80%
freshly prepared: 91%
NBoc
NBoc
kept in solution at rt
kept in solution at rt
Et
t = 5 weeks: 47%
t = 10 weeks: 12%
t = 15 weeks: 17%
t = 5 weeks: 90%
t = 10 weeks: 81%
t = 15 weeks: 54%
Ph
5e
O2N
O2N
5d
Scheme 2 Stability testing of four- and five-membered carbo- and
heterocyclic organoboronates
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

C
A. N. Baumann et al.
Special Topic
Synthesis
R2X
n-BuLi
B(Oi-Pr)3
B
Li
Li
Pd
R1
B(Oi-Pr)3
R1
R2
R1
I
R1
Li
Et2O
–78 °C, 30 min
THF
–78 °C to rt
Pd(dppf)Cl2
(4 mol%)
A
1a
3a–q
Me
N
O
Me
N
Me
Me
O
N
N
NO2
Ac
3b (X = I, 81%)
3c (X = I, 62%)
3d (X = I, 64%)
3e (X = I, 72%)
Me
F
Me
Me
Me
N
Me
O
EtO2C
HO2C
OH
3f (X = I, 51%)
3g (X = I, 82%)
3h (X = I, 80%)
3i (X = I, 96%)
N
Me
Me
NO2
NH2
N
Me
CN
N
N
N
3j (X = Br, 74%)
3k (X = Br, 94%)
3l (X = Br, 91%)
Me
Me
OH
N
SF5
3m (X = Br, 95%)
3n (X = Br, 74%)
Me
N
N
Me
Me
O2N
EtO2C
3p (X = Cl, 23%)
NO2
3o (X = Cl, 66%)
3q (X = OTf, 96%)
Scheme 3 In situ preparation and further Suzuki cross-coupling of cyclobutenylboronates
The study was then pursued with five-membered rings,
utilizing cyclopentenyl iodides as starting materials17 in a
similar one-pot sequence (Scheme 4). Halogen–lithium ex-
change on 1b was followed by transmetalation with B(Oi-
Pr)3 and further palladium-catalyzed cross-coupling with
diverse aromatic halides. A comparable functional group
tolerance was observed for these larger cycloalkenylboro-
nates, as ketone, nitro, amide and aldehyde moieties could
be introduced, giving a wide range of unique functionalized
cyclopentenes 4a–h in moderate to excellent yields (52 to
96%).16 When a β-styryl iodide was used, the reaction re-
sulted in partial double bond isomerization and 4i was ob-
tained in 95% yield and an 82:18 E/Z ratio.
action, but rather promote the direct transmetalation of the
newly generated lithium species (Scheme 5), as previously
exemplified by Li et al.18 As a result, the undesired alkyla-
tion reaction was to be suppressed without having to use
Et2O, avoiding the previously required mixture of solvents.
As a proof of concept, the halogen–metal exchange was
performed on 1a and 1b in the presence of B(Oi-Pr)3 at –78 °C,
and ultimately engaged in the cross-coupling reaction with
a representative partner (1-iodo-3-nitrobenzene). Similar
results were collected from this simplified procedure (93 to
96% yield).
Toward a more convenient setup, a step further was
then taken by developing conditions that would not require
low temperatures for the formation of organoboronates. We
envisioned that room-temperature metal insertion in the
presence of boron alkoxides should lead to the expected
intermediate boron species through in situ transmetalation
Next, we investigated the iodine–lithium exchange in
the presence of boron isopropoxide. Given that the ex-
change reaction should proceed at a higher rate than the
nucleophilic addition of n-BuLi to the boron atom, the pres-
ence of boron species should not perturb the exchange re-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

D
A. N. Baumann et al.
Special Topic
Synthesis
R1X
n-BuLi
B(Oi-Pr)3
B
Li
Pd
Me
Li
Me
B(Oi-Pr)3
Me
R1
Me
I
Et2O
–78 °C, 30 min
THF
–78 °C to rt
Pd(dppf)Cl2
(4 mol%)
1b
B
4a–i
Me
Me
Me
NO2
Me
Ac
4a (X = I, 96%)
4b (X = I, 70%)
4c (X = I, 88%)
Me
F
O
Me
Me
MeO
CHO
N
O
N
N
MeO
MeO
4d (X = I, 52%)
4e (X = I, 69%)
4f (X = I, 74%)
Me
N
Me
O
Me
CN
CHO
CF3
4g (X = I, 88%)
4h (X = Br, 76%)
4i (X = I, 95%)
(E/Z = 88:12)
Scheme 4 In situ preparation and further Suzuki cross-coupling of cyclopentenylboronates
of the transitional cycloalkenylmagnesium species (Scheme
6).
Magnesium powder was then employed, furnishing the
n
R2X
Mg(0)
B(Oi-Pr)3
B
intermediary magnesium salt D, being an analog of A and B.
Performing the full sequence at room temperature afforded
the desired cross-coupling products in excellent yields,
comparable to those obtained via the lithium path (up to
96%). The reaction also showed similarly high functional
group tolerance, with the ability to introduce unprotected
amines (4j, 4m: 69 to 93%) and a carboxylic acid (4k, 94%).
In addition, we recently demonstrated the potential of
in situ generated azetinylboronates to undergo unprece-
dented cross-coupling, transposing the methodology to
n
R1
I
MgI
n
Mg
Pd
R1
R2
R1
B(Oi-Pr)3
THF, rt
Pd(dppf)Cl2
(4 mol%)
D
3, 4
Me
N
Me
Me
NO2
O2N
NO2
3a (X = I, 90%)
3r (X = OTf, 70%)
3o (X = Cl, 72%)
NH2
Me
Me
Me
R2X
B(Oi-Pr)3 n-BuLi
Li
NO2
COOH
Li
B(Oi-Pr)3
n
n
n
B
Pd
R1
R1
R2
R1
I
4a (X = I, 96%)
4j (X = I, 93%)
4k (X = I, 94%)
THF
–78 °C, 30 min
Pd(dppf)Cl2
(4 mol%)
Me
similar conversions and yields
avoids solvent mixtures
N
Me
N
N
Me
O2N
Me
Me
NO2
information on rates of
exchange vs transmetalation
NO2
NH2
4m (X = Br, 69%)
O2N
4l (X = I, 82%)
4n (X = Cl, 84%)
3a (X = I, 93%)
4a (X = I, 97%)
Scheme 5 Iodine–lithium exchange in the presence of B(Oi-Pr)3 for
Scheme 6 Formation of organoboronates through magnesium inser-
direct transmetalation
tion and in situ transmetalation
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

E
A. N. Baumann et al.
Special Topic
Synthesis
heterocyclic four-membered structures. A one-pot se-
quence was designed to access the desired boronates
through a double α-lithiation of readily available azetidines
6, followed by trapping with boron isopropoxide and palla-
dium-catalyzed cross-coupling. Representative examples
are given in Scheme 7. Alkyl, aryl, alkynyl and silyl groups
were introduced at position 3, and the cross-coupling was
performed using a large range of functionalized aromatic
halides.15
In conclusion, we have assembled a new efficient one-
pot sequence for the synthesis of cyclobutenes, cyclo-
pentenes and azetines by using in situ prepared boron
alkoxides possessing a remarkable functional group toler-
ance. Diverse conditions were successfully developed rely-
ing either on halogen/metal exchanges or on an advanta-
geous room temperature insertion/transmetalation proce-
dure. Through the intermediate formation of stable
organoboronate building blocks, we have unlocked a wide
library of unexplored strained architectures, opening mod-
ern organic chemistry to new classes of modules for further
applications.
R–I
[Pd]cat.
s-BuLi
TMEDA
s-BuLi
NBoc
NBoc
NBoc
R2
MeO
Li
Li
B
Pd
R1
R1
R1
THF
–78 °C
30 min
2
B(Oi-Pr)3
can be isolated
or used in-situ
5f–k
6
Commercially available starting materials were used without further
purification unless otherwise stated. All reactions were carried out
under N2 atmospheres in flame-dried glassware. Syringes, which
were used to transfer anhydrous solvents or reagents, were purged
with nitrogen prior to use. CH2Cl2 was predried over CaCl2 and dis-
tilled from CaH2. THF was refluxed and distilled from sodium benzo-
phenone ketyl under nitrogen. Et2O was predried over CaCl2 and
passed through activated Al2O3 (using a solvent purification system
SPS-400-2 from Innovative Technologies Inc.). Toluene was predried
over CaCl2 and distilled from CaH2. n-BuLi was purchased from Rock-
wood Lithium GmbH; [n-BuLi] = 2.44 M in hexane (titration with iso-
propanol/1,10-phenanthroline).
