Fluorescent dyad for cooperative recognition of copper cation and halogen anion

Article abstract of DOI:10.1016/j.tetlet.2013.01.119

TMS-ethynyl triazolyl benzothiadiazole (BTD) derivatives have been successfully synthesized by mono deprotection of di-TMS-ethynyl BTD followed by click chemistry. The fluorescence intensity of TMS-ethynyl triazolyl BTD-DCM dyad 8, as well as triazolyl BTD 3, and the DCM derivative 7 could be selectively quenched by Cu²⁺, but almost not affected by different tested anions. Interestingly, the fluorescence emission of DCM-based fluorophores 7 and 8 was highly sensitive to a combination of Cu²⁺, F^-, or Br^- in a sequence dependent manner. With the dyad 8, the detection limit as low as 0.13 ppb could be attained for F^- in MeCN. The Cu²⁺-promoted aerobic oxidative dimerization of DCM moiety to tetrahydrofuran derivatives has also been demonstrated for the first time.

Full text of DOI:10.1016/j.tetlet.2013.01.119

Tetrahedron Letters 54 (2013) 1877–1883
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Fluorescent dyad for cooperative recognition of copper cation
and halogen anion
Yanhua Yu a,b, Nicolas Bogliotti a, Stéphane Maisonneuve a, Jie Tang b, Juan Xie a,
⇑
a PPSM, ENS Cachan, CNRS, UMR8531, 61 Avenue du Président Wilson, 94235 Cachan Cedex, France
b Institute of Medicinal Chemistry, Department of Chemistry, East China Normal University, Shanghai 200062, China
a r t i c l e i n f o
a b s t r a c t
Article history:
TMS-ethynyl triazolyl benzothiadiazole (BTD) derivatives have been successfully synthesized by mono
deprotection of di-TMS-ethynyl BTD followed by click chemistry. The fluorescence intensity of TMS-ethy-
nyl triazolyl BTD–DCM dyad 8, as well as triazolyl BTD 3, and the DCM derivative 7 could be selectively
quenched by Cu2+, but almost not affected by different tested anions. Interestingly, the fluorescence emis-
sion of DCM-based fluorophores 7 and 8 was highly sensitive to a combination of Cu2+, FÀ, or BrÀ in a
sequence dependent manner. With the dyad 8, the detection limit as low as 0.13 ppb could be attained
for FÀ in MeCN. The Cu2+-promoted aerobic oxidative dimerization of DCM moiety to tetrahydrofuran
derivatives has also been demonstrated for the first time.
Received 28 November 2012
Revised 24 January 2013
Accepted 28 January 2013
Available online 4 February 2013
Keywords:
Dicyanomethylene-4H-pyran (DCM)
Benzothiadiazole
Fluorescence
Ó 2013 Elsevier Ltd. All rights reserved.
Chemodosimeter
Click chemistry
The development of fluorescent chemosensors and chemodosi-
meters for sensing environmentally or biologically important me-
tal ions and anions has gained considerable attention in recent
years.1 For example, fluorescent sensors for Cu2+ have been exten-
sively investigated as it is a significant metal pollutant due to its
wide industrial use, and it is also implicated in various biological
activities as enzyme cofactors, in neurogenerative diseases and
oxidative stress.2 Most Cu2+ chemosensors (chelation-based pro-
bes1b) are based on PET (photoinduced electron transfer)/EET (elec-
tron energy transfer) mechanisms. Chemodosimeters (reaction-
based probes1b) for Cu2+ by oxidation of aromatic amine3 or phenol
derivatives,4 and hydrolysis5 have been recently reported. On the
other hand, FÀ triggered Si–O bond cleavage has been used for
the design of fluoride specific chemodosimeters.6 However, the de-
sign of chemosensors for the detection of both cation and anion is
more challenging.4b
around 370 nm. Such a spectroscopic property is favorable to en-
ergy transfer between these two fluorophores. As a continuing
interest in the development of fluorescent molecules,9 we envi-
sioned to conjugate these two fluorophores with the click chemis-
try to prepare the dyad 8 with the trimethylsilyl (TMS) group on
the BTD moiety so as to study their sensing properties toward var-
ious cations and anions. Such a system may exhibit the phenome-
non of fluorescence resonance energy transfer from BTD to DCM.
The triazolyl BTD 3 was synthesized for comparison.
4,7-Di-trimethylsilylethynyl benzothiadiazole 110 can be mono
desilylated with a catalytic amount of KOH in MeOH to 2 (Scheme 1).
