Alkynylated phenazines: Synthesis, characterization, and metal-binding properties of their bis-triazolyl cycloadducts

Article abstract of DOI:10.1021/jo3012978

We have synthesized a series of ethynylated phenazines and their bis-triazolyl cycloadducts to serve as metal ion sensors. Binding of metal ions is achieved through coordination to the phenazine nitrogen atom and the triazole ring. To allow metal sensing

Full text of DOI:10.1021/jo3012978

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Article
Alkynylated Phenazines: Synthesis, Characterization, and
Metal-Binding Properties of Their Bis-triazolyl Cycloadducts
Jonathan J. Bryant, Yexiang Zhang, Evan A. Davey, Anthony Lucas
Appleton, Benjamin Daniel Lindner, Xuhong Qian, and Uwe H. F. Bunz
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo3012978 • Publication Date (Web): 15 Aug 2012
Downloaded from http://pubs.acs.org on August 19, 2012
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Alkynylated Phenazines: Synthesis, Characterization, and Metal-
Binding Properties of Their Bis-triazolyl Cycloadducts
†
1
‡║1
†
‡
Jonathan J. Bryant , Yexiang Zhang , Benjamin D. Lindner , Evan A. Davey , Anthony Lucas
‡
║
†‡
Appleton , Xuhong Qian , U. H. F. Bunz *
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†
Organisch Chemisches Institut, Universität Heidelberg, Im Neuenheimer Feld 270 Heidelberg,
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9120 Germany
‡
School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Dr.
Atlanta, GA 30332 USA
║
Shanghai Key Laboratory of Chemical Biology, State Key Laboratory of Bioreactor
Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai,
200237, China
Uwe.bunz@oci.uni-heidelberg.de
1
These authors contributed equally to this work
Abstract
We have synthesized a series of ethynylated phenazines and their bis-triazolyl cycloadducts to
serve as metal ion sensors. Binding of metal ions is achieved through coordination to the
phenazine nitrogen atom and the triazole ring. To allow metal-sensing in aqueous solution, the
triazole units are substituted with water-soluble ethylene glycol chains. These phenazine
cycloadducts exhibit a selective affinity for binding silver ions. Examination of the halogenated
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analogues reveals a lowering of the band gap, and the corresponding bathochromic shifts in the
absorption and emission spectra. The electron-withdrawing properties of these halogens also
result in significantly decreased metal binding activity of the phenazine cycloadducts.
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Introduction
The redox properties of phenazine and its derivatives have garnered some interest, finding use in
1
2
3-5
biofuel cells, solar cells, and OLEDs, but an even more attractive aspect of phenazines is their
role in pharmaceutical applications. They are biosynthesized by bacteria and many possess broad-
6
-8
9,10
spectrum antifungal and antibiotic activity, as well as the capacity for DNA intercalation.
Sensing schemes involving water-soluble phenazine-based dyes include electrochemical
11,12
13
detection of biological molecules
and colorimetric pH sensing. Less attention has been paid
14
to phenazines themselves, though they have demonstrated the ability to bind silver , and their
1
5
peralkynylated counterparts have also shown an affinity for binding metals.
We decided to further investigate the metal-binding properties of alkynylated phenazine
derivatives. The ethynyl functional group can be transformed via the alkyne-azide 1,3-dipolar
1
6,17
cycloaddition pioneered by Huisgen.
Since the discovery of Cu(I) as a catalyst for this
18,19
20-23
24,25
reaction,
this ‘click’ chemistry has flourished,
appearing in bioconjugation,
polymer
2
6-32
33
and materials chemistry,
and organic synthesis. With regards to heteroaromatic molecules,
3
4,35
the triazole ring influences the electronic properties,
and its electron-donating ability can be
36,37
used to bind metal ions.
Functionalization of the phenazine core with a sufficiently hydrophilic azide produces a water-
soluble fluorophore suitable for metal ion detection. We previously reported water-soluble metal
sensors with benzo- and naphtho-thiadiazole at their core, synthesized by the addition of
3
8
triethylene glycol-substituted azides to the alkynylated thiadiazoles. The hydrophilic arms
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provide water solubility, while the triazole moiety forms an efficient binding pocket with the
nitrogen of the thiadiazole. Introduction of a branched ethylene glycol side chain on the triazole
should further improve the solubility in water, as well as the quantum efficiency of the
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fluorophore, thanks to its aggregation-suppressing ability.
4
0-45
Some fluorescence based silver ion sensors are known,
but with exception of the recent Pt-
4
2
containing polyfluorene, they do not work in water. THF or ethanol is used, which is not
optimal, and also avoids the thorny issues of the preservation of fluorescence in water and the
competition of water as a ligand. Here, we report on a series of ethynylated phenazines, and the
successful application of the silver ion-sensing capabilities of their triazolyl cycloadducts in
water.
Results and Discussion
The synthesis of the alkynylated phenazines and their corresponding cycloadducts is shown in
Scheme 1. Alkynylated phenazines 4a-d and 5a-d were synthesized via condensation of 1 or 2
with 3a-d. Ethanol was used as a solvent, but in the case of the fluorinated compounds,
nucleophilic solvents had to be avoided, as they undergo substitution side reactions at the
fluorinated carbons.
Scheme 1. Synthesis of Cycloadducts 8 and 9
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From the trimethylsilyl-protected phenazine core 4a-c, deprotection with potassium carbonate
gave 6a-c. To avoid degradation of 6, reaction with either 7a or 7b was carried out immediately
to give 8 or 9. The targets 9a-b were obtained in 27-30% yield, while the TEG-substituted 8a and
8c formed in 46-61% yield. The poor yields for this well-known reaction prompted us to vary the
conditions slightly. Water has been postulated as an ideal solvent for stabilization of copper
4
6
acetylide intermediates, but the presence of water as co-solvent had no effect on our reaction,
though it is necessary when using CuSO as catalyst. Performing the reaction at elevated
4
temperatures (50˚C) did not improve the yield, nor did variation of the copper catalyst
(Cu(PPh ) Br or CuSO /ascorbate). Due to the reactive nature of the ethynylated species 6, a one-
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pot deprotection/cycloaddition reaction would be ideal; however, such attempts turned out to be
less reliable overall, and in the best case, resulted in a similar yield.
