Metal cation binding to acetylenic tetrathiafulvalene–pyridine conjugates: affinity tuned by preorganization and cavity size

Article abstract of DOI:10.1016/j.tet.2016.08.001

A series of three structurally related mono-, bidentate and macrocyclic TTF-pyridine hosts were prepared and titrated with several metal cations including Ag⁺and Pb²⁺and studied using NMR- and UV–vis spectroscopy and cyclic voltammetry. For Ag⁺, we found an eightfold increase in binding affinity between the bidentate and macrocyclic host and conversely, for Pb²⁺, a 100-fold drop. Density functional theory (DFT) calculations support the increased binding affinity for Ag⁺is due to an N?N distance for the uncomplexed macrocycle very much suited for binding of Ag⁺but being too small for Pb²⁺. The bidentate host, on the other hand, is of a suitable size for Pb²⁺.

Full text of DOI:10.1016/j.tet.2016.08.001

Accepted Manuscript
Metal cation binding to acetylenic tetrathiafulvalene-pyridine conjugates: affinity tuned
by preorganization and cavity size
Søren Lindbæk Broman, Cecilie Lindholm Andersen, Martyn Jevric, Christian Gregers
Tortzen, Ole Hammerich, Mogens Brøndsted Nielsen
PII:
S0040-4020(16)30759-1
10.1016/j.tet.2016.08.001
TET 27982
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 29 February 2016
Revised Date: 12 July 2016
Accepted Date: 1 August 2016
Please cite this article as: Broman SL, Andersen CL, Jevric M, Tortzen CG, Hammerich O, Nielsen
MB, Metal cation binding to acetylenic tetrathiafulvalene-pyridine conjugates: affinity tuned by
preorganization and cavity size, Tetrahedron (2016), doi: 10.1016/j.tet.2016.08.001.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Ag+
Kf = 21 x 103 M-1
Kf = 18 x 104 M-1
8-fold increase
N
N
BuS
BuS
BuS
S
SBu
SBu
S
S
S
S
S
S
S
S
S
S
M+/2+
M+/2+
S
BuS
N
N
Pb2+
Kf = 10 x 103 M-1
Kf = 97 M-1
100-fold increase

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Metal Cation Binding to Acetylenic Tetrathiafulvalene-
Pyridine Conjugates: Affinity Tuned by Preorganization
and Cavity Size
Søren Lindbæk Broman, Cecilie Lindholm Andersen, Martyn Jevric, Christian Gregers Tortzen, Ole
Hammerich, Mogens Brøndsted Nielsen*
University of Copenhagen, Department of Chemistry, Universitetsparken 5, DK-2100 Copenhagen Ø.
E-mail: mbn@chem.ku.dk
Abstract
A series of three structurally related mono-, bidentate and macrocyclic TTF-pyridine hosts were prepared
and titrated with several metal cations including Ag+ and Pb2+ and studied using NMR- and UV-Vis
spectroscopy and cyclic voltammetry. For Ag+, we found an 8-fold increase in binding affinity between the
bidentate and macrocyclic host and conversely, for Pb2+, a 100-fold drop. Density functional theory (DFT)
calculations support the increased binding affinity for Ag+ is due to an N---N distance for the uncomplexed
macrocycle very much suited for binding of Ag+ but being too small for Pb2+. The bidentate host, on the
other hand, is of a suitable size for Pb2+.
1. Introduction
Bidentate amines and pyridines have strong affinities for cations depending on coordination angles, bond
lengths and electronic properties. Tetramethylethylenediamine (TMEDA) and cyclic derivatives such as
trans-1,2-diaminocyclohexane strongly bind metal ions such as Cu+ and have been used as ligands for
catalytic C-N or C-C couplings such as the Glaser-Hay coupling.1 Also more elaborate systems have been
developed like classical (aza or thio)crown ethers and cryptands which show high affinities for a large range
of cations.2 1,2-Bis(pyridylethynyl)benzene 1a (bpeb, Figure 1) is able to coordinate not only metal cations3
but also halonium ions (Br+, Cl+)4 allowing complex structures including the 1,2-bis(pyridylethynyl)benzene
moiety to function as catalysts or reagents in displacement reactions or coupling reactions.5 More recently
the cyclic derivative 1b (cpeb) has been prepared, which exhibits altered emission properties upon cation
complexation.6
For the development of molecular sensors, the cation-binding host is often combined with redox-active
units, which change their electrochemical properties upon ion complexation on account of electrostatic
interactions, which may either favor or disfavor the redox event. Tetrathiafulvalene (TTF) is a strong
electron donor, which can undergo two reversible one-electron oxidations,7 and it has been extensively
studied in relation to supramolecular chemistry.8 Owing to its versatility, TTF remains one of the go-to
organic molecules for construction of advanced functional structures. Several examples of oxa/aza/thio
podands, crown ethers, and cryptands linked to TTF9 or extended TTFs10 have been developed as hosts for
cations, either alkali or transition metal cations. In several of these studies the absorption spectra of the TTFs
were strongly influenced, and expulsion of the metal was often observed upon electrochemical oxidation of
the TTF. TTF has also been combined with the pyridine ligand. For example, the simple pyridylethynyl-
TTFs 2a/b/c bind Pb2+ (log Ks = 3.76 in MeCN) but do not show any affinity for other metal cations.11 The
same observations were made with structurally related TTF-imine-pyridine conjugates (such as 3a/b/c),12
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which were found to bind Pb2+ slightly weaker (log Ks = 3.5 in CH2Cl2 / MeCN), but still no binding to other
cations including Ag+, Hg2+, or Zn2+ was reported. A rather strong binding of Pb2+ was observed for 4c (log
Ks = 5.42).13 The bis(2-pyridylethynyl)-TTF 5a, however, binds Cu+ and Cu2+, and a charge-transfer from the
TTF to the metal ion was observed.14 Self-assembled Pb2+/Pt2+ cages/containers based on TTFs/extended
TTFs with pyridyl ligands have also been reported,15 while TTF-phenanthroline macrocycles have been
employed as redox responsive sensors for Cu+ and Ag+ ions in precatenate complexes,16 and TTF-annelated
calix[n]pyrroles17 or calixarenes18 have been reported to bind several anions, cations and also neutral
aromatics.
Figure 1. Structures of pyridine ligands and TTF-pyridine conjugates able to bind metal cations.
Here, we present the synthesis and a detailed study of the metal-binding properties of a hybrid of 1b and
5b, the macrocycle 6; combining the redox-activity of TTF, the bidentate pyridine scaffold, and the rigidity
of a macrocyclic core. The macrocycle 6 was prepared using a multi-step procedure and the synthesis
required a carefully controlled cross-coupling, iodination, and further cross-coupling for assembly of the
macrocycle, not only on the account of an induced ring-strain but also significant repulsion between the
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internal pyridine lone-pairs. Using UV-Vis absorption spectroscopy, the association constants for
complexation between 5b, 7, or 6 and Ag+ and Pb2+ were determined. We found that the affinity for these
metals was strongly influenced by the size and preorganization of the binding pocket, which was supported
by density functional theory calculations and electrochemical experiments.
2. Results and Discussion
2.1 Synthesis
The synthesis of the bidentate TTF-pyridine ligand 5b and the initially attempted synthesis of the macrocycle
6 are shown in Scheme 1, both starting from the known 4,5-diiodo-TTF 8.19 Treatment of 8 with 2-
ethynylpyridine20 in a two-fold Sonogashira cross-coupling reaction gave TTF-pyridine 5b in 78% yield.
Although this illustrates the well-established reactivity of the diiodo-TTF 8, these same reaction conditions
proved fruitless for the preparation of the desired macrocycle 6 in a one-pot four-fold Sonogashira cross-
coupling reaction between diiodo-TTF 8 and 2,6-diethynylpyridine 921 under conditions used to prepare a
structurally related macrocycle.22 Triphosphine gold(I) complexes of terminal alkynes are known to exhibit
high stability,23 but using compound 10 as a substrate in the cross-coupling reaction,24 prepared using our
newly reported procedure,25 also failed to provide 6. Instead, we subjected diethynyl-TTF 11 and 2,6-
diiodopyridine 1226 to the same conditions, in the hope that the high reactivity of 12 would help to afford the
desired compound; however, this gave a complex mixture of oligomers. It should be noted that we observe a
different outcome under more concentrated conditions (vide infra).
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Scheme 1. Initially attempted synthesis of the macrocycle 6 by four-fold Sonogashira cross-couplings from either
diiodo-TTF 8 and diethynylpyridine 9 or diethynyl-TTF 11 and diiodopyridine 12. Preparation of bidentate pyridine-
TTF 5b by a two-fold Sonogashira cross-coupling between diiodo-TTF 8 and 2-ethynylpyridine. [Pd] = palladium
catalyst; see notes in SI.
The diiodo-TTF 819 was prepared in three steps from triphenylphosphonium tetrafluoroborate salt 1327
and dithiolium iodide 1428 using a modified analogous procedure29 as shown in Scheme 2. This procedure
involves more steps than the known procedure but avoids tedious purifications and the use of Hg(OAc)2.
Firstly, the TTF 15 was prepared by treatment of 13 with 14 in the presence of Et3N at 0 °C. This slight
modification enables preparation of 15 in large batches of up to 6 g in 90% yield with a smaller excess of 14
needed. The cyanoethyl protection groups were exchanged with butyl groups in a two-step one-pot reaction
by treatment with NaOEt in EtOH/THF followed by BuI to give 1630 in good yield (81%). A two-fold
iodination was achieved by deprotonation using sodium hexamethyldisilazide (NaHMDS) followed by
addition of 1,2-diiodoethane, which gave the diiodo-TTF 8 in 79% yield.
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Scheme 2. Three-step preparation of diiodo-TTF 8.
