Acetylenic homocoupling methodology towards the synthesis of 1,3-butadiynyl macrocycles: [142]-Alleno-acetylenic cyclophanes

Article abstract of DOI:10.1002/ejoc.201301701

[14₂]-Alleno-acetylenic cyclophanes were synthesized through two different approaches: an intermolecular coupling between two alkynyl fragments, and an intramolecular ring-closure of a linear acyclic bisalkynyl oligomer. The symmetry of the target dictates the choice of the most suitable method. To illustrate these approaches we have used 1,3-diethynyl-substituted allenes as building blocks. Due to the stereogenic character of the allene moiety, the alleno-acetylenic cyclophanes were obtained as a mixture of diastereoisomers, and the major twist isomers were resolved by preparative HPLC. The different symmetry of the isomers allowed the assignment of the relative configuration of the major twist isomers by taking into consideration the number of nonequivalent groups in the respective NMR spectra.

Full text of DOI:10.1002/ejoc.201301701

FULL PAPER
DOI: 10.1002/ejoc.201301701
Acetylenic Homocoupling Methodology Towards the Synthesis of
1,3-Butadiynyl Macrocycles: [142]-Alleno-Acetylenic Cyclophanes
Inmaculada R. Lahoz,[a] Armando Navarro-Vázquez,[a] José Lorenzo Alonso-Gómez,*[a] and
M. Magdalena Cid*[a]
Keywords: Allenes / Cyclophanes / Cyclization / Macrocycles / Cross-coupling / Conformation analysis
[142]-Alleno-acetylenic cyclophanes were synthesized
stereogenic character of the allene moiety, the alleno-acet-
through two different approaches: an intermolecular cou- ylenic cyclophanes were obtained as a mixture of diastereo-
pling between two alkynyl fragments, and an intramolecular
ring-closure of a linear acyclic bisalkynyl oligomer. The sym-
metry of the target dictates the choice of the most suitable
method. To illustrate these approaches we have used 1,3-di-
ethynyl-substituted allenes as building blocks. Due to the
isomers, and the major twist isomers were resolved by pre-
parative HPLC. The different symmetry of the isomers al-
lowed the assignment of the relative configuration of the
major twist isomers by taking into consideration the number
of nonequivalent groups in the respective NMR spectra.
We have previously reported the synthesis of [74]-alleno-
acetylenic cyclophanes 1a[4a] and 1c[4d] through an intramo-
lecular approach, using 2 (Scheme 1) to gain control over
the cyclization process and thus avoid the formation of un-
desired cyclic oligomers. We also obtained [142]-alleno-acet-
ylenic cyclophane 3b[3b] through an intermolecular dimer-
ization.
In our search for an efficient protocol with which to pre-
pare diverse alleno-acetylenic cyclophanes, we compared
the efficiency of two alternative approaches, namely inter-
and intramolecular ring closures. Here, we present our re-
sults regarding the preparation of twist-[142]-alleno-acetyl-
enic cyclophanes 3 through an intermolecular acetylenic
homocoupling between two units of monomer 4 and, as an
alternative synthetic method, an intramolecular macrocycli-
zation of bisalkynyl oligomer 5. Due to the presence of a
1,3-diynyl moiety, we envisaged an oxidative coupling of
terminal alkynes as the key step. Both heterotrimer 4 and
oligomer 5 can be prepared from commercially available
2,5-, 2,6-dibromopyridine or 9,10-dibromoanthracene
through palladium-catalyzed Sonogashira cross-coupling
reactions with diethynylallene (Ϯ)-6 (Scheme 2).
Introduction
Functionalized shape-persistent macrocycles, in particu-
lar cyclophanes, are intriguing and attractive structures be-
cause of their chemical, physiochemical, and biological
properties.[1] However, despite the efforts made during the
last decades, the synthesis of these compounds remains a
challenge. The availability of acetylenic building blocks and
the application of modern metal-catalyzed coupling reac-
tions to form sp-sp2 and sp-sp carbon–carbon bonds have
significantly advanced this field.[2]
Generally, alleno-acetylenic macrocycles can be synthe-
sized by either an intermolecular ring closure of
bisfunctionalized oligomers,[3] or an intermolecular cou-
pling between two or more ring fragments followed by a
unimolecular cyclization.[4] Both strategies have inherent
advantages and disadvantages. An intramolecular cycliza-
tion guarantees the highest selectivity toward formation of
a single cyclic product and, as a result, purification is
greatly simplified. Moreover, this approach allows func-
tional groups to be introduced at defined positions of the
oligomeric sequence, leading to macrocycles with diverse
backbone structures. On the other hand, by using an inter-
molecular approach, the starting materials can typically be
prepared in fewer steps, which often renders this procedure
more time efficient. Unfortunately, the probability of form-
ing numerous cyclooligomeric macrocycles is high, making
purification of the target molecule difficult.[5]
Results and Discussion
Intermolecular Approach
[a] Departamento de Química Orgánica, Universide de Vigo,
Edificio de Ciencias Experimentais,
The first step towards the preparation of alleno-acetyl-
enic cyclophanes 3 involved the synthesis of racemic dieth-
ynylallene [DEA; (Ϯ)-6]. For this purpose, by following a
reported procedure,[6] we prepared DEA (Ϯ)-7a and 7b
through a Pd-catalyzed SN2Ј reaction of pentafluorobenzo-
ate (Ϯ)-8 with acetylenes 9a and 9b, respectively. Selective
Campus Lagoas-Marcosende, 36310 Vigo, Spain
E-mail: lorenzo@uvigo.es
mcid@uvigo.es
http://webs.uvigo.es/webqo3/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301701.
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FULL PAPER
Scheme 1. Synthesis of alleno-acetylenic cyclophanes 1a,[4a] 1c,[4d] and 3b.[3b]
deprotection of these DEAs gave the desired DEA (Ϯ)-6a ive homocoupling reactions, modifications of the conven-
and (Ϯ)-6b in 76 and 67% overall yield, respectively tional Glaser method[7] such as Hay [CuCl, TMEDA, O2,
(Scheme 3) (see the Supporting Information for further de- (CH2)2Cl2],[8] Eglinton and Galbraith (CuSO4, pyridine,
tails).