Figure 1 shows the absorption spectra of the bis-ethynylphenazines 5a-c and 6a-c. The TMS- and
TIPS-protected compounds show very similar absorption spectra, with less distinct local maxima
for the TMS-protected series (similar to the broad spectra of 5b). Halogen substitution causes
red-shifts which increase upon descending in the group. The same effect is seen in the emission
profiles (Figure 2), with the exception of the bromine-substituted phenazine, which is non-
emissive. The heavy atom effect of the bromine leads to the decrease of the fluorescence
quantum yield of 5d. The optical properties of 5a-d are summarized in Table 1 and are consistent
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with the previously reported properties of halogenated azaacenes and pentacenes.
4a
2
4b
4c
5a
5b
1.5
5c
6a
6
b
c
1
6
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0
325
375
425
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525
575
Wavelength (nm)
Figure 1. Absorption spectra of 5a-c and 6a-c in dichloromethane
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Figure 2. Emission spectra of 5a-c and 6a-c in dichloromethane
Table 1. Photophysical Properties Recorded for Compounds 5a-d in DCM
-1
Compound Abs. λmax (nm) Em. λmax (nm) Stokes Shift (cm )
Φ
± 0.1
τ (ns)
f
f
5a
416
443
451
453
492
528
540
n/a
3710
3630
3650
n/a
0.02
0.50
0.11
n/a
0.37
10
5b
5c
5d
2.5
n/a
To gain further insight into the spectral properties of these compounds, we performed quantum
chemical calculations. The calculated energies of the frontier orbitals and a comparison of the
experimental and calculated band gaps are recorded in Table 2. Upon chlorination of the
alkynylated phenazine, the LUMO is stabilized by 0.49 eV, whereas the HOMO is stabilized by
only 0.30 eV. This results in a lowering of the optical gap by 0.19 eV, which agrees closely with
the experimentally observed change of 0.20 eV. From the visual representations of the frontier
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molecular orbitals (Figure 3a), it is apparent that the coefficients of the HOMO on the
halogenated ring are smaller than those of the LUMO. Therefore, the stabilizing effect of
halogenation is greater for the LUMO than the HOMO, resulting in the observed bathochromic
shifts. This effect is seen to a greater extent in the cycloaddition products, where the HOMOs are
located almost exclusively on the triazole-containing axis, resulting in even greater bathochromic
shifts upon halogenation.
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Table 2. Calculated and Experimental HOMO-LUMO Gaps (gas phase)
a
a
b
Compound
HOMO (eV)
LUMO (eV)
calc. gap (eV)
3.13
exp. gap (eV)
6
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6
a
b
c
-6.24
-6.60
-6.54
-5.81
-6.13
-6.10
-3.11
-3.60
-3.60
-3.01
-3.51
-3.56
2.96
2.85
2.76
2.76
2.59
2.53
3.00
2.94
c
9a
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c
9b
2.62
c
8c
2.54
a
c
b
Calculated by SPARTAN 10 using the B3LYP method with the 6-311++G** basis set. Acquired from the λmax of absorption.
Triazole substituent approximated by a methyl group.
What is the conformation of the triazole unit with respect to the phenazine ring? Quantum
chemical calculations always give the rotamer, in which the C-H-group is close to the N-unit of
the phenazine nucleus, and never the one in which the bidentate binding pocket is formed. We
calculated the internal rotation around the C-C-bond that connects the phenazine with the triazole
rings (Figure 3b, B3LYP-6-311++G**). The rotamer forming the binding pocket is ca. 9 kcal
-1
mol higher in energy. The reason for the energy difference is probably the mutual electrostatic
repulsion of the two adjacent electron pairs of the participating heterocyclic nitrogens (Figure
3
b,c). Upon the coordination of silver ions the binding pocket forms through rotation. We have
+
calculated the structure of the Ag complex of a simplified model (Figure 3d, B3LYP 6-31G**)
in the absence of further ligands. The silver ion forces the ligand into a conformation that
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accommodates the cation optimally. This conformation is not planar but has a torsion angle of
around 40˚. Additionally, one can see that in the optimized structure the distance of the triazole
nitrogen to the silver cation is 2.24 Å, while the distance to the phenazine nitrogen is 2.35 Å.
Upon fluorination of the unsubstituted part of the phenazine, the geometry changes and the Ag-
triazole distance is reduced to 2.21 Å, while the distance to the now much more electron poor
phenazine is increased to 2.45 Å. As a consequence of the geometrical change the torsion angle is
now only 35˚. While these are only gas phase calculations without added ligands or counter ions,
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they are supported by 2D H- H NOESY NMR (see supporting info). In the absence of silver, the
predicted rotamer is observed, with no interaction between the triazole hydrogen and the aromatic
hydrogen (at the 2 or 3 position). After addition of silver ion, there is a clear interaction between
these hydrogen atoms, made possible through the rotation of the triazole ring.
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Figure 3. a) Frontier orbitals for 6a-c (top) and simplified models of 9a-c (bottom). b)
Electrostatic potential map highlighting the localization of electron density on the nitrogen atoms,
particularly those of the triazole ring. c) Rotational profile of a simplified model of 8a and 9a.
The left conformation (green) displays the lowest relative energy. The other conformation is 8.96
-1
kcal mol higher in energy. d) Simplified model of 8b and 9b showing the predicted
+
conformation when binding to Ag .
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Figure 4 shows the absorption spectra of 9a-b and 8c in both water and dichloromethane. Though
these compounds are soluble in both solvents, there is a considerable hypsochromic shift in the
absorption profiles when going from organic to aqueous solvent, as much as 30 nm. This trend
exists to a varying degree in each of the cycloadducts. The reverse occurs in the emission spectra
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(Figure 5), with aqueous solvent inducing either a bathochromic shift or none at all. A large
Stokes shift results in water. Variation of the water-soluble triazole substituent does not have any
appreciable effect on the absorption or emission. The spectra of 8a are nearly identical to those of
9a and are therefore not shown.