NBoc
MeO
NBoc
NBoc
N
OMe
N
Me
N
N
MeO
Me
5f (X = I, 79%)
5g (X = I, 90%)
5h (X = I, 92%)
NBoc
NBoc
NBoc
Ph
Si
CHO
NO2
Ph
Me
Chromatographic purifications were performed using silica gel (SiO2,
0.040–0.063 mm, 230–400 mesh ASTM) from Merck. The spots were
visualized under UV (254 nm) or by staining the TLC plate with
KMnO4 solution [K2CO3 (10 g), KMnO4 (1.5 g), H2O (150 mL), NaOH
(10% in H2O, 1.25 mL)] or p-anisaldehyde (PAA) solution [concd H2SO4
(10 mL), EtOH (200 mL), AcOH (3 mL), p-anisaldehyde (4 mL)]. Melting
points were determined on a Büchi B-540 apparatus and are uncor-
N
Ph
OMe
5i (X = Br, 92%)
5j (X = Br, 47%)
5k (X = I, 80%)
Scheme 7 Single-pot access to 3,4-disubstituted azetines through a
lithiation/transmetalation/cross-coupling sequence
rected. Diastereoisomeric ratios were determined by 1H NMR and 13
C
Furthermore, we showed the applicability of this strate-
gy to pyrroles, furans and hydropyrans to open the scope to
a larger array of heterocyclic scaffolds. A simple metalation
with n-BuLi was performed to access the initial organo-
metallic derivatives, before transmetalation with B(Oi-Pr)3.
Heteroaromatic starting materials furnished the desired
cross-coupled compounds 7a16 and 7b in good yields (up to
96%). However, employing hydrofuran resulted in only 43%
of the substituted styrene derivative 7c (Scheme 8).
NMR spectroscopy. 1H and 13C NMR spectra were recorded on VARIAN
Mercury 200, BRUKER ARX 300, VARIAN VXR 400 S and BRUKER AMX
600 instruments. Chemical shifts are reported as δ values in ppm rel-
ative to the residual solvent peak (1H NMR) or the solvent peak (13
C
NMR) in deuterated chloroform (CDCl3: δ 7.26 for 1H NMR and δ 77.16
for 13C NMR). Abbreviations for multiplicities are as follows: s (sin-
glet), d (doublet), t (triplet), q (quartet), quin (quintet), m (multiplet)
and br (broad). Reaction endpoints were determined by GC monitor-
ing. Gas chromatography was performed with an Agilent Technolo-
gies 7890 instrument, using a column of type HP 5 (Agilent 5%
phenylmethylpolysiloxane; length: 15 m; diameter: 0.25 mm; film
thickness: 0.25 μm) or Hewlett-Packard 6890 or 5890 series II instru-
ments, using a column of type HP 5 (Hewlett-Packard, 5% phenyl-
methylpolysiloxane; length: 15 m; diameter: 0.25 mm; film thick-
ness: 0.25 μm). High-resolution mass spectra (HRMS) and low-resolu-
tion mass spectra (LRMS) were recorded on Finnigan MAT 95Q,
Finnigan MAT 90 or JEOL JMS-700 instruments. Single crystals (for X-
ray analysis) were grown in small quench vials with a volume of 5.0
mL from slow evaporation of dichloromethane/hexanes mixtures at
room temperature. Suitable single crystals were then introduced into
perfluorinated oil and mounted on top of a thin glass wire. Data col-
lection was performed at 100 K with a Bruker D8 Venture TXS
equipped with a Spellman generator (50 kV, 40 mA) and a Kappa CCD
detector operating with Mo-Kα radiation (l = 0.71071 Å).
R–I
[Pd]cat.
n-BuLi
H
R
Li
B
Pd
B(Oi-Pr)3
7a–c
NO2
NO2
CN
Me
N
O
O
7a (72%)
7b (96%)
7c (43%)
Scheme 8 Extension to other heterocycles
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

F
A. N. Baumann et al.
Special Topic
Synthesis
General Procedure A
Yield: 1.48 g, 7.09 mmol (71%); Rf = 0.79 (hexane; UV, KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 2.74–2.54 (m, 2 H), 2.31 (t, J = 8.5 Hz, 2
H), 2.04–1.82 (m, 2 H), 1.80–1.72 (m, 3 H).
To a solution of cycloalkenyl iodide (1.00 equiv) in Et2O (0.5 M) was
slowly added a solution of n-BuLi (2.44 M in hexane, 1.10 equiv) at
–78 °C. After stirring for 30 min at the aforementioned temperature,
B(Oi-Pr)3 (1.15 equiv) and THF (total concn 0.25 M) were added and
the resulting mixture stirred for an additional 1 h at room tempera-
ture. Pd(dppf)Cl2·CH2Cl2 (4 mol%), the cross-coupling partner (aro-
matic or vinylic iodide, bromide, tosylate or chloride) (0.90 equiv) and
an aqueous solution of NaOH (1.5 equiv 1.00 M) were subsequently
added and the reaction mixture was stirred overnight. The crude ma-
terial was extracted with Et2O (3 × 20 mL), washed with a saturated
aqueous solution of sodium chloride (20 mL), dried over magnesium
sulfate, filtered, concentrated and purified via flash column chroma-
tography.
Spectroscopic data are in agreement with the previously reported
characterization.15
1-(2-Methylcyclobut-1-en-1-yl)-3-nitrobenzene (3a)
Using 1-iodo-2-methylcyclobut-1-ene and 1-iodo-3-nitrobenzene
according to general procedure A provided 3a as a yellow solid.
Yield: 49 mg, 0.26 mmol (96%); Rf = 0.32 (hexane/EtOAc, 98:2; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 8.09 (t, J = 2.0 Hz, 1 H), 8.01 (ddd, J =
8.1, 2.4, 1.0 Hz, 1 H), 7.60 (dt, J = 7.7, 1.4 Hz, 1 H), 7.47 (t, J = 7.9 Hz, 1
H), 2.70–2.63 (m, 2 H), 2.52–2.42 (m, 2 H), 2.08–1.99 (m, 3 H).
General Procedure B
13C NMR (101 MHz, CDCl3): δ = 148.6, 143.0, 137.7, 135.7, 131.2,
Magnesium powder (1.30 equiv) and LiCl (1.10 equiv) were placed in
a reaction tube and flame-dried in vacuo three times. After cooling to
ambient temperature, enough THF was added to cover the solids. The
magnesium was activated by addition of a few drops of dibro-
moethane and heating. After cooling back to ambient temperature,
B(Oi-Pr)3 (1.00 equiv) was added. The cycloalkenyl iodide was added
dropwise as a solution in THF (1.00 equiv, 0.5 M) and the resulting
solution stirred for 2 h, after which a grey suspension had formed,
which was divided into equimolar portions in new reaction tubes. To
the portions were then added Pd(dppf)Cl2·CH2Cl2 (4 mol%), the cross-
coupling partner (aromatic iodide, bromide, tosylate or chloride)
(0.80 equiv) and an aqueous solution of NaOH (1.5 equiv 1.00 M). The
reaction mixture was stirred overnight and then extracted with Et2O
(3 × 20 mL), washed with a saturated aqueous solution of sodium
chloride (20 mL), dried over magnesium sulfate, filtered, concentrated
and purified via flash column chromatography.
129.3, 121.0, 120.0, 30.2, 26.3, 16.5.
MS (EI): m/z (%) = 189 (11) [M]+, 172 (43), 141 (67), 128 (100), 115
(58).
HRMS (EI): m/z [M]+ calcd for C11H11NO2: 189.0790; found: 189.0783.
Compound 3a was also synthesized according to general procedure B.
Yield: 41 mg, 0.22 mmol (90%); mp 115–117 °C.
