Monofunctionalized pillar[5]arene as a host for alkanediamines

Article abstract of DOI:10.1021/ja111418j

Alkanediamines serve as neutral guests for the recently discovered host pillar[5]arene. The proposed [2]pseudorotaxane nature of the superstructure of the 1:1 host-guest complexes is supported by the template-directed synthesis of a related [2]rotaxane. A

Full text of DOI:10.1021/ja111418j

COMMUNICATION
pubs.acs.org/JACS
Monofunctionalized Pillar[5]arene as a Host for Alkanediamines
Nathan L. Strutt,† Ross S. Forgan,† Jason M. Spruell,† Youssry Y. Botros,†,‡,§,|| and J. Fraser Stoddart*,†
†Department of Chemistry and ‡Department of Materials Science and Engineering, Northwestern University, 2145 Sheridan Road,
Evanston, Illinois, 60208, United States
§Intel Labs, Building RNB-6-61, 2200 Mission College Boulevard, Santa Clara, California 95054, United States
National Center for Nano Technology Research, King Abdulaziz City for Science and Technology, P.O. Box 6086, Riyadh 11442,
Kingdom of Saudi Arabia
S Supporting Information
b
these compounds has largely been performed using mass
spectrometry.16 For these and other reasons, we decided to
ABSTRACT: Alkanediamines serve as neutral guests for
the recently discovered host pillar[5]arene. The proposed
[2]pseudorotaxane nature of the superstructure of the 1:1
host-guest complexes is supported by the template-direc-
ted synthesis of a related [2]rotaxane. A synthetic route to
monofunctional pillar[5]arenes has also been developed,
allowing for the creation of a fluorescent sensor for alkyl-
amine binding. The precursors to this host could act as
starting points for a large library of monofunctional pillar-
[5]arene macrocycles.
investigate the ability of pillar[5]arenes to both encapsulate and
detect the presence of alkanediamines in aqueous solution.
We first investigated the ability of alkanediamines to
form 1:1 complexes with 1,4-dimethoxypillar[5]arene
(DMpillar[5]arene).10 Host-guest complexation was assessed
1
by H NMR titration of DMpillar[5]arene into a 15 mM solu-
tion of 1,8-diaminooctane in CDCl3 (Figure 1). Addition of
4.0 equiv of the host resulted in upfield shifts of 0.7 ppm for
upramolecular chemists have extensively studied the host-
S
guest chemistry1 of macrocycles such as cyclodextrins,2
crown ethers,3 calixarenes,4 and cucurbiturils.5 An important
application of these macrocyclic hosts is their ability to bind to,
and often to act as sensors for, a variety of guests (analytes),
including metal and organic cations,6 neutral molecules,7 anions,8
and biomolecules.9
Pillar[5]arene, first reported by Ogoshi et al.10 in 2008, is the
product of the condensation of 1,4-dimethoxybenzene and
formaldehyde in the presence of the Lewis acid BF3 OEt2.
3
The hydroquinone units of this macrocycle are connected by
methylene bridges in the para positions of the benzene rings,
affording a D5-symmetric structure with an overall cylindrical or
pillarlike shape. Pillar[5]arene and its derivatives have been
shown11 to act as good hosts for viologens. The stabilization of
these host-guest complexes can be attributed10 to charge-trans-
fer interactions occurring between the electron-rich cavities
inside the macrocycles and the encircled electron-poor viologens.
The construction of pseudorotaxanes and [n]rotaxanes from
polyviologen threads and pillar[5]arene macrocycles using these
interactions has been reported.11d,12
Despite extensive research11 on the interactions between
viologens and pillar[5]arenes, only a minimal effort13 has been
invested to date in studying the affinities of other small-molecule
guests for this new host. On the basis of their affinities for
cucurbit[6]uril,5a a well-studied host with a similar structure and
shape, we speculated that alkylamines and alkanediamines might
be ideal guests for pillar[5]arenes.
Aliphatic amines are widely used in industry (e.g., hexamethy-
lenediamine is produced on the million ton scale annually and
used in the production of nylon-6,6) and known to be slightly
toxic.14 Tuaminoheptane and methylhexanamine are stimulants
banned by the World Anti-Doping Agency.15 Identification of
Figure 1. 1H NMR titration (500 MHz, CDCl3, 298 K) of DMpillar-
[5]arene into a 15 mM solution of 1,8-diaminooctane in CDCl3. Com-
plexation with the electron-rich cavity of DMpillar[5]arene (host)
causes the protons of 1,8-diaminooctane (guest) to shift upfield. A Ka
value of 70 ( 10 M-1 was calculated for the complex.
Received: December 19, 2010
Published: March 28, 2011
r
2011 American Chemical Society
5668
dx.doi.org/10.1021/ja111418j J. Am. Chem. Soc. 2011, 133, 5668–5671
|