Copper-catalyzed Huisgen [3+2] cycloaddition11 of the crude 2 with
ethyl 3-azidopropanoate led to compound 312 in 62% yield for two
steps. The azido functionalized DCM 7 was prepared by condensa-
tion of tert-butyl DCM 613 with the azido aldehyde 5 which was
obtained by mesylation of the hydroxy aldehyde 4 followed by sub-
stitution with NaN3 in DMF at 90 °C. The (E)-isomer was obtained in
75% yield. Click reaction of 714 with the monotrimethylsilyl ethynyl
BTD 2 led to the target compound 815 in 46% for two steps.
As expected, compounds 3 and 7 displayed the usual photo-
physical properties of BTD (kemission = 498 nm when excited at
370 nm, Fig. 1 and S1) and DCM (kemission = 615 nm when excited
at max. absorption of 457 nm, Fig. 2 and S2), while the dyad 8 dis-
plays an emission band of DCM fluorophore (605 nm, Fig. 3) when
excited at 370 nm (absorption of BTD, Fig. S3), as a consequence of
the energy transfer from BTD to DCM moiety (Fig. S4). The fluores-
cence quantum yield (UF) for 3 and 7 was determined to be 0.79
and 0.30 with reference to quinine sulfate in MeCN, with a molar
Dicyanomethylene-4H-pyran (DCM) derivatives, thanks to their
excellent optical-electronic properties (red light emission, high
fluorescent yield, and good photostability), have been investigated
for OLED emitters, logic gates, optical chemosensors and bioimag-
ing.7 Benzothiadiazole (BTD) derivatives have also been used in the
development of organic light-emitting materials or fluoroiono-
phores for Ni2+ and Cu2+ 8
. DCM derivatives have absorption near
450–500 nm and emission around 600–650 nm; while the emis-
sion band of BTD derivatives appears near 500 nm when excited
⇑
Corresponding author.
E-mail address: joanne.xie@ens-cachan.fr (J. Xie).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.01.119

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Y. Yu et al. / Tetrahedron Letters 54 (2013) 1877–1883
extinction coefficient of 11,800 and 43,000 molÀ1 L cmÀ1, respec-
S
S
N
N
N
N
tively. The molar extinction coefficient was found to be
40,700 molÀ1 L cmÀ1 for compound 8. To get an insight into the
binding properties of compounds 3, 7, and 8, we first investigated
absorption and emission changes upon addition of 8 equiv of
selected cations and anions in MeCN. Through deprotection of
the TMS group, FÀ induces a slight fluorescence quenching of
compounds 3 and 8, associated with a slight blue shift from 496
to 489 nm in the case of compound 3. No influence on fluorescence
emission was observed with other tested anions on 3, 7, and 8
(Figs. 1–3).
KOH cat
MeOH
Me3Si
SiMe3
H
SiMe3
1
2
CuSO4
Na ascorbate
CH2Cl2, H2O
N3
62%
EtO2C
S
N
N
N
N
N
SiMe3
EtO2C
3
Among the metal cations tested, Cu2+, Ni2+, and to a lower
extent Hg2+, Co2+ and Fe2+ induced a significant decrease in fluores-
cence intensity in 3 (Fig. 1). For DCM derivative 7, the presence of
Cu2+ resulted in a complete quenching of fluorescence, while Fe2+
and Hg2+ induced a decrease of fluorescence intensity to ca. 75%
and 60% of their initial value, respectively (Fig. 2). In the case of
dyad 8, addition of Cu2+ immediately resulted in a discoloration
of the solution, associated with the apparition of the characteristic
fluorescence of BTD around 490 nm (Fig. 3). Moreover, the max.
absorption band of the DCM fluorophore at 457 nm disappeared
upon addition of Cu2+ to compounds 7 and 8 (Figs. S2 and S3).
Among other metal cations tested, the most notable effects were
exhibited by Ni2+, Fe2+, and Hg2+, resulting in a ca. 50–70% quench-
ing of fluorescence.
OHC
1) MsCl, Et3N, CH2Cl2
OHC
OH
2) NaN3, DMF, 90 °C
99%
N3
N
Me
N
Me
5
4
NC CN
NC CN
piperidine
+ 5
Ar, MeCN, Δ
tBu
O
tBu
O
75%
N3
N
Me
7
6
2, CuSO4
Na ascorbate
CH2Cl2, H2O
46%
NC CN
Having established the selectivity of ion recognition by fluoro-
phores 3, 7, and 8, our interest then focused on studying the effect
of combining cations and anions. Our choice turned to Cu2+ as a
cation, since it affects both DCM and BTD moieties. FÀ (which in-
duces TMS-alkyne deprotection) and BrÀ (inert) were selected as
anions, on the basis of their ability to form stable complexes of
S
N
N
N
tBu
O
N
N
SiMe3
N
Me
8
Scheme 1. Synthesis of fluorophores 3, 7, and dyad 8.