Several other attempts were made to prepare the macrocycle 6 as detailed in the SI. Ultimately, to gain
control over the cyclization, we turned our attention to the preparation of 6 in a different step-wise fashion
inspired by the recently reported preparation of TTF-radiaanulenes.25, 31 Firstly, a double Sonogashira cross-
coupling between 2,6-diethynylpyridine 921 and monoiodo-TTF 1732 was achieved using
bis(diphenylphoshino)ferrocene / bis(palladium) tris(benzylidene acetone) (dppf / Pd2dba3) in neat Et3N at 50
°C which gave 7 in 66% yield (81% per step) on a 570 mg-scale. Although we have recently reported this
same reaction using Pd(PPh3)4 at rt in an excellent yield of 80% (90% per step) on a 40 mg-scale,31 we were
unable to perform the reaction in larger portions than 290 mg (71% in two steps) even at 50 °C, and for that
reason we were required to use the bidentate ligand dppf at an elevated temperature. Next, a double
iodination using 4.0 molar equiv. NaHMDS followed by 6 molar equiv C6F13I gave 18 in 76% yield.
Surprisingly, unreliable results were achieved in this step using lithium diisopropylamide or BuLi in the
deprotonation step. Also, it was observed that using 1,2-diiodoethane instead of C6F13I gave a slightly lower
isolated yield although this could be due to a varying purity of the 1,2-diiodoethane. If not fully
deprotonated, a significant amount of the monoiodo-TTF 1933 was formed, which was difficult to separate
from the desired product by column chromatography. Finally the desired macrocycle 6 was obtained by
treatment of 18 with 9 in a two-fold Sonogashira cross-coupling reaction again using the dppf / Pd2dba3
catalyst (introduced in THF for solubility) in Et3N, in a yield of 4-8% (with minor impurities) along with
significant amounts of the byproduct 20 resulting from a two-fold Sonogashira cross-coupling reaction
followed by an intramolecular Glaser-Hay coupling. The highest recorded yield was obtained by stirring at rt
for 16 h followed by heating to 70 °C for 3 h. Despite our efforts to optimize the conditions, no product
could be isolated using a variety of catalytic systems including; Pd(PPh3)4, PdCl2(PPh3)2, and AsPh3 /
Pd2dba3 in mixtures of THF and Et3N or (i-Pr2)NH though the desired product was observed several times
using MALDI-MS. Although encouraged by finally being able to synthesize the desired macrocycle 6, we
were only able to obtain 0.40 mg of spectroscopically pure compound using this method. Thus, a total of 14
consecutive chromatographic purifications on the crude material were required to separate the desired
macrocycle from the byproduct 20, with a natural loss of material. For that reason, we decided to split the
last two-fold Sonogashira cross-coupling into two steps to enable step-wise purification. Firstly, treating 18
with 2-ethynyl-6-(triisopropylsilylethynyl)pyridine 22 under careful exposure to ultrasound gave 23 in a 21%
yield along with the byproduct 24 resulting from a two-fold cross-coupling (Figure 2). A desilylation was
effected by treatment with Bu4NF (TBAF) in THF, which gave the terminal acetylene 21 without significant
decomposition and treatment with Pd(PPh3)4 and CuI in neat Et3N or dppf / Pd2dba3 in Et3N / THF at 60 °C
for 3 h formed 6 as judged by MALDI-MS inspections. However, we did not manage to isolate the
macrocycle analytically pure using this procedure.
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Scheme 3. Step-wise preparation of macrocycle 6 by a two-fold Sonogashira, two-fold iodination and two-fold
Sonogashira methodology.
Building block 22 was prepared in three steps from 2,6-dibromopyridine (Scheme 4). Firstly, two
subsequent Sonogashira cross-couplings were performed with, in the first step, TIPS-acetylene, which gave
2534 in a 56% yield and, in the second step, with TMS-acetylene, which gave 26 in 96% yield. A final
deprotection of the TMS-group using NaOH in MeOH / THF gave 22 in 98% yield.
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Scheme 4. Three-step synthesis of 22 by sequential Sonogashira cross-couplings with firstly TIPS-acetylene and
secondly TMS-acetylene followed by a selective desilylation.
The structures of byproducts 19, 20 and 24 are shown in Figure 2. The monoiodo TTF-pyridine 19 could
be prepared in 34% yield by an iodination of 7 (see Experimental Section).
Figure 2. Structures of byproducts of diiodonation and macrocylization steps in the synthesis of 6; monoiodo-TTF 19,
macrocycle 20 and doubly coupled TTF-pyridine 24.35
The final TTF-pyridine 6 was prepared in 11 steps (longest linear sequence) and despite electrostatic
repulsion between nitrogen lone-pairs and significant ring-strain, a controlled macrocyclization was
developed.
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2.2 Spectroscopic Properties and Complexation Studies
The TTF-pyridines were studied using UV-Vis absorption spectroscopy. All TTF-pyridines show a broad
charge-transfer (CT) band at 400 – 680 nm with absorption maxima at 485, 501, and 439 nm for 5b, 6 and 7,
respectively, along with higher energy absorptions characteristic of TTF in the region between 240 – 400
nm. The UV-Vis absorption spectra for TTFs derivatives are shown in Figure 3 and the relevant absorption
maxima are listed in Table 1; in comparison to compounds 18 and 27 (Figure 4; for synthesis; see SI).
5b
6
7
18
27
60
40
20
0
300
400
500
600
Wavelength (nm)
Figure 3. UV-Vis absorption spectra of 5b, 6, 7, 27, and 18 in CH2Cl2 / MeCN (1:1).
Figure 4. Structure of bidentante TTF 27.
Table 1. Absorption maxima for TTF-pyridine hosts in CH2Cl2 / MeCN (1:1).
Compound
λmax (ε)[a]
484 (2.06)
501 (4.19)
434 (10.4)
439 (6.1)
506 (3.82)
444 (7.45)
334 (19.1)
337 (66.1)
317 (58.6)
320 (34)
306 (25.9)
311 (66.2)
-
-
5b
6
264 (43.8)
269 (43.3)
267 (26)
267 (36.5)
261 (39.7)
7
7[b]
27
18
-
328 (sh)[c]
328 (47.0)
313 (49.1)
314 (46.4)
[a][λmax] = nm. [ε] = 103 M-1 cm-1. [b]Measured in CH2Cl2.31 [c]Shoulder.
In general, the bidentate TTF-pyridine host 5b was found to bind metal cations such as Ag+, Cu+, Pb2+,
Pd2+, and Zn2+, but Hg2+ was found to show some interaction to the TTF-pyridine host. As seen in Figure 5,
upon addition of Ag(MeCN)4BF4 to 5b, a redshift of the CT-band from 484 to 529 nm (10 equiv. Ag+) was
observed due to the formation of a stable complex; 5b•Ag+. A titration curve was obtained by plotting the
absorbance, A, at 566 nm (obtained by curve deconvolution) versus the concentration of Ag+, and the
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association constant, Kf, and the extinction coefficient of the complex (ε) were determined by fitting the data
with the same non-linear fitting procedure36 (Figure 5c) and a Kf value of 2.1×104 M-1 and an extinction
coefficient of 1.5×103 M-1 cm-1 were determined. Although many similar studies use the Benesi-Hildebrand
equation to determine association constants, the requirements of this otherwise reasonable approximation are
not fulfilled here as not all data were collected using a large excess of the cation. The 5b•Ag+ complex was
evaluated by mass spectrometry (MALDI-TOF) and the presence of a 5b•Ag+ complex was confirmed (m/z =
1
690.19 [M+Ag]+). The 1:1 host-cation stoichiometry was established by a Job plot using H / 13C NMR
spectroscopy (Figure 5b and Figures S37 and S40).
It has been reported that a structurally related compound 5a (Figure 1) shows a strong coordination to
Cu+,14 so we were surprised to find that addition of up to 10 equivalents of Cu(MeCN)4BF4 had almost no
effect on the absorption spectrum of 5b, and addition of 100 equivalents simply led to a broad absorption
with λmax at ca. 830 nm due to oxidation of the TTF to its radical cation (TTF•+), presumably due to trace
amounts of Cu2+ ions in the Cu+-source. The complex could, however, be observed by mass spectrometry
(MALDI-TOF) by the presence of a signal that was assigned to 5b•Cu+ (m/z = 645.20 [M+Cu]+). Addition of
Zn2+ (Zn(OTf)2), however, had an effect on the absorption spectrum of 5b as a large redshift of the longest-
wavelength absorption was observed. Mass spectrometry showed the presence of a 5b•Zn(OTf)+ complex
(m/z = 795.02 [M+Zn(OTf)]+). However, the lack of isosbestic points at a large excess of Zn2+ ions made
reliable curve deconvolution impossible; thus a trustworthy determination of an association constant was not
possible. Also addition of Pb2+ (Pb(ClO4)2) resulted in a strong redshift of the CT-band. Gratifyingly, reliable
curve deconvolution was possible and using non-linear curve fitting an association constant of 10.000 M-1
was determined (see SI; Figure S43, right). To determine the 1:1 host-cation stoichiometry of the 5b•Pb2+
complex, we did a Job plot (Figure 5b). Somewhat surprisingly, addition of Hg(ClO4)2 under similar
conditions resulted in the formation of a complicated UV-Vis absorption spectrum with the desired
redshifted CT-band (λmax = 565 nm) in addition to a broad absorption band with λmax at 835 nm. Upon
stepwise addition of 0.50 equiv and 1.0 equiv. of Hg(ClO4)2, the CT-band disappeared slowly while the
lower energy band appeared. We believe Hg2+ is initially trapped within the cavity but then an oxidation of
the TTF to its radical cation (TTF•+) slowly commences.
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a)
0.20
0.15
0.10
0.05
0.00
2.5
2.0
1.5
1.0
0.5
0.0
400
500
600
700
300
400
500
600
700
800
Wavelength (nm)
b)
0.10
0.08
0.06
0.04
0.02
0.00
2+
+
Pb
Ag
0.0
0.2
0.4
0.6
0.8
1.0
+
2+
Mole fraction Ag / Pb
Figure 5. a) UV-Vis absorption spectra of 5b (6.33 x 10-5 M) in CH2Cl2 / MeCN (1:1) treated with 0.05 to 10.00
1
equivalents of Ag+ ions in form of Ag(MeCN)4BF4 (0.317 x 10-5 – 56.7 x 10-5 M). b) Job plots (based on H NMR
spectroscopy, using the change in chemical shift, ∆δ, of a signal in the aromatic region) for complexation of 5b with
Ag+ or Pb2+, respectively, acquired in CD2Cl2 / CD3CN (1:1); for more information see SI; Figure S41. c) Titration-plot
depicting the absorption of 5b•Ag+ (obtained by curve deconvolution) vs. [Ag+] at a fixed concentration of 5b (6.33 x
10-5 M).