1-[4-(2-Methylcyclobut-1-en-1-yl)phenyl]ethan-1-one (3b)
Using 1-iodo-2-methylcyclobut-1-ene and 1-(4-iodophenyl)ethan-1-
one according to general procedure A provided 3b as a colorless oil.
Yield: 30 mg, 0.16 mmol (81%); Rf = 0.5 (hexane/EtOAc, 95:5; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 8.4 Hz, 2 H), 7.37 (d, J = 8.4
Hz, 2 H), 2.66–2.63 (m, 2 H), 2.58 (s, 3 H), 2.49–2.44 (m, 2 H), 2.05–
2.02 (m, 3 H).
1-Iodo-2-methylcyclopent-1-ene (1b)
13C NMR (101 MHz, CDCl3): δ = 197.7, 143.4, 140.7, 137.1, 134.9,
Commercially available 5-iodopent-1-yne (1.93 g, 10 mmol, 1.0
equiv) was dissolved in dry pentane (30 mL) in a Schlenk tube and
cooled to –78 °C. n-BuLi (2.39 M, 10 mmol, 1.0 equiv) was then added
dropwise and the reaction mixture was stirred for 30 min before be-
ing warmed to –50 °C for 5 min. The mixture was then cooled back to
–78 °C and dimethylaluminum chloride (1 M in CH2Cl2, 10 mmol, 1.0
equiv) was added dropwise and the resulting mixture stirred for a
further 30 min. The mixture was then allowed to reach room tem-
perature. In another Schlenk flask, zirconocene dichloride (2.93 g, 10
mmol, 1.0 equiv) was dissolved in CH2Cl2 (25 mL) and trimethylalumi-
num (2 M, 20 mmol, 2.0 equiv) was added at room temperature and
the mixture stirred for 1 h. The first Schlenk flask was then cooled
back to –78 °C before dropwise addition of the solution from the sec-
ond Schlenk flask. The combined reaction mixture was allowed to
reach room temperature and stirred for 1 h. The solvent was then re-
moved in vacuo and a red solid remained, which was dissolved in THF
(50 mL). After 30 min, complete conversion into the cyclized pentene
was confirmed by GC–MS. The reaction mixture was cooled to –78 °C
and iodine (5.58 g, 22 mmol, 2.2 equiv) was added portionwise. The
mixture was allowed to reach room temperature and then poured
into ice-cold HCl (2 M, 200 mL). The layers were separated and the
aqueous layer was extracted with hexane (2 × 100 mL). The combined
organics were washed with a saturated sodium thiosulfate solution.
The organics were dried over MgSO4, filtered and the solvent evapo-
rated at 20 °C (60 mbar) due to the volatility of the desired product.
Column chromatography (hexane) yielded the desired product as a
colorless oil, which was stored at –20 °C to avoid decomposition.
128.7, 125.4, 30.3, 26.7, 26.2, 16.7.
MS (EI): m/z (%) = 186 [M]+ (30), 171 (20), 143 (80), 128 (100), 115
(40).
HRMS (EI): m/z [M]+ calcd for C13H14O: 186.1045; found: 186.1037.
1-[4-(2-Methylcyclobut-1-en-1-yl)phenyl]-3-morpholino-5,6-di-
hydropyridin-2(1H)-one (3c)
Using 1-iodo-2-methylcyclobut-1-ene and 1-(4-iodophenyl)-3-mor-
pholino-5,6-dihydropyridin-2(1H)-one according to general proce-
dure A provided 3c as a colorless oil.
Yield: 40 mg, 0.12 mmol (62%); Rf = 0.2 (hexane/EtOAc, 6:4; UV, KM-
nO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 7.37–7.27 (m, 4 H), 5.63 (t, J = 4.7 Hz, 1
H), 3.84–3.80 (m, 4 H), 3.78 (t, J = 6.7 Hz, 2 H), 2.93–2.86 (m, 4 H),
2.64–2.55 (m, 2 H), 2.48 (td, J = 6.7, 4.6 Hz, 2 H), 2.44–2.39 (m, 2 H),
2.00–1.94 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 161.3, 143.8, 140.8, 139.0, 137.0,
134.1, 125.6, 124.7, 114.2, 66.7, 50.5, 48.6, 29.8, 26.1, 23.4, 16.2.
1-(2-Methylcyclobut-1-en-1-yl)isoquinoline (3d)
Using 1-iodo-2-methylcyclobut-1-ene and 1-iodoisoquinoline ac-
cording to general procedure A provided 3d as a colorless oil.
Yield: 25 mg, 0.13 mmol (64%); Rf = 0.3 (hexane/EtOAc, 9:1; UV,
KMnO4, PAA).
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1H NMR (400 MHz, CDCl3): δ = 8.52 (d, J = 5.6 Hz, 1 H), 8.30 (d, J = 8.5
Hz, 1 H), 7.80 (d, J = 7.0 Hz, 1 H), 7.67–7.63 (m, 1 H), 7.56 (ddd, J = 8.2,
6.8, 1.3 Hz, 1 H), 7.50 (d, J = 5.6 Hz, 1 H), 3.11–3.06 (m, 2 H), 2.63–2.57
(m, 2 H), 2.02 (s, 3 H).
HRMS (EI): m/z [M]+ calcd for C17H20O2: 256.1463; found: 256.1458.
4-[2-(2-Methylallyl)cyclobut-1-en-1-yl]phenol (3h)
Using 1-iodo-2-(2-methylallyl)cyclobut-1-ene and 4-iodophenol ac-
cording to general procedure A provided 3h as a colorless oil.
13C NMR (101 MHz, CDCl3): δ = 155.3, 147.5, 142.5, 137.8, 136.8,
129.9, 127.1, 126.9, 126.7, 126.6, 119.2, 31.1, 29.9, 17.2.
MS (EI): m/z (%) = 194 [M – H]+ (100), 180 (100), 167 (30), 154 (20).
Yield: 32 mg, 0.16 mmol (80%); Rf = 0.3 (hexane/EtOAc, 8:2; UV,
KMnO4, PAA).
HRMS (EI): m/z [M – H]+ calcd for C14H12N: 194.0970; found:
194.0962.
1H NMR (400 MHz, CDCl3): δ = 7.25–7.21 (m, 2 H), 6.83–6.76 (m, 2 H),
4.81 (d, J = 5.6 Hz, 3 H), 3.04 (s, 2 H), 2.64–2.59 (m, 2 H), 2.47–2.40 (m,
2 H), 1.78 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 154.4, 142.9, 138.6, 137.7, 129.4,
2-(2-Methylcyclobut-1-en-1-yl)-5-nitropyridine (3e)
Using 1-iodo-2-methylcyclobut-1-ene and 2-iodo-5-nitropyridine
127.2, 115.3, 111.5, 39.0, 28.3, 26.2, 23.1.
according to general procedure A provided 3e as a yellow oil.
MS (EI): m/z (%) = 200 [M]+ (30), 185 (80), 171 (20), 158 (100), 144
Yield: 27 mg, 0.14 mmol (72%); Rf = 0.5 (hexane/EtOAc, 9:1; UV,
(30).
KMnO4, PAA).
HRMS (EI): m/z [M]+ calcd for C14H16O: 200.1201; found: 200.1195.
1H NMR (400 MHz, CDCl3): δ = 9.37 (d, J = 2.6 Hz, 1 H), 8.39 (dd, J = 8.7,
2.7 Hz, 1 H), 7.26 (d, J = 8.7 Hz, 1 H), 2.81–2.70 (m, 2 H), 2.59–2.49 (m,
2 H), 2.21 (t, J = 1.9 Hz, 3 H).
3-[2-(2-Methylallyl)cyclobut-1-en-1-yl]benzoic Acid (3i)
Using 1-iodo-2-(2-methylallyl)cyclobut-1-ene and 3-iodobenzoic
acid according to general procedure A provided 3i as a colorless oil.
13C NMR (101 MHz, CDCl3): δ = 159.2, 153.3, 145.5, 141.5, 136.8,
131.4, 119.6, 31.1, 26.1, 17.2.
MS (EI): m/z (%) = 190 [M]+ (40), 175 (100), 143 (60), 129 (70).
Yield: 44 mg, 0.19 mmol (96%); Rf = 0.3 (hexane/EtOAc, 95:5; UV, KM-
nO4, PAA).