2
9a (DCM)
9a (H2O)
9b (DCM)
9b (H2O)
8c (DCM)
8c (H2O)
1.5
1
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Wavelength (nm)
Figure 4. Absorption spectra of the cycloadducts 9a-b and 8c in water and dichloromethane
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Figure 5. Fluorescence spectra of the cycloadducts 9a-b and 8c in water and dichloromethane
The phenazine cycloadducts (Table 3) possess rather long lifetimes (greater than 10 ns in organic
solvents). It is unclear how much this is due to the phenazine core. The radiative rate of
phenazine is very low; the dominant decay pathway from the excited singlet states is intersystem
4
9,50
crossing to the triplet states.
indicates that non-radiative decay is still efficient. Further substitution of the phenazine ring
with halogens or triazole rings) increases the quantum yield, as well as the lifetime (Table 1).
The low quantum yield of the alkynylated phenazine 5a
(
The cycloadducts 8 and 9 have even longer lifetimes, suggesting the triazole rings to modulate
the photophysical properties of the molecules.
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Table 3. Photophysical Data for 8 and 9
-
1
Abs. λmax (nm)
Em. λmax (nm) Stokes Shift (cm )
Φ ± 0.1
τf (ns)
f
Compound
DCM
450
H O
DCM
559
H O
DCM
4333
3945
H O
DCM
0.31
0.27
H O
DCM
19
H O
2
2
2
2
2
0
1
2
3
4
5
6
7
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9
0
1
2
3
4
5
6
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8
9
0
1
2
3
4
5
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9
0
1
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3
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5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
8
9
9
a
a
b
433
428
573
569
5643
5790
0.01
0.04
< 0.01
1.7
4.0
4.5
458
559
19
479
496
448
486
603
610
604
619
4293
3768
5765
4421
0.04
0.06
7.9
16
<
a
8c
a
6.8
0.01
a
2
determined in MeOH/H O
The ready solubility of the bis-triazolylphenazine adducts in water and the acceptable quantum
yield of 9a allow the examination of its metal binding properties in aqueous solution. Screened
+
+
+
+
2+
2+
2+
2+
2+
2+
2+
2+
metals include Na , K , Li , Ag , Mg , Ca Zn , Cu , Ni , Hg , Cd , and Pb . The
halogenated fluorophores showed little if any response to metal ions. These are apparently so
electron-poor as to preclude efficient metal binding in water. For the unsubstituted phenazine
2
+
2+
cycloadducts 8a and 9a, only minimal quenching upon exposure to Cu and Hg was observed.
+
As seen in Figure 6, the fluorescence quenching by Ag was pronounced, indicating that these
compounds may serve as a fluorescent sensor for silver ions.
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Figure 6. Relative fluorescence quenching of 9aby metal ions in water.
Due to the increasing prevalence of silver in industrial applications, and its toxicity, the U.S.
Environmental Protection Agency has set a secondary maximum contaminant level of 0.1 mg/L
5
1
for silver. As a result, there exists a desire for sensitive and selective methods of silver ion
detection in aqueous media. As fluorescent sensors, the phenazine cycloadducts possess attractive
-1
properties. Their Stokes shifts are quite large (>5000 cm ), allowing the excitation wavelength to
be far removed from the emission wavelength. The auxochromic effect of the triazole units
pushes the luminescence of these compounds from the blue/green region to the yellow and
beyond, allowing cellular background fluorescence to be easily filtered out. The lifetimes are also
relatively long, enabling such techniques as time-gated detection, though the lifetimes are lower
in water than in dichloromethane.
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Titrations of 8a and 9a with AgNO were performed to determine the strength of the binding.
3
Significant deviation from linearity occurred when the data were fitted to the typical Stern-
5
2-54
Volmer equation. The data however could be fitted well by equation 1,
0
1
2
3
4
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6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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8
9
0
1
2
3
4
5
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
(1)
where ΔI is the change in fluorescent intensity, [F] is the concentration of the fluorophore, [Q] is
the concentration of the quencher, and α is a constant. The binding constant K can be extracted
from equation 1 using a non-linear least-squares curve fitting. The titration curve is shown in
1
1
Figure 7. The data agree with a 1:1 binding ratio, which is also supported by H- H NOESY
NMR (see supporting info). The binding constant for silver(I) was determined to be log(K) = 3.75
±
0.09 for 8a and log(K) = 2.84 ± 0.02 for 9a.
Figure 7. Representative titration (inset) and binding curve of 8a
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Previous evidence that phenazine and peralkynylated phenazine are able to bind silver begs
the question of whether the triazole is necessary for the binding event. We investigated the
interaction of bare phenazine and alkynylated phenazine 5a with silver ions. Titrations of the
three different phenazine compounds (including the cycloadduct 8a) were performed in ethanol,
which provides sufficient solubility and is somewhat comparable to water. Complex formation
10
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between silver ion and phenazine itself was observed only at excess concentrations of silver
5
(
>10 equivalents), and no binding constant could be extracted. The binding constant for 8a was
determined to be log K = 3.44 ± 0.05, similar to the result obtained in water, while the value for
a was significantly lower (log K = 2.70 ± 0.02). The participation of the triazole ring serves to
5
strengthen the binding affinity towards silver ions, though it is not strictly necessary. The
selectivity of the phenazine cycloadducts for silver ion stems from the phenazine, and adjustment
of the electronic properties of the phenazine core leads to changes in the metal-binding activity.
The more electron-poor halogen-substituted phenazine compounds are unable to bind metal ions,
despite the presence of the triazole. Interestingly, the cycloadduct 8a is more sensitive to Ag(I)
than 9a. This suggests that the ethylene glycol side chains interfere with the binding of silver in
some way, but the exact nature of this interaction is not clear.
