Preparation and Synthetic Applications of [2.2]Paracyclophane Trifluoroborates: An Efficient and Convenient Route to Nucleophilic [2.2]Paracyclophane Cross-Coupling Building Blocks

Article abstract of DOI:10.1002/ejoc.201901171

We report the synthesis of [2.2]paracyclophane (PCP) trifluoroborate building blocks that can be used for the incorporation of the PCP moiety into a wide range of (hetero)aryl chlorides, bromides and triflates by a Pd(II)/RuPhos mediated Suzuki–Miyaura cross-coupling reaction. The PCP trifluoroborate species are bench stable with extended shelf life and easily accessible on a multigram scale by a two-step synthesis from commercially available PCP. They can be handled conveniently without special precautions, thus overcoming many of the limitations of other PCP cross-coupling reagents. Additionally, a high yielding regioselective monolithiation/borylation protocol for the synthesis of pseudo-para and pseudo-ortho PCP halotrifluoroborates and their subsequent Suzuki–Miyaura cross-coupling are described.

Full text of DOI:10.1002/ejoc.201901171

A Journal of
Accepted Article
Title: Preparation and Synthetic Applications of [2.2]Paracyclophane
Trifluoroborates:An Efficient and Convenient Route to a
Nucleophilic [2.2]Paracyclophane Cross-Coupling Building Block
Authors: Daniel Knoll, Helena Simek, Zahid Hassan, and Stefan Bräse
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201901171
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10.1002/ejoc.201901171
European Journal of Organic Chemistry
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Preparation and Synthetic Applications of [2.2]Paracyclophane
Trifluoroborates: An Efficient and Convenient Route to a
Nucleophilic [2.2]Paracyclophane Cross-Coupling Building Block
Daniel M. Knoll,a Helena Šimek,a Zahid Hassan,a Stefan Bräse*a, b
Abstract: We report the synthesis of [2.2]paracyclophane (PCP)
trifluoroborate building blocks that can be used for the incorporation
of the PCP moiety into a wide range of (hetero)aryl chlorides,
bromides and triflates by a Pd(II)/RuPhos mediated Suzuki-Miyaura
cross-coupling reaction. The PCP trifluoroborate species are bench
stable with extended shelf life and easily accessible on a multigram
scale by a two-step synthesis from commercially available PCP. They
can be handled conveniently without special precautions, thus
overcoming many of the limitations of other PCP cross-coupling
reagents. Additionally, a high yielding regioselective monolithiation-
/borylation protocol for the synthesis of pseudo-para and pseudo-
ortho PCP halotrifluoroborates and their subsequent Suzuki-Miyaura
cross-coupling are described.
common methods to forge new carbon-carbon and carbon-
heteroatom bonds, the unique electronic properties and
geometric shape of the PCP make cross-coupling chemistry
cumbersome,[7] sometimes surprising products are obtained,[8] or
no conversion is observed altogether.
In cumulated work spanning decades, chemists succeeded in
making most known cross-coupling reactions available for the
functionalization of PCP.[9]
Our group has recently reported on efficient synthesis of carbon-
carbon bond formation employing palladium-catalyzed reactions
in combination with different PCP-based nucleophiles, for
instance, PCP derivatives of magnesium (Kumada-Corriu), tin
(Stille-Migita) and zinc (Negishi) (Scheme 1).[10] An exploration of
[2.2]paracyclophane boronic acids in Suzuki-Miyaura cross-
coupling have been examined.[11] However, PCP borates and
their synthetic applications in carbon-carbon bond formation have
not been reported to be successful so far (Scheme 1).