HRMS (EI): m/z [M – H]+ calcd for C10H9N2O2: 189.0664; found:
189.0656.
1H NMR (400 MHz, CDCl3): δ = 8.07 (s, 1 H), 7.95 (d, J = 7.7 Hz, 1 H),
7.57 (d, J = 7.7 Hz, 1 H), 7.43 (t, J = 7.7 Hz, 1 H), 4.84 (s, 2 H), 3.13 (s, 2
H), 2.73–2.67 (m, 2 H), 2.53–2.46 (m, 2 H), 1.80 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 172.3, 142.4, 142.2, 138.2, 136.4,
129.5, 128.7, 128.3, 127.4, 111.9, 39.1, 28.6, 26.2, 23.1.
3-Fluoro-6-methoxy-4-(2-methylcyclobut-1-en-1-yl)quinoline
(3f)
Using 1-iodo-2-methylcyclobut-1-ene and 3-fluoro-4-iodo-6-me-
thoxyquinoline according to general procedure A provided 3f as a col-
orless oil.
MS (EI): m/z (%) = 228 [M]+ (5), 212 (10), 183 (100), 167 (20), 155 (50).
HRMS (EI): m/z [M]+ calcd for C15H16O2: 228.1150; found: 228.1143.
Yield: 25 mg, 0.10 mmol (51%); Rf = 0.3 (hexane/EtOAc, 9:1; UV,
KMnO4, PAA).
6-(2-Methylcyclobut-1-en-1-yl)picolinonitrile (3j)
Using 1-iodo-2-methylcyclobut-1-ene and 6-bromopicolinonitrile
according to general procedure A provided 3j as a colorless oil.
1H NMR (400 MHz, CDCl3): δ = 8.60 (d, J = 1.7 Hz, 1 H), 7.97 (d, J = 9.1
Hz, 1 H), 7.30 (dd, J = 9.1, 2.8 Hz, 1 H), 7.26 (d, J = 4.1 Hz, 1 H), 3.92 (s,
3 H), 2.98–2.89 (m, 2 H), 2.72–2.58 (m, 2 H), 1.84 (d, J = 1.3 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 158.6, 154.0 (d, J = 254.5 Hz), 148.4,
141.8 (d, J = 2.3 Hz), 138.6 (d, J = 29.3 Hz), 131.4, 130.2, 128.3 (d, J =
3.4 Hz), 124.8 (d, J = 12.7 Hz), 120.8 (d, J = 2.7 Hz), 103.9 (d, J = 5.4 Hz),
55.6, 32.0, 30.5 (d, J = 2.8 Hz), 17.4 (d, J = 2.1 Hz).
Yield: 25 mg, 0.15 mmol (74%); Rf = 0.5 (hexane/EtOAc, 8:2; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 7.72 (t, J = 7.8 Hz, 1 H), 7.44 (d, J = 7.6
Hz, 1 H), 7.31 (d, J = 8.1 Hz, 1 H), 2.73–2.63 (m, 2 H), 2.53–2.44 (m, 2
H), 2.16 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 155.9, 149.6, 137.0, 136.2, 133.6,
125.4, 123.0, 117.8, 30.6, 26.0, 16.8.
MS (EI): m/z (%) = 170 [M]+ (20), 155 (100), 142 (10), 129 (10), 115
MS (EI): m/z (%) = 243 [M]+ (90), 228 (70), 212 (100), 200 (30).
HRMS (EI): m/z [M]+ calcd for C15H14FNO: 243.1059; found: 243.1053.
(10).
Ethyl 2-[2-(2-Methylallyl)cyclobut-1-en-1-yl]benzoate (3g)
HRMS (EI): m/z [M]+ calcd for C11H10N2: 170.0844; found: 170.0843.
Using 1-iodo-2-(2-methylallyl)cyclobut-1-ene and ethyl 2-iodoben-
zoate according to general procedure A provided 3g as a yellowish oil.
6-(2-Methylcyclobut-1-en-1-yl)imidazo[1,2-a]pyrazine (3k)
Yield: 42 mg, 0.16 mmol (82%*), *with minor impurities due to the
starting material (aryl-I); Rf = 0.6 (hexane/EtOAc, 9:1; UV, KMnO4,
PAA).
1H NMR (400 MHz, CDCl3): δ = 7.67 (d, J = 7.6 Hz, 1 H), 7.39 (t, J = 8.1
Hz, 1 H), 7.31–7.19 (m, 2 H), 4.74 (d, J = 6.8 Hz, 2 H), 4.31 (q, J = 7.1 Hz,
2 H), 2.85 (s, 2 H), 2.68–2.61 (m, 2 H), 2.46–2.36 (m, 2 H), 1.68 (s, 3 H),
1.34 (t, J = 7.1 Hz, 3 H).
Using 1-iodo-2-methylcyclobut-1-ene and 6-bromoimidazo[1,2-
a]pyrazine according to general procedure A provided 3k as a yellow-
ish oil.
Yield: 35 mg, 0.19 mmol (94%); Rf = 0.1 (hexane/EtOAc, 5:5; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 9.06 (s, 1 H), 7.85 (s, 1 H), 7.75 (s, 1 H),
7.63 (s, 1 H), 2.72–2.61 (m, 2 H), 2.55–2.43 (m, 2 H), 2.15 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 144.5, 143.3, 139.8, 137.5, 135.7,
133.7, 114.1, 113.7, 30.5, 25.7, 16.5.
13C NMR (101 MHz, CDCl3): δ = 168.6, 142.9, 141.9, 140.2, 136.1,
131.1, 130.3, 129.6, 129.4, 126.7, 111.6, 61.3, 38.2, 29.2, 28.7, 23.0,
14.4.
MS (EI): m/z (%) = 256 [M]+ (10), 241 (5), 227 (5), 209 (30), 195 (100),
MS (EI): m/z (%) = 185 [M]+ (70), 184 (100), 170 (100), 157 (5), 144 (5).
181 (20).
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HRMS (EI): m/z [M – H]+ calcd for C11H10N3: 184.0875; found:
13C NMR (101 MHz, CDCl3): δ = 153.6, 151.9, 147.2, 144.4, 133.6,
184.0869.
131.4, 120.8, 31.6, 27.5, 17.2.
MS (EI): m/z (%) = 172 (5), 160 (950), 145 (30), 130 (90), 117 (100).
HRMS (EI): m/z [M – H]+ calcd for C10H9N2O2: 189.0664; found:
189.0657.
5-(2-Methylcyclobut-1-en-1-yl)-3-nitropyridin-2-amine (3l)
Using 1-iodo-2-methylcyclobut-1-ene and 5-bromo-3-nitropyridin-
2-amine according to general procedure A provided 3l as a yellow oil.
Yield: 37 mg, 0.18 mmol (91%); Rf = 0.1 (hexane/EtOAc, 8:2; UV,
Ethyl 2-(2-Methylcyclobut-1-en-1-yl)nicotinate (3p)
KMnO4, PAA).
Using 1-iodo-2-methylcyclobut-1-ene and ethyl 2-chloronicotinate
according to general procedure A provided 3p as a yellowish oil.
1H NMR (400 MHz, CDCl3): δ = 8.40 (d, J = 2.2 Hz, 1 H), 8.25 (d, J = 2.1
Hz, 1 H), 6.69 (s, 2 H), 2.66–2.56 (m, 2 H), 2.50–2.40 (m, 2 H), 1.99 (s, 3
H).
13C NMR (101 MHz, CDCl3): δ = 153.3, 151.7, 140.2, 132.8, 130.5,
128.0, 123.7, 30.4, 26.1, 16.5.
MS (EI): m/z (%) = 205 [M]+ (100), 190 (90), 176 (40), 157 (60), 144
Yield: 10 mg, 0.05 mmol (23%); Rf = 0.6 (hexane/EtOAc, 8:2; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 8.65 (dd, J = 4.8, 1.8 Hz, 1 H), 7.87 (dd,
J = 7.8, 1.8 Hz, 1 H), 7.13 (dd, J = 7.8, 4.8 Hz, 1 H), 4.36 (q, J = 7.2 Hz, 2
H), 2.76–2.71 (m, 2 H), 2.48–2.42 (m, 2 H), 2.01 (s, 3 H), 1.38 (t, J = 7.2
Hz, 3 H).