Journal of the American Chemical Society
COMMUNICATION
the HB protons of the guest. An association constant (Ka) of
70 ( 10 M-1 in this nonpolar solvent17 was calculated using
curve-fitting analysis [see the Supporting Information (SI)]. The
uncharged aliphatic guest had no significant impact on the
observed chemical shifts of the host protons. Binding of
n-octylamine in the cavity of DMpillar[5]arene was also probed
by a 1H NMR titration, and a Ka value of 20 ( 2 M-1 was obtained
(see the SI).18 Investigations of the host-guest complexation
between DMpillar[5]arene and both 1,8-diaminooctane and
n-octylamine employing Job plots (see the SI) indicated the
formation of 1:1 complexes believed to be of a pseudorotaxane
type19 (i.e., with the guest threaded through the host cavity).
We synthesized a [2]rotaxane from the host-guest complex
formed between DMpillar[5]arene and 1,8-diaminooctane by
reacting the primary amino groups of the guest with 3,5-di-tert-
butylbenzaldehyde. Subsequent reduction (Scheme S1 in SI) of the
diimine with NaBH4 in THF gave the [2]rotaxane 2 in 7% yield.20
Even though this template-directed synthesis lacks efficiency at this
time, all of the reactants, except for DMpillar[5]arene, are commer-
cially available, rendering the [2]rotaxane an easily attainable
Scheme 1. Synthesis of Pyrene-Functionalized Pillar-
[5]arene 6; The Energy-Minimized Structure (MMFF94) of 6
Is Also Shown (H Atoms Have Been Omitted for Clarity)
1
mechanically interlocked molecule (MIM). The H NMR spec-
trum (Figure 2) of 2 reveals dramatic upfield shifts for the centrally
located methylene groups on the dumbbell component of
DMpillar[5]arene (e.g., the proton HD resonance is at -1.2 ppm)
compared with those for the free dumbbell 1. The synthesis and
characterization of the [2]rotaxane 2 is a first step in the production
of a wide range of MIMs in which pillar[5]arenes serve as the ring
compounds. It also implies the formation of a 1:1 complex of a
[2]pseudorotaxane nature as a precursor to the [2]rotaxane.
Having confirmed the pseudorotaxane nature of the host-
guest complex, we sought to prepare a substituted pillar[5]arene
capable of sensing the presence of the guest. Monofunctionaliza-
tion of macrocycles is a known strategy21 for incorporating sensor
capabilities without significantly altering the binding ability of the
host. We devised a synthetic approach (Scheme 1) wherein a mix-
ture of two monomers affords a monofunctionalized pillar[5]arene
(Figure 3)22 onto which an azide moiety can subsequently be
installed, allowing further functionalization with a fluorophore using
the Huisgen-type23 copper(I)-catalyzed 1,3-dipolar azide-alkyne
cycloaddition (CuAAC).
Employing this strategy (Scheme 1), we obtained the monofunc-
tionalized pillar[5]arene 3 by condensation of 5.0 equiv24 of 1,4-
dimethoxybenzene with 1.0 equiv of the unsymmetrical hydroqui-
none derivative 1-(2-bromoethoxy)-4-methoxybenzene25 and 5.0
equiv of paraformaldehyde in the presence of BF3 OEt2. The Br
3
on 3 was substituted with an azide group, creating pillar[5]arene
derivative 4, which can be functionalized through CuAAC. This
example is the first involving a pillar[5]arene substituted with a
functional group at a single position and able to undergo further
reaction. Since CuAAC is high-yielding, functional-group-tolerant,
and compatible with a wide range of substrates,26 4 can serve as a
general precursor for a whole array of substituted pillar[5]arenes.
Primary amines are well-known27 to quench fluorescence
through photoinduced electron transfer (PET). In order to
detect alkylamines and alkanediamines at low concentrations
1
Figure 2. Comparison of the H NMR spectra (CDCl3, 500 MHz,
Figure 3. Models of three types of nonsymmetric pillar[5]arenes: (a)
differentiated-rim pillar[5]arene; (b) copillar[5]arene, where one hy-
droquinone unit is different from the other four; c) monofunctional
pillar[5]arene. Green spheres represent generic functional groups; H
atoms have been omitted for clarity.
15 mM, 298 K) of dumbbell 1 and [2]rotaxane 2 containing pillar-
[5]arene. Because of shielding caused by DMpillar[5]arene, the inner
aliphatic region of 1 is shifted upfield to the extent that protons C and D
exhibit negative chemical shifts.
5669
dx.doi.org/10.1021/ja111418j |J. Am. Chem. Soc. 2011, 133, 5668–5671