Introduction
The intriguing shape of [2.2]paracyclophane has fascinated
researchers for over 70 years. It has been the subject of countless
studies concerning its slightly off-aromatic character caused by
the nonplanar geometry of the two co-facially stacked benzene
rings. This has been described by Cram et al. as “bent and
battered”.[1]
Besides this fundamental curiosity, PCP has received increasing
attention for its wide applications as a planar chiral ligands in
asymmetric synthesis,[2] purely carbon and hydrogen based
optical materials,[3] molecular junctions[4] and as a rigid backbone
in light-emitting diode TADF emitters.[5]
Scheme 1. Stable and cross-coupling active PCP borates have not been
reported until very recently.[12]
In the last couple of years, transition-metal mediated cross-
coupling reactions have dramatically changed the face of modern
paracyclophane chemistry.[6] However, a common struggle in
PCPs’ synthetic transformation is the often unexpected and non-
analogue reactivity when compared to the seemingly similar
benzene or p-xylene chemistry. This disparity in chemical
reactivity is most pronounced in cross-couplings and related
reactions. Although cross-coupling reactions are among the most
Results and Discussion
Free PCP boronic acids suffer from prompt decomposition, while
the corresponding boronic esters are inactive under catalytic
reaction conditions.[11] To overcome this hurdle, very recently, we
reported on the missing puzzle piece in the form of trifluoroborate
2. This nucleophilic Suzuki-Miyaura cross-coupling building block
is easily accessible in two steps from the PCP parent compound
in high yield and gram scale batches (Scheme 2).[12]
[a]
Daniel M. Knoll, Helena Šimek, Dr. Zahid Hassan, Prof. Dr. Stefan
Bräse
Institute of Organic Chemistry (IOC),
Karlsruhe Institute of Technology (KIT),
Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
E-mail: braese@kit.edu
ORCID: 0000-0003-4845-3191
http://www.ioc.kit.edu/braese/index.php
https://twitter.com/braeselab
[b]
Prof. Dr. Stefan Bräse
Scheme 2. Synthesis of PCP trifluoroborate 2.
Institute of Toxicology and Genetics (ITG),
Karlsruhe Institute of Technology (KIT),
Hermann-von-Helmholtz-Platz 1, D-76344 Eggenstein-
Leopoldshafen, Germany.
We reported on a cross-coupling protocol with the new PCP
trifluoroborate to efficiently access pyridine and pyrimidine
substituted PCPs.[12] The substrate scope was limited to 6-
membered N-heterocycles. Various attempts to increase the
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201901171
European Journal of Organic Chemistry
FULL PAPER
reactivity of the catalyst system by use of common promotor-
ligands like SPhos and XPhos were met with failure (even
diminishing yields). RuPhos has been reported as the ligand of
choice for the cross-coupling of alkyltrifluoroborates,[13] which in
face of PCP’s bulky, electron-rich and bent – thus less aromatic –
character seemed like a possible solution to this challenge.
Indeed, in stark contrast to the other phosphine ligands we have
tested, the use of RuPhos not only gave better yields (Table 1)
but showed great potential when applied to previously unreacting
aryl halides.
Table 2. Substrate scope of the Suzuki-Miyaura cross-
coupling protocol.
Table 1. Effect of different phosphine ligands to promote the
cross-coupling of bromopyridine.
Entry
1
Halide
Product
Yield
(%)a
42
92
2
3
4
5
Cl 69
Br 81
OTf 79
Entry
catalyst/ligand [mol%]
5/- ligand-free
5/15 SPhos
Yield [%]
1
2
3
4
37
25
35
42
87
74
5/15 XPhos
5/15 RuPhos
6
7
8
89
91
86
After careful optimization of the reaction parameters including
palladium source/ligand (Pd(OAc)2/RuPhos), temperature
(80 °C) and solvent effects (toluene/water), we subsequently
studied the diverse substrate scope of [2.2]paracyclophane
trifluoroborates in Suzuki-Miyaura cross-coupling reaction. The
results are shown in Table 2. The protocol tolerates a wide range
of functional groups like nitriles, esters, ethers, hydroxides,
alkynes, ketones, nitroarenes and amines. The PCP can be
coupled efficiently regardless of the steric and electronic effects
of the coupling substrates. Even though electron withdrawing
groups (entries 2-6) consistently lead to better results, electron
rich derivatives (entries 7-10) were obtained in high yields as well.