(60).
HRMS (EI): m/z [M]+ calcd for C10H11N3O2: 205.0851; found:
13C NMR (101 MHz, CDCl3): δ = 168.0, 152.9, 151.1, 148.6, 137.0,
205.0840.
136.9, 126.0, 120.4, 61.8, 30.8, 28.3, 16.7, 14.4.
MS (EI): m/z (%) = 217 [M]+ (10), 187 (100), 174 (15).
HRMS (EI): m/z [M]+ calcd for C13H15NO2: 217.1103; found: 217.1099.
Pentafluoro{3-[2-(2-methylallyl)cyclobut-1-en-1-yl]phenyl}-λ6-
sulfane (3m)
Using 1-iodo-2-(2-methylallyl)cyclobut-1-ene and (3-bromophe-
nyl)pentafluoro-λ6-sulfane according to general procedure A provid-
ed 3m as a colorless oil.
1-[2-(2-Methylallyl)cyclobut-1-en-1-yl]-4-nitrobenzene (3q)
Using 1-iodo-2-(2-methylallyl)cyclobut-1-ene and 4-nitrophenyl tri-
fluoromethanesulfonate according to general procedure A provided
3q as a colorless oil.
Yield: 59 mg, 0.19 mmol (95%); Rf = 0.6 (hexane; UV, KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 7.68 (s, 1 H), 7.59–7.53 (m, 1 H), 7.45–
7.36 (m, 2 H), 4.83 (d, J = 9.7 Hz, 2 H), 3.08 (s, 2 H), 2.73–2.63 (m, 2 H),
2.52–2.44 (m, 2 H), 1.78 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 154.3, 143.4, 142.0, 137.7, 136.8,
128.8, 128.5, 123.9, 123.3, 112.1, 39.1, 28.9, 26.2, 23.0.
MS (EI): m/z (%) = 310 [M]+ (60), 295 (60), 282 (10), 269 (5), 253 (5).
HRMS (EI): m/z [M]+ calcd for C14H15F5S: 310.0815; found: 310.0807.
Yield: 44 mg, 0.19 mmol (96%); Rf = 0.7 (hexane/EtOAc, 9:1; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 8.17 (d, J = 8.8 Hz, 2 H), 7.42 (d, J = 8.8
Hz, 2 H), 4.83 (d, J = 16.7 Hz, 2 H), 3.12 (s, 2 H), 2.84–2.61 (m, 2 H),
2.58–2.41 (m, 2 H), 1.79 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 146.9, 146.0, 141.9, 141.6, 137.8,
126.1, 124.0, 112.2, 39.3, 29.1, 26.1, 23.1.
MS (EI): m/z (%) = 229 [M]+ (2), 212 (90), 182 (100), 168 (50), 153 (50).
HRMS (EI): m/z [M]+ calcd for C14H15NO2: 229.1103; found: 229.1102.
3-[2-(2-Methylallyl)cyclobut-1-en-1-yl]pyridin-2-ol (3n)
Using 1-iodo-2-(2-methylallyl)cyclobut-1-ene and 3-bromopyridin-
2-ol according to general procedure A provided 3n as a colorless oil.
1-(2-Methylcyclobut-1-en-1-yl)-4-nitrobenzene (3r)
Yield: 30 mg, 0.15 mmol (74%); Rf = 0.1 (hexane/EtOAc, 7:3; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 7.31 (dd, J = 7.0, 2.0 Hz, 1 H), 7.21 (dd,
J = 6.5, 2.0 Hz, 1 H), 6.25 (t, J = 6.7 Hz, 1 H), 4.79–4.74 (m, 2 H), 3.29 (s,
2 H), 2.68–2.63 (m, 2 H), 2.45–2.39 (m, 2 H), 1.75 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 162.8, 144.5, 143.9, 137.0, 135.0,
132.4, 127.7, 111.2, 106.8, 40.3, 28.5, 26.9, 23.1.
MS (EI): m/z (%) = 201 [M]+ (100), 186 (50), 167 (30), 134 (30).
HRMS (EI): m/z [M]+ calcd for C13H15NO: 201.1154; found: 201.1149.
Using 1-iodo-2-methylcyclobut-1-ene and 4-nitrophenyl trifluoro-
methanesulfonate according to general procedure B provided 3r as a
yellow oil.
Yield: 32 mg, 0.17 mmol (70%); Rf = 0.29 (hexane/EtOAc, 98:2; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 8.19–8.09 (m, 2 H), 7.46–7.28 (m, 2 H),
2.76–2.57 (m, 2 H), 2.57–2.40 (m, 2 H), 2.15–1.96 (m, 3 H).
13C NMR (101 MHz, CDCl3): δ = 145.9, 145.8, 142.3, 136.3, 125.7,
124.0, 30.6, 26.2, 16.7.
MS (EI): m/z (%) = 189 [M]+ (23), 172 (34), 143 (63), 128 (100), 115
(50), 102 (14).
2-(2-Methylcyclobut-1-en-1-yl)-3-nitropyridine (3o)
HRMS (EI): m/z [M]+ calcd for C11H11NO2: 189.0790; found: 189.0783.
Using 1-iodo-2-methylcyclobut-1-ene and 2-chloro-3-nitropyridine
according to general procedure A provided 3o as a yellowish oil.
Yield: 25 mg, 0.13 mmol (66%).
1-(2-Methylcyclopent-1-en-1-yl)-3-nitrobenzene (4a)
Compound 3o was also synthesized according to general procedure B.
Using 1-iodo-2-methylcyclopent-1-ene and 1-iodo-3-nitrobenzene
according to general procedure A provided 4a as a light-yellow oil.
Yield: 32 mg, 0.17 mmol (72%); Rf = 0.6 (hexane/EtOAc, 8:2; UV,
KMnO4, PAA).
Yield: 39 mg, 0.19 mmol (96%); Rf = 0.2 (hexane/EtOAc, 99:1; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 8.72 (dd, J = 4.7, 1.6 Hz, 1 H), 7.92 (dd,
J = 8.1, 1.6 Hz, 1 H), 7.21 (dd, J = 8.2, 4.7 Hz, 1 H), 2.72–2.61 (m, 2 H),
2.55–2.46 (m, 2 H), 2.10 (s, 3 H).
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1H NMR (400 MHz, CDCl3): δ = 8.13 (t, J = 1.9 Hz, 1 H), 8.04 (dd, J = 9.1,
2.1 Hz, 1 H), 7.59 (d, J = 7.8 Hz, 1 H), 7.48 (t, J = 7.9 Hz, 1 H), 2.80–2.72
(m, 2 H), 2.54 (t, J = 7.9 Hz, 2 H), 1.94 (quin, J = 7.5 Hz, 2 H), 1.88 (s, 3
H).
3,4-Dimethoxy-5-(2-methylcyclopent-1-en-1-yl)benzaldehyde
(4e)
Using 1-iodo-2-methylcyclopent-1-ene and 3-iodo-4,5-dimethoxy-
benzaldehyde according to general procedure A provided 4e as a col-
orless oil.
13C NMR (101 MHz, CDCl3): δ = 148.3, 140.5, 138.7, 133.7, 132.4,
129.0, 122.4, 120.9, 40.4, 37.2, 21.9, 15.6.
MS (EI): m/z (%) = 203 [M]+ (80), 188 (100), 156 (20), 141 (78), 128
Yield: 34 mg, 0.14 mmol (69%); Rf = 0.35 (hexane/EtOAc, 9:1; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 9.87 (s, 1 H), 7.34 (d, J = 1.9 Hz, 1 H),
7.24 (d, J = 1.9 Hz, 1 H), 3.92 (s, 3 H), 3.79 (s, 3 H), 2.76–2.61 (m, 2 H),
2.47 (t, J = 7.0 Hz, 2 H), 1.95 (quin, J = 7.5 Hz, 2 H), 1.65 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 191.6, 153.6, 152.7, 138.0, 133.6,
132.10, 132.08, 127.6, 108.7, 60.8, 56.1, 38.9, 37.8, 22.7, 15.4.
(58), 115 (81).
HRMS (EI): m/z [M]+ calcd for C12H13NO2: 203.0946; found: 203.0939.
Compound 4a was also synthesized according to general procedure B.