MeOH),[9] and Breslow (CuCl, CuCl2 oxygen-free pyr-
The synthesis of alleno-acetylenic cyclophanes 3 were idine)[10] have been most often used for the preparation of
carried out by the application of intermolecular acetylenic macrocycles containing buta-1,3-diyl units. More recently,
homocoupling reactions on the respective bisallenoacetyl- the use of PdII as cocatalyst in the presence of CuI and O2
enes 4, which were prepared by Sonogashira cross-coupling has emerged as an alternative to the traditional CuI/CuII
reaction using 2.1 equiv. of monoprotected DEA (Ϯ)-6a homocoupling-based methods.[11]
and the appropriate dibromoaromatic spacers in the pres-
The bisallenoacetylenes 4a, 4b, and 4c were subjected to
ence of [Pd(PPh3)2Cl2] and CuI (Scheme 4). Thus, when three different macrocyclization reaction conditions, namely
9,10-dibromoanthracene or 2,5-dibromopyridine was Breslow, and modified Hay conditions, and Pd/Cu-cata-
treated with 2.1 equiv. of (Ϯ)-6a in the presence of 5 mol- lyzed homocoupling reaction; the results are summarized in
% [PdCl2(PPh3)2], 2 mol-% CuI and Et3N in CH3CN at Table 1.
80 °C, the protected bisallenoacetylene 10a and 10c were
When Hay conditions were employed, namely, addition
afforded in 66 and 48% yield, respectively. Subsequent de- of deprotected bisacetylenes 4a, 4b or 4c under pseudo-
silylation with tetrabutylammonium fluoride (TBAF) in high-dilution to a solution of CuI and the bidentate ligand
tetrahydrofuran (THF) at 25 °C gave 4a and 4c, in 74 and TMEDA in dichloroethane under an O2 atmosphere, 2,6-
83% yield, respectively. When 2,6-dibromopyridine was pyrido-allenoacetylenic 4b gave the desired macrocycle 3b
treated with 2.1 equiv. (Ϯ)-6a in the presence of 2 mol-% in 68% yield along with other compounds that were iden-
[PdCl2(PPh3)2], 5 mol-% CuI, and tetramethylethylenedi- tified by mass spectroscopy analysis as the diiodo com-
amine (TMEDA) in toluene at 110 °C followed by desil- pound 11b and the diiodo oligomer 12b (Figure 1).[3b] This
ylation with TBAF in THF at 25 °C, 4b was obtained in result was not reproducible and, in practically all cases, only
74% overall yield.[3b]
the diiodo compounds were obtained. The formation of
With heterotrimers 4 in hand, we investigated the forma- these iodide compounds, also observed for 4a and 4c, could
tion of the 1,3-diynyl moieties. Among the available oxidat- be due to reductive elimination across CuII species.[12]
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Towards the Synthesis of 1,3-Butadiynyl Macrocycles
Scheme 2. Retrosynthetic analysis of [142]-alleno-acetylenic cyclophanes 3.
Scheme 3. Synthesis of DEA (Ϯ)-6a and (Ϯ)-6b.
Synthesis of 3a–c was then carried out under Pd/Cu-cata- 13a. Compounds 4b[3b] and 4c (Figure 1) gave the corre-
lyzed homocoupling conditions. Solutions of the heterotri- sponding cyclophanes 3b and 3c, respectively, as diastereo-
mers 4a–c in toluene were added under pseudo-high-di- isomeric mixtures in 56% yield.
lution to a solution of CuI, [Pd(PPh3)Cl2] and TMEDA in
Finally, when the reactions were run under Breslow con-
toluene under air atmosphere at 60 °C to give, in the case ditions, that is, bisallenoacetylenes 4a–c were treated with
of 4a, the desired alleno-acetylenic cyclophanes 3a in good CuCl (75 mol-%) and CuCl2 (11 mol-%) in oxygen-free pyr-
yield (63%) along with traces of a larger [143] macrocycle idine at 25 °C under pseudo-high-dilution, the correspond-
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I. R. Lahoz, A. Navarro-Vázquez, J. L. Alonso-Gómez, M. M. Cid
FULL PAPER
Scheme 4. Intermolecular approach. Synthesis of alleno-acetylenic cyclophanes 3.
Figure 1. Side products: diiodinated derivatives 11 and 12, and [143]-alleno-acetylenic cyclophane 13. The compounds were obtained as
diastereoisomeric mixtures.
Table 1. Reaction conditions for macrocyclization of 4a, 4b, and Intramolecular Approach
4c.[a]
With the results of the intermolecular approach in hand,
Reaction conditions
Yield [%]
3b
we proceeded with the synthesis of alleno-acetylenic cy-
clophanes 3 through an intramolecular macrocyclization. In
the case of alleno-acetylenic cyclophanes 3a and 3b, for
which the two reactive positions are equivalent, the inter-
molecular approach may be appropriate. However, for pre-
cursors bearing nonequivalent reactive positions, such as
bisallenoacetylene 4c, it is highly likely that performing the
reaction in an intermolecular manner would lead to the cor-
responding cyclophanes as a mixture of regioisomers. In
contrast, the intramolecular synthesis of 3c precludes the
formation of the C2 symmetric regioisomer.
3a
3c
Hay[b]
–
63
58
–
trace
56
54
[e]
Pd/Cu[c]
Breslow[d]
56
63
[a] The alleno-acetylenic cyclophanes were obtained as diastereo-
isomeric mixtures. [b] Hay reaction conditions: CuI, TMEDA,
(CH2)2Cl2, 25 °C, air. [c] Pd/Cu catalyzed homocoupling reaction
conditions: CuI, [Pd(PPh3)Cl2], TMEDA, toluene, 60 °C, air.
[d] Breslow reaction conditions: CuCl, CuCl2, pyridine, 25 °C, Ar.
[e] Not reproducible.
ing cyclophanes 3 were obtained in good yields (58, 63, and
Thus, the synthesis of 3c through a stepwise intramolecu-
54% for 3a, 3b,[3b] and 3c, respectively). Compound 3a was lar approach started with two regioselective Sonogashira
obtained along with traces of 13a (Figure 1), as revealed cross-coupling reactions between 2,5-dibromopyridine and
by its mass spectrum. Due to the nonequivalent reactive the two different diethynylallenes, first (Ϯ)-6b, which gave
positions of 4c, 3c was obtained as a mixture of regioiso- monoallenoacetylene 14c, and then (Ϯ)-6a to render the
mers. In fact NMR spectroscopic analysis showed a very asymmetrically disubstituted hetero-oligomer 15c in 58%
complex set of signals.
overall yield. Selective deprotection of the acetonide group
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Towards the Synthesis of 1,3-Butadiynyl Macrocycles
Scheme 5. Intramolecular approach. Synthesis of alleno-acetylenic cyclophanes 3c as a mixture of diastereoisomers.
by reaction with anhydrous NaOH in benzene gave 16c[4d]
in 82% yield. Acetylenic oxidative coupling under an air
atmosphere and subsequent deprotection of both TIPS
groups with TBAF in THF at 25 °C led to the precursor
of macrocycle 5c in 71% overall yield. A very successful
intramolecular ring-closing of 5c under treatment with
CuCl and CuCl2 in pyridine at 25 °C for 1 h (Breslow con-
ditions) afforded the desired 2,5-pyridoalleno-acetylenic cy-
clophanes 3c in 75% yield regioselectively (Scheme 5).