Complexation studies similar to those done on 5b with Ag(MeCN)4BF4 were also performed on the
macrocyclic TTF-pyridine 6. By addition of 20 equivalents of Ag+, no further increase in the redshifted
absorption was observed. Thus, at saturation, a broad absorption with λmax = 564 nm was observed. Using the
same non-linear fitting procedure as described earlier, an association constant of 1.8 x 105 M-1 and an
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extinction coefficient of 2.7 x 103 M-1 cm-1 were determined. We attribute this much higher association
constant to the fact that in this macrocyclic structure the two pyridine lone-pairs, responsible for the
complexation, are already locked into place and the TTF-pyridine does not lose any further degrees of
freedom by directing the lone-pairs towards one another. Also, the lone-pairs are clearly pointing away from
each other in the most stable conformation of 5b (vide infra), and thus significant electrostatic repulsion
would arise from rotation about the linkers to face each other. The macrocyclic TTF-pyridine was also
treated with Pb2+ (Pb(ClO4)2) and a redshift of the CT-band was observed. However, with this much larger
cation, even by addition of almost 250 equiv. of Pb2+ full complexation was not achieved. Using the non-
linear fitting procedure an association constant of merely 97 M-1 was determined. Thus, for Pb2+, the
macrocyclic core is far too rigid to allow for an effective binding to the ligand and the much larger metal
cation cannot fit into the cavity. The UV-Vis absorption spectra of 6 and the complexes resulting from
titration using up to 30 equivalents of Ag(MeCN)4BF4 are shown in Figure 6a and a titration plot of 6 upon
addition of Ag+ is shown in Figure 6b.
a)
0.12
2.0
0.08
1.5
0.04
0.00
1.0
400
500
600
700
0.5
0.0
300
400
500
600
700
800
Wavelength (nm)
Figure 6. UV-Vis absorption spectra of 6 (2.95 x 10-5 M) in CH2Cl2 / MeCN (1:1) treated with 0.25 to 30.0 equivalents
of Ag+ ions in form of Ag(MeCN)4BF4 (0.737 x 10-5 – 87.4 x 10-5 M). b) Titration-plot depicting the absorption of
6•Ag+ (obtained by curve deconvolution) vs. [Ag+] at a fixed concentration of 6.
The monodentate TTF-pyridines 7 and 18 did not show a similar strong affinity for Ag+. Thus, addition of
up to 1600 equivalents of Ag(MeCN)4BF4 resulted in a weak redshift of the CT-band for both 7 and 18.
Thus, determinations of association constants were not possible. However, for both compounds, titration of
Pb2+ (Pb(ClO4)2) resulted in redshifted absorptions (Figure 7) and using the non-linear curve fitting
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procedure an association constant of 53 M-1 was determined for 7. We were unable to determine this value
for compound 18. For these compounds colorimetric sensing of Pb2+ was possible by the naked eye as 149
and 146 nm redshifts were observed for 7 and 18, respectively. Thus, upon addition of Pb2+, a clear color
change from yellow to blue is observed; however large excesses of Pb2+ are needed. Compared to that of
structurally similar TTF-pyridine 2a (Figure 1), the association constants of 7 and 18 are almost identical
but, as expected, significantly lower than that of 5b (bidentate vs. monodentate ligand), but the redshift of the
CT-absorptions are much larger as two TTF-units are affected. For the other bidentante TTF-pyridine 27,
incorporating two iodo-substituents on the pyridines, only very weak binding of both Ag+ and Pb2+ were
observed.
a)
2.0
1.5
1.0
0.5
0.0
300
400
500
600
700
800
Wavelength (nm)
1.0
0.8
0.6
0.4
0.2
0.0
b)
300
400
500
600
700
800
Wavelength (nm)
Figure 7. UV-Vis absorption spectra of; a) 7 and b) 18 in CH2Cl2 / MeCN (1:1) treated with up to 250 equiv. Pb2+ ions
in Pb(ClO4)2.
The determined association constants obtained from the titrations of metal ions to TTF-pyridines 5b, 6, 7,
and 18 together with their absorption maxima are collected in Table 2. For titration with Ag+ under similar
conditions, we have found a very weak binding for the monodentate host 7, a moderate binding for bidentate,
but flexible, host 5b, and a very high binding for macrocyclic host 6. A more than 8 fold higher association
constant between the 5a and 6 hosts was observed. For titration with Pb2+ a weak binding for the
monodentate TTF-pyridine 7 and a moderate binding for the bidentate TTF-pyridine 5b were observed.
However, for the macrocyclic TTF-pyridine 6 only a weak binding was found due to a rigid core unable to fit
the large cation and a 100 fold decrease in affinity was observed.
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Care must be taken when directly comparing the determined association constants in the present study
with the association constants determined for known TTF-pyridine conjugates such as 2a/b/c, 3a/b/c, and 4c.
The Benesi-Hildebrand equation is often used for determination of association constants, but it requires the
guest concentration to be significantly larger than the host concentration,37 a fact which is often ignored.
Also, the Benesi-Hildebrand equation is only valid for estimation of association constants in certain
concentration intervals38 and only for 1:1 host-guest complexes.39 In the examples where the requirements
for the Benesi-Hildebrand were met, we have in Table 2 included the value determined for comparison. In
general, we have found a slightly smaller value for the association constant using Benesi-Hildebrand
compared to that of using the non-linear fitting procedure.
Table 2. Association constants for cation complexation (Kf)[a] in CH2Cl2 / MeCN (1:1) at 25 °C.
[f]
M+/2+[b]
Pb2+
Kf[c]
50
Kf[d]
-
ε[e] TTF•M+/2+λmax
2a11
2b11
2c11
3a12a
3b12a
3c12b
4c13
5b
575
5.75 x 103
18.2 x 103
2.24 x 103
3.2 x 103
263 x 103
Pb2+
Pb2+
Ag+
Pb2+
Ag+
Pb2+
Pb2+
Pb2+
21 x 103 1.5
566
558
565
10 x 103
180 x 103 2.7
6
83
43
27
97
53
580
7
18
[a][Kf] = M-1 (1:1 complexes) [b]Ag+ = Ag(MeCN)4BF4 and Pb2+ = Pb(ClO4)2. [c]Determined using the Benesi-
Hildebrand equation. [d]Determined using non-linear fitting procedure. [e][ε] = 103 M-1 cm-1. [f]Obtained by
curve deconvolution.
2.3 Electrochemical Properties and Complexation Studies
The TTF hosts 5b, 6, 7, 18, and 27 were also studied using cyclic voltammetry (CV) in CH2Cl2 / MeCN (1:1)
containing 0.1 M Bu4NPF6 or Bu4NBF4 and the oxidation potentials are collected in Table 3. Not
surprisingly, the CVs of the TTF-pyridines reveal two reversible redox couples at higher oxidation potentials
relative to parent TTF; for 5b at 204 mV and 498 mV vs. Fc/Fc+, corresponding to the first and second
oxidation processes, respectively. This is due to the electron withdrawing effect of the ethynylpyridines. The
dimeric TTF 7 has the lowest oxidation potentials at 113 mV and 431 mV. Both the first and the second
oxidation of TTF-pyridines, both monomeric and dimeric, were affected by the presence of the slightly
electron-withdrawing iodines in 27 and 18, relative to those of 5b and 7, respectively. Thus, an increase in
the oxidation potential was seen by placing an iodine on either the pyridine or the TTF itself. As expected,
the height of the first oxidation peak of the 5b and 27, which contain only one TTF unit, was half that of 7
and 18; as the monomeric TTFs undergo one-electron processes and the dimeric two-electron processes
(Table 3).
The cyclic voltammograms upon step-wise addition of up to two equivalents of Ag(MeCN)4BF4 to 5b are
shown in Figure 8. The redox events move to higher potentials upon titration with Ag+; however, the second
oxidation wave is affected to a much lesser extent than the first one. The increase in oxidation potential
indicates that Ag+ coordinates strongly with the TTF-pyridine host and weaker with the radical cation TTF-
pyridine host. Addition of Cu(MeCN)4BF4 to 5b showed very similar oxidations (see SI; Figure S50)
13

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although the second oxidation is polluted by the oxidation of Cu+ to Cu2+ (see SI; Figure S49). Addition of
Zn(OTf)2 (Figure S51) also showed a large change in the oxidation potentials of 5b; however, with this
divalent metal cation the complexation did not initially show reproducible oxidation peaks in CV. When two
scans were performed right after each other, the oxidation peaks had shifted slightly. Luckily, this was
simply due to a slow complexation and by simply waiting for ca. 15 min after addition of Zn2+, equilibrium
was reached and reversible and reproducible oxidations were observed. We deduce that the missing
isosbestic points in the UV-Vis experiment are in actuality a consequence of this very slow complexation,
though when the experiment was repeated and allowing a 30-minute complexation time, no improvements
were ever seen. This might be due to a much lower concentration which also means an even slower
complexation. Also, inclusion of Pd2+ was observed by cyclic voltammetry (Figure S52) and very similar
behavior to the Zn2+ experiment was observed. A schematic representation of metal complexation followed
by electrochemical oxidation to the TTF-radical cation and exclusion of the metal cation is shown in Scheme
5.
Figure 8. Cyclic voltammograms (oxidation) of 5b (1 mM) and its corresponding complexes formed upon titration with;
Ag(MeCN)4BF4.
Scheme 5. Representation of complexation of a metal cation into the TTF-pyridine cavity followed by an
electrochemical oxidation induced exclusion of the metal cation due to formation of a TTF-radical cation. Indications of
bond angles A in 5b and B in 5b•M+/2+ (vide infra).
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Macrocyclic TTF-pyridine 6 was likewise studied using CV under addition of Ag+ ions (see SI; Figure S53).
We were unfortunately unable to determine the concentration of 6, as only very little of the compound had
been obtained for this purpose. As shown in Figure 9, compound 6 shows two reversible oxidation events at
236 mV and 499 mV, for the first and second oxidation, respectively. The first redox event shows a broad
shoulder which indicates an interaction between the two TTF units in the flat rigid macrocyclic structure.