Conclusion
Water-soluble bis-triazolyl cycloadducts were synthesized from hitherto unknown alkynylated
phenazines to serve as selective silver ion sensors. Halogenation of the phenazine core lowers the
band gap of these materials, and also diminishes the capacity for metal binding. The properties of
these phenazine cycloadducts and their selectivity for silver ions make them promising aqueous
fluorescent sensors for silver ions, while the known biological activity of phenazine derivatives
hints that these water-soluble phenazine cycloadducts may yet prove useful in other areas.
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Experimental
Quantum yield measurements were measured relative to an appropriate standard (quinine sulfate
in dilute sulfuric acid, or fluorescein in dilute sodium hydroxide solution). Time-correlated single
photon counting lifetime measurements were made with a pulsed laser diode.
0
1
2
3
4
5
6
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8
9
0
1
2
3
4
5
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0
3
,6-Bis((trimethylsilyl)ethynyl)benzene-1,2-diamine (1)
,7-Bis((trimethylsilyl)ethynyl)benzo[c][1,2,5]thiadiazole
5
5-57
4
(5.19 g, 15.8 mmol) and dry THF
(50 mL) were added to an oven dried Schlenk flask, which was purged with nitrogen gas and
cooled to 0˚C. Lithium aluminum hydride (1.50 g, 39.5 mmol) was slowly added to the reaction
mixture over a period of 30 minutes. The reaction was then allowed to stir for 30 minutes under
nitrogen, at which point it was slowly quenched with saturated aqueous NH Cl (30 mL) at 0˚C.
4
The resulting product was extracted with diethyl ether (3 x 200 mL), dried over magnesium
sulfate, and the solvent was removed under reduced pressure. Purification by silica gel
chromatography (9:1 hexanes:Et O) gave compound 1 as an air-sensitive yellow solid (4.31 g,
2
-
1
1
2
2
4.3 mmol, 91% yield). mp = 140-144˚C; IR (cm ): 3425, 3420, 3335, 3075, 2956, 2897, 2788,
1
142, 1616, 1608, 1451, 1411, 1247, 1245, 1184, 1123; H NMR (400 MHz, CDCl ):  = 6.77 (s,
3
13
H), 3.94 (s, 4H), 0.26 (s, 18H); C NMR (100 MHz, CDCl ):  = 136.9, 122.4, 110.0, 102.1,
3
+
101.3, 0.4; HRMS (EI) m/z: [M] Calcd for C H N Si = 300.1478; Found = 300.1472.
1
6
24
2
2
3
,6-Bis((triisopropylsilyl)ethynyl)benzene-1,2-diamine (2)
,7-Bis((triisopropylsilyl)ethynyl)benzo[c][1,2,5]thiadiazole
55-57
4
(3.26 g, 6.56 mmol) and dry
THF (50 mL) were added to an oven dried Schlenk flask, which was purged with nitrogen gas
and cooled to 0˚C. Lithium aluminum hydride (0.622 g, 16.4 mmol) was slowly added to the
reaction mixture over a period of 30 minutes. The reaction was then allowed to stir for 12 hours
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under nitrogen, at which point it was slowly quenched with saturated aqueous NH Cl (30 mL) at
4
0
˚C. The resulting product was extracted with diethyl ether (3 x 200 mL), dried over magnesium
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
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4
4
4
4
4
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5
5
5
5
5
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5
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5
6
sulfate, and the solvent was removed under reduced pressure. Purification by silica gel
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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4
5
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8
9
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1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
chromatography (9:1 hexanes:Et O) gave compound 2 as an air-sensitive light yellow solid (2.92
2
-1
g, 6.23 mmol, 95% yield). mp = 127-129˚C; IR (cm ): 3436, 3328, 3070, 2954, 2862, 2715,
1
2
2
9
611, 2140, 1612, 1481, 1269, 1384, 1361, 1253, 1184; H NMR (400 MHz, CDCl ):  = 6.80 (s,
3
13
H), 3.97 (s, 4H), 1.14 (s, 42H); C NMR (75 MHz, CDCl ):  = 136.9, 122.5, 110.3, 104.0,
3
+
7.5, 19.1, 11.6; HRMS (EI) m/z: [M] Calcd for C H N Si = 468.3356; Found = 468.3359.
28
48
2
2
General Procedure 1
The diamine (1 or 2) was added to a solution of 3 in EtOH (10 mL) or DCM (50 mL), along with
AcOH (3 mL). The reaction mixture was stirred overnight (~16 h). The solution was then
extracted with saturated aqueous NaHCO (50 mL) and DCM (2 x 50 mL). The organic fractions
3
were collected and dried over sodium sulfate, the solvent was removed under reduced pressure,
and the product was purified by silica gel chromatography.
1
,4-Bis((trimethylsilyl)ethynyl)phenazine (4a)
The ortho-benzoquinone was freshly prepared by stirring a solution of catechol (1.10 g, 9.98
mmol) in CHCl (200 mL) into a solution of K Cr O (5.88 g, 20.0 mmol) in 1 M H SO (100
3
2
2
7
2
4
mL). After stirring for 10 min. at room temperature, the organic fraction was collected, the
solvent was removed under reduced pressure, and the benzoquinone was reacted with 1 (1.00 g,
3.33 mmol) according to general procedure 1, using EtOH as solvent. The reaction mixture was
heated to 40˚C and stirred overnight at this temperature. Purification by silica gel
chromatography (3:1 hexanes:DCM) gave the product 4a as a yellow solid (780. mg, 2.09 mmol,
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1
1
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1
1
1
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1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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4
4
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5
5
5
5
5
5
5
5
5
6
-1
6
1
7

3%). mp = 166-168˚C; IR (cm ): 3089, 3040, 2963, 2954, 2897, 2152, 1919, 1518, 1473, 1406,
1
281, 1138, 1118, 1025; H NMR (400 MHz, CDCl ):  = 8.29 (dd, J = 3.4 Hz, J = 6.7 Hz, 2H),
3
1
3
.95 (s, 2H), 7.83 (dd, J = 3.4 Hz, J = 6.7 Hz, 2H), 0.35 (s, 18H); C NMR (100 MHz in CDCl ):
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
= 143.6, 143.0, 134.4, 131.2, 130.3, 124.3, 104.2, 101.6, 0.1; HRMS (EI) m/z: [M] Calcd for
C H N Si = 372.1478; Found = 372.1488.