Figure 1. Fluorescence intensity ratio (left) and emission spectra (right) of 3 (10 lM in MeCN) after addition of 8 equiv ions (kex = 370 nm).

Y. Yu et al. / Tetrahedron Letters 54 (2013) 1877–1883
1879
Figure 2. Fluorescence intensity ratio (left) and emission spectra (right) of 7 (10 lM in MeCN) after addition of 8 equiv ions (kex = 457 nm).
Figure 3. Fluorescence intensity ratio (left) and emission spectra (right) of 8 (10 lM in MeCN) after addition of 8 equiv ions (kex = 370 nm).

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Y. Yu et al. / Tetrahedron Letters 54 (2013) 1877–1883
Figure 4. Emission spectra of 7 (top; 10 lM in MeCN, kex = 457 nm) and 3 (bottom; 10 lM in MeCN, kex = 370 nm) after addition of 1 equiv Cu(ClO4)2, Bu4NF and/or Bu4NBr.
the type [Cu(X)n](2Àn)+ in MeCN, characterized by association con-
stants in the range of 107–1015 16 Addition of 1 equiv Cu2+ to 3 in-
[Cu]2+
S
S
1 equiv.
Cu2+
N
N
N N
.
N
N
N
N
N
N
duced a ca. twofold decrease in fluorescence emission intensity,
which further diminished when another equiv Cu2+ was added to
the solution (Fig. 4c). This behavior is in agreement with the results
reported by Bunz for similar triazolyl-containing ion sensors.17 In
contrast, when 1 equiv FÀ or BrÀ was introduced after 1 equiv
Cu2+, fluorescence intensity was restored to ca. 80–90% of its initial
level. Interestingly, when halide ion addition preceded Cu2+, the
fluorescence intensity remained almost unchanged (Fig. 4d). Such
a behavior presumably originates from the Cu2+ complexation
between a nitrogen atom of BTD and N(3) of triazole leading to
complex [3ÁCu] (Scheme 2), as evidenced by Job’s plot indicating
a 1:1 binding stoichiometry (Fig. S5).18,19 Fluorescence titration
provided a stability constant log K = 5.17 0.03 MÀ1 in MeCN (Figs.
S6 and S7). Subsequent halide addition results in the formation of
complexes of the type [3ÁCuX], with de-coordination of one of the
N-atoms. Further halide addition results in the regeneration of 3
and the formation of species of the type [Cu(X)n](2Àn)+ (Figs. S8
and S9). Conversely, the presence of halide ions prior to Cu2+ addi-
tion presumably prevents formation of [3ÁCu] (through formation
of [Cu(X)n](2Àn)+), as revealed by the conservation of optical
properties.
TMS
TMS
R
R
[3.Cu]
3 R = (CH2)2CO2Et
1 equiv. X–
[CuX2]
1 equiv. X–
X
X
[Cu]+
N
[Cu]+
S
N
S
N
N
N
N
N
N
N
N
and/or
TMS
TMS
R
R
[3.CuX]
[3.CuX]
Scheme 2. Proposed mechanism for the effect of Cu2+ and halide ions on 3.
acid.20 Epoxidation of C–C double bond has been observed as a side
reaction during the oxidation of phenothiazine derivatives with
Cu(NO3)2 in CH2Cl2 under sonication.21 We then decided to isolate
the oxidation product by treating compound 7 with 1 equiv
Cu(ClO4)2 during 5 min in MeCN.22 Tetrahydrofurans 9a and 9b
were isolated as a complex mixture of regio and stereoisomers in
20% yield (Scheme 3), as confirmed by HRMS data (Fig. S18). For-
Addition of Cu2+ to the solution of the DCM derivative 7 resulted
in an instantaneous and complete extinction of fluorescence,
which was only very weakly recovered after halide ion addition
(Fig. 4a). This result cannot be explained by a simple complexation
mechanism as in the case of 3. The disappearance of the DCM
absorbance at 457 nm (Fig. S2) indicated a structural modification
induced by Cu2+. Copper-catalyzed aerobic oxidation has been ob-
served with aromatic amine,3 phenol4 as well as hydroxamic
+
mation of Cu(MeCN)4 complex has been considered as a part of
driving force of Cu2+-mediated oxidation in MeCN.3c In 1H NMR,
four signals of tetrahydrofuran CH–O protons were observed at
5.07, 5.22, 5.33, and 5.47 ppm which could correspond to two dia-
stereoisomers of 9a and 9b, with the corresponding CHb protons at
3.57, 3.62, 3.76, and 3.84 ppm (Fig. S17). This oxidation reaction
was further confirmed by the observation that when Cu2+ was

Y. Yu et al. / Tetrahedron Letters 54 (2013) 1877–1883
1881
Scheme 3. Cu2+-mediated aerobic oxidation of 7.