Figure 9. Cyclic voltammogram (oxidation) of 6 (ca. 0.1 mM) in CH2Cl2 / MeCN (1:1).
Also structurally related monomeric TTF 27 and dimeric TTF 7 were investigated for their ability to bind
Ag+ and Cu+ ions. Here it was found that even though 27 has the same structural features as 5b, no binding to
these ions was found by CV as shown for Ag+ or Cu+ (see SI, Figures S55 and S56). This might be because
of the large iodine atoms which, because of steric hindrance, do not allow rotation about the linkers and do
not allow the two pyridines to face one another. As one might expect, CV showed only a small change of the
oxidation potentials when Ag+ was added to 7; thus, this monodentate pyridine ligand shows a weak binding
to Ag+ ions (see SI, Figure S54).
Table 3. Measured oxidation potentials (Eox)[a] and concentration normalized heights (iP,1/c)[b] obtained from cyclic
voltammetry.
[c]
[d]
E1
E1
E2
E2
iP,1/c
204
-
-
-
-
498
-
-
-
-
15.4
5b
Ag+
Cu+
Zn2+
Pd2+
6
258
212
222
256
-
517
547
503
520
-
-
-
-
-
-
236[e]
499
113
-
431
-
28.6
7
(150[f])
(550[f])
Ag+
27
-
116
-
221
223
-
-
436
-
509
511
-
-
225
-
-
509
-
-
15.3
-
-
Ag+
Cu+
18
215
534
28.9
[a][Eox] = mV vs. ferrocene / ferrocenium. [iP,1/c] = ꢀA/M. [c]Upon addition of 1.00 equiv. M+/2+
.
[d]Upon addition of
[b]
2.00 equiv. M+/2+ [e]The first oxidation process is accompanied by association. [f]Acquired in CH2Cl2.31
.
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2.4 Computational Studies
To gain further structural information about the TTF-pyridine • M+ complexes, we performed density
functional theory (DFT) calculations (RB3LYP/DGDZVP – this basis set includes elements up to Xe)
focusing on the Ag+ and Cu+ complexes of 7, 5b, 6, and 27. Compound 7 forms an X-shaped 2:1 symmetric
complex with Ag+ located directly in the middle with an intermolecular N---N distance of 4.50 Å (see SI,
Figure S61) while 5b and 6 both form 1:1 complexes with intramolecular N---N distances of 4.50 Å, and
4.51 Å, respectively (see SI, Figures S59 (left) and S64). We note that we do not observe a 1:2 complex
experimentally but it is simply constructed computationally for determination of a N-M+-N distance. As
expected, when not bound to a metal, the nitrogen lone-pairs of 5b seek to point away from each other by
rotation about the triple-bond linkers (referred to as Nout-conformation); however, a local minimum was
found in which the two nitrogens face one another with an N---N distance of 5.38 Å (referred to as Nin-
conformation). Upon introduction of a metal cation, the pyridines must direct themselves and the distance
must shorten ca. 0.9 Å for Ag+ and ca. 1.5 Å for Cu+ to effectively bind a metal. This results in significant
loss of entropy in addition to some strain due to deviation from optimum bond angles as indicated in Scheme
5 (A > B). For complexation of Pb2+, however, TTF-pyridine 5b has a more suitable N---N distance, as the
N-Pb2+-N distance of a bis(pyridine)Pd2+-complex40 was determined to be 5.272 Å, almost exactly that of 5b
(Nin-conformation). As an X-ray crystal structure of 5a, as well as of several Cu-complexes of 5a, are
known,14 we get a chance to benchmark our calculations. A calculated N-Cu+-N distance of 3.85 Å is in good
agreement with the measured N-Cu+-N distances of the known 5a•Cu+-complexes of 3.789 to 3.817 Å.14
In 6, the N---N distance in an uncomplexed molecule is almost exactly the same as the when Ag+ is
encapsulated into the cavity as well as exactly the same as in the completely free 2:1 7•Ag+ complex. Thus,
we calculate an insignificant 0.02 Å difference in the N---N distance between 6 and 6•Ag+. This nicely
explains the significantly larger association constant of 6 for Ag+ compared to that of 5b. The calculated N---
N and N-M+-N distances are listed in Table 4.
Table 4. N---N distances (in Å) in the ligands and in the corresponding Cu+ and Ag+ complexes.[a]
7
-
5b
6
27
[b]
N---N
5.38[c]
3.85
4.50
4.49
3.93
4.51
5.46[c]
3.93
4.67
N-Cu+-N
N-Ag+-N
3.86[d][e]
4.50[d][e]
[a]Results from DFT calculations (RB3LYP/DGDZVP). [b]Not relevant. [c]Not most stable conformation; local minimum
with nitrogen atoms facing one another for comparison; referred to as Nin-conformation. [d]Local minimum with same
geometry as 6 for comparison; referred to as endo,endo-conformation. [e]Intermolecular N-M+-N distance between two 7
molecules in n 7•M+•7-complex.
3. Conclusion
In conclusion, we have prepared a selection of mono-, bidentate and macrocyclic TTF-pyridine hosts and
investigated their binding to mono- and bivalent metals including Ag+, Cu+, Zn2+, Pd2+, Hg2+, and Pb2+. It was
found that while the monodentate TTF-pyridine host bound Ag+ too weakly to enable determination of an
association constant, a stronger binding of this metal ion to the bidentate host 5b (Kf = 2.1 x 104 M-1) and an
even stronger binding to the macrocyclic host 6 (Kf = 1.8 x 105 M-1) were observed. Using DFT-calculations
the N---N distances have been determined and the significantly larger association constant for Ag+ was
explained by a snug fit of Ag+ into its cavity since this required very little conformational change and no loss
of entropy (as in the case of 5b). Thus, the bidentate TTF-pyridine 5b has to refrain from optimum bond
16

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angels in a pincer-like movement to fit Ag+ whereas the macrocycle is tailored to have the perfect N---N
distance to bind this metal. Conversely, we have found that while both monodentate 7 and macrocyclic 6
only showed weak binding to Pb2+ (Kf = 53 M-1 and 97 M-1 for 7 and 6, respectively), bidentate 5b showed a
100-fold larger affinity towards this cation compared to that of 6. Thus, Pb2+ is too large to fit into the cavity
of 6 but a more appropriate size for inclusion into 5b (10 x 103 M-1).
4. Experimental Section
4.1 General Procedures
All reactions were performed under an inert atmosphere of nitrogen (using a gas-bubbler) or argon
(balloon-technique). Coupling reactions using palladium catalysts were performed in solvent flushed with
argon, by letting the argon flow through the solvent for at least 20 minutes while exposed to ultrasound. All
chemicals and solvents were used as received, unless otherwise stated. Al2O3 (Brockman 1) was dried at 200
°C (>16 h) prior to use. Acetonitrile and CH2Cl2 for CV were purified and dried using activated Al2O3.
Tetrahydrofuran (THF) was purified and dried by distillation from a Na / benzophenone couple. CDCl3 (not
stabilized by Ag) was purified by passing through activated Al2O3 to remove residual DCl. All TTFs were
stored in the dark below -18 °C. If purple, perfluorohexyliodide was passed through activated Al2O3 prior to
use. If purple, 1,2-diiodoethane was purified by repeated washings with absolute EtOH and drying in
vacuum prior to use. Thin layer chromatography (TLC) was carried out on commercially available precoated
plates (silica 60) with fluorescence indicator. All melting points are uncorrected. Chromatographic
purifications were done on silica (SiO2) with a pore-size of 60Å and a particle size of of 40–63 ꢀm for flash
column chromatography and 15–40 ꢀm for dry column vacuum chromatography.41 Reactions exposed to
ultrasound were done using a Sonorex Digital 10P at 35 KHz (instrument set at 40% of the 640 W
maximum). IR spectra were obtained using the attenuated total reflectance (ATR) method on diamond. All
UV-Vis spectroscopic measurements were performed in a 1-cm path length quartz cuvette. UV-Vis
absorption spectra were obtained by scanning the wavelength from 800 to 200 nm. Low-resolution MALDI
were performed using a time-of-flight instrument calibrated using a peptide-mix in a separate experiment.
High-resolution mass spectra were collected on an ESP-MALDI-FT-ICR instrument equipped with a 7T
magnet (prior to the experiments, the instrument was calibrated using NaTFA cluster ions). All NMR spectra
were acquired on a 500-MHz instrument equipped with a (non-inverse) cryoprobe (500.1300 MHz /
125.7578 MHz), or in a few examples with a 300-MHz (300.0787 Hz) or 500-MHz (499.9704 MHz)
instrument equipped with a penta-probe. All chemical shift values in 1H and 13C NMR spectra are referenced
to the residual solvent peak (CDCl3 δH = 7.26 ppm, δC = 77.16 ppm. DMSO-d6 δH = 2.50 ppm, δC = 39.52
ppm. CD2Cl2 δH = 5.32 ppm, δC = 54.00 ppm. CD3CN δH = 1.94 ppm, δC = 1.32 ppm). For the 1:1-mixtures
of CD2Cl2 and CD3CN, the residual CD2HCN was used. All NMR values are given in ppm with two
decimals (signal widths; 13C: approximately 0.004 ppm). Elemental analyses were performed at the
Department of Chemistry, University of Copenhagen or at London Metropolitan University.
Cyclic voltammetry measurements were performed using an Autolab PGSTAT12 instrument and the
Nova 1.11 software. The cyclic voltammograms were recorded with scan rates of 0.1 V/s at 298 K. For all
measurements a 3 mm diameter Glassy-Carbon disk sealed in a Teflon body was used as the working
electrode, a Pt wire as the counter electrode, and a silver wire immersed in the solvent-supporting electrolyte
mixture and physically separated from the solution containing the substrate by a ceramic frit as the reference
electrode. The reference electrode potential was referenced to the ferrocene/ferrocenium (Fc/Fc+) redox
couple measured separately before and after each experiment (1 mM). All cyclic voltammograms were
recorded in an Argon atmosphere by purging the solutions with solvent saturated argon for minimum ten
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minutes. The voltammograms of the compounds were recorded in a CH2Cl2 / MeCN (1:1) solvent mixture
containing 0.1 M Bu4NBF4 supporting electrolyte. The solvent mixture was chosen in order to obtain high
solubility of the receptor species (CH2Cl2) and of the metal complexes (MeCN). The iR-compensation of 200
ohm was applied for the CH2Cl2 / MeCN solvent mixture in order to compensate for the solvent resistance.