The successful coupling of sterically very demanding mesitylene
(entry 15), thiophene (entry 14) and benzylic nitrile (entry 16)
derivatives emphasize the versatility of this approach. The
substrate scope not only comprises bromides but also triflates and
less reactive chlorides which were converted in good yields (entry
3). However, sp3-hybridized cyclohexylbromide 4q did not give
the desired product (entry 17). Aromatic amines proved to be
challenging substrates and lead to a significantly reduced yield of
23% (entry 9).
9
23
88
10
11
12
90
78
13
34
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10.1002/ejoc.201901171
European Journal of Organic Chemistry
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14
87
Inspired by the work on iterative cross-coupling methodology
developed by Burke et al.,[14] we then set out to synthesize PCP
halotrifluoroborates. The required monolithiation of dibromo PCPs
exploits the following finding: The two-fold metal-halogen
15
16
25
51
-
exchange
of
pseudo-ortho
and
pseudo-para
dibromo[2.2]paracyclophane (5 and 7) has been described as
tedious and requires tert-butyllithium or large excess of n-
[15]
butyllithium in THF.
Thus, the synthesis of unexplored
halotrifluoroborates containing a bromide substituent for further
transformation was achieved in good yield for the pseudo-para
and pseudo-ortho derivatives 6 and 8 (Scheme 3). These PCP
halotrifluoroborates can be utilized to produce a wide range of
diverse PCP molecular architectures.
17
aisolated yields.
The substrate scope shows good to excellent yields for a wide
range of electrophiles. Optimization to improve reaction
conditions for the synthesis of the sluggishly reacting 4a was
conducted as shown in Table 3. The combination of sodium
carbonate as base and a mixture of toluene and water (1:1)
provided 3a in excellent yields of up to 82%. Further increasing
the water content of the solvent mixture (entries 14-15) did not
lead to improved results. The yield obtained in this way is almost
a twofold improvement when compared to our earlier reports
employing the Stille cross-coupling protocol.[10, 12] However, the
newly optimized reaction conditions did not improve yields for
entries 2-17 in Table 2. The cross-coupling of bromopyridines
seems to generally require different conditions, as already was
shown by the substrate scope of our previous report.[12]
Scheme 3. Synthesis of the pseudo-para and pseudo-ortho
halotrifluoroborate salts 6 and 8.
Table 3. Optimization study for the synthesis of 3.
A
subsequent Suzuki-Miyaura cross-coupling reaction was
carried out halotrifluoroborate 6 with 2-(4-bromophenyl)pyridine
leading to the desired product 9. However, the product was
obtained in a poor yield of 20–30%. This drastic change in
reactivity apparently imparted by just one remote bromide
substituent has been reported before.[16]
Optimization of the reaction conditions lead to satisfying yields of
50% for 9 (Table 4). Interestingly, increasing the equivalents of
the trifluoroborate salt had the adverse effect of lowering the yield,
while equimolar amounts led to an increase in yield (entry 2 and
3). Concentration of the reagents in the organic phase seem to be
the most important aspect where 0.2 M seems to be the sweet
spot as more and less concentrated conditions both led to lower
yields (entry 1 and 6). We have also examined the Suzuki-
Miyaura cross-coupling reaction employing halotrifluoroborate 8
based on the pseudo-ortho regioisomer. While NMR analysis
confirm the coupling product, however our efforts using the
standard optimized protocol were disappointing as we were not
able yet to improve/isolate the resulting coupling product in
sufficient purity. One possible explanation might be the high steric
repulsion.