Figure 5. Emission spectra of 8 (10 lM in MeCN) after addition of 1 equiv Cu(ClO4)2, Bu4NF and/or Bu4NBr. kex = 370 nm.
added to a degassed solution of 7 in MeCN under inert atmosphere,
no reaction occurred during at least 30 min, as revealed by the ab-
sence of discoloration of the orange solution. Furthermore, the
presence of FÀ or BrÀ in the solution prior to Cu2+ maintained a sig-
nificantly high fluorescence intensity (ca. 70–90% of the blank va-
lue; Fig. 4b), so preventing 7 from air oxidation, presumably
through the formation of the complex [Cu(X)n](2Àn)+. To the best
of our knowledge, oxidation of DCM derivatives by Cu2+ to tetrahy-
drofuran derivative has never been reported before.
For dyad 8, addition of 1 equiv Cu2+ followed by FÀ resulted in a
complete extinction of fluorescence, while BrÀ led to a conserva-
tion of BTD emission around 490 nm, when excited at 370 nm (
Fig. 5). In contrast, addition of FÀ before Cu2+ induced only a slight
reduction of fluorescence intensity at ca. 600 nm, while addition of
Cu2+ after BrÀ leads to partial quenching of DCM fluorescence with
concomitant partial appearance of fluorescence emission of BTD
around 490 nm. Such a behavior is presumably the consequence
of a competition between formation of complexes of the type
[Cu(X)n](2Àn)+ and DCM oxidative cyclization. Introduction of BrÀ
after Cu2+ has no detectable influence compared to Cu2+ ion alone,
whereas FÀ leads to complete quenching of fluorescence of BTD
moiety, revealing a modification of the BTD moiety though the pre-
cise mechanism remains to be elucidated. Figure 6 shows the color
change of 8 in the presence of FÀ, BrÀ, and Cu2+ and combinations
of both cation and halide ion. Spectral titration of 8 in the presence
of increasing concentrations of Cu2+ (Fig. S10) showed a limit of
Figure 6. Color (up) and fluorescence (bottom) changes of compound 8 in MeCN,
after addition (1 equiv each) of FÀ, Cu2+, FÀ then Cu2+, Cu2+ then FÀ, BrÀ, BrÀ then
Cu2+, and Cu2+ then BrÀ, upon excitation at 365 nm.
detection of 1.31 (kem 608/486 nm) to 2.28 ppb (kem 486/608 nm)
in MeCN. Titration of a solution of 8 and BrÀ (1 equiv) with Cu2+
displayed a detection limit of 69.0 (kem 605/490 nm) to 88.2 ppb
(kem 490/605 nm) (Fig. S11). Notably, compound 8 had a detection
limit for FÀ that reached 0.13 ppb with prior addition of 1 equiv
Cu2+ (Fig. S12).

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Y. Yu et al. / Tetrahedron Letters 54 (2013) 1877–1883
(30 mL), washed with water (30 mL) and brine (30 mL), dried over MgSO4,
In summary, a new TMS-ethynyl triazolyl BTD–DCM dyad 8 was
filtered, and concentrated. To the solid dissolved in CH2Cl2 (10 mL) and H2O
(1 mL), were added ethyl 3-azidopropanoate (87 mg, 0.61 mmol), CuSO4Á5H2O
(25 mg, 0.1 mmol) and Na ascorbate (40 mg, 0.2 mmol). The reaction mixture
was vigorously stirred at rt for 12 h, then CH2Cl2 (20 mL) was added. The
solution was washed with water (30 mL), dried over MgSO4, filtered, and
synthesized by click chemistry. This compound, together with the
model compounds TMS-ethynyl triazolyl BTD 3 and the DCM
derivative 7 exhibited a selective fluorescence quenching in the
presence of Cu2+, with few sensibility toward tested anions. How-
ever, the fluorescence emission of DCM-based compounds 7 and 8
is highly sensitive to a combination of Cu2+, FÀ, and/or BrÀ in a
sequence- and halide-dependent way, with an excellent detection
limit for Cu2+ and FÀ. We have also demonstrated for the first time
the Cu2+-promoted aerobic oxidative dimerization of DCM moiety
to tetrahydrofuran derivatives, leading to the quenching of the
DCM’s fluorescence.