Table 2. Nonequivalent groups for the different isomers of alleno-
acetylenic cyclophanes 3a–c.[a]
Isomer
C=C=C[b]
tBu[c]
3a
3b
3c
Twist (P,M,M,M)/(M,P,P,P)
Crown (P,P,P,P)/(M,M,M,M)
Chair (P,M,M,P)
4
1
1
1
1
8[d]
2
2
2
2
8[e]
2[e]
2[e]
2[e]
2[e]
8[e]
8[e]
4
Boat (P,M,P,M)
Couch (P,P,M,M)
Twist (P,M,M,M)/(M,P,P,P)
Crown (P,P,P,P)/(M,M,M,M)
Chair (P,M,M,P)
Boat (P,M,P,M)
Couch (P,P,M,M)
4
1
1
1
1
Characterization of Twist-alleno-acetylenic Cyclophanes 3a,
3b and 3c
Twist-1 (P,M,M,M)/(M,P,P,P)
Twist-2 (M,P,M,M)/(P,M,P,P)
Crown (M,M,M,M)/(P,P,P,P)
Chair (P,P,M,M)
Boat (P,M,P,M)
Couch (P,M,M,P)/(M,P,P,M)
4
4
2
2
2
2
We have shown in our previous work that the diastereo-
isomeric mixtures can be resolved by using HPLC and char-
acterized, in some cases, by symmetry analysis of the NMR
spectra. Again here, the use of the allene as racemate gave
alleno-acetylenic cyclophanes 3 as diastereoisomeric mix-
tures (see Table 2), in which formation of the (P,M,M,M)/
(M,P,P,P)-twist isomers is statistically favored over the for-
mation of the others. As an illustration, the AM1 geome-
tries of 3c diastereoisomers are included in the Supporting
4
4
4
[a] All diastereoisomers of 3 can present different conformations.
[b] Number of nonequivalent cummulenic carbon atoms in the
13C NMR spectra. [c] Number of nonequivalent tert-butyl protons
1
in the H NMR spectra. [d] Not characterized due to photochemi-
Information. The optimized geometries of the different cal isomerization. [e] Isolated and characterized.
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I. R. Lahoz, A. Navarro-Vázquez, J. L. Alonso-Gómez, M. M. Cid
FULL PAPER
twist isomers for each alleno-acetylenic cyclophane are de-
picted in Figure 2.
Experimental Section
Materials and General Methods: Reagents and solvents were pur-
chased as reagent grade and used without further purification un-
less stated otherwise. THF was freshly distilled from sodium benzo-
phenone ketyl; (CH2)2Cl2, amines, and pyridine were freshly dis-
tilled from CaH2. All reactions were performed in oven- or flame-
dried glassware under an inert atmosphere of argon unless stated
otherwise. Chromatography refers to flash chromatography (FC)
on SiO2 60 (230–400 mesh) from Merck; a head pressure of around
0.2 bar was applied. TLC was performed on UV254 SiO2-coated
plates from Merck with visualization by UV light (254 nm). HPLC:
Waters 510 pump controlled by PMC pump controller, with U6K
injector and UV detector. Solvents were HPLC grade and degassed
with He. UV/Vis spectra were recorded with a Varian-CARY 100
Bio Scan or a 500 Scan spectrophotometer with a 1 cm cell at
1
25 °C. H, 13C, and 19F NMR spectra were recorded with Bruker
600 MHz, Bruker 500 MHz, Bruker 400 MHz, or Varian Gemini
300 MHz spectrometers at 298 K with residual solvent peaks as
internal reference; chemical shifts are reported in δ (ppm) and cou-
pling constants J are given in Hz. The multiplicities are expressed
as follows: s singlet, d doublet, t triplet, m multiplet. IR spectra
were recorded with a JASCO FT/IR-4200 infrared spectrometer;
peaks are quoted in wavenumbers (cm–1). Mass spectra were re-
corded at the Cacti Universidade de Vigo with a Hewlett–Packard
HP59970 instrument operating at 70 eV by electron ionization and
with an APEX III FT-ICR MS (Bruker Daltonics, Billerica, MA)
equipped with a 7 T actively shielded magnet. High-resolution
mass spectra were recorded with a VG Autospec instrument. Ele-
mental analyses were performed with a Fisons EA-1108. See the
Supporting Information for further details.
Figure 2. Tube models of geometries optimized at the AM1 level
of theory. Top: twist (P,M,M,M)-3a and (M,P,P,P)-3b; bottom:
twist-1 (P,M,M,M)-3c and twist-2 (M,P,M,M)-3c. Only one of the
enantiomers of each racemate is depicted.
The different number of chemically nonequivalent
groups in the NMR spectra allowed the twist-symmetrical
diastereoisomers of these cyclophanes to be distinguished
(Table 2). Whereas 3a and 3b showed only one twist isomer,
3c showed two, twist-1 and twist-2, due to the asymmetry
around the nitrogen of the pyridine rings.
Computational Methods: Structures for all diastereoisomers of cy-
clophane 3c were first optimized in vacuo by using the OPLS 2005
Our next goal was to isolate and characterize the major
diastereoisomers of all cyclophanes 3. Thus, the mixtures force field[15] as implemented in the MacroModel program. Al-
though the macrocycles present a very rigid skeleton, some confor-
mational mobility is present due to the rotation of the pyridine
rings. Hence, a short Monte Carlo conformational search was per-
formed for each of the diastereoisomers. As expected, the found
rotamers were nearly degenerate in energy. In the case of the sym-
metric diastereoisomers, the lowest energy rotamers close to maxi-
mum symmetry structures were chosen and symmetrized by using
the SYMMOL program.[16] The geometries so obtained were reop-
timized in vacuo at the semiempirical AM1[17] level of theory by
using the Gaussian09 program.[18] AM1 geometries were also com-
puted for 3a and 3b major twist isomers. Frequencies were analyti-
cally computed to verify the nature of the obtained stationary
points as minima.
were resolved by preparative HPLC on the stationary phase
“Buckyclutcher 1” (for more details see the Supporting In-
formation).[13] Because of its fast isomerization to the origi-
nal diastereomeric mixture probably due to the presence of
the anthracene unit favoring photochemical isomerization
at low UV energies, the major compound for 3a, twist-3a,
was not isolated in pure form.[14] The major compound was
successfully isolated in pure form and fully characterized
for twist-3b,[3b] twist-1-3c and twist-2-3c.