Entry
Base
temp
(°C)
80
80
80
80
80
80
80
60
100
80
80
80
80
80
80
Solventa
Yield
(%)b
1
2
3
4
5
6
7
8
K3PO4
K3PO4
K3PO4
K2CO3
Tol/H2O 10:1
Tol/H2O 3:1
Tol/H2O 1:1
Tol/H2O 1:1
Tol/H2O 1:1
Tol/H2O 1:1
Tol/H2O 1:1
Tol/H2O 1:1
Tol/H2O 1:1
Tol/H2O 1:1
Tol/H2O 1:1
Tol/H2O 1:1
Tol/H2O 1:1
Tol/H2O 1:2
Tol/H2O 1:5
39
41
48
63
58
KOH
Cs2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
61
71 (73)c
56 (60)c
42
9
10d
11f
12e
13g
14
15
57
66
73
48
70
71
Table 4. Optimization study for the synthesis of 9.
a0.1 M, 10 mol% catalyst load. byield determined by NMR,
1,3,5-Trimethoxybenzene as standard. cafter 3 days. d0.2
M. e5 mol% catalyst load. f2 mol% catalyst load. 1 mol%
g
catalyst load.
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10.1002/ejoc.201901171
European Journal of Organic Chemistry
FULL PAPER
hours. After removal of the solvents under reduced pressure, the
white residue was triturated with acetone (2 × room temperature,
2 × boiling, 50 mL each) and the acetone removed under reduced
pressure subsequently. The white residue was washed with
dichloromethane and diethylether (100 mL each) and dried in high
vaccum to yield a powdery white crystalline solid (4.79 g, 87%).
1H NMR (400 MHz, Acetone-d6) δ [ppm] = 6.76 (dd, J = 7.8, 1.5
Hz, 1H), 6.69 (s, 1H), 6.43 (d, J = 1.7 Hz, 2H), 6.30 (dd, J = 7.8,
1.5 Hz, 1H), 6.17 (d, J = 1.7 Hz, 2H), 3.67 (ddd, J = 12.5, 10.5,
2.5 Hz, 1H), 3.15 – 3.00 (m, 3H), 2.93 – 2.70 (m, 4H). – 13C NMR
(101 MHz, Acetone-d6) δ [ppm] = 144.1 (Cquat.), 141.1 (Cquat.),
139.6 (Cquat.), 137.4 (Cquat.), 137.1 (Cquat.), 134.7 (+, CArH), 134.7
(+, CArH), 133.7 (+, CArH), 133.6 (+, CArH), 132.8 (+, CArH), 132.6
(+, CArH), 131.2 (+, CArH), 36.51 (–, CH2), 36.41 (–, CH2), 36.33
(–, CH2), 36.16 (–, CH2). 11B NMR (128 MHz, Acetone-d6) δ [ppm]
–15.2 (d, J = 59.2 Hz). – 19F NMR (376 MHz, Acetone-d6) δ [ppm]
–143.23 (m) – IR (ATR) ṽ = 3569 (w), 3378 (w), 2925 (w), 2851
(w), 1894 (vw), 1589 (w), 1552 (vw), 1500 (vw), 1478 (vw), 1436
(vw), 1410 (w), 1330 (w), 1231 (w), 1186 (vw), 1149 (w), 1107 (w),
938 (w), 901 (w), 834 (w), 793 (w), 736 (w), 719 (w), 643 (w), 615
(vw), 590 (vw), 511 (w), 482 (vw) – HRMS (FAB) (C16H1511B1F3K1)
calc. 314.0856, found 314.0854.
Entry
Deviation from standard
none
1.00 eq. 6
Yield (%)a
1
2
3
4
5
6
7
8
9
22
35
18
50
50
37
16
43
44
3.00 eq. 6
Tol/H2O 10:1 0.2 M
Tol/H2O 1:1 0.2 M
Tol/H2O 1:1 0.6 M
Na2CO3, 0.2 M
K2CO3,0.2 M
Cs2CO3, 0.2 M
aNMR yields, 1,3,5-Trimethoxybenzene as standard.