concentrated to
a solid which was purified by column chromatography
(petroleum ether/EtOAc: 10/1) to afford compound 3 (250 mg, 62%). TLC:
Rf = 0.36 (petroleum ether/EtOAc: 15/1). mp 124 °C. 1H NMR (400 MHz, CDCl3):
d = 8.84 (s, 1H, CH), 8.50 (d, J = 7.4 Hz, 1H, CH), 7.88 (d, J = 7.4 Hz, 1H, CH), 4.79
(t, J = 6.4 Hz, 2H, CH2), 4.17 (q, J = 7.2 Hz, 2H, CH2), 3.06 (t, J = 6.4 Hz, 2H, CH2),
1.25 (t, J = 7.2 Hz, 3H, CH3) 0.34 (s, 9H, Si(CH3)3), 13C NMR (100 MHz, CDCl3):
d = 170.4, 154.9, 151.4, 142.8, 134.2, 125.1, 123.9, 115.8, 102.2, 100.3, 61.3,
45.8, 34.8, 14.1, 0.0; IR (KBr): 2146, 1729, 1591 cmÀ1
C
. HRMS (ESI) for
18H22N5O2SSi [M+H]+: calcd 400.1263, found: 400.1263.
13. Yao, Y.-S.; Xiao, J.; Wang, X.-S.; Deng, Z.-B.; Zhang, B.-W. Adv. Funct. Mater.
2006, 16, 706–718.
14. Synthesis of 7. To a stirred solution of 513 (6.02 g, 0.029 mol) and 6 (6.32 g,
0.029 mol) in distilled MeCN (60 mL) under argon, was added piperidine
(3.9 mL, 0.039 mol). The mixture was refluxed for 3–4 h (monitoring by TLC)
and cooled to rt. The filtered precipitate was washed with cold MeCN (10–
20 mL) and cyclohexane (200–400 mL). The filtrate was evaporated under
Acknowledgment
We thank Yi-Bin Ruan for helpful discussions.
vacuum and the residue triturated with
a minimum of cold MeCN and
Supplementary data
filtered. Combination of the two solids afforded 7 (8.79 g, 75%) as an orange-
red solid. A portion of 7 (6.2 g) was recrystallized from MeCN (110 mL). TLC:
Rf = 0.33 (petroleum ether/EtOAc: 7/3). mp 156 °C. 1H NMR (400 MHz,
CDCl3): d = 7.45 (d, J = 8.7 Hz, 2H, Ph), 7.34 (d, J = 15.6 Hz, 1H, CH@), 6.73
(d, J = 8.7 Hz, 2H, Ph), 6.61 (d, J = 1.8 Hz, 1H, CH@), 6.53 (d, J = 1.8 Hz, 1H,
CH@), 6.53 (d, J = 1.8 Hz, 1H, CH@), 6.51 (d, J = 16.0 Hz, 1H, CH@), 3.63 (t,
J = 6.0 Hz, 2H, CH2), 3.51 (t, J = 5.7 Hz, 2H, CH2), 3.11 (s, 3H, N-Me), 1.38 (s,
9H, tBu). 13C NMR (100 MHz, CDCl3): d = 172.0, 160.1, 156.9, 150.3, 138.2,
129.9, 123.2, 115.84, 115.77, 113.6, 112.1, 105.8, 102.5, 77.2, 58.2, 51.6, 49.0,
Supplementary data (experimental procedures, spectroscopic
data and copies of NMR spectra for all new compounds) associated
with this article can be found, in the online version, at http://
dx.doi.org/10.1016/j.tetlet.2013.01.119.
C
23H24N6ONa [M+Na]+ 423.1904, found:
References and notes
39.0, 36.8, 28.2. HRMS (ESI) for
423.1903.