The concentrations of the receptor species were 1 mM for 5b, and 0.5 mM for 27, 7, and 18. The
concentration of 6 was unknown, however, under the assumption of identical diffusion coefficients of 6 and
7, the concentration of 6 was estimated to be 0.1 mM. The titration experiments were performed by
progressive addition of the metal cations in portions of 0.25 equivalents (except for 6 for which the
concentration was unknown) until a total equivalence of 2 in metal cation was reached. The metal cation
stock solutions were 0.2 M for Ag+, and 0.05 M for Cu+, Pd2+, and Zn2+ in CH2Cl2 / MeCN (1:1), 0.1 M
Bu4NBF4. A cyclic voltammogram was recorded for each addition of metal cation. The receptor-Zn2+
solution was allowed 15 min reaction time before the cyclic voltammograms were recorded.
4.2 Synthesis
2,2'-((4',5'-Bis(butylthio)-[2,2'-bi(1,3-dithiolylidene)]-4,5-diyl)bis(ethyne-2,1-diyl))dipyridine (5b).
To a solution of 2-trimethylsilylethynylpyridine (310 mg, 1.77 mmol) in THF (15 mL), a solution of NaOH
(280 mg, 0.700 mmol, ca. 4 equiv.) in MeOH (10 mL) was added, and the colorless reaction mixture was
stirred for 5 min. The reaction mixture was diluted with Et2O (50 mL) and washed with water (50 mL) and
brine (25 mL), dried with Na2SO4, filtered, and concentrated in vacuum. The resulting colorless oil was
dissolved in Et3N (10 mL) and the solution flushed with argon while exposed to ultrasound for 10 min. This
solution was transferred, via cannula to a solution of diiodo-TTF 8 (234 mg, 0.370 mmol) in argon-flushed
Et3N (15 mL) followed by addition of dppf (20.5 mg, 37.0 µmol, 10 mol%), Pd2dba3 (16.9 mg, 18.5 µmol, 5
mol%), and CuI (1.4 mg, 7.4 µmol, 2 mol%). The resulting cloudy orange to brown reaction mixture was
exposed to ultrasound at 40 °C for 30 min, after which the reaction mixture was heated by the means of
conventional heating at 50 °C for 30 min. According to TLC analysis (20% CH2Cl2 / heptanes) no
transformation had occurred. Pd(PPh3)4 (42.8 mg, 0.370 mmol) was added and the reaction mixture was
flushed with argon for 10 min and the reaction mixture was stirred for 2 h at 50 °C. The resulting strongly
wine-red reaction mixture was diluted with Et2O (100 mL) and washed with saturated aqueous NH4Cl (50
mL) and brine (50 mL), dried with Na2SO4, filtered, and concentrated in vacuum. Purification by flash
column chromatography (CH2Cl2 → 15% EtOAc / CH2Cl2) gave 5b (168 mg, 0.288 mmol, 78%) as a red to
1
black oil which solidified. Rf = (10% EtOAc / CH2Cl2): Rf = 0.48. M.p. = 78–79 °C. H NMR (500 MHz,
CD2Cl2) δ 8.63 (ddd, J = 4.9, 1.8, 1.0 Hz, 2H), 7.74 (td, J = 7.7, 1.8 Hz, 2H), 7.63 (ddd, J = 7.7, 1.0, 1.2 Hz,
2H), 7.32 (ddd, J = 7.7, 4.9, 1.2 Hz, 2H), 2.85 (br t, J = 7.3 Hz, 4H), 1.62 (br p, J = 7.3 Hz, 4H), 1.45 (sext, J
= 7.3 Hz, 4H), 0.93 (t, J = 7.3 Hz, 6H) ppm. 13C NMR (126 MHz, CD2Cl2) δ 150.58, 142.27, 137.17, 128.53,
124.35, 122.44, 114.01, 108.73, 98.71, 80.46, 36.67, 32.39, 22.20, 13.93 ppm. 1H NMR (500 MHz, CDCl3) δ
8.63 (ddd, J = 4.9, 1.8, 1.0 Hz, 2H), 7.68 (td, J = 7.7, 1.8 Hz, 2H), 7.58 (dt, J = 7.9, 1.0 Hz, 2H), 7.29–7.26
(m, 2H), 2.83 (t, J = 7.3 Hz, 4H), 1.67–1.58 (m, 4H), 1.45 (p, J = 7.4 Hz, 4H), 0.94 (t, J = 7.4 Hz, 6H) ppm
(not all spin-systems paired). 13C NMR (126 MHz, CDCl3) δ 150.44, 142.50, 136.33, 128.03, 127.99, 123.64,
122.02, 113.03, 108.99, 98.36, 80.12, 36.27, 31.94, 21.81, 13.75 ppm. HR-MS (MALDI+ FT-ICR,
+
dithranol): m/z = 583.05026 (100), 584.05390 (21), 585.04632 (14) [M+H]+ calc. for (C28H27N2S6 ) m/z =
583.04930 (100), 584.05265 (30), 585.04509 (27). C28H26N2S6 (582.91): calcd. C 57.69, H 4.50, N 4.81;
found C 57.60, H 4.57, N 4.82.
Bis(pyridyl)bis(tetrathiafulvanyl)macrocycle (6) and Tris(pyridyl)bis(tetrafulvanyl)macrocycle (20).
Method 1) To a solution of 18 (144.1 mg, 126.8 µmol) in argon-flushed Et3N (140 mL), CuI (4.8 mg, 25
18

ACCEPTED MANUSCRIPT
µmol, 20 mol%) and 2,6-diethynylpyridine (16.1 mg, 126.8 µmol, 1 equiv) were added. A solution of dppf
(70.3 mg, 126.8 µmol, 1 equiv) and Pd2dba3 (58.1 mg, 63.4 µmol, 50 mol%) in argon-flushed THF (10 mL)
was added via cannula to the reaction mixture and the resulting dark orange solution was stirred for 16 h by
which time it had changed color to a cloudy dark reddish or brown color. A TLC inspection revealed the
presence of unreacted starting material. The temperature was raised to 70 °C and the mixture stirred for 3 h
after which a TLC-inspection revealed complete consumption of starting material and the presence of 3
purple spots. The reaction mixture was allowed to cool to rt and saturated aqueous NH4Cl (50 mL) and
CH2Cl2 (100 mL) were added. The phases were separated and the organic phase was washed with a 0.5 M
aqueous solution of EDTA (3 x 30 mL) and brine (50 mL) after which it was dried with Na2SO4, filtered, and
concentrated in vacuum. The black residue was suspended in CH2Cl2 (10 mL) and filtered through cotton
wool and concentrated in vacuum. Purification by flash column chromatography (70% CH2Cl2 / heptanes)
gave 6 and 20 as purple solids with impurities. Repeated flash column chromatography (a total of 13
consecutive purifications using 70% CH2Cl2 / heptanes → CH2Cl2) gave 6 (0.40 mg, 0.40 µmol, 0.3%) as a
purple glassy solid. Compound 20 was further purified by a recrystallization from CH2Cl2 / MeOH which
gave 20 (3.2 mg, 2.8 µmol, 2%) as a fluffy blue solid. Method 2) To a stirred solution of 23 (18 mg, 14
µmol) in THF (18 mL), water (0.05 mL) and a 1 M solution of tetrabutylammonium fluoride (0.017 mL, 17
µmol, 1.2 equiv.) in THF were added and the reaction mixture was stirred for 10 min. The reaction was
quenched by addition of saturated aqueous NH4Cl (20 mL) and the mixture extracted with Et2O (3 x 50 mL).
The combined organic extracts were dried with Na2SO4, filtered, and concentrated in vacuum to almost
dryness. At this point, the crude intermediate was not isolated but kept in solution at all times. All handling
of the crude was done at room temperature. Et3N (20 mL) was added and using rotary evaporation the
remaining Et2O and THF were removed. The reaction mixture was flushed with argon while carefully
exposed to ultrasound. Pd(PPh3)4 (7.7 mg, 6.7 µmol, 40%) and CuI (0.3 mg, 2 µmol, 10 mol%) were added
and the reaction mixture was stirred at 60 °C for 2 h. The reaction mixture was allowed to cool to rt and
saturated aqueous NH4Cl (50 mL) and CH2Cl2 (100 mL) were added. The phases were separated and the
organic phase was washed with a 0.5 M aqueous solution of EDTA (3 x 30 mL) and brine (50 mL) after
which it was dried with Na2SO4, filtered, and concentrated in vacuum. The black residue was suspended in
CH2Cl2 (10 mL) and filtered through cotton wool and concentrated in vacuum. Purification by flash column
chromatography (70% CH2Cl2 / heptanes) gave 6 with major impurities. [6] TLC (CH2Cl2): Rf = 0.39
(purple). 1H NMR (500 MHz, CDCl3) δ 7.62 (t, J = 7.9 Hz, 2H), 7.34 (d, J = 7.9 Hz, 4H), 2.83 (t, J = 7.3 Hz,
8H), 1.63 (tt, J = 7.4, 7.3 Hz, 8H), 1.45 (sext, J = 7.4 Hz, 8H), 0.93 (t, J = 7.4 Hz, 12H) ppm. 13C NMR (126
MHz, CDCl3) δ 143.56, 136.56, 128.08, 126.34, 123.13, 113.87, 108.44, 99.05, 80.63, 36.32, 31.93, 21.81,
13.74 ppm. HR-MS (MALDI+ FT-ICR, dithranol): m/z = 1007.00830 (100), 1009.00387 (49), 1008.01128
(47), 1010.00748 (20), 1010.99997 (9.6) [MH+], calc. for (C46H43N2S12+) m/z = 1007.00692 (100),
1
1009.00272 (54), 1008.01028 (50), 1010.00607 (27), 1010.99851 (14). [20] H NMR (500 MHz, CDCl3) δ
8.59 (d, J = 7.9 Hz, 2H), 8.22 (t, J = 7.9 Hz, 1H), 7.70 (t, J = 7.8 Hz, 2H), 7.44 (br d, J = 7.8 Hz, 2H), 7.43
(br d, J = 7.8 Hz, 2H), 2.86 (t, J = 7.3 Hz, 4H), 2.83 (t, J = 7.3 Hz, 4H), 1.67 – 1.59 (m, 8H), 1.49 – 1.42 (m,
8H), 0.944 (t, J = 7.4 Hz, 6H), 0.936 (t, J = 7.4 Hz, 6H) ppm. 13C NMR (126 MHz, CDCl3) δ 143.53, 142.51,
142.31, 138.18, 136.93, 131.62, 128.67, 127.43, 126.50, 126.30, 124.95, 122.73, 113.42, 108.58, 100.52,
98.24, 82.95, 82.63, 81.75, 73.45, 36.30, 36.25, 31.95, 31.93, 21.82, 21.81, 13.76, 13.76 ppm. HR-MS
(MALDI+ FT-ICR, dithranol): m/z = 1132.03531 (100), 1133.03804 (56), 1134.03060 (50), 1135.03390
(24), 1136.02605 (11) [MH+], calc. for (C55H46N3S12+) m/z = 1132.03347 (100), 1133.03683 (60),
1134.02927 (54), 1135.03262 (32), 1134.04018 (17), 1136.02506 (14).