22
24
2
2
1
,2,3,4-Tetrafluoro-6,9-bis((trimethylsilyl)ethynyl)phenazine (4b)
The tetrafluoro-ortho-quinone was freshly prepared before use according to a previously
5
8
published procedure. 1 (1.10 g, 3.66 mmol) and 3b (2.00 g, 11.1 mmol) were reacted according
to general procedure 1, using DCM as solvent. The reaction mixture was heated to reflux and
stirred overnight at this temperature. Purification by silica gel chromatography (10:1
hexanes:DCM) yielded 4b as a yellow solid (292 mg, 0.657 mmol, 18%). mp = 207-210˚C; IR
-1
(
cm ): 2957, 2901, 2853, 2153, 1675, 1595, 1536, 1485, 1341, 1245, 1073, 833, 755, 686, 625,
1
13
4
64; H NMR (300 MHz, CDCl ):  = 8.03 (s, 2H), 0.38 (s, 18H); C NMR (75 MHz, CDCl ): 
3
3
=
143.1, 135.7, 124.5, 106.3, 100.5, 1.4 (the carbons next to the fluorine atoms could not be
1
9
identified); F NMR (300 MHz, CDCl ):  = -149.61 (dd, J = 16.2 Hz, J = 3.6 Hz, 2F), -150.34
3
+
(
dd, J = 15.0 Hz, J = 3.0 Hz, 2F); HRMS (ESI) m/z: [M + H] Calcd for C H F N Si =
22
21
4
2
2
4
45.1174; Found = 445.1180.
1
,2,3,4-Tetrachloro-6,9-bis-((trimethylsilyl)ethynyl)phenazine (4c)
1 (0.600 g, 2.00 mmol) and 3c (0.982 g, 3.99 mmol) were reacted according to general procedure
, using EtOH as solvent. The reaction mixture was heated to 40˚C and stirred overnight at this
temperature. Purification by silica gel chromatography (20:1 hexanes:DCM) yielded 4c as a
1
-1
yellow solid (819 mg, 1.60 mmol, 80%). mp = 201-203˚C; IR (KBr, cm ): 2958, 2899, 2152,
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1
573, 1551, 1488, 1454, 1371, 1245, 1132, 1050; H NMR (400 MHz, CDCl ):  = 8.02 (s, 2H),
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
3
0.36 (s, 18H); C NMR (100 MHz, CDCl ):  = 143.3, 138.7, 135.4, 135.1, 132.2, 124.3, 105.8,
3
+
1
00.2, -0.1; HRMS (EI) m/z: [M] Calcd for C H Cl N Si = 507.9919; Found = 507.9918.
22
20
4
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
,2,3,4-Tetrabromo-6,9-bis-((trimethylsilyl)ethynyl)phenazine (4d)
1 (0.300 g, 0.998 mmol) and compound 3d (0.846 g, 2.00 mmol) were reacted according to
general procedure 1. The reaction mixture was heated to 40˚C and stirred overnight at this
temperature. Purification by silica gel chromatography (hexanes) yielded 4d as a yellow solid
-1
(303 mg, 0.440 mmol, 48%). mp = 137˚C (decomposition); IR (cm ): 2958, 2925, 2899, 2852,
1
2
153, 1893, 1573, 1446, 1359, 1254, 1247, 1099, 1044; H NMR (400 MHz, CDCl ):  = 8.04 (s,
3
1
3
2H), 0.38 (s, 18H); C NMR (100 MHz, CDCl ):  = 149.0, 145.0, 140.5, 137.1, 133.9, 129.2,
3
+
1
10.8, 105.5, 5.1; HRMS (EI) m/z: [M] Calcd for C H Br N Si = 683.7899; Found =
2
2
20
4
2
2
683.7895.
1,4-Bis((triisopropylsilyl)ethynyl)phenazine (5a)
The ortho-benzoquinone was freshly prepared by stirring a solution of catechol (0.692 g, 6.40
mmol) in CHCl (200 mL) into a solution of K Cr O (3.76 g, 12.8 mmol) in 1 M H SO (100
3
2
2
7
2
4
mL). After stirring for 10 min. at room temperature, the organic fraction was collected, the
solvent was removed under reduced pressure, and the benzoquinone was reacted with 2 (1.00 g,
2
.13 mmol) according to general procedure 1, using EtOH as solvent. The reaction mixture was
heated to reflux and stirred overnight. Purification by silica gel chromatography (3:1
hexanes:DCM) gave the product 5a as a yellow solid (0.480 g, 0.887 mmol, 42%). mp = 96-
-
1
98˚C; IR (cm ): 3062, 2962, 2864, 2756, 2723, 2154, 1946, 1886, 1568, 1521, 1461, 1409, 1257,
1
1
118; H NMR (300 MHz, CDCl ):  = 8.24 (dd, J = 3.4 Hz, J = 6.7 Hz, 2H), 7.94 (s, 2H), 7.84
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1
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
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5
5
5
5
5
5
5
5
6
13
(
dd, J = 3.4 Hz, J = 6.7 Hz, 2H), 1.26 (s, 42H); C NMR (75 MHz, CDCl ):  = 143.9, 143.8,
3
+
133.9, 131.2, 130.5, 124.8, 104.0, 101.0, 19.2, 11.9; HRMS (EI) m/z: [M] Calcd for C H N Si
3
4
48
2
2
=
540.3356; Found = 540.3354.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
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0
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8
9
0
1
,2,3,4-Tetrafluoro-6,9-bis((triisopropylsilyl)ethynyl)phenazine (5b)
The tetrafluoro-ortho-quinone was freshly prepared before use, according to a previously
5
8
published procedure. 2 (0.500 g, 1.07 mmol) and 3b (0.576 g, 3.20 mmol) were reacted
according to general procedure 1, using DCM as solvent. The reaction mixture was heated to
reflux and stirred overnight. Purification by silica gel chromatography (10:1 hexanes:DCM)
-1
yielded 5b as a yellow solid (152 mg, 0.248 mmol, 23%). mp = 107-108˚C; IR (cm ): 2939,
1
2
891, 2864, 2159, 1675, 1595, 1536, 1480, 1341, 1260, 1076, 993, 881, 809, 678, 453; H NMR
1
3
(300 MHz, CDCl ):  = 8.03 (s, 2H), 1.24 (s, 42H); C NMR (75 MHz, CDCl ):  = 143.5,
3
3
1
35.5, 124.8, 102.8, 102.6, 19.0, 11.8 (the carbons next to the fluorine atoms could not be
1
9
identified); F NMR (300 MHz, CDCl ):  = -148.80 (dd, J = 15.0 Hz, J = 3.0 Hz, 2F), -149.91
3
+
(
dd, J = 16.2 Hz, J = 3.6 Hz, 2F); HRMS (ESI) m/z: [M + H] Calcd for C H F N Si =
34
45
4
2
2
6
13.3052; Found = 613.3067.