15. Synthesis of 8. To a solution of 110 (200 mg, 0.61 mmol) in MeOH (15 mL) was
1. (a) Callan, J. F.; de Silva, A. P.; Magri, D. C. Tetrahedron 2005, 61, 8551–8588; (b)
Quang, D. T.; Kim, J. S. Chem. Rev. 2010, 110, 6280–6301; (c) Kaur, K.; Saini, R.;
Kumar, A.; Luxami, V.; Kaur, N.; Singh, P.; Kumar, S. Coord Chem. Soc. Rev. 2012,
256, 1992–2028; (d) Du, J.; Hu, M.; Fan, J.; Peng, X. Chem. Soc. Rev. 2012, 41,
4511–4535; (e) Chen, X.; Zhou, G.; Peng, X.; Yoon, J. Chem. Soc. Rev. 2012, 41,
4610–4630; (f) Chen, X.; Pradhan, T.; Wang, F.; Kim, J. S.; Yoon, J. Chem. Rev.
2012, 112, 1910–1956; (g) Jeong, Y.; Yoon, J. Inorg. Chim. Acta 2012, 381, 2–14;
(h) Wu, J.; Liu, W.; Ge, J.; Zhang, H.; Wang, P. Chem. Soc. Rev. 2011, 40, 3483–
3495.
2. Barnham, K. J.; Masters, C.; Bush, A. I. Nat. Rev. Drug Disc. 2004, 3, 205–214.
3. (a) Lin, W.; Long, L.; Chen, B.; Tan, W.; Gao, W. Chem. Commun. 2010, 46, 1311–
1313; (b) Wang, D.; Shiraishi, Y.; Hirai, T. Chem. Commun. 2011, 47, 2673–2675;
(c) Ajayakumar, G.; Sreenath, K.; Gopidas, K. R. Dalton Trans. 2009, 1180–1186;
(d) Jo, J.; Lee, H. Y.; Liu, W.; Olasz, A.; Chen, C.-H.; Lee, D. J. Am. Chem. Soc. 2012,
134, 16000–16007; (e) Li, J.; Zeng, Y.; Hu, Q.; Yu, X.; Guo, J.; Pan, J. Dalton Trans.
2012, 41, 3623–3626.
4. (a) Kennedy, D.; Kormos, C. M.; Burdette, S. C. J. Am. Chem. Soc. 2009, 131, 8578–
8586; (b) Senthilvelan, A.; Ho, I.-T.; Chang, K.-C.; Lee, G.-H.; Liu, Y.-H.; Chung,
W.-S. Chem. Eur. J. 2009, 15, 6152–6160.
5. (a) Yu, M.-M.; Li, Z.-X.; Wei, L.-H.; Tang, M.-S. Org. Lett. 2008, 10, 5115–5118;
(b) Zhao, C.; Feng, P.; Cao, J.; Wang, X.; Yang, Y.; Zhang, Y.; Zhang, J.; Zhang, Y.
Org. Biomol. Chem. 2012, 10, 3104–3109; (c) Kumar, M.; Kumar, N.; Bhalla, V.;
Sharma, P. R.; Kaur, T. Org. Lett. 2012, 14, 406–409; (d) Li, N.; Xiang, Yu; Tong, A.
Chem. Commun. 2010, 46, 3363–3365.
added 1 M aqueous KOH (30 lL), and the mixture was stirred at rt under argon
over night. After evaporation of the solvent, the residue was dissolved in EtOAc
(30 mL), washed with water (30 mL) and brine (30 mL), dried over MgSO4,
filtered, and concentrated. To the solid dissolved in CH2Cl2 (10 mL) and H2O
(1 mL) were added 7 (243 mg, 0.61 mmol), CuSO4Á5H2O (25 mg, 0.1 mmol) and
Na ascorbate (40 mg, 0.2 mmol). The reaction mixture was vigorously stirred at
rt for 12 h, then CH2Cl2 (20 mL) was added. The solution was washed with
water (30 mL), dried over MgSO4, filtered, and concentrated to a solid which
was purified by column chromatography (petroleum ether/EtOAc/CH2Cl2: 3/3/
1) to afford 8 (300 mg, 46%) as a red solid. TLC: Rf = 0.34 (petroleum ether/
EtOAc: 2/1). mp 132 °C. 1H NMR (400 MHz, CDCl3): d = 8.65 (s, 1H, CH), 8.50 (d,
J = 7.4 Hz, 1H, CH), 7.88 (d, J = 7.4 Hz, 1H, CH), 7.42 (d, J = 8.7 Hz, 2H, Ph), 7.30
(d, J = 16.0 Hz, 1H, CH), 6.71 (d, J = 8.7 Hz, 2H, Ph), 6.60 (d, J = 2.3 Hz, 1H, CH@),
6.53 (d, J = 2.3 Hz, 1H, CH@), 6.47 (d, J = 16.0 Hz, 1H, CH@), 4.71 (m, 2H, CH2),
4.05 (m, 2H, CH2), 2.94 (s, 3H, CH3), 1.37 (s, 9H, 3 Â CH3), 0.34 (s, 9H, Si(CH3)3).