Conclusions
9,10-Bis[3,5-di(tert-butyl)-7-(triisopropysilyl)hepta-3,4-diene-1,6-di-
ynyl]anthracene (10a): Two solutions were prepared: (1) A solution
of (Ϯ)-6a (50 mg, 0.14 mmol) and Et3N (30 μL, 0.20 mmol) in
CH3CN (2.0 mL) in a Schlenk tube; (2) A solution of [PdCl2-
We have shown using the synthesis of alleno-acetylenic
cyclophanes 3 the utility of both intra- and intermolecular
ring-closing processes in oxidative acetylenic homocoupling
reactions. Choosing one or the other depends on the sym- (PPh3)2] (2 mg, 0.003 mmol) and 9,10-dibromoanthracene (21 mg,
0.06 mmol) in CH3CN (1.0 mL). Both solutions were degassed with
Ar. CuI (0.23 mg, 1.2 μmol) was added to Solution 2, which was
further degassed with Ar. Solution 2 was transferred by cannula to
Solution 1. After sparging the reaction, it was stirred and heated
to reflux (80 °C) under Ar for 12 h. The reaction mixture was then
filtered through silica gel with hexane and the solvent was removed
under reduce pressure. Purification by FC on silica gel (hexane)
metry of the target system: in the case of symmetrical spa-
cers (a and b), the intermolecular approach should be pre-
ferred because it involves fewer steps and proceeds in good
overall yields. On the other hand, for unsymmetrical spa-
cers (c), the intramolecular approach is preferred because it
avoids the formation of regioisomeric products. In this way,
cyclophane 3c was obtained with total regioselectivity in
good yield. HPLC resolution along with NMR experiments
allowed the major diastereomers of 3 to be characterized as
the twist isomers.
1
afforded 10a (41 mg, 66%) as a brown solid. H NMR (300 MHz,
CDCl3, 25 °C): δ = 8.55 (dd, J = 6.7, 3.2 Hz, 4 H), 7.58 (dd, J =
6.7, 3.2 Hz, 4 H), 1.37 (s, 18 H, tBu), 1.27 (s, 18 H, tBu), 1.12 (s,
42 H, TIPS) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 212.8
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Towards the Synthesis of 1,3-Butadiynyl Macrocycles
calcd. for C44H46 [M]+ 574.3600; found 574.3616. C44H46 (574.8):
+
(2 C, C=C=C), 131.9 (4 C), 127.2 (4ϫCH), 126.5 (4ϫCH), 118.6
(2 C), 104.0 (2 C), 103.7 (2 C), 100.1 (2 C), 96.5 (2 C), 94.6 (2 C), calcd. C 91.93, H 8.07; found C 91.90, H 8.22.
89.5 (2 C), 35.8 (2 C, tBu), 35.7 (2 C, tBu), 29.5 (6ϫCH3, tBu),
2,5-Bis[3,5-di(tert-butyl)hepta-3,4-diene-1,6-diyn-1-yl]pyridine (4c):
29.2 (6 ϫ CH3, tBu), 18.8 (12 ϫ CH3, TIPS), 11.5 (6 ϫ CH,
By following the same procedure described for 4a, to a solution of
10c (95 mg, 0.12 mmol) in anhydrous THF (14 mL), TBAF (1M in
THF, 270 μL, 0.27 mmol) was added under an Ar atmosphere. Af-
ter stirring for 3 h at 25 °C, workup and purification by flash
chromatography on silica gel (hexane/EtOAc, 95:5) afforded 4c
(47 mg, 83%) as a white solid. 1H NMR (400 MHz, CDCl3, 25 °C):
δ = 8.62 (dd, J = 2.1, 0.8 Hz, 1 H), 7.67 (dd, J = 8.1, 2.1 Hz, 1 H),
7.38 (dd, J = 8.1, 0.8 Hz, 1 H), 3.02 (s, 1 H), 3.04 (s, 1 H), 1.22 (s,
9 H, tBu), 1.21 (s, 9 H, tBu), 1.18 (s, 9 H, tBu), 1.17 (s, 9 H,
tBu) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 212.9 (C,
C=C=C), 212.4 (C, C=C=C), 152.2 (CH), 142.0 (C), 138.4 (CH),
126.6 (CH), 119.7 (C), 103.5 (C), 103.3 (C), 103.1 (C), 103.0 (C),
92.0 (C), 89.4 (C), 85.5 (C), 81.2 (CH, -CϵC-H), 81.1 (CH, -CϵC-
H), 35.9 (C, tBu), 35.8 (C, tBu), 35.5 (C, tBu), 35.5 (C, tBu), 29.2
(3 ϫ CH3, tBu), 29.1 (3 ϫ CH3, tBu), 29.0 (3 ϫ CH3, tBu), 28.9
(3 ϫ CH3, tBu) ppm. HRMS (ESI): m/z calcd. for C35H42N+
476.33118; found 476.33158.
TIPS) ppm. MALDI-MS: m/z = 910 (56) [M + Na]+, 887 (48) [M+],
830 (100) [M – Me3C]+. HRMS (MALDI): calcd. for C62H86Si2
+
[M]+ 886.6268; found 886.6229. IR (neat): ν = 2960, 2863, 2139,
˜
1460, 1437, 1361, 1243, 1094, 1017, 995, 882, 764, 740, 676 cm–1.
C62H86Si2 (887.5): calcd. C 83.90, H 9.77, Si 6.33; found C 83.76,
H 9.76. UV/Vis (hexane): λmax (ε, Lmol–1 cm–1) = 221 (67400), 271
(105500), 304 (27800), 431 (34800), 457 (42100) nm. Fluorescence
spectrum (hexane, λex = 315 nm): λmax = 468, 500 nm; f = 0.51.