2,6-Bis((4',5'-bis(butylthio)-[2,2'-bi(1,3-dithiolylidene)]-4-yl)ethynyl)pyridine (7).31 To a stirred solution
of 17 (1.00 g, 1.97 mmol) and 2,6-diethynylpyridine 9 (99.9 mg, 0.987 µmol) in argon-flushed Et3N (125
19

ACCEPTED MANUSCRIPT
mL), CuI (18.8 mg, 98.7 mmol, 5 mol%) was added followed by a solution of dppf (109 mg, 197 µmol, 10
mol%), Pd2dba3 (90.4 mg, 98.7 µmol, 5 mol%) in argon-flushed THF (5 mL) and the reaction mixture was
stirred at 50 °C for 16 h (Note). The reaction was quenched by addition of saturated NH4Cl (50 mL)
followed by water (50 mL), and the mixture was extracted with CH2Cl2 (200 mL). The organic extract was
washed three times with a mixture of saturated aqueous NH4Cl (50 mL) and water (50 mL), dried with
aqueous Na2SO4, filtered and concentrated in vacuum. Purification by flash column chromatography (SiO2
40% CH2Cl2 / petroleum ether → 50% CH2Cl2, loaded using 40% CH2Cl2 / petroleum ether), followed by
size-exclusion chromatography (biobeads S-X3, CH2Cl2) gave 7 (577 mg, 652 µmol, 66%) as a red oil which
slowly solidified. TLC (50% CH2Cl2 / heptanes): Rf = 0.36 (red to orange). M.p. 91–92 °C (CH2Cl2 /
heptanes). IR (neat): 3075 (w), 2954 (m), 2925 (m), 2865 (m), 2208 (m) cm-1. 1H NMR (400 MHz, CDCl3) δ
7.65 (br t, J = 7.8 Hz, 1H), 7.39 (d, J = 7.8 Hz, 2H), 6.72 (s, 2H), 2.83 (t, J = 7.3 Hz, 4H), 2.82 (t, J = 7.3 Hz,
4H), 1.67–1.57 (m, 8H), 1.49–1.39 (m, 8H), 0.931 (t, J = 7.3 Hz, 6H), 0.927 (t, J = 7.3 Hz, 6H) ppm. 13C
NMR (126 MHz, CDCl3) δ 143.01, 136.78, 128.29, 127.80, 127.65, 126.78, 115.05, 111.99, 110.21, 91.89,
80.97, 36.20, 31.94, 31.92, 21.81, 21.81, 13.76, 13.75 ppm. Note: TLC (50% CH2Cl2 / heptanes): Rf = 0.69
(17).
(13) The phosphonium salt 13 was prepared in five steps according to slightly modified literature
procedures of Becher et al. and Howard et al.27
(14) The 1,3-dithiolium iodide 14 was prepared in a four--step fashion according to a slightly modified
literature procedure from Moore and Bryce.28
2,6-Bis((4',5'-bis(butylthio)-5-iodo-[2,2'-bi(1,3-dithiolylidene)]-4-yl)ethynyl)pyridine (18). To
a
solution of 7 (129.4 mg, 146.3 µmol) in freshly distilled THF (60 mL) at –78 °C was dropwise added a 0.6
M solution of NaHMDS (0.975 mL, 585 µmol, 4.0 equiv.) in toluene. The resulting dark orange solution was
stirred for 6 h after which a solution of perfluorohexyliodide (0.19 mL, 0.88 mmol, 6.0 equiv) in freshly
distilled THF (20 mL), cooled to –78 °C, was added dropwise. The reaction mixture was stirred for 16 h
while allowed to slowly rise to rt. The dark red solution was poured into a mixture of water (50 mL) and
saturated aqueous NH4Cl (50 mL) and the mixture was extracted with Et2O (3 x 100 mL). The organic
extract was washed with a mixture of water (80 mL) and brine (20 mL), dried with Na2SO4, filtered and
concentrated in vacuum. Purification by flash column chromatography (40% CH2Cl2 / heptanes) gave 18
(126.1 mg, 111.0 µmol, 76%) as a bright red oil or solid. TLC (50% CH2Cl2 / heptanes): Rf = 0.56 (yellow to
red spot). IR (neat): 2954 (m), 2923 (m), 2866 (m), 2200 (m) cm-1. 1H NMR (500 MHz, CDCl3) δ 7.69 (t, J =
7.8 Hz, 1H), 7.50 (d, J = 7.8 Hz, 2H), 2.824 (t, J = 7.4 Hz, 4H), 2.819 (t, J = 7.4 Hz, 4H), 1.65–1.59 (m, Hz,
8H), 1.48–1.40 (m, 8H), 0.93 (t, J = 7.4 Hz, 12H) ppm. 13C NMR (126 MHz, CDCl3) δ 143.04, 136.69,
128.36, 127.75, 127.57, 118.79, 112.85, 112.57, 95.01, 82.62, 78.54, 36.28, 36.26, 31.93, 31.91, 21.80, 13.75
ppm (two aliphatic signals missing due to overlap). HR-MS (MALDI+ FT-ICR, dithranol): m/z =
1134.78240 (100), 1136.77857 (54), 1135.78583 (35), 1137.78180 (18), 1138.77415 (13) [Mꢁ+], calc. for
(C37H39I2NS12ꢁ+) m/z = 1134.78203 (100), 1136.77783 (54), 1135.78539 (40), 1137.78119 (22), 1138.77363
(14). C37H39I2NS12 (1136.30): C 39.11, H 3.46, N 1.23; found C 39.33, H 3.39, N 1.23.
2-((4',5'-Bis(butylthio)-5-iodo-[2,2'-bi(1,3-dithiolylidene)]-4-yl)ethynyl)-6-((4',5'-bis(butylthio)-[2,2'-
bi(1,3-dithiolylidene)]-4-yl)ethynyl)pyridine (19). To a solution of 7 (36.8 mg, 41.6 µmol) in dry THF (30
mL) at – 78 °C, was added a 0.6 M solution of NaHMDS (0.21 mL, 0.12 mmol, 3 equiv) in toluene and the
reaction mixture was stirred for 2 h (Note). C6F13I (18 µL, 83 µmol, 2 equiv) was added and the temperature
was allowed to slowly reach rt while the mixture was stirred overnight. The resulting red solution was
concentrated to dryness by blowing a stream of nitrogen gas over it. Purification by flash column
20

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chromatography (30% - 40% CH2Cl2 / heptanes) gave 19 (14.1 mg, 14.0 µmol, 34%) and 7 (18.0 mg, 20.4
1
µmol, 49%) as red solids. H NMR (500 MHz, CDCl3) δ 7.67 (t, J = 7.9 Hz, 1H), 7.48 (dd, J = 7.9, 1.0 Hz,
1H), 7.42 (dd, J = 7.9, 1.0 Hz, 1H), 6.73 (s, 1H), 2.84–2.80 (m, 8H), 1.65–1.59 (m, 8H), 1.48–1.40 (m, 8H),
0.95–0.91 (m, 12H) ppm. 13C NMR (126 MHz, CDCl3) δ 143.12, 142.94, 136.74, 128.35, 128.30, 127.81,
127.75, 127.71, 127.34, 127.03, 118.79, 115.05, 112.84, 112.55, 112.00, 110.22, 95.00, 91.90, 82.54, 81.06,
78.50, 36.27, 36.25, 36.20, 31.94, 31.93, 31.92, 31.91, 21.81, 21.80, 13.74 ppm (six aliphatic signals missing
due to overlap). HR-MS (MALDI+ FT-ICR): calcd. for [C37H40INS12]ꢁ+ 1008.88484 (100), 1010.88064 (54),
1009.88820 (40), 1011.88399 (22), 1012.87643 (14) [M]ꢁ+ found 1008.88624 (100), 1010.88230 (49),
1009.89472 (40), 1011.89033 (21), 1012.87759 (12). Note: To probe the deprotonation, samples of 1 mL
were taken out and poured directly into ca. 100 µL of C6F13I. By TLC-inspection, the progress was
determined. The reaction was quenched when TLC-inspections showed formation of 18.
Tris(pyridyl)bis(tetrafulvanyl)macrocycle (20). See preparation of 6.
2-Ethynyl-6-((triisopropylsilyl)ethynyl)pyridine (22). To a stirred solution of 25 (289 mg, 813 µmol) in
a mixture of THF (6 mL) and MeOH (6 mL), NaOH (179 mg, 4.48 mmol, 5.5 equiv.) was added and the
reaction mixture was stirred for 10 min. The reaction was quenched by addition of saturated aqueous NH4Cl
(20 mL). The reaction mixture was extracted with Et2O (3 x 50 mL), dried with Na2SO4, filtered and
concentrated in vacuum which gave 22 (227 mg, 813 µmol, 98%) as a slightly yellow solid (stored in
freezer). TLC (20% CH2Cl2 / heptanes): Rf = 0.09. M.p. 51.5–52.5 °C. IR (neat): 3306 (w), 3208 (w), 2943
1
(m), 2892 (w), 2865 (m), 2161 (w), 2108 (w) cm-1. H NMR (500 MHz, CDCl3) δ 7.61 (t, J = 7.8 Hz, 1H),
7.43 (dd, J = 7.8, 1.1 Hz, 1H), 7.40 (dd, J = 7.8, 1.1 Hz, 1H), 3.15 (s, 1H), 1.14 (br s, 21H) ppm. 13C NMR
(126 MHz, CDCl3) δ 144.00, 142.68, 136.39, 127.81, 126.74, 105.30, 92.74, 82.52, 77.71, 18.78, 11.39 ppm.