Yield: 39 mg, 0.19 mmol (96%).
MS (EI): m/z (%) = 246 [M]+ (100), 231 (27), 217 (18), 203 (18), 189
(24), 161 (26), 115 (35).
HRMS (EI): m/z [M]+ calcd for C15H18O3: 246.1256; found: 246.1250.
1-Methyl-4-(2-methylcyclopent-1-en-1-yl)benzene (4b)
Using 1-iodo-2-methylcyclopent-1-ene and 1-iodo-4-methylbenzene
according to general procedure A provided 4b as a colorless oil.
Yield: 24 mg, 0.14 mmol (70%); Rf = 0.7 (hexane; UV, KMnO4, PAA).
3-Fluoro-6-methoxy-4-(2-methylcyclopent-1-en-1-yl)quinoline
(4f)
1H NMR (400 MHz, CDCl3): δ = 7.44–7.29 (m, 4 H), 2.95–2.86 (m, 2 H),
2.73–2.60 (m, 2 H), 2.52 (s, 3 H), 2.07 (t, J = 7.5 Hz, 2 H), 2.05–1.99 (m,
3 H).
13C NMR (101 MHz, CDCl3): δ = 135.9, 135.7, 134.7, 134.6, 128.8,
127.6, 40.2, 37.4, 22.0, 21.3, 15.6.
MS (EI): m/z (%) = 172 [M]+ (70), 157 (100), 142 (40), 129 (40), 115
(30).
HRMS (EI): m/z [M]+ calcd for C13H16: 172.1252; found: 172.1245.
Using 1-iodo-2-methylcyclopent-1-ene and 3-fluoro-4-iodo-6-me-
thoxyquinoline according to general procedure A provided 4f as col-
orless oil.
Yield: 38 mg, 0.15 mmol (74%); Rf = 0.3 (hexane/EtOAc, 9:1; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 8.62 (d, J = 9.2 Hz, 1 H), 8.00 (d, J = 9.2
Hz, 1 H), 7.31 (dd, J = 9.2, 2.8 Hz, 1 H), 6.99 (d, J = 2.8 Hz, 1 H), 3.89 (s,
3 H), 2.86–2.74 (m, 1 H), 2.71–2.66 (m, 1 H), 2.62 (t, J = 7.3 Hz, 2 H),
2.20–1.99 (m, 2 H), 1.56 (s, 3 H).
1-[4-(2-Methylcyclopent-1-en-1-yl)phenyl]ethan-1-one (4c)
13C NMR (101 MHz, CDCl3): δ = 158.9, 154.3 (d, J = 252.4 Hz), 142.0,
141.9, 138.9 (d, J = 29.3 Hz), 131.7, 129.4 (d, J = 3.6 Hz), 128.8 (d, J =
14.4 Hz), 126.7, 120.8 (d, J = 3.2 Hz), 104.1 (d, J = 5.9 Hz), 55.9, 39.2,
37.8 (d, J = 2.1 Hz), 23.5, 15.9.
Using 1-iodo-2-methylcyclopent-1-ene and 1-(4-iodophenyl)ethan-
1-one according to general procedure A provided 4c as a colorless oil.
Yield: 35 mg, 0.18 mmol (88%); Rf = 0.3 (hexane/EtOAc, 95:5; UV,
KMnO4, PAA).
MS (EI): m/z (%) = 257 [M]+ (100), 242 (25), 226 (20), 214 (40), 198
(22), 184 (36), 172 (20).
HRMS (EI): m/z [M]+ calcd for C16H16FNO: 257.1216; found: 257.1210.
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 8.4 Hz, 2 H), 7.37 (d, J = 8.4
Hz, 2 H), 2.80–2.71 (m, 2 H), 2.60 (s, 3 H), 2.53 (t, J = 7.1 Hz, 2 H),
1.97–1.90 (m, 2 H), 1.88 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 197.9, 143.9, 138.5, 134.8, 134.2,
128.3, 127.7, 40.5, 37.1, 26.7, 22.0, 15.9.
5-(2-Methylcyclopent-1-en-1-yl)furan-2-carbaldehyde (4g)
MS (EI): m/z (%) = 200 [M]+ (57), 185 (100), 157 (22), 142 (25), 128
(32).
HRMS (EI): m/z [M]+ calcd for C14H16O: 200.1201; found: 200.1195.
Using 1-iodo-2-methylcyclopent-1-ene and 5-iodofuran-2-carbalde-
hyde according to general procedure A provided 4g as a crystalline
solid.
Yield: 31 mg, 0.18 mmol (88%); mp 93–97 °C; Rf = 0.2 (hexane/EtOAc,
98:2; UV, KMnO4, PAA).
1-[4-(2-Methylcyclopent-1-en-1-yl)phenyl]-3-morpholino-5,6-di-
1H NMR (400 MHz, CDCl3): δ = 9.56 (s, 1 H), 7.23 (d, J = 3.7 Hz, 1 H),
6.34 (d, J = 3.7 Hz, 1 H), 2.80–2.65 (m, 2 H), 2.60–2.48 (m, 2 H), 2.12
(quin, J = 1.6 Hz, 3 H), 1.93 (quin, J = 7.6 Hz, 2 H).
hydropyridin-2(1H)-one (4d)
Using 1-iodo-2-methylcyclopent-1-ene and 1-(4-iodophenyl)-3-mor-
pholino-5,6-dihydropyridin-2-(1H)-one according to general proce-
dure A provided 4d as a light yellow sticky oil.
13C NMR (101 MHz, CDCl3): δ = 177.0, 159.1, 151.2, 144.1, 124.1,
123.4, 109.4, 40.9, 34.4, 22.1, 16.4.
Yield: 35 mg, 0.10 mmol (52%); Rf = 0.3 (hexane/EtOAc, 1:1; UV, KM-
MS (EI): m/z (%) = 176 [M]+ (100), 161 (50), 147 (78), 129 (21), 119
nO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 7.35–7.25 (m, 4 H), 5.63 (t, J = 4.7 Hz, 1
H), 3.84–3.76 (m, 6 H), 2.91 (t, J = 4.4 Hz, 4 H), 2.75–2.66 (m, 2 H),
2.53–2.43 (m, 4 H), 1.95–1.84 (m, 2 H), 1.84 (s, 3 H).
(46), 105 (22).
HRMS (EI): m/z [M]+ calcd for C11H12O2: 176.0837; found: 176.0831.
13C NMR (101 MHz, CDCl3): δ = 161.5, 143.9, 140.6, 136.6, 135.6,
6-(2-Methylcyclopent-1-en-1-yl)picolinonitrile (4h)
134.3, 128.0, 124.5, 114.2, 66.9, 50.6, 48.7, 40.2, 37.3, 23.5, 21.9, 15.6.
MS (EI): m/z (%) = 338 [M]+ (14), 320 (100), 307 (20), 281 (35), 253
Using 1-iodo-2-methylcyclopent-1-ene and 6-bromopicolinonitrile
according to general procedure A provided 4h as a colorless oil.
(34), 239 (31), 207 (55).
HRMS (EI): m/z [M]+ calcd for C21H26N2O2: 338.1994; found:
Yield: 28 mg, 0.15 mmol (76%); Rf = 0.3 (hexane/EtOAc, 95:5; UV,
KMnO4, PAA).
338.1988.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

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A. N. Baumann et al.
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Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.74 = (t, J = 7.9 Hz, 1 H), 7.46 (d, J = 7.6
Hz, 1 H), 7.41 (d, J = 8.1 Hz, 1 H), 2.85–2.76 (m, 2 H), 2.58 (t, J = 7.4 Hz,
2 H), 2.10 (s, 3 H), 1.92 (quin, J = 7.6 Hz, 2 H).
13C NMR (101 MHz, CDCl3): δ = 158.8, 145.2, 136.9, 133.1, 132.4,
125.2, 125.1, 117.8, 41.3, 35.8, 21.7, 16.4.
MS (EI): m/z (%) = 184 [M]+ (70), 169 (100), 155 (46), 142 (36), 129
(13), 118 (12), 103 (17).
HRMS (EI): m/z [M]+ calcd for C12H12N2: 184.1000; found: 184.0994.