2,5-Bis[3,5-di(tert-butyl)-7-(triisopropysilyl)hepta-3,4-diene-1,6-di-
ynyl]pyridine (10c): Two solutions were prepared: (1) A solution of
(Ϯ)-6a (50 mg, 0.14 mmol) and Et3N (30 μL, 0.20 mmol) in
CH3CN (2.0 mL) in a Schlenk tube; (2) A solution of [PdCl2-
(PPh3)2] (2 mg, 3.5 μmol) and 2,5-dibromopyridine (16 mg,
0.07 mmol) in CH3CN (1.0 mL). Both solutions were degassed with
Ar. CuI (0.3 mg, 1.4 μmol) was added to Solution 2 and oxygen-
containing air was purged out with Ar. Solution 2 was transferred
by using a cannula to Solution 1. After sparging the reaction mix-
ture, it was stirred and heated to reflux (80 °C) under Ar for 6 h.
The solvent was then removed under vacuum and the crude mate-
rial was partitioned between 0.45 m aqueous KCN solution and
CH2Cl2. The aqueous phase was extracted with CH2Cl2, the com-
bined organic phases were dried (Na2SO4), and the solvent was
removed under reduced pressure. Purification by FC on silica gel
(hexane/CH2Cl2, 7:2) afforded 10c (27 mg, 48%) as a colorless oil.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.62 (dd, J = 2.1, 0.8 Hz,
1 H), 7.67 (dd, J = 8.1, 2.1 Hz, 1 H), 7.39 (dd, J = 8.1, 0.8 Hz, 1
H), 1.21 (s, 9 H, tBu), 1.19 (s, 9 H, tBu), 1.18 (s, 9 H, tBu), 1.17
(s, 9 H, tBu), 1.09 (s, 21 H, TIPS), 1.08 (s, 21 H, TIPS) ppm. 13C
NMR (100 MHz, CDCl3, 25 °C): δ = 212.7 (C, C=C=C), 212.3 (C,
C=C=C), 152.0 (CH), 141.9 (C), 138.0 (CH), 126.3 (CH), 119.5
(C), 104.4 (C), 104.3 (C), 102.5 (C), 102.2 (C), 99.8 (C), 99.7 (C),
94.84 (C), 94.77 (C), 91.6 (C), 89.0 (C), 88.3 (C), 85.4 (C), 35.93
(C, tBu), 35.89 (C, tBu), 35.52 (C, tBu), 35.50 (C, tBu), 29.19
(3ϫCH3, tBu), 29.15 (3ϫCH3, tBu), 29.01 (3ϫCH3, tBu), 28.99
(3ϫCH3, tBu), 18.8 (12ϫCH3, TIPS), 11.5 (6ϫCH, TIPS) ppm.
MALDI-MS: m/z = 789 (100) [M + H]+, 775 (30), 745 (29) [M –
Me2HC]+, 732 (25) [M + HMe3C]+. HRMS (MALDI): calcd for
5,5Ј-(3,5,10,12-Tetra-tert-butyltetradeca-3,4,10,11-tetraen-1,6,8,13-
tetrayne-1,14-diyl)bis[2-(3,5-di-tert-butylhepta-3,4-dien-1,6-diyn-1-
yl)pyridine] (5c): Monodeprotected heterotrimer 16c[4d] (1.33 g,
2.10 mmol) was dissolved in toluene (100.0 mL). To this solution,
[PdCl2(PPh3)2] (0.10 g, 0.15 mmol), CuI (29 mg, 0.15 mmol) and
TMEDA (480 μL, 3.10 mmol) were added, and the mixture was
stirred and heated to reflux (110 °C) under an air atmosphere for
28 h. The reaction mixture was then partitioned between saturated
aqueous NH4Cl solution and dichloromethane. The combined or-
ganic phases were dried (Na2SO4) and the solvent was removed
under reduced pressure. The crude material obtained was redis-
solved in THF (80 mL), TBAF was added (1 m in THF, 2.6 mL,
2.6 mmol), and the reaction mixture was stirred at 25 °C under an
argon atmosphere. After 1 h, the solvent was removed under re-
duced pressure and the residue was partitioned between saturated
aqueous NaHCO3 solution and dichloromethane. The aqueous
phase was extracted with dichloromethane, the combined organic
phases were dried (Na2SO4), and the solvent was removed under
reduced pressure. Purification by FC on silica gel (hexane/CH2Cl2,
1:1) afforded 5c (740 mg, 71 %) as a brown solid. 1H NMR
(400 MHz, CDCl3, 25 °C): δ = 8.61 (d, J = 1.6 Hz, 2 H), 7.66 (dd,
J = 8.1, 1.6 Hz, 2 H), 7.37 (d, J = 8.1 Hz, 2 H), 3.04 (s, 2 H), 1.22
(s, 18 H), 1.20 (s, 18 H), 1.17 (s, 36 H) ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ = 214.3 (2 C, C=C=C), 212.2 (2 C, C=C=C),
152.1 (2 ϫ CH), 141.9 (2 ϫ C), 138.1 (2 ϫ CH), 126.4 (2 ϫ CH),
119.5 (2 ϫ C), 103.7 (2 ϫ C), 103.6 (2 ϫC), 103.4 (2ϫ C), 102.8
(2ϫC), 92.3 (2ϫC), 89.3 (2ϫC), 87.9 (2ϫC), 84.5 (2ϫC), 80.9
(2ϫC), 77.6 (2ϫC), 77.1 (2ϫC), 75.1 (2ϫC), 36.0 (2ϫC, tBu),
35.9 (2 ϫ C, tBu), 35.6 (2 ϫ C, tBu), 35.3 (2 ϫ C, tBu), 29.05
(6ϫCH3, tBu), 29.00 (12ϫCH3, tBu), 28.8 (6ϫCH3, tBu) ppm.
C53H82NSi2+ [M]+ 788.5980; found 788.5972. IR (NaCl): ν = 2961,
˜
2864, 2210, 2140, 1737, 1581, 1540, 1463, 1361, 1218, 1103, 1072,
1016, 995, 882, 839, 752, 720 cm–1. UV/Vis (hexane): λmax (ε,
Lmol–1 cm–1) = 222 (43000), 233 (39500), 245 (28000), 329 (52000),
339 (41700) nm.