HR-MS (MALDI+ FT-ICR, dithranol): m/z = 284.18375 [M+H]+, calc. for (C18H26NSi+) m/z = 284.18290.
2-((4',5'-Bis(butylthio)-5-((6-((triisopropylsilyl)ethynyl)pyridin-2-yl)ethynyl)-[2,2'-bi(1,3-
dithiolylidene)]-4-yl)ethynyl)-6-((4',5'-bis(butylthio)-5-iodo-[2,2'-bi(1,3-dithiolylidene)]-4-
yl)ethynyl)pyridine (23) and 2,6-bis((4',5'-bis(butylthio)-5-((6-((triisopropylsilyl)ethynyl)pyridin-2-
yl)ethynyl)-[2,2'-bi(1,3-dithiolylidene)]-4-yl)ethynyl)pyridine (24). To a stirred solution of 18 (92.6 mg,
81.5 µmol) in argon-flushed Et3N (45 mL), CuI (1.6 mg, 8.2 µmol, 10 mol%) and Pd(PPh3)4 (18.8 mg, 16.3
µmol, 20 mol%) were added and the solution was flushed with argon for 10 min. Compound 22 (23.1 mg,
81.5 µmol, 1 equiv) was and the resulting deep red reaction mixture was exposed to ultrasound for 2 h while
slowly heated to 40 °C. When no more progress could be detected by TLC-inspection, the reaction was
quenched by addition of saturated aqueous NH4Cl (20 mL) and extracted with CH2Cl2 (3 x 50 mL). The
combined extracts were washed with saturated aqueous NH4Cl (3 x 50 mL), dried with Na2SO4, filtered and
concentrated in vacuum. Purification by flash column chromatography (40% CH2Cl2 / heptanes → 50%
CH2Cl2 / heptanes) gave 23 (21.6 mg, 16.7 µmol, 21% based on 18) and 24 (35.2 mg, 24.3 µmol, 60% based
on 22) as purple solids. [23] TLC (50% CH2Cl2 / heptanes): Rf = 0.63 (brown / purple). IR (neat): 2956 (m),
2942 (m), 2929 (m), 2892 (w), 2864 (m), 2202 (w) cm-1. 1H NMR (500 MHz, CDCl3) δ 7.70 (t, J = 7.8 Hz,
1H), 7.67 (t, J = 7.8 Hz, 1H), 7.613 (d, J = 7.8 Hz, 1H), 7.611 (d, J = 7.8 Hz, 1H), 7.48 (dd, J = 7.8, 1.1 Hz,
1H), 7.44 (dd, J = 7.8, 1.1 Hz, 1H), 2.86–2.83 (m, 8H), 1.67–1.58 (m, 8H), 1.49–1.39 (m, 8H), 1.14 (br s,
21H), 0.95–0.91 (m, 12H) ppm (not all spin-systems paired). 13C NMR (126 MHz, CDCl3) δ 144.10, 143.09,
142.89, 142.58, 136.76, 136.61, 128.30, 128.07, 127.98, 127.96, 127.82, 127.78, 127.47, 127.41, 123.05,
122.28, 118.73, 113.36, 112.94, 112.42, 108.71, 105.44, 98.44, 97.89, 95.18, 92.93, 82.35, 81.16, 80.60,
78.56, 36.27, 36.25, 31.93, 31.92, 31.91, 21.81, 21.79, 18.82, 13.75, 13.74, 11.41 ppm (seven aliphatic
signals missing due to overlap). HR-MS (MALDI+ FT-ICR, dithranol): m/z = 1291.05614 [M+H]+, calc. for
(C55H64IN2S12Si+) m/z = 1291.05264 (isotope pattern analysis not possible due to overlap with [M•+]). [24]
21

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TLC (50% CH2Cl2 / heptanes): Rf = 0.56 (purple). 1H NMR (500 MHz, CDCl3) δ 7.72 (br t, J = 7.8 Hz, 1H),
7.66 (t, J = 7.8 Hz, 2H), 7.59 (dd, J = 7.8, 1.1 Hz, 2H), 7.58 (d, J = 7.8 Hz, 2H), 7.42 (dd, J = 7.7, 1.1 Hz,
2H), 2.84 (t, J = 4H), 2.83 (t, J = 4H), 1.67 – 1.59 (m, 8H), 1.49 – 1.41 (m, 8H), 1.14 (s, 42H), 0.94 (td, J =
13
7.4 Hz, 12H) ppm. C NMR (126 MHz, CDCl3) δ 144.08, 142.99, 142.47, 136.85, 136.59, 128.21, 128.00,
127.90, 127.60, 127.47, 123.13, 122.12, 113.53, 108.55, 105.38, 98.57, 98.02, 92.93, 80.90, 80.56, 36.27,
36.26, 31.94, 31.93, 21.81, 21.80, 18.81, 13.75, 11.40 ppm (one aliphatic signal missing due to overlap). HR-
MS (MALDI+ FT-ICR, dithranol): m/z = 1446.32010 [M+H]+, calc. for (C73H87N3S12Si2 ) m/z = 1446.31598
+
(isotope pattern analysis not possible due to overlap with [M•+]). Note: TLC (50% CH2Cl2 / heptanes): Rf =
0.69 (18), 0.63 (brown / purple), 0.56 (purple), 0.52 (22).
2-((Triisopropylsilyl)ethynyl)-6-((trimethylsilyl)ethynyl)pyridine (26). To a stirred solution of 25
(1.70 g, 5.02 mmol) in a mixture of argon-flushed THF (20 mL) and Et3N (5.6 mL), Pd(PPh3)2Cl2 (176 mg,
0.251 mmol, 5 mol%) and CuI (29 mg, 0.15 mmol, 3 mol%) were added and the mixture was exposed to
ultrasound for 10 minutes while flushed with argon. At once, trimethylsilylacetylene (2.15 mL, 15.1 mmol, 3
equiv) was added and the reaction mixture was stirred overnight (Note). The reaction was quenched by
addition of saturated aqueous NH4Cl (20 mL) and the mixture was extracted with Et2O (100 mL). The
organic phase was separated, dried with Na2SO4, filtered, and concentrated in vacuum. Purification by flash
column chromatography (10-20% CH2Cl2 / petroleum spirit) gave 26 (1.72 g, 4.84 mmol, 96%) as a slightly
yellow oil or low-melting solid (stored in freezer). TLC (20% CH2Cl2 / heptanes): Rf = 0.26. M.p. 50.5–52.0
1
°C. IR (neat): 2959 (m), 2943 (m), 2895 (w), 2865 (m), 2158 (w) cm-1. H NMR (500 MHz, CDCl3) δ 7.57
(t, J = 7.9 Hz, 1H), 7.383 (t, J = 7.9 Hz, 1H), 7.381 (t, J = 7.9 Hz, 1H), 1.13 (s, 21H), 0.26 (s, 9H) ppm. 13C
NMR (126 MHz, CDCl3) δ 143.86, 143.45, 136.22, 127.52, 126.80, 105.46, 103.37, 95.52, 92.55, 18.79,
11.40, -0.16 ppm. Note: GC-MS (EI+): 1,4-bis(trimethylsilyl)buta-1,3-diyne: R.T. = 11.54 min, 70.1%, m/z =
194.1 (100), 195.1 (21); 26: R.T. = 20.28 min, 29.9%, m/z = m/z: 355.3 (100), 356.2 (34), 357.2 (12.0%).
+
HR-MS (MALDI+ FT-ICR, dithranol): m/z = 356.22344 [M+H]+, calc. for (C21H34NSi2 ) m/z = 356.22243.
C21H33NSi2 (355.66): C 70.92, H 9.35, N 3.94; found C 70.74, H 9.31, N 3.86.
5. Acknowledgements
The Villum Foundation is acknowledged for financial support.
6. Supporting Information
NMR and UV-Vis spectra, cyclic voltammograms, Job-plots, titration data and computational details.
7. References and notes
1
a) Glaser, C. Annalen der Chemie und Pharmacie 1870, 154, 137–171. b) Hay, A. S. J. Org. Chem. 1962, 27, 3320–
3321. c) Vilhelmsen, M. H.; Jensen, J.; Tortzen, C. G.; Nielsen, M. B. Eur. J. Org. Chem. 2012, 701–711.
2
a) An, H.; Bradshaw, J. S.; Izatt, R. M. Chem. Rev., 1992, 92, 543–572. b) Gokel, G. W.; Leevy, W. M.; Weber, M.
E. Chem. Rev. 2004, 104, 2723–2750.
3 Bosch, E.; Barnes, C. L. Inorg. Chem. 2001, 40, 3097–3100.
4 Neverov, A. A.; Feng, H. X.; Hamilton, K.; Brown, R. S. J. Org. Chem. 2003, 68, 3802–3810.
5 Suzaki, Y.; Shimada, K.; Chihara, E.; Saito, T.; Tsuchido, Y.; Osakada K. Org. Lett., 2011, 13, 3774–3777.
6 Suzaki, Y.; Saito, T.; Ide, T.; Osakada, K. Dalton Trans., 2014, 43, 6643–6649.
7
Glass, R. Sulfur-, Selenium-, and Tellurium-Containing Compounds. In Organic Electrochemistry, 5th ed.;
Hammerich, O.; Speiser, B. Ed.; CRC Press.
8
a) Nielsen, M. B.; Lomholt, C.; Becher, J. Chem. Soc. Rev., 2000, 29, 153–164. b) Jeppesen, J. O; Nielsen, M. B.;
Becher, J. Chem. Rev. 2004, 104, 5115-5132. c) Canavet, D.; Sallé, M; Zhang, D.; Zhu, D. Chem. Commun. 2009,
2245-2269.