1,2,3,4-Tetrachloro-6,9-bis-((triisopropylsilyl)ethynyl)phenazine (5c)
2 (0.200 g, 0.427 mmol) and 3c (0.115 g, 0.469 mmol) were reacted according to general
procedure 1, using EtOH as solvent. The reaction mixture was heated to reflux and stirred
overnight. Purification by silica gel chromatography (20:1 hexanes:DCM) yielded 5c as a yellow
-1
solid (54.0 mg, 0.0796 mmol, 19%). mp = 100-102˚C; IR (cm ): 2964, 2866, 2725, 2156, 1949,
1
13
1
458, 1369, 1263, 1107, 1031; H NMR (400 MHz, CDCl ):  = 8.02 (s, 2H), 1.21 (s, 42H); C
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NMR (100 MHz, CDCl ):  = 143.3, 138.8, 135.9, 133.7, 132.2, 124.5, 102.4, 102.0, 18.8, 11.4;
3
+
HRMS (EI) m/z: [M] Calcd for C H Cl N Si = 676.1797; Found = 676.1776.
3
4
44
4
2
2
1,2,3,4-Tetrabromo-6,9-bis-((triisopropylsilyl)ethynyl)phenazine (5d)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2
(0.200 g, 0.427 mmol) and 3d (0.271 g, 0.640 mmol) were reacted according to general
procedure 1. The reaction mixture was heated to reflux and stirred overnight. Purification by
silica gel chromatography (hexanes) yielded 5d as a yellow solid (65.0 mg, 0.0759 mmol, 18%).
-1
mp = 107˚C (decomposition); IR (cm ): 2941, 2891, 2864, 2725, 2150, 1892, 1701, 1573, 1463,
1
13
1
448, 1359, 1269, 1126; H NMR (400 MHz, CDCl ):  = 8.03 (s, 2H), 1.21 (s, 42H); C NMR
3
(100 MHz, CDCl ):  = 143.7, 139.9, 136.1, 131.7, 128.7, 124.3, 102.5, 101.8, 18.8, 11.4; HRMS
3
+
(EI) m/z: [M] Calcd for C H Br N Si = 851.9777; Found = 851.9739.
34 44
4
2
2
1,4-Diethynylphenazine (6a)
4
a (0.186 g, 0.499 mmol) was dissolved in 1:1 THF:MeOH (20 mL), to which K CO (0.190 g,
2 3
4
.99 mmol) was added. The solution was stirred for 30 min at room temperature. The product
mixture was then poured over H O (50 mL) and extracted with DCM (2 x 50 mL). The resulting
2
solution was dried over sodium sulfate, and the solvent was removed under reduced pressure.
Purification by silica gel chromatography (10:1 hexanes:EtOAc) gave 6a as a yellow solid (0.105
-1
g, 0.460 mmol, 92%). mp = 80˚C (decomposition); IR (cm ): 3298, 3270, 3232, 3205, 2101,
1
1
521, 1473, 1334, 1112, 1034; H NMR (400 MHz, CDCl ):  = 8.36 (dd, J = 10.2 Hz, J = 3.3
3
13
Hz, 2H), 8.01 (s, 2H), 7.87 (dd, J = 10.2 Hz, J = 3.3 Hz, 2H), 3.76 (s, 2H); C NMR (100 MHz,
+
CDCl ):  = 144.0, 143.2, 134.9, 131.7, 130.4, 124.0, 86.1, 80.6; HRMS (EI) m/z: [M] Calcd for
3
C H N = 228.0687; Found = 228.0690.
16
8
2
1,2,3,4-Tetrafluoro-6,9-diethynylphenazine (6b)
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b (59 mg, 0.13 mmol) was dissolved in THF (10 mL), to which K CO (0.18 g, 1.3 mmol) was
2
3
added. The solution was stirred for 2 hours at room temperature. The reaction did not go to
completion, and no progress was seen after 2 hours, even after 24 hours. The product mixture was
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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8
9
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3
4
5
6
7
8
9
0
then poured over H O (50 mL) and extracted with DCM (2 x 50 mL). The resulting solution was
2
dried over sodium sulfate, and the solvent was removed under reduced pressure. Purification by
silica gel chromatography (20:1 hexanes:EtOAc) gave 6b as a yellow solid (0.018 g, 0.060 mmol,
-1
4
5%). mp = 51˚C (decomposition); IR (cm ): 3263, 2955, 2923, 2356, 2036, 1615, 1489, 1261,
1
13
1069, 800; H NMR (300 MHz, CDCl ):  = 8.11 (s, 2H), 3.79 (s, 2H); C NMR (75 MHz,
3
CDCl ):  = 137.4, 136.4, 124.2, 87.3, 79.4 (the carbons next to the fluorine atoms could not be
3
1
9
identified); F NMR (400 MHz):  = -148.80 (dd, J = 16.2 Hz, J = 3.6 Hz, 2F), -149.91 (dd, J =
+
1
3
5 Hz, J = 3.0 Hz, 2F); HRMS (FAB) m/z: [M + H] Calcd for C H N F = 301.0383; Found =
1
6
5
2 4
01.0419.