9,10-Bis[3,5-di(tert-butyl)hepta-3,4-diene-1,6-diynyl]anthracene (4a):
To a solution of 10a (100 mg, 0.11 mmol) in anhydrous THF
(15.0 mL), TBAF (1 m in THF, 60 μL, 0.06 mmol) was added under
Ar and the mixture was stirred for 1 h at 25 °C. The reaction mix-
ture was partitioned between saturated aq. NH4Cl solution and
hexane. The aqueous phase was extracted with hexane, the com-
bined organic phases were dried (MgSO4), and the solvent was re-
moved under reduced pressure. Purification by FC on silica gel
(hexane/CH2Cl2, 80:20) afforded 4a (48 mg, 74%) as a brown solid.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.54 (dd, J = 6.6, 3.3 Hz,
4 H), 7.60 (dd, J = 6.6, 3.3 Hz, 4 H), 3.09 (s, 2 H, CϵCH), 1.39
(s, 18 H, tBu), 1.28 (s, 18 H, tBu) ppm. 13C NMR (100 MHz,
HRMS (ESI): calcd for C70H81N2 [M + H]+ 949.6394; found
+
949.6362.
Intermolecular Approach
4,6,11,13,19,21,26,28-Octa-tert-butyl-1,16(9,10)dianthracenacyclo-
triacontaphane-4,5,11,12,19,20,26,27-octaen-2,7,9,10,14,17,
22,24,29-octayne (3a)
Hay Coupling Reaction: A round-bottom flask was flame-dried un-
CDCl3, 25 °C): δ = 212.7 (2 C, C=C=C), 132.0 (4 C), 127.1 der a flow of dry argon. To the flask, CuI (35 mg, 0.18 mmol),
(4ϫCH), 126.7 (4ϫCH), 118.7 (2 C), 104.6 (2 C), 102.6 (2 C), TMEDA (54 mg, 0.46 mmol), and dichloroethane (5 mL) were
96.0 (2 C), 90.0 (2 C), 80.8 (2ϫCH), 77.4 (2 C), 35.7 (2 C, tBu), added. Oxygen was bubbled into the solution for 1 h at ambient
35.6 (2 C, tBu), 29.3 (6ϫCH3, tBu), 29.0 (6ϫCH3, tBu) ppm. MS
temperature to afford the Hay catalyst. In the second round-bot-
tom flask, a solution of 4a (14 mg, 0.024 mmol) in dichloroethane
(FAB): m/z = 574 (100) [M+], 517 (20) [M – tBu]+. HRMS (FAB):
Eur. J. Org. Chem. 2014, 1915–1924
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1921

I. R. Lahoz, A. Navarro-Vázquez, J. L. Alonso-Gómez, M. M. Cid
FULL PAPER
(9 mL) was prepared. The solution was stirred at ambient tempera-
ture while oxygen was bubbled from an inlet tube. The solution of
4a was added dropwise by using a syringe pump to the Hay catalyst
over a period of 29 h. After stirring the reaction for an additional
92 h, the dichloromethane was evaporated under reduced pressure
and the residue was washed with KCN. The aqueous layers were
extracted with CH2Cl2 and the combined organic layers were
washed with water, dried with Na2SO4, filtered, and concentrated
in vacuo. Purification by flash column chromatography on silica
gel (hexane/CH2Cl2, 4:1) gave diiodinated 11a (17 mg, 85%) and
traces of 12a.
29.2 ppm. MALDI-MS: m/z (%) = 1741 (5) [M + Na]+, 1661 (30)
[M – Me3C]+. C132H132 (1718.5): C 92.26, H 7.74; found C 92.24,
H 7.75. UV/Vis (hexane): λmax (ε, Lmol–1 cm–1) = 213 (89300), 233
(86300), 273 (154000), 303 (57500), 433 (49200), 459 (50700) nm.
4,6,11,13,19,21,26,28-Octa-tert-butyl-1,16(2,5)dipyridinecyclotria-
contaphane-4,5,11,12,19,20,26,27-octaen-2,7,9,10,14,17,22,24,29-
octayne (3c)
Hay Coupling Reaction: A round-bottom flask was flame-dried un-
der a flow of dry argon. To the flask, CuI (83 mg, 0.43 mmol),
TMEDA (132 mg, 1.13 mmol) and dichloroethane (10 mL) were
added. Oxygen was bubbled into the solution for 1 h at ambient
temperature to afford the Hay catalyst. In the second round-bot-
tom flask a solution of 4c (24 mg, 0.05 mmol) in dichloroethane
(22 mL) was prepared. The solution was stirred at ambient tem-
perature while oxygen was bubbled from an inlet tube. The solution
of 4c was added dropwise by using a syringe pump to the Hay
catalyst over a period of 40 h. After stirring the reaction for an
additional 105 h, the dichloromethane was evaporated under re-
duced pressure and the residue was washed with KCN. The aque-
ous layers were extracted with CH2Cl2 and the combined organic
layers were washed with water, dried with Na2SO4, filtered, and
concentrated in vacuo. Purification by flash column chromatog-
raphy on silica gel (hexane/CH2Cl2, 70:30) afforded the diiodo
compounds 11c (26 mg, 71%) and 12c (identified by mass spec-
troscopy) along with traces of pyrido-alleno-acetylenic cyclophane
3c.
Pd/Cu Method: Two solutions were prepared: (1) A solution of
[PdCl2(PPh3)2] (2.8 mg, 4 μmol), CuI (1.6 mg, 8.4 μmol), and
TMEDA (77 mg, 0.66 mmol) in toluene (4.5 mL); (2) A solution of
4a (19 mg, 0.033 mmol) in toluene (12 mL). Both solutions were
bubbled with oxygen for 1 h at ambient temperature. Solution 1
was heated at 60 °C, then Solution 2 was added dropwise by using
a syringe pump over a period of 30 h. After stirring the reaction
for an additional 18 h, the toluene was evaporated and the residue
was washed with NH4Cl. The aqueous layers were extracted with
CH2Cl2 and the combined organic layers were washed with water,
dried with Na2SO4, filtered, and concentrated in vacuo. Purifica-
tion by flash column chromatography on silica gel (hexane/CH2Cl2,
4:1) gave 3a (12 mg, 63%) along with 13a (5 mg, 26%).