13C NMR (100 MHz, CDCl3): d = 172.0, 159.9, 156.8, 155.0, 151.4, 149.8, 143.1,
137.9, 134.2, 129.9, 125.2, 125.1, 123.6, 123.5, 116.0, 115.7, 115.6, 113.9, 112.2,
105.9, 102.5, 100.2, 58.3, 52.7, 47.8, 39.0, 36.7, 28.1, 0.0. IR (KBr): 2207, 1642,
1597, 1548 cmÀ1. HRMS (ESI) for C36H37N8OSSi [M+H]+: calcd 657.2580, found:
657.2571.
16. Studies regarding the formation of Cu(II)-halide complexes in MeCN: (a) Sestili,
L.; Furlani, C.; Ciana, A.; Garbassi, F. Electrochim. Acta 1970, 15, 225–235; (b)
Barnes, J. H.; Hume, D. N. Inorg. Chem. 1963, 2, 444–448; (c) Manahan, S. E.;
Iwamoto, R. T. Inorg. Chem. 1965, 4, 1409–1413; (d) Ukpong, E. J.; Akpanudo, N.
W.; Prasad, J. Afr. J. Pure Appl. Chem. 2010, 4, 38–43; In other solvents: (e) Dali,
S.; Benghanem, F.; Khan, M. A.; Meullemeestre, J.; Vierling, F. Polyhedron 1991,
10, 2529–2533; (f) Khan, M. A.; Meullemeestre, J.; Schwing, M. J.; Vierling, F.
Inorg. Chem. 1989, 28, 3306–3309; (g) Ichihashi, M.; Wakita, H.; Mibuchi, T.;
Masuda, I. Bull. Chem. Soc. Jpn. 1982, 55, 3160–3164; (h) Barnes, J. C.; Hume, D.
N. J. Phys. Chem. 1963, 67, 526; (i) Mesaric, S. S.; Hume, D. N. Inorg. Chem. 1963,
2, 1063–1064.
17. (a) Bryant, J. J.; Lindner, B. D.; Bunz, U. H. F. J. Org. Chem. Article ASAP, http://
dx.doi.org/10.1021/jo3024889.; (b) Brombosz, S. M.; Appleton, A. L.; Zappas, A.
J., II; Bunz, U. H. F. Chem. Commun. 2010, 46, 1419–1421; (c) Bryant, J. J.; Zhang,
Y.; Lindner, B. D.; Davey, E. A.; Appleton, A. L.; Qian, X.; Bunz, U. H. F. J. Org.
Chem. 2012, 77, 7479–7486.
18. Examples of copper complexes of BTD: (a) Papaefstathiou, G. S.; Tsohos, A.;
Raptopoulou, C. P.; Terzis, A.; Psycharis, V.; Gatteschi, D.; Perlepes, S. P. Cryst.
Growth Des. 2001, 1, 191–194; (b) Munakata, M.; He, H.; Kuroda-Sowa, T.;
Maekawa, M.; Suenaga, Y. J. Chem. Soc., Dalton Trans. 1998, 1499–1502; (c)
Munakata, M.; Kuroda-Sowa, T.; Maekawa, M.; Nakamura, M.; Akiyama, S.;
Kitagawa, S. Inorg. Chem. 1994, 33, 1284–1291.
19. Examples of copper complexes of 1,2,3-triazole: (a) Tamanini, E.; Rigby, S. E. J.;
Motevalli, M.; Todd, M. H.; Watkinson, M. Chem. Eur. J. 2009, 15, 3720–3728;
(b) Donnelly, P. S.; Zanatta, S. D.; Zammit, S. C.; White, J. M.; Williams, S. J.
Chem. Commun. 2008, 2459–2461; (c) Wu, T.; Li, M.; Li, D.; Huang, X.-C. Cryst.
Growth Des. 2008, 8, 568–574; (d) Garcia, L.; Maisonneuve, S.; Xie, J.; Guillot, R.;
Dorlet, P.; Rivière, E.; Desmadril, M.; Lambert, F.; Policar, C. Inorg. Chem. 2010,
49, 7282–7288.
6. (a) Zhu, B.; Yuan, F.; Li, R.; Li, Y.; Wei, Q.; Ma, Z.; Du, B.; Zhang, X. Chem.