1,2,3,4-Tetrachloro-6,9-diethynylphenazine (6c)
4
c (0.200 g, 0.392 mmol) was dissolved in 1:1 THF:MeOH (20 mL), to which K CO (0.542 g,
2 3
3
.92 mmol) was added. The solution was stirred for 30 min at room temperature. The product
mixture was then poured over H O (50 mL) and extracted with DCM (2 x 50 mL). The resulting
2
solution was dried over sodium sulfate, and the solvent was removed under reduced pressure.
Purification by silica gel chromatography (20:1 hexanes:EtOAc) gave 6c as a yellow solid (0.119
-1
g, 0.325 mmol, 83%). mp = 40˚C (decomposition); IR (cm ): 3269, 2958, 2954, 2924, 2109,
1
1
727, 1549, 1454, 1368, 1287, 1247, 1051, 1039; H NMR (400 MHz, CDCl ):  = 8.09 (s, 2H),
3
13
3.77 (s, 2H); C NMR (100 MHz, CDCl ):  = 143.1, 138.9, 136.1, 135.4, 132.1, 124.0, 86.8,
3
+
7
9.2; HRMS (EI) m/z: [M] Calcd for C H Cl N = 363.9129; Found = 363.9133.
16
4
4
2
1
-Azido-2-(2-(2-methoxyethoxy)ethoxy)ethane (7a)
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2
-(2-(2-Methoxyethoxy)ethoxy)ethyl 4-methylbenzenesulfonate (12.9 g, 40.5 mmol) and NaN
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
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4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
5.27g, 81.0 mmol) were stirred into 1:1 H O:MeOH (100 mL). The reaction was heated to
2
reflux, and stirred overnight (16 h). The reaction mixture was cooled, and extracted with DCM (2
x 70 mL). The organic fractions were collected, dried over magnesium sulfate, and the solvent
was removed under reduced pressure. Purification by silica gel chromatography (1:1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
-1
hexanes:EtOAc) gave 7a as a pale yellow oil (6.76 g, 35.7 mmol, 88%). IR (cm ): 2872, 2097,
1
1
453, 1284, 1106, 934, 851; H NMR (400 MHz, CDCl ):  = 3.67 (m, 8 H), 3.55 (m, 2H), 3.38
3
1
3
(t, J = 5.1 Hz, 2H), 3.37 (s, 3H); C NMR (100 MHz, CDCl ):  = 72.0, 70.8, 70.8, 70.7, 70.1,
3
5
9.1, 50.8.
1
3-Azido-2,5,8,11,15,18,21,24-octaoxapentacosane (7b)
5
9
2,5,8,11,15,18,21,24-Octaoxapentacosan-13-yl 4-methylbenzenesulfonate (8.90 g, 16.5 mmol)
and NaN (5.37, 82.6 mmol) were stirred into 4:1 H O:EtOH (250 mL). The reaction was heated
3
2
to reflux, and stirred for 2 d. The reaction mixture was cooled, and extracted with DCM (3 x 75
mL). The organic fractions were collected, dried over magnesium sulfate, and the solvent was
removed under reduced pressure. Purification by silica gel chromatography (EtOAc) gave 7b as a
-1
1
pale yellow oil (6.2 g, 15 mmol, 92%). IR (cm ): 2866, 2092, 1455, 1269, 1098, 849, 731; H
1
3
NMR (300 MHz, CDCl ):  = 3.48-3.35 (m, 29H), 3.20 (s, 6H); C NMR (75 MHz, CDCl ):  =
3
3
+
7
1.67, 70.64, 70.38, 70.35, 70.28, 70.24, 60.3, 58.7; HRMS (ESI) m/z: [M + Na] Calcd for
C H N O Na = 432.2316; Found = 432.2319.
17
35
3
8
1
,4-Bis(1-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)phenazine (8a)
6
a (0.300 g, 1.31 mmol) and 7a (0.746 g, 3.94 mmol) were dissolved in a 5:1 THF:H O solution
2
(20 mL) and deoxygenated via the freeze-pump-thaw method (3x). Under a flow of nitrogen,
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4
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5
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5
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5
5
5
5
5
6
CuSO • 5H O (0.820 g, 3.29 mmol) and sodium ascorbate (0.651 g, 3.29 mmol) were added, and
4
2
the reaction was then sealed and stirred overnight at room temperature. The crude mixture was
then filtered through celite with DCM, and the solvent was dried with sodium sulfate and
removed in vacuo. The product 8a was purified via silica gel flash chromatography (DCM,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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0
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2
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4
5
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0
-1
followed by EtOAc), and isolated as an orange oil (487 mg, 0.803 mmol, 61%). IR (cm ): 2942,
2
1
921, 2871, 2783, 2772, 2739, 2739, 1751, 1653, 1647, 1558, 1447, 1430, 1352, 1332, 1229,
1
108, 1098, 1064, 1030; H NMR (300 MHz, CDCl ):  = 9.20 (s, 2H), 8.96 (s, 2H), 8.32 (dd, J
3
= 10.2 Hz, J = 3.3 Hz, 2H), 7.88 (dd, J = 10.2 Hz, J = 3.3 Hz, 2H), 4.74 (t, J = 5.4 Hz, 4H), 4.04
13
(
t, J = 5.4 Hz, 4H), 3.68 (m, 8H), 3.57 (m, 9H), 3.25 (s, 6H); C NMR (100 MHz, CDCl ):  =
3
143.1, 142.0, 140.2, 130.5, 129.6, 128.6, 128.0, 126.4, 71.78, 70.77, 70.53, 70.50, 69.74, 58.9,
+
5
0.4; HRMS (EI) m/z: [M] Calcd for C H N O = 606.2914; Found = 606.2903.