Conclusions
We have successfully prepared and characterized PCP
trifluoroborate building blocks that are a convenient starting point
for the incorporation of the PCP core by palladium-catalyzed
Suzuki-Miyaura cross-coupling into a wide range of (hetero)aryl
bromides, chlorides and triflates. These [2.2]paracyclophane
trifluoroborates can be easily prepared on a multigram-scale by a
two-step synthesis from commercially available PCP. The
nucleophilic species are bench-stable without special
precautions/degradation for months comparing to their boronic
acid/boronate esters and other counterparts which overcome
many of the limitations and can find widespread use as alternative
to boronic acids in PCP-based cross-coupling reactions. The
reaction is generally high-yielding and tolerates most functional
Synthesis of potassium 4-bromo-16-trifluoroborate[2.2]para-
cyclophane (6).
A flame-dried 1 L Schlenk flask was charged with 4,16-dibromo-
[2.2.]paracyclophane (3.00 g, 8.20 mmol, 1.00 equiv.) and dry
THF (900 mL). The reaction mixture was stirred at room
temperature until the starting material was completely dissolved
and then was cooled to –78 °C and n-BuLi (3.61 mL, 9.01 mmol,
1.10 equiv.) was added dropwise via syringe. The solution
became orange in color and faded to a pale yellow. This step was
allowed to proceed for 30 minutes. Then dry trimethyl borate (2.08
mL, 9.01 mmol, 1.10 equiv.) was added all at once. The mixture
was stirred for 30 minutes and allowed to warm slowly to room
temperature. The next day, sat. aqueous potassium hydrogen
fluoride (10.9 mL, 49.2 mmol, 6 equiv.) was added and the
mixture stirred for 1 h. The solvents were removed under reduced
pressure. The residue was triturated with hot acetone (4 × 100
mL). After removal of the solvent, the residue was washed
thoroughly with diethyl ether and dichloromethane and dried
under reduced pressure to yield the pure product as a white solid.
Yield 2.55 g, 79 %. – 1H NMR (500 MHz, Chloroform-d) δ [ppm] =
6.87 (dd, J = 7.6, 1.7 Hz, 1H), 6.80 (dd, J = 7.5, 2.1 Hz, 1H), 6.71
(d, J = 2.1 Hz, 1H), 6.50 (d, J = 1.7 Hz, 1H), 6.33 (d, J = 7.7 Hz,
1H), 6.15 (d, J = 7.6 Hz, 1H), 3.70 (dd, J = 10.7, 8.8 Hz, 1H), 3.32
(ddd, J = 13.1, 10.3, 2.8 Hz, 1H), 3.14 – 3.03 (m, 2H), 2.95 – 2.73
(m, 5H). – 13C NMR (101 MHz, CDCl3) δ [ppm] = 143.9, 143.8,
138.9, 137.7, 137.7, 136.9, 136.9, 136.0, 133.7, 132.8, 126.8,
126.5, 36.0, 35.9, 35.3, 34.7. 11B NMR (128 MHz, Acetone-d6) δ
[ppm] -14.9. – 19F NMR (376 MHz, Acetone-d6) δ [ppm] -143.1. –
HRMS (C16H14BBrF3K) calc. 391.9961, found 391.9963.
groups.
Selective
monolithiation/borylation/Suzuki-Miyaura
coupling offers entry into dissymmetric PCPs by exclusive cross-
coupling of the trifluoroborate moiety described herein and
subsequent functionalization of the remaining bromide substituent.
Research efforts towards the development of dissymmetric metal-
based bitopic ligand systems based on the corresponding PCP-
hetero(aryl) products are currently underway in our laboratories.
Experimental Section
Synthesis of potassium 4-trifluoroborate[2.2]paracyclo-
phane (2).