Commun. 2011, 47, 7098–7100; (b) Lu, H.; Wang, Q.; Li, Z.; Lai, G.; Jiang, J.; Shen,
Z. Org. Biomol. Chem. 2011, 9, 4558–4562; (c) Sokkalingam, P.; Lee, C.-H. J. Org.
Chem. 2011, 76, 3820–3828; (d) Perry-Feigenbaum, R.; Sella, E.; Shabat, D.
Chem. Eur. J. 2011, 17, 12123–12128.
7. Guo, Z.; Zhu, W.; Tian, H. Chem. Commun. 2012, 48, 6073–6084.
8. (a) Fang, Q.; Xu, B.; Jiang, B.; Fu, H. T.; Chen, X. Y.; Cao, A. Chem. Commun. 2005,
1468–1470; (b) Maisonneuve, S.; Fang, Q.; Xie, J. Tetrahedron 2008, 64, 8716–
8720; (c) Ruan, Y.-B.; Maisonneuve, S.; Li, C.; Tang, J.; Xie, J. Front. Chem. Chin.
2010, 5, 208–213; (d) Garcia, L.; Maisonneuve, S.; Oudinet-Sin Marcu, J.;
Guillot, R.; Lambert, F.; Xie, J.; Policar, C. Inorg. Chem. 2011, 50, 11353–11362.
9. (a) David, O.; Maisonneuve, S.; Xie, J. Tetrahedron Lett. 2007, 48, 6527–6530; (b)
Xie, J.; Ménand, M.; Maisonneuve, S.; Métivier, R. J. Org. Chem. 2007, 72, 5980–
5982; (c) Ruan, Y. B.; Li, C.; Tang, J.; Xie, J. Chem. Commun. 2010, 46, 9220–9222;
(d) Li, C.; Henry, E.; Mani, N. K.; Tang, J.; Brochon, J.-C.; Deprez, E.; Xie, J. Eur. J.
Org. Chem. 2010, 2395–2405; (e) Ruan, Y. B.; Xie, J. Tetrahedron 2011, 67, 8717–
8723; (f) Ruan, Y. B.; Maisonneuve, S.; Xie, J. Dyes Pigment 2011, 90, 239–244;
(g) Yi, H.; Maisonneuve, S.; Xie, J. Synthesis 2012, 44, 1647–1656; (h) Tang, Y.-
H.; Qu, Y.; Song, Z.; He, X.-P.; Xie, J.; Hua, J.; Chen, G.-R. Org. Biomol. Chem. 2012,
10, 555–560.
10. DaSilveira Neto, B. A.; Sant’ Ana Lopes, A.; Ebeling, G.; Gonçalves, R. S.; Costa, V.
E. U.; Quina, F. H.; Dupont, J. Tetrahedron 2005, 61, 10975–10982.
11. (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004–
2021; (b) Tornoe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67,
3057–3064.
12. Synthesis of 3. To a solution of 110 (200 mg, 0.61 mmol) in MeOH (15 mL) was
20. Frazier, C. P.; Engelking, J. R.; Read de Alaniz, J. J. Am. Chem. Soc. 2011, 133,
10430–10433.
added 1 M aqueous KOH (30
over night. After evaporation of the solvent, the residue was dissolved in EtOAc
lL), and the mixture was stirred at rt under argon

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1883
21. Ga˘ina˘, L.; Csámpai, A.; Túrós, G.; Lovász, T.; Zsoldos-Mády, V.; Silberg, I. A.;
Sohár, P. Org. Biomol. Chem. 2006, 4, 4375–4386.
layers were dried over MgSO4, evaporated to give a yellow solid which was
purified by column chromatography (petroleum ether/EtOAc: 2/1) to afford
10 mg of 9a and 9b (20%) as a light yellow solid. 1H and 13C NMR indicated a
complex mixture of four regio- and diastereoisomers (Fig. S17). TLC: Rf = 0.34
(petroleum ether/EtOAc: 1/1). HRMS (ESI) for
817.4045, found: 817.4043.
22. Oxidation of 7. To a solution of 7 (50 mg, 0.125 mmol) in 3 mL MeCN was added
Cu(ClO4)2Á6H2O (46 mg, 0.125 mmol). After stirring at rt for 5 min, the solvent
was removed under vacuum to give a green solid which was exclusively
soluble in MeCN. The green solid was dissolved in 5 mL MeCN, washed with
1 M EDTA, then extracted with EtOAc (2 Â 20 mL). The combined organic
C
46H49N12O3 [M+H]+: calcd