30
38
8
6
1
,2,3,4-Tetrachloro-6,9-bis(1-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-
yl)phenazine (8c)
6
c (0.080 g, 0.22 mmol) and 7a (0.12 g, 0.66 mmol) were dissolved in a 5:1 THF:H O solution
2
(20 mL) and deoxygenated via the freeze-pump-thaw method (3x). Under a flow of nitrgoen,
CuSO • 5H O (0.14 g, 0.55 mmol) and sodium ascorbate (0.11 g, 0.55 mmol) were added, and
4
2
the reaction was then sealed and stirred overnight at room temperature. The crude mixture was
then filtered through celite with DCM, and the solvent was dried with sodium sulfate and
removed in vacuo. The product 8c was purified via silica gel flash chromatography (DCM
-1
followed by EtOAc) and isolated as a red oil (75 mg, 0.10 mmol, 46%). IR (cm ): 2904, 2883,
1
2
9
869, 2854, 1734, 1653, 1558, 1457, 1374, 1252, 1108, 1099; H NMR (400 MHz, CDCl ):  =
3
1
3
.15 (s, 2H), 8.98 (s, 2H), 4.70 (t, 4H), 4.00 (t, 4H), 3.64 (m, 8H), 3.49 (m, 8H), 3.21 (s, 6H); C
NMR (100 MHz, CDCl ):  = 141.8, 138.9, 136.4, 134.3, 131.4, 129.5, 128.2, 126.3, 71.86,
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+
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0.77, 70.56, 69.58, 59.0, 50.5; HRMS (EI) m/z: [M] Calcd for C H Cl N O = 742.1355;
30
34
4
8
6
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Found = 742.1333.
1,4-Bis(1-(2,5,8,11,15,18,21,24-octaoxapentacosan-13-yl)-1H-1,2,3-triazol-4-yl)phenazine (9a)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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5
6
7
8
9
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3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
6
a (48 mg, 0.21 mmol) and 7b (190 mg, 0.46 mmol) were stirred together in H O (1 mL) and
2
THF (5 mL). The solution was then deoxygenated via the freeze-pump-thaw method (3x). Under
a flow of nitrogen, Cu(PPh ) Br (0.020 g, 0.021 mmol) was added. The reaction was then sealed
3
3
under the inert atmosphere and stirred at 50˚C for 2 d. The reaction mixture was then extracted
with saturated aqueous NH Cl (25 mL) and DCM (5 x 25 mL), the organic fractions were
4
collected and dried over sodium sulfate, and the solvent was removed under reduced pressure.
Purification by silica gel chromatography (gradient elution, EtOAc → 20:1 EtOAc:MeOH →
-
1
1
1
8
0:1 EtOAc:MeOH) gave 9a as an orange oil (66 mg, 0.063 mmol, 30%). IR (cm ): 2870, 1717,
1
584, 1435, 1218, 1095, 851, 767; H NMR (300 MHz, CDCl ):  = 9.27 (s, 2H), 9.00 (s, 2H),
3
.32 (dd, J = 10.2 Hz, J = 3.3 Hz, 2H), 7.89 (dd, J = 10.2 Hz, J = 3.3 Hz, 2H), 5.09 (p, J = 6.0
1
3
Hz, 2H), 4.09 (d, J = 6.3 Hz, 8H), 3.70-3.40 (m, 48H), 3.30 (s, 12H); C NMR (75 MHz,
CDCl ):  = 143.2, 142.5, 140.8, 130.9, 130.1, 129.1, 128.6, 126.1, 72.15, 71.31, 70.88, 70.85,
3
+
7
0.76, 70.75, 70.63, 61.3, 59.3; HRMS (ESI) m/z: [M + H] Calcd for C H N O = 1047.5609;
50 79
8
16
Found = 1047.5618.
6
,9-Bis(1-(2,5,8,11,15,18,21,24-octaoxapentacosan-13-yl)-1H-1,2,3-triazol-4-yl)-1,2,3,4-
tetrafluorophenazine (9b)
6b (18 mg, 0.060 mmol) and 7b (61 mg, 0.15 mmol) were stirred together in H O (1 mL) and
2
THF (5 mL). The solution was then deoxygenated via the freeze-pump-thaw method (3x). Under
a flow of nitrogen, Cu(PPh ) Br (0.011 g, 0.012 mmol) was added. The reaction was then sealed
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4
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under the inert atmosphere and stirred at 50˚C for 2 d. The reaction mixture was then extracted
with saturated aqueous NH Cl (25 mL) and DCM (5 x 25 mL), the organic fractions were
4
collected and dried over sodium sulfate, and the solvent was removed under reduced pressure.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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4
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Purification by silica gel chromatography (gradient elution, EtOAc → 20:1 EtOAc:MeOH →
-
1
1
1
5
1
7
0:1 EtOAc:MeOH) gave 9b as a red oil (18 mg, 0.016 mmol, 27%). IR (cm ): 2923, 2856,
1
737, 1456, 1260, 1092, 198, 464; H NMR (300 MHz, CDCl ):  = 9.24 (s, 2H), 9.15 (s, 2H),
3
.11 (p, J = 6.0 Hz, 2H), 4.09 (d, J = 6.3 Hz, 8H), 3.70-3.55 (m, 41H), 3.48 (m, 8H), 3.33 (s,
1
3
2H); C NMR (75 MHz, CDCl ):  = 142.4, 140.4, 130.3, 129.3, 126.0, 72.22, 71.36, 70.93,
3
0.91, 70.81, 70.59, 61.4, 59.3 (the carbons next to the fluorine atoms could not be identified);
1
9
F NMR (400 MHz, CDCl ):  = -150.88 (dd, J = 16.2 Hz, J = 3.6 Hz, 2F), -152.06 (dd, J = 15.0
3
+
Hz, J = 3.0 Hz, 2F); HRMS (ESI) m/z: [M + H] Calcd for C H F N O = 1119.5232; Found =
50
75
4
8
16
1
119.5230.
Supporting Information. Copies of NMR spectra. This material is available free of charge via
the Internet at http://pubs.acs.org.
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8
9
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