1-(2-Methylcyclopent-1-en-1-yl)isoquinoline (4l)
Using 1-iodo-2-methylcyclopent-1-ene and 1-iodoisoquinoline ac-
cording to general procedure B provided 4l as a light yellow oil.
Yield: 34 mg, 0.16 mmol (82%); Rf = 0.2 (hexane/EtOAc, 9:1; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 8.53 (d, J = 5.7 Hz, 1 H), 7.97 (d, J = 8.4
Hz, 1 H), 7.82 (d, J = 8.2 Hz, 1 H), 7.70–7.62 (m, 1 H), 7.57–7.51 (m, 2
H), 2.97–2.82 (m, 2 H), 2.62 (t, J = 7.1 Hz, 2 H), 2.09 (quin, J = 7.5 Hz, 2
H), 1.55 (s, 3 H).
(E)-1-[2-(2-Methylcyclopent-1-en-1-yl)vinyl]-4-(trifluorometh-
13C NMR (101 MHz, CDCl3): δ = 160.2, 142.5, 139.9, 136.5, 134.5,
yl)benzene (4i)
130.1, 127.5, 127.1, 127.0, 126.9, 119.3, 39.4, 38.6, 22.9, 15.6.
MS (EI): m/z (%) = 208 [M – H]+ (100), 191 (11), 180 (40), 167 (15).
HRMS (EI): m/z [M – H]+ calcd for C15H14N: 208.1126; found:
Using 1-iodo-2-methylcyclopent-1-ene and (Z)-1-(2-iodovinyl)-4-
(trifluoromethyl)benzene according to general procedure A provided
4i (E/Z = 88:12 by crude GC, isolated E/Z = 56:44) as a colorless oil.
208.1120.
Yield: 48 mg, 0.19 mmol (95%); Rf = 0.56/0,68 (hexane; UV, KMnO4,
PAA).
5-(2-Methylcyclopent-1-en-1-yl)-3-nitropyridin-2-amine (4m)
1H NMR (400 MHz, CDCl3): δ = 7.59–7.46 (m, 3 H), 7.37–7.30 (m, 1 H),
6.46–6.33 (m, 2 H), 2.36–2.28 (m, 2 H), 2.22–2.11 (m, 2 H), 1.75 (quin,
J = 7.4 Hz, 2 H), 1.67 (s, 3 H).
Using 1-iodo-2-methylcyclopent-1-ene and 5-bromo-3-nitropyridin-
2-amine according to general procedure B provided 4m as a yellow
solid.
13C NMR (101 MHz, CDCl3): δ = 142.6 (d, J = 1.6 Hz), 142.3, 133.8,
129.2, 128.7 (d, J = 5.0 Hz), 128.0, 125.9, 124.7 (q, J = 3.8 Hz), 123.1 (d,
J = 1.5 Hz), 38.6, 35.8, 22.8, 15.1.
MS (EI): m/z (%) = 252 [M]+ (91), 237 (100), 209 (75), 183 (53), 159
(35), 141 (34), 115 (22).
Yield: 30 mg, 0.14 mmol (69%); mp 177–180 °C; Rf = 0.2 (hexane/EtOAc,
9:1; UV, KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 8.36 (d, J = 2.1 Hz, 1 H), 8.31 (d, J = 2.0
Hz, 1 H), 6.70 (s, 2 H), 2.76–2.64 (m, 2 H), 2.51 (t, J = 7.1 Hz, 2 H), 1.93
(quin, J = 7.5 Hz, 2 H), 1.86 (s, 3 H).
HRMS (EI): m/z [M]+ calcd for C15H15F3: 252.1126; found: 252.1119.
13C NMR (101 MHz, CDCl3): δ = 155.1, 151.7, 137.6, 133.0, 129.7,
127.9, 125.4, 40.2, 36.9, 21.8, 15.7.
2-(2-Methylcyclopent-1-en-1-yl)aniline (4j)
MS (EI): m/z (%) = 219 [M]+ (100), 204 (67), 173 (22), 158 (30).
Using 1-iodo-2-methylcyclopent-1-ene and 2-iodoaniline according
to general procedure B provided 4j as a light yellow oil.
HRMS (EI): m/z [M]+ calcd for C11H13N3O2: 219.1008; found:
219.0992.
Yield: 32 mg, 0.19 mmol (93%); Rf = 0.2 (hexane/EtOAc, 95:5; UV,
KMnO4, PAA).
2-(2-Methylcyclopent-1-en-1-yl)-3-nitropyridine (4n)
1H NMR (400 MHz, CDCl3): δ = 7.07 (td, J = 7.8, 1.5 Hz, 1 H), 6.98 (dd,
J = 7.5, 1.4 Hz, 1 H), 6.79–6.69 (m, 2 H), 3.66 (s, 2 H), 2.68–2.57 (m, 2
H), 2.48 (t, J = 7.3 Hz, 2 H), 1.96 (quin, J = 7.5 Hz, 2 H), 1.61 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 143.6, 136.9, 133.4, 129.3, 127.7,
124.9, 118.2, 115.2, 38.8, 37.9, 22.6, 15.2.
MS (EI): m/z (%) = 173 [M]+ (67), 158 (22), 144 (100), 130 (53), 117
(22), 77 (20).
HRMS (EI): m/z [M]+ calcd for C12H15N: 173.1204; found: 173.1198.
Using 1-iodo-2-methylcyclopent-1-ene and 2-chloro-3-nitropyridine
according to general procedure B provided 4n as a yellow oil.
Yield: 26 mg, 0.17 mmol (84%); Rf = 0.3 (hexane/EtOAc, 8:2; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 8.79 (dd, J = 4.7, 1.6 Hz, 1 H), 8.15 (dd,
J = 8.2, 1.6 Hz, 1 H), 7.34 (dd, J = 8.2, 4.7 Hz, 1 H), 2.84–2.70 (m, 2 H),
2.50 (t, J = 8.0 Hz, 2 H), 2.01 (quin, J = 7.5 Hz, 2 H), 1.61 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 152.9, 152.6, 146.5, 142.1, 132.2,
132.0, 121.8, 39.4, 36.7, 22.8, 15.0.
3-(2-Methylcyclopent-1-en-1yl)benzoic Acid (4k)
MS (EI): m/z (%) = 187 (70), 174 (35), 156 (95), 147 (100), 130 (75),
Using 1-iodo-2-methylcyclopent-1-ene and 3-iodobenzoic acid ac-
117 (65), 103 (23).
cording to general procedure B provided 4k as a light brown solid.
HRMS (EI): m/z [M – H]+ calcd for C11H11N2O2: 203.0821; found:
Yield: 38 mg, 0.19 mmol (94%); mp 116–120 °C; Rf = 0.4 (hexane/1%
203.0814.
MeOH; UV, KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 11.39 (s, 1 H), 8.01 (s, 1 H), 7.91 (d, J =
7.6 Hz, 1 H), 7.47 (d, J = 7.4 Hz, 1 H), 7.36 (t, J = 7.3 Hz, 1 H), 2.72 (s, 2
H), 2.49 (s, 2 H), 1.90 (quin, J = 7.2 Hz, 2 H), 1.83 (s, 3 H).
13C NMR (101 MHz, CDCl3): δ = 172.8, 139.1, 136.7, 134.1, 132.7,
129.9, 129.4, 128.2, 127.9, 40.3, 37.3, 22.0, 15.6.
MS (EI): m/z (%) = 202 [M]+ (100), 187 (81), 157 (52), 128 (77), 115
(67), 77 (28).
HRMS (EI): m/z [M]+ calcd for C13H14O2: 202.0994; found: 202.0989.
1-Methyl-2-(3-nitrophenyl)-1H-pyrrole (7a)
To a solution of 1-methyl-1H-pyrrole (90 μL, 1.014 mmol) and TMEDA
(200 μL, 1.33 mmol, 1.33 equiv) in Et2O (2 mL, 0.5 M) was slowly add-
ed a solution of n-BuLi (410 μL, 2.44 M in hexane, 1.00 equiv) at 0 °C.