Journal of the American Chemical Society
COMMUNICATION
and viologen salts reported by Ogoshi et al.10 Once again, the
existence of 1:1 complexes was confirmed by making a Job plot
with 1,8-diaminooctane (see the SI). The large difference
between these Ka values and those observed for DMpillar-
[5]arene and 1,8-diaminooctane by 1H NMR titration is attrib-
uted to the very different solvent polarities of CDCl3 and
aqueous MeCN as well as the significant role that hydrophobic
interactions play in the complexation of 6 with its guests.
Alkylamines with only a single terminal amine group had a
smaller effect on the fluorescence of 6. The two possible
orientations of an n-alkylamine inside the cavity of 6 have the
terminal amino group either directed toward the pyrene residue
(and hence able to quench the fluorescence) or facing away from
the fluorophore (and thus unable to cause such a profound
effect). The orientation issue, coupled with the loss of one amino
group (relative to an alkanediamine) to interact with the oxygen
atoms on the rim of 6 by means of hydrogen bonding, offers an
explanation for the lower Ka values. Titrations with 1,6-hexanediol
did not decrease the fluorescence of 6, even after the addition of
5.0 equiv of diol. 1-Aminoadamantane, which is too bulky to fitinside
the cavity of pillar[5]arene,10 only decreased fluorescence to 85% of
the initial intensity after addition of 5.0 equiv.
Figure 4. Fluorescence quenching experiment (57.2 μM, 1:1 MeCN/
H2O, λex = 355 nm, λem = 395 nm). The fluorescence of 6 (57.2 μM, 1:1
MeCN/H2O, λex = 355 nm) was followed as 1,5-diaminopentane was
titrated into the solution.
by fluorescence, we chose to react the alkyne-substituted 1-pyr-
enemethanol derivative 5 with 4 to give the monofunctional
pillar[5]arene 6. Since this derivative can be dissolved in 1:1 (v/v)
MeCN/H2O at the low concentration required for fluorescence
spectroscopy, titrations with various alkylamines and alkanedia-
mines into a solution of 6 in the highly polar solvent could be
followed by fluorescence spectroscopy.
The quenching of fluorescence (Figure 4) was found to be
significant enough that we could measure quantitatively
(Table 1) the Ka values for a wide range of 1:1 complexes formed
with 6. The association constants for the series of alkanediamines
containing three to eight carbon atoms are all in the vicinity of
104 M-1 and hence on the same order of magnitude as the Ka
values for the formation of complexes between pillar[5]arene
Titration of these amines into solutions of DMpillar[5]arene
or pyrene employing the same conditions did not result in a
reduction of fluorescence, indicating that only 6 provides both a
suitable cavity for the guest and a fluorophore that can interact
photochemically with the guest. The relatively strong complexes
formed between the alkanediamines and pillar[5]arene are most
likely the result of hydrophobic interactions between the alipha-
tic chain and the pillar[5]arene cavity in addition to [C-H π]
3 3 3
interactions.13a Although hydrogen bonding between the primary
amino groups and the oxygen atoms on the rims of the macrocycle
may also contribute to the host-guest interactions, further investi-
gations are required to establish the mode of binding between the
pillar[5]arenes and their amine and diamine guests.
Table 1. Association Constants for 6 and Alkylamines
Calculated from Fluorescence Quenching Experimentsa
In conclusion, we have discovered and evaluated the encapsu-
lation of uncharged aliphatic amines by the recently reported
macrocycle pillar[5]arene and exploited the binding motif to
prepare a [2]rotaxane with pillar[5]arene as the ring component.
We have also devised a synthetic strategy to prepare monofunc-
tionalized derivatives from a single azide-functionalized com-
pound. By installation of a fluorophore via CuAAC “click” chemi-
stry, a sensor for alkanediamines was obtained. Future work will
probe the many interactions between pillar[5]arenes and alkyl-
amines and target the design of novel MIMs.
’ ASSOCIATED CONTENT
S
Supporting Information. Synthesis and characterization
b
of all new compounds, results of NMR and fluorescence quench-
ing experiments, and Job plots. This material is available free of
charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
stoddart@northwestern.edu
’ ACKNOWLEDGMENT
a Fluorescence measurement conditions: 57.2 μM, 1:1 MeCN/H2O,
λex = 355 nm. Ka values were calculated using curve-fitting analysis
software (see the SI).
The research at Northwestern University (NU) was spon-
sored by the National Center for Nano Technology Research at
the King Abdulaziz City for Science and Technology (KACST)
5670
dx.doi.org/10.1021/ja111418j |J. Am. Chem. Soc. 2011, 133, 5668–5671

Journal of the American Chemical Society
COMMUNICATION
in Saudi Arabia. The authors thank Dr. Turki S. Al-Saud,
Dr. Soliman H. Alkhowaiter and Dr. Mohamed B. Alfageeh of
KACST for their generous support of this program of research at
NU. N.L.S. thanks the National Science Foundation for a
Graduate Research Fellowship.
(11) (a) Li, C.; Xu, Q.; Li, J.; Yao, F.; Jia, X. Org. Biomol. Chem. 2010,
8, 1568. (b) Ogoshi, T.; Hashizume, M.; Yamagishi, T.-A.; Nakamoto, Y.
Chem. Commun. 2010, 46, 3708. (c) Ogoshi, T.; Kitajima, K.; Aoki, T.;
Yamagishi, T.-A.; Nakamoto, Y. J. Phys. Chem. Lett. 2010, 1, 817. (d)
Ogoshi, T.; Nishida, Y.; Yamagishi, T.-A.; Nakamoto, Y. Macromolecules
2010, 43, 3145.
(