22

ACCEPTED MANUSCRIPT
9
a) Hansen, T. K.; Jørgensen, T.; Stein, P. C.; Becher, J. J. Org. Chem., 1992, 57, 6403–6409. b) Gasiorowski, R.;
Jørgensen, T.; Moller, J.; Hansen, T. K.; Pietraszkiewicz, M.; Becher, J. Adv. Mater. 1992, 4, 568–670. c) Hansen, T.
K.; Jørgensen, T.; Becher, J. J. Chem. Soc., Chem. Commun. 1992, 1550–1552. d) Jørgensen, T.; Girmay, B.; Hansen,
T. K.; Becher, J.; Underhill, A. E.; Hursthouse, M. B.; Harman, M. E.; Kilburn, J. D. J. Chem. Soc., Perkin Trans. 1,
1992, 2907–2911. e) Le Derf, F.; Sallé, M.; Mercier, N.; Becher, J.; Richomme, P.; Gorgues, A.; Orduna, J.; Garín, J.
Eur. J. Org. Chem. 1998, 1861–1865. f) Le Derf, F.; Mazari, M.; Mercier, N.; Levillain, E.; Richomme, P.; Becher, J.;
Garín, J.; Orduna, J.; Gorgues, A.; Sallé, M. Inorg. Chem. 1999, 38, 6096–6100. g) Le Derf, F.; Mazari, M.; Mercier,
N.; Levillain, E.; Richomme, P.; Becher, J.; Garín, J.; Orduna, J.; Gorgues, A.; Sallé, M. Chem. Commun. 1999, 1417–
1418. h) Trippé, G.; Levillain, E.; Le Derf, F.; Gorgues, A.; Sallé, M.; Jeppesen, J. O.; Nielsen, K.; Becher, J. Org. Lett.
2002, 4, 2461–2464. i) Lyskawa, J.; Le Derf, F.; Levillain, E.; Mazari, M.; Sallé, M.; Dubois, L.; Viel, P.; Bureau, C.;
Palacin, S. J. Am. Chem. Soc. 2004, 126, 12194–12195. j) Trippé, G.; Le Derf, F.; Lyskawa, J.; Mazari, M.; Roncali, J.;
Gorgues, A.; Levillain, E.; Sallé, M. Chem. Eur. J. 2004, 10, 6497. k) Delogu, G.; Fabbri, D.; Dettori, M. A.; Sallé, M.;
Le Derf, F.; Blesa, M.-J.; Allain, M. J. Org. Chem. 2006, 71, 9096–9103. l) Zhao, Y-P.; Wang, X.-J.; Wang, J.-J.; Si,
G.; Liu, Y.; Tunga, C.-H.; Wu, L.-Z. New J. Chem., 2009, 33, 813–817.
10
Bryce, M. R.; Batsanov, A. S.; Finn, T.; Hansen, T. K.; Moore, A. J.; Howard, J. A. K.; Kamenjicki, M.; Lednev, I.
K.; Asher, S. A. Eur. J. Org. Chem. 2001, 933–940.
11 Zhao, Y.-P.; Wu, L.-Z.; Si, G.; Liu, Y.; Xue, H.; Zhang, L.-P.; Tung, C.-H. J. Org. Chem. 2006, 72, 3632–3639.
12
a) Wang, J.-J.; Wang, X.-J.; Geng, Y.; Tung, C.-H.; Wu, L.-Z. Sci China Ser B-Chem 2009, 52, 752–770. b)
Balandier, J.-Y.; Belyasmine, A.; Sallé, M. Eur. J. Org. Chem. 2008, 269–276.
13 Xue, H.; Tang, X.-J.; Wu, L.-Z.; Zhang, L.-P.; Tung, C.-H. J. Org. Chem. 2005, 70, 9727–9734.
14 Isomura, E.; Tokuyama, Tohru, K.; Nishinaga, K.; Iyoda, M. Tetrahedron Lett., 2007, 48, 5895–5898.
15 a) J. Am. Chem. Soc. 2012, 134, 11968–11970. b) J. Am. Chem. Soc. 2013, 135, 10018–10021.
16 Bang, K. S.; Nielsen, M. B.; Zubarev, R.; Becher, J.; Chem. Commun. 2000, 215–216.
17 a) Nielsen, K. A.; Jeppesen, J. O.; Levillain, E.; Becher, J. Angew. Chem. Int. Ed. 2003, 42, 187–191. b) Nielsen, K.
A.; Cho, W.-S.; Jeppesen, J. O.; Lynch, V. M.; Becher, J.; Sessler, J. L. J. Am. Chem. Soc. 2004, 126, 16296–16297. c)
Nielsen, K. A.; Cho, W.-S.; Lyskawa, J.; Levillain, E.; Lynch, V. M.; Sessler, J. L.; Jeppesen, J. O. J. Am. Chem. Soc.
2006, 128, 2444–2451. d) Park, J. S.; Bejger, C.; Larsen, K. R.; Nielsen, K. A.; Jana, A.; Lynch,V. M.; Jeppesen, J. O.;
Kim, D.; Sessler, J. L. Chem. Sci. 2012, 3, 2685–2689.
18 María-Jesús Blesa, M.-J.; Zhao, B.-T.; Allain, M.; Le Derf, F.; Sallé, M. Chem. Eur. J. 2006, 12,1906–1914.
19 Hara, K.; Hasegawa, M.; Kuwatani, Y.; Enozawa, H.; Iyoda, M. Heterocycles, 2010, 80, 909–915.
20 Prepared analogously to: Al-Taweela, S. A. Phosphorus, Sulfur, Silicon Relat. Elem. 2002, 177, 1041–1045.
21 Prepared analogously to: Orita, A.; Nakano, T.; An, D. L.; Tanikawa, K.; Wakamatsu, K.; Otera, J. J. Am. Chem. Soc.
2004, 126, 10389–10396.
22 Iyoda, M.; Enozawa, H.; Miyake, Y. Chem. Lett. 2004, 33, 1098–1099.
23 Bruce, M. I.; Duffy, D. N. Aust. J. Chem. 1986, 39, 1697-1701.
24 Li, P.; Ahrens, B.; Bond, A. D.; Davies, J. E.; Koentjoro, O. F.; Raithby, P. R.; Teat, S. J. Dalton Trans. 2008, 1635–
1646.
25 Mazzanti, V.; Jiang, H.; Gotfredsen, H.; Morsing, T. J.; Parker, C. R.; Nielsen, M. B. Org. Lett., 2014, 16, 3736–3739
26
Prepared by modified procedure of: Harzmann, G. D.; Neuburger, M.; Mayor M.; Eur. J. Inorg. Chem. 2013, 2013,
3334–3347.
27 a) Svenstrup, N.; Rasmussen, K. M.; Hansen, T. K.; Becher, J. Synthesis 1994, 1994, 809–812. b) Binet, L.; Fabre, J.
M.; Montginoul, C.; Simonsen, K. B.; Becher, J. J. Chem. Soc., Perkin Trans. 1 1996, 783–788. c) Wang, C.; Batsanov,
A. S.; Bryce, M. R.; Howard, J. A. K. Synthesis 1998, 11, 1615–1618.
28 Moore, A. J.; Bryce, M. R. Synthesis 1997, 1997, 407–409.
29
a) Iyoda, M.; Kuwatani, Y.; Hara, K.; Ogura, E.; Suzuki, H.; Ito, H.; Mori, T.; Chem. Lett., 1997, 26, 599–600. b)
Moore, A. J.; Bryce, M. R.; Batsanov, A. S.; Heaton, J. N.; Lehmann, C. W.; Howard, J. A. K.; Robertson, N.;
Underhill, A. E.; Perepichka, I. F.; J. Mat. Chem., 1998, 8, 1541–1550. c) Lincke, K.; Frellsen, A. F.; Parker, C. R.;
Bond, A. D.; Hammerich, O.; Nielsen, M. B. Angew. Chem. Int. Ed., 2012, 51, 6099–6102.
30 Hasegawa, M.; Takano, J.; Enozawa, H.; Kuwatani, K.; Iyoda, M. Tetrahedron Lett. 2004, 45, 4109–4112.
31
Jiang, H.; Mazzanti, V.; Parker, C. R.; Broman, S. L.; Wallberg, J. H.; Lušpai, K.; Brincko, A.; Kjaergaard, H. G.;
Kadziola, A.; Rapta, P.; Hammerich, O.; Nielsen, M. B. Beilstein J. Org. Chem. 2015, 11, 930–948.
32 Hasegawa, M.; Enozawa, H.; Kawabata, Y.; Iyoda, M. J. Am. Chem. Soc. 2007, 129, 3072–3073.
33 A synthesis of 19 is included in the experimental section.
34 Joosten, A.; Trolez, Y.; Collin, J.-P.; Heitz, V.; Sauvage, J.-P. J. Am. Chem. Soc. 2012, 134, 1802–1809.
35 An optimized structure can be found in supporting information.
36 Hargrov, A. E.; Zhong, Z.; Sessler, J. L.; Anslyn, E. V. New J. Chem. 2010, 34, 348–354.
37 Qureshi, P.; Varshney, R.; Singh, S. Spectrochim. Acta A. 1994, 50, 1789–90.
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38 Kuntz, I. D.; Gasparro, F. P.; Johnston, M. D.; Taylor, R. P. J.Am. Chem. Soc. 1968, 90, 4778-4781.
39 Arnold, B.; Euler, A.; Fields, K.; Zaini, R. J. Phys. Org. Chem. 2000, 13, 729–34.
40 Appleton, S. E.; Briand, G. G.; Decken A.; A. S. Smith Acta Cryst. Sect. E 2011, 67, 714.
41 a) Pedersen, D. S.; Rosenbohm, C. Synthesis 2001, 16, 2431–2434. b) Broman, S. L.; Petersen, A. U.; Tortzen, C. G.;
Vibenholt, J.; Bond, A. D.; Nielsen, M. B. Org. Lett. 2012, 14, 318–321. c) Broman, S. L.; Jevric, M.; Bond, A. D.;
Nielsen, M. B. J. Org. Chem. 2014, 79, 41–64.
24