In
a
round
bottom-flask
under
argon,
4-
bromo[2.2]paracyclophane (5.02 g, 17.5 mmol, 1.00 equiv.) was
dissolved in 250 mL anhydrous THF. The solution was cooled to
–78 °C and n-BuLi (7.70 mL, 2.5 m, 19.3 mmol, 1.10 equiv.) was
added dropwise by syringe. After one hour, the yellow solution
was quenched with trimethylborate (6.1 mL, 26.2 mmol,
1.50 equiv.). The now colorless solution was allowed to slowly
warm to room temperature. The next day, aqueous potassium
hydrogen difluoride (23.3 mL, 4.5 m, 105 mmol, 6.00 equiv.) was
added by syringe and the mixture was stirred vigorously for 3
Synthesis of potassium 4-bromo-12-trifluoroborate[2.2]para-
cyclophane (8).
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10.1002/ejoc.201901171
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A flame-dried 1 L Schlenk flask was charged with 4,16-dibromo-
[2.2.]paracyclophane (3.00 g, 8.20 mmol, 1.00 equiv.) and dry
THF (300 mL). The reaction mixture was stirred at room
temperature until the starting material was completely dissolved
and then was cooled to –78 °C and n-BuLi (3.61 mL, 9.01 mmol,
1.10 equiv.) was added dropwise via syringe. The solution
became orange in color and faded to a pale yellow. This step was
allowed to proceed for 30 minutes. Then dry trimethyl borate (2.08
mL, 9.01 mmol, 1.10 equiv.) was added all at once. The mixture
was stirred for 30 minutes and allowed to warm slowly to room
temperature. The next day, sat. aqueous potassium hydrogen
fluoride (10.9 mL, 49.2 mmol, 6 equiv.) was added and the
mixture stirred for 1 h. The solvents were removed under reduced
pressure. The residue was triturated with hot acetone (4 × 100
mL). After removal of the solvent, the residue was washed
thoroughly with diethyl ether and dichloromethane and dried
under reduced pressure to yield the pure product as a white solid.
Yield 2.13 g, 66 %. – 1H NMR (500 MHz, Chloroform-d) δ [ppm] =
7.29 (d, J = 2.1 Hz, 1H), 6.83 (d, J = 1.6 Hz, 1H), 6.54 (dd, J = 7.7,
1.6 Hz, 1H), 6.47 (d, J = 7.7 Hz, 1H), 6.31 (d, J = 7.6 Hz, 1H), 6.23
(dd, J = 7.6, 2.1 Hz, 1H), 3.67 (ddd, J = 12.1, 10.4, 1.8 Hz, 1H),
3.38 – 3.29 (m, 1H), 3.11 – 2.94 (m, 2H), 2.92 – 2.83 (m, 2H),
2.82 – 2.67 (m, 2H). – 13C NMR (101 MHz, CDCl3) δ [ppm] = 144.0,
143.5, 139.2, 138.2, 138.2, 138.1, 138.1, 136.8, 135.2, 133.3,
133.3, 133.3, 131.8, 131.5, 127.6, 36.7, 36.6, 35.1, 33.8. 11B NMR
(128 MHz, Acetone-d6) δ [ppm] -15.0. – 19F NMR (376 MHz,
Acetone-d6) δ [ppm] -144.0. – HRMS (C16H14BBrF3K) calc.
391.9961, found 391.9962.
Keywords: [2.2]Paracyclophane • Halotrifluoroborates •
Borylation • Palladium Catalysis • Suzuki-Miyaura coupling •
General cross-coupling procedure for the synthesis of (3a-q).
In a vial fitted with a magnetic stirring bar, potassium 4-
trifluoroborate[2.2]paracyclophane
(1.50 equiv.),
potassium
phosphate (4.00 equiv.), palladium acetate (0.05 equiv.), RuPhos
(0.15 equiv.) and the respective halide (1.00 equiv., if solid) were
placed. The vial was capped, evacuated and backfilled with argon
three times. After addition of the solvent (toluene/water 10:1, 0.1
M), the respective halide (1.00 equiv., if liquid) was added via
syringe. The vial was put into a vial heating block and heated to
80 °C for 24 hours. The reaction was cooled to ambient
temperature and quenched with sat. aq. ammonium chloride.