After stirring for 2 h at ambient temperature, B(Oi-Pr)3 (230 μL, 1.00
mmol, 1.00 equiv) and THF (2 mL) were added and the resulting mix-
ture stirred for another 1 h at room temperature. Pd(dppf)Cl2 di-
chloromethane adduct (16 mg, 4 mol%), 1-iodo-3-nitrobenzene (125
mg, 0.5 mmol, 0.5 equiv) and an aqueous solution of sodium hydrox-
ide (1.5 mL, 1.5 equiv 1.00 M) were subsequently added and the mix-
ture stirred overnight. The mixture was extracted with Et2O (3 × 20
mL), washed with a saturated aqueous solution of sodium chloride
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

K
A. N. Baumann et al.
Special Topic
Synthesis
(20 mL), dried over magnesium sulfate, filtered, concentrated and pu-
rified via flash column chromatography. Compound 7a was obtained
as a yellow solid.
5.50 (t, J = 4.2 Hz, 1 H), 4.17 (t, J = 5.3 Hz, 2 H), 2.24 (td, J = 6.4, 4.1 Hz,
2 H), 1.96–1.85 (m, 2 H).
13C NMR (101 MHz, CDCl3): δ = 150.2, 140.5, 132.0, 124.7, 119.2,
Yield: 73 mg, 0.36 mmol (72%); mp 73–75 °C; Rf = 0.09 (hexane/EtO-
110.9, 101.0, 66.7, 22.2, 21.0.
Ac, 98:2; UV, KMnO4, PAA).
MS (EI): m/z (%) = 185 [M]+ (56), 170 (9), 156 (6), 140 (7), 130 (100),
1H NMR (400 MHz, CDCl3): δ = 8.27 (t, J = 2.0 Hz, 1 H), 8.13 (ddd, J =
8.3, 2.3, 1.1 Hz, 1 H), 7.74 (ddd, J = 7.7, 1.7, 1.1 Hz, 1 H), 7.57 (t, J = 8.0
Hz, 1 H), 6.79 (t, J = 2.3 Hz, 1 H), 6.36 (dd, J = 3.7, 1.8 Hz, 1 H), 6.24 (dd,
J = 3.7, 2.7 Hz, 1 H), 3.73 (s, 3 H).
116 (5), 102 (44).
HRMS (EI): m/z [M]+ calcd for C12H11NO: 185.0841; found: 185.0834.
13C NMR (101 MHz, CDCl3): δ = 148.5, 135.0, 134.1, 132.1, 129.5,
125.4, 122.8, 121.4, 110.4, 108.5, 35.4.
Funding Information
MS (EI): m/z (%) = 202 [M]+ (100), 156 (45), 141 (11), 128 (35), 115
(25).
HRMS (EI): m/z [M]+ calcd for C11H10N2O2: 202.0742; found:
A.N.B., M.E., A.M. and D.D. are grateful to the Fonds der Chemischen
Industrie, the Deutsche Forschungsgemeinschaft (DFG grant: DI
2227/2-1) and the SFB749 for Ph.D. funding and financial support.
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Supporting Information
2-(3-Nitrophenyl)furan (7b)
Supporting information for this article is available online at
To a solution of furan (75 μL, 1.014 mmol) in Et2O (2 mL, 0.5 M) was
slowly added a solution of n-BuLi (410 μL, 2.44 M in hexane, 1.00
equiv) at 0 °C. After stirring for 1 h at ambient temperature, B(Oi-Pr)3
(230 μL, 1.00 mmol, 1.00 equiv) and THF (2 mL) were added and the
resulting mixture stirred for another 1 h at room temperature. Pd(dp-
pf)Cl2 dichloromethane adduct (16 mg, 4 mol%), 1-iodo-3-nitroben-
zene (125 mg, 0.5 mmol, 0.5 equiv) and an aqueous solution of sodi-
um hydroxide (1.5 mL, 1.5 equiv 1.00 M) were subsequently added
and the mixture stirred overnight. The mixture was extracted with
Et2O (3 × 20 mL), washed with a saturated aqueous solution of sodium
chloride (20 mL), dried over magnesium sulfate, filtered, concentrated
and purified via flash column chromatography. Compound 7b was
obtained as a colorless oil.
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References
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Yield: 91 mg, 0.48 mmol (96%); Rf = 0.14 (hexane/EtOAc, 98:2; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 8.46 (t, J = 1.9 Hz, 1 H), 8.06 (dd, J = 8.2,
1.7 Hz, 1 H), 7.93 (d, J = 7.8 Hz, 1 H), 7.57–7.42 (m, 2 H), 6.79 (d, J = 3.5
Hz, 1 H), 6.52 (dd, J = 3.4, 1.8 Hz, 1 H).
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13C NMR (101 MHz, CDCl3): δ = 151.6, 148.8, 143.4, 132.4, 129.8,
129.3, 121.7, 118.5, 112.2, 107.4.
MS (EI): m/z (%) = 189 [M]+ (100), 143 (23), 131 (10), 115 (100), 102
(7).
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HRMS (EI): m/z [M]+ calcd for C10H7NO3: 189.0426; found: 189.0420.
4-(3,4-Dihydro-2H-pyran-6-yl)benzonitrile (7c)
To a solution of 3,4-dihydro-2H-pyran (90 μL, 1.014 mmol) and TMEDA
(50 μL, 0.33 mmol, 0.33 equiv) in Et2O (2 mL, 0.5 M) was slowly added
a solution of n-BuLi (550 μL, 2.44 M in hexane, 1.34 equiv) at ambient
temperature. After stirring for 30 min, B(Oi-Pr)3 (230 μL, 1.00 mmol,
1.00 equiv) and THF (2 mL) were added and the resulting mixture
stirred for 1 h at room temperature. Pd(dppf)Cl2 dichloromethane ad-
duct (16 mg, 4 mol%), 4-bromobenzonitrile (91 mg, 0.5 mmol, 0.5
equiv) and an aqueous solution of sodium hydroxide (1.5 mL, 1.5
equiv 1.00 M) were subsequently added and the mixture stirred over-
night. The mixture was extracted with Et2O (3 × 20 mL), washed with
a saturated aqueous solution of sodium chloride (20 mL), dried over
magnesium sulfate, filtered, concentrated and purified via flash col-
umn chromatography. Compound 7c was obtained as a yellow oil.
(11) Haag, B. A.; Sämann, C.; Jana, A.; Knochel, P. Angew. Chem. Int.
Ed. 2011, 50, 7290.
(12) (a) Boardman, L. D.; Bagheri, V.; Sawada, H.; Negishi, E.-i. J. Am.
Chem. Soc. 1984, 106, 6105. (b) Liu, F.; Negishi, E.-i. Tetrahedron
Lett. 1997, 38, 1149.
Yield: 40 mg, 0.22 mmol (43%); Rf = 0.17 (hexane/EtOAc, 98:2; UV,
KMnO4, PAA).
1H NMR (400 MHz, CDCl3): δ = 7.65–7.59 (m, 2 H), 7.59–7.54 (m, 2 H),
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

L
A. N. Baumann et al.
Special Topic
Synthesis
(13) (a) Eisold, M.; Didier, D. Angew. Chem. Int. Ed. 2015, 54, 15884.
(b) Eisold, M.; Kiefl, G. M.; Didier, D. Org. Lett. 2016, 18, 3022.
(c) Eisold, M.; Baumann, A. N.; Kiefl, G. M.; Emmerling, S. T.;
Didier, D. Chem. Eur. J. 2017, 23, 1634. (d) Baumann, A. N.;
Eisold, M.; Didier, D. Org. Lett. 2017, 19, 2114. (e) Eisold, M.;
Didier, D. Org. Lett. 2017, 19, 4046.
(16) CCDC 1825251 (3a), CCDC 1826225 (4g) and CCDC 1825250
(7a) contain the supplementary crystallographic data for this
manuscript. The data can be obtained free of charge from The
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/getstructures. See the Supporting Infor-
mation for details.
(14) Hodgson, D. M.; Pearson, C. I.; Kazmi, M. Org. Lett. 2014, 16, 856.
(15) Baumann, A. N.; Eisold, M.; Music, A.; Haas, G.; Kiw, Y. M.;
Didier, D. Org. Lett. 2017, 19, 5681.
(17) Negishi, E.-i.; Sawada, H.; Tour, J. M.; Wei, Y. J. Org. Chem. 1988,
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Larsen, R. D.; Reider, P. J. J. Org. Chem. 2002, 67, 5394.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L