Breslow Method: CuCl (156 mg, 1.57 mmol) and CuCl2 (31 mg,
0.23 mmol) were dissolved in anhydrous pyridine (12 mL), and the
solution was degassed by bubbling Ar for 60 min. A solution of 4a
(12 mg, 0.021 mmol) in anhydrous pyridine (8.4 mL) was added
over a period of 25 h. After 115 h, the solvent was removed under
reduced pressure; the remaining solid was dissolved in CH2Cl2 and
washed with saturated aqueous KCN solution. The aqueous phase
was extracted with CH2Cl2, dried with Na2SO4, and the solvents
were evaporated to dryness. The obtained solid was purified by
flash chromatography (SiO2; hexane/CH2Cl2, 4:1) to give 3a (7 mg,
58 %) along with 13a (2 mg, 17 %) as a brown solid. 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 8.46–8.36 (m, 8 H), 7.53–7.44 (m, 8
H), 1.41–1.32 (m, 36 H, tBu), 1.31–1.25 (m, 36 H, tBu) ppm. 13C
NMR (75 MHz, CDCl3, 25 °C): δ = 215.0–214.6 (C=C=C), 131.9–
131.7 (overlapped signals), 127.1–126.7 (overlapped), 126.6–126.4
(overlapped), 118.6–118.2 (overlapped), 105.6–104.8 (overlapped),
103.4–103.2 (overlapped), 96.1–95.4 (overlapped), 90.9–90.3 (over-
lapped), 77.7–77.1 (overlapped), 75.6–75.2 (overlapped), 36.4–35.2
(overlapped), 29.6–29.1 (overlapped) ppm. MALDI-MS: m/z =
1145 (41) [M+], 1088 (93) [M – Me3C]+. HRMS (MALDI): calcd.
Pd/Cu Method: Two solutions were prepared: (1) A solution of
[PdCl2(PPh3)2] (1.5 mg, 2.1 μmol), CuI (1 mg, 5.2 μmol), and
TMEDA (37 mg, 0.32 mmol) in toluene (2 mL). (2) A solution of
4c (6 mg, 0.012 mmol) in toluene (6 mL). Both solutions were
bubbled with oxygen for 1 h at ambient temperature. Solution 1
was heated at 60 °C, then Solution 2 was added dropwise by using
a syringe pump over a period of 23 h. After stirring the reaction
for an additional 72 h, the toluene was evaporated and the residue
was washed with KCN. The aqueous layers were extracted with
CH2Cl2 and the combined organic layers were washed with water,
dried with Na2SO4, filtered, and concentrated in vacuo. Purifica-
tion by flash column chromatography on silica gel (hexane/CH2Cl2,
70:30) gave 3c (3.5 mg, 56%).
Breslow Method: CuCl (172 mg, 1.73 mmol) and CuCl2 (34 mg,
0.25 mmol) were dissolved in anhydrous pyridine (13 mL), and the
solution was degassed by bubbling Ar for 60 min. A solution of 4c
(11 mg, 0.023 mmol) in anhydrous pyridine (8.5 mL) was added
over a period of 21 h. After 89 h, the solvent was removed under
reduced pressure and the remaining solid was dissolved in CH2Cl2
and washed with a saturated aqueous EDTA solution. The aqueous
phase was extracted with CH2Cl2, dried with Na2SO4, and the sol-
vents were evaporated to dryness. The obtained solid was purified
by flash chromatography (SiO2; hexane/CH2Cl2, 70:30) to give 3c
(6 mg, 54%) as a white solid.
for C88H88+ [M]+ 1144.6886; found 1144.6870. IR (neat): ν = 2962,
˜
1737, 1474, 1459, 1392, 1361, 1222, 1125, 1077, 1025, 906, 764,
639 cm–1. UV/Vis (hexane): λmax (ε, Lmol–1 cm–1) = 213 (133200),
233 (97900), 273 (200300), 303 (70600), 433 (61200), 459
(59300) nm.
9,10-Bis(3,5-di-tert-butyl-7-iodohepta-3,4-dien-1,6-diyn-1-yl)anthra-
1
cene (11a): H NMR (400 MHz, CDCl3, 25 °C): δ = 8.57–8.49 (m,
1 H), 7.68–7.56 (m, 1 H), 1.39 (s, 9 H), 1.27 (s, 9 H) ppm. 13C
NMR (100 MHz, CDCl3, 25 °C): δ = 213.74 (C=C=C), 132.2 (C),
27.3 (CH), 126.9 (CH), 118.8 (C), 105.0 (C), 104.3 (C), 96.3 (C),
90.2 (C), 87.41 (C), 36.2 (C, tBu), 36.1 (C, tBu), 29.5 (CH3, tBu),
2,5-Bis[3,5-di(tert-butyl)-7-iodohepta-3,4-diene-1,6-diyn-1-yl]pyrid-
ine (11c): 1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.61 (dd, J =
2.1, 0.8 Hz, 1 H), 7.67 (dd, J = 8.1, 2.1 Hz, 1 H), 7.38 (dd, J = 8.1,
0.8 Hz, 1 H), 1.21 (s, 9 H), 1.20 (s, 9 H), 1.16 (s, 9 H), 1.15 (s, 9
H) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 213.9 (C,
C=C=C), 213.4 (C, C=C=C), 152.2 (CH), 141.9 (C), 138.4 (CH),
126.6 (CH), 119.7 (C), 104.7 (C), 104.6 (C), 103.8 (C), 103.5 (C),
+
29.21 (CH3, tBu) ppm. HRMS (ESI): m/z calcd. for C44H44I2
827.15981; found 827.16051.
1
Data for 13a: H NMR (300 MHz, CDCl3, 25 °C): δ = 8.55–8.44
(m, 12 H), 7.59–7.53 (m, 12 H), 1.37 (s, 27 H), 1.36 (s, 27 H), 1.27 92.0 (C), 91.9 (C), 89.4 (C), 88.4 (C), 87.1 (C), 87.1 (C), 36.0 (C,
(s, 54 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 214.7–214.2 (m, tBu), 36.0 (C, tBu), 36.0 (C, tBu), 29.2 (3 ϫ CH3, tBu), 29.1
C=C=C), 132.1–131.9 (m), 127.1, 126.7, 118.6, 105.2–104.9, 103.3–
(3 ϫ CH3, tBu), 29.0 (3 ϫ CH3, tBu), 29.0 (3 ϫ CH3, tBu) ppm.
103.1, 95.8–95.4, 90.6–90.3, 77.7–77.1, 75.3, 36.4–35.7, 29.3, HRMS (ESI): calcd. for C35H40I2N+ 728.1244; found 728.12684.
1922
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 1915–1924

Towards the Synthesis of 1,3-Butadiynyl Macrocycles
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Chem. Soc. Rev. 2010, 39, 4158–4168, and references cited
therein.
a) Metal-Catalyzed Cross-Coupling Reactions (Eds.: A. de Mei-
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Navarro-Vázquez, A. L. Llamas-Saiz, J. L. Alonso-Gómez,
M. M. Cid, Chem. Eur. J. 2012, 18, 13836–13843.
a) S. Odermatt, J. L. Alonso-Gómez, P. Seiler, M. M. Cid, F.
Diederich, Angew. Chem. 2005, 117, 5203; Angew. Chem. Int.