After separation of the phases, the aqueous phase was extracted
with dichloromethane (3 × 15 mL). The organic phases were dried
over sodium sulfate and the solvent was removed under reduced
pressure. The crude product was purified via column
chromatography (silica, pentane/ethyl acetate).
Supporting Information
Supporting information for this article is available on the WWW
under xxx.
Acknowledgments
We thank the SFB1176 (C6) and SBF/TRR88 3MET (B2) for
funding this project.
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10.1002/ejoc.201901171
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[1]
[2]
D. J. Cram, J. M. Cram, Acc. Chem. Res. 1971, 4, 204-213.
Z. Hassan, E. Spuling, D. M. Knoll, J. Lahann, S. Bräse, Chem. Soc. Rev.
2018, 47, 6947-6963.
[10] C. Braun, E. Spuling, N. B. Heine, M. Cakici, M. Nieger, S. Bräse, Adv.
Synth. Catal. 2016, 358, 1664-1670.
[11] A. J. Roche, B. Canturk, Org. Biomol. Chem. 2005, 3, 515-519.
[12] D. M. Knoll, S. Bräse, ACS Omega 2018, 3, 12158-12162.
[13] G. A. Molander, D. L. Sandrock, Curr. Opin. Drug Discovery Dev. 2009,
12, 811-823.
[3]
[4]
M. Gon, Y. Morisaki, Y. Chujo, Chem. Eur. J. 2017, 23, 6323-6329.
D. S. Seferos, S. A. Trammell, G. C. Bazan, J. G. Kushmerick, Proc. Natl.
Acad. Sci. U. S. A. 2005, 102, 8821-8825.
[5]
[6]
E. Spuling, N. Sharma, I. D. W. Samuel, E. Zysman-Colman, S. Bräse,
Chem. Commun. 2018, 54, 9278-9281.
[14] E. P. Gillis, M. D. Burke, Aldrichim. Acta 2009, 42, 17-27.
[15] a) G. Meyer-Eppler, R. Sure, A. Schneider, G. Schnakenburg, S. Grimme,
A. Lützen, J. Org. Chem. 2014, 79, 6679-6687; b) C. Braun, S. Bräse, L.
L. Schafer, Eur. J. Org. Chem. 2017, 1760-1764.
A. de Meijere, B. Stulgies, K. Albrecht, K. Rauch, H. A. Wegner, H. Hopf,
L. T. Scott, L. Eshdat, I. Aprahamian, M. Rabinovitz, Pure Appl. Chem.
2006, 78, 813-830.
[16] B. Qu, Y. Ma, Q. Ma, X. Liu, F. He, C. Song, J. Org. Chem. 2009, 74,
6867-6869.
[7]
[8]
[9]
M. Kreis, C. J. Friedmann, S. Bräse, Chem. Eur. J. 2005, 11, 7387-7394.
C. Braun, M. Nieger, S. Bräse, Chem. Eur. J. 2017, 23, 16452-16455.
Z. Hassan, E. Spuling, D. M. Knoll, S. Bräse, Angew. Chem. Int. Ed. 2019,
DOI
10.1002/anie.201904863;
Angew.
Chem.
2019,
10.1002/ange.201904863
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10.1002/ejoc.201901171
European Journal of Organic Chemistry
FULL PAPER
FULL PAPER
[2.2]Paracyclophane Cross-coupling*
Daniel M. Knoll, Helena Šimek, Zahid
Hassan, Stefan Bräse
Page No. – Page No.
Preparation and Synthetic
Applications of [2.2]Paracyclophane
Trifluoroborates: An Efficient and
Convenient Route to a Nucleophilic
[2.2]Paracyclophane Cross-Coupling
Building Block
Preparation and synthetic applications of [2.2]paracyclophane trifluoroborates in the
Suzuki-Miyaura cross-coupling reaction is described. The trifluoroborates and
halotrifluoroborates described herein are bench-stable, crystalline solids accessible
on multi-gram scale and can be cross-coupled with a wide range of aryl(hetero)
halides.
This article is protected by copyright. All rights reserved.