Ed. 2005, 44, 5074–5078; b) J. L. Alonso-Gómez, P. Rivera-
Fuentes, N. Harada, N. Berova, F. Diederich, Angew. Chem.
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c) P. Rivera-Fuentes, J. L. Alonso-Gómez, A. G. Petrovic, P.
Seiler, F. Santoro, N. Harada, N. Berova, H. S. Rzepa, F. Died-
erich, Chem. Eur. J. 2010, 16, 9796–9807; d) J. L. Alonso-
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15, 6495–6503; e) P. Rivera-Fuentes, B. Nieto-Ortega, W. B.
Schweizer, J. T. López Navarrete, J. Casado, F. Diederich,
Chem. Eur. J. 2011, 17, 3876–3885; f) M. D. Tzirakis, N. Mar-
ion, W. B. Schweizer, F. Diederich, Chem. Commun. 2013, 49,
7605–7607.
Intramolecular Approach
4,6,11,13,19,21,26,28-Octa-tert-butyl-1,16(2,5)dipyridinecyclotri-
acontaphane-4,5,11,12,19,20,26,27-octaen-2,7,9,10,14,17,22,24,29-
octayne (3c): Compound 5c (36 mg, 0.04 mmol) was dissolved in
O2-free pyridine (20.0 mL) and treated with anhydrous CuCl
(620 mg, 6.08 mmol) and anhydrous CuCl2 (91 mg, 0.61 mmol) for
1 h at 25 °C. The solvent was then removed under reduced pressure
and the residue was partitioned between saturated aqueous EDTA
(sat) and EtOAc. The aqueous phase was extracted with EtOAc,
the combined organic phases were dried (Na2SO4), and the solvent
was removed under reduced pressure. Purification by FC on silica
gel (hexane/CH2Cl2, 1:1) gave 3c (27 mg, 75%) as a solid.
[2]
[3]
[4]
Pyrido-alleno-acetylenic cyclophanes 3c was obtained as a mixture
of six diastereoisomers, which could be isolated by HPLC
(peaks A–F) on the stationary phase Rexchrom “Buckyclutcher 1”
[preparative; 10 μm 100 Å Trident-TriDNP; 50 cmϫ21.1 mm ID;
hexane/CH2Cl2, 22%; 10 mL/min; λ = 320 nm) (see Figure SI.1 in
the Supporting Information).
1
Data for 3c-A: H NMR (400 MHz, CDCl3, 25 °C): δ = 8.60–8.56
(m, 2 H), 7.67–7.65 (m, 2 H), 7.39–7.37 (m, 2 H), 1.21 (s, 18 H),
1.19 (s, 18 H), 1.173 (s, 18 H), 1.167 (s, 18 H) ppm. 13C NMR
(100 MHz, CDCl3, 25 °C): δ = 215.0 (2ϫC, C=C=C), 214.7 (2ϫC,
C=C=C), 151.9 (2 ϫCH), 142.0 (2 C), 138.3 (2ϫCH), 126.7
(2ϫCH), 119.4 (2ϫC), 103.9 (C), 103.7 (C), 103.6 (C), 103.5 (C),
92.3 (4ϫC), 89.8 (4ϫC), 87.5 (4ϫC), 84.6 (4ϫC), 75.5 (2ϫC),
75.3 (2ϫC), 35.69–35.61 (m, 8ϫC, tBu), 29.1–29.0 (m, 24ϫCH3,
tBu) ppm. HRMS (ESI): calcd. for C70H79N2+ [M
947.6238; found 947.6236.
+
2H]+
Data for twist-3c-B: 1H NMR (600 MHz, CDCl3, 25 °C): δ = 8.60–
8.57 (m, 2 H), 7.67–7.64 (m, 2 H), 7.41–7.35 (m, 2 H), 1.22 (s, 18 H,
tBu), 1.20–1.16 (m, 54 H, tBu) ppm. 13C NMR (100 MHz, CDCl3,
25 °C): δ = 215.2, 215.0, 214.5, 214.5, 151.9, 151.9, 142.0, 138.4,
138.3, 138.3, 138.2, 126.6, 119.4, 119.3, 104.0, 103.8, 103.8, 103.7,
103.6, 103.5, 92.5, 92.3, 89.9, 89.8, 87.7, 87.6, 84.8, 84.7, 35.6, 29.7,
29.1, 29.0 ppm. HRMS ESI: calcd. for C70H79N2+ [M + 2H]+
947.6238; found 947.6251.
Data for twist-3c-D: 1H NMR (600 MHz, CDCl3, 25 °C): δ = 8.59–
8.57 (m, 2 H), 7.66–7.62 (m, 2 H), 7.39 (d, J = 8.1 Hz, 2 H), 1.17
(s, 9 H), 1.18 (s, 9 H), 1.20 (s, 9 H), 1.20 (s, 9 H), 1.20 (s, 9 H),
1.20 (s, 27 H) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 214.9,
214.9, 214.8, 214.7, 151.8, 141.9, 141.9, 138.3, 138.2, 126.7, 126.6,
119.4, 119.3, 103.9, 103.7, 103.7, 103.7, 103.7, 103.6, 103.5, 92.4,
92.3, 89.9, 89.8, 87.7, 87.6, 84.9, 84.8, 35.6, 35.6, 35.5, 29.0,
28.8 ppm. HRMS (ESI): calcd. for C70H79N2+ [M + 2H]+ 947.6238;
found 947.6224.
[5]
[6]
a) D. Zhao, J. S. Moore, Chem. Commun. 2003, 807–818; b) D.
Zhao, J. S. Moore, Angew. Chem. 2006, 118, 4524; Angew.
Chem. Int. Ed. 2006, 45, 4416–4439; c) A. L. Sadowy; R. R.
Tykwinski, in: Modern Supramolecular Chemistry: Strategies
for Macrocycle Synthesis (Eds.: F. Diederich, P. J. Stang, R. R.
Tykwinski), Wiley-VCH, Weinheim, Germany, 2008, chapter 6,
p. 185–231.
a) R. C. Livingston, L. R. Cox, V. Gramlich, F. Diederich, An-
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Acknowledgments
The authors acknowledge Gobierno de España and Xunta de Gal-
icia for financial support (RyC and IPP contracts to A. N. V. and
J. L. A. G., CTQ2010-18576 to J. L. A. G. and CTQ2011-28831 to
A. N. V.). The Centro de Supercomputación de Galicia (CESGA)
is also acknowledged for providing generous allocation of super-
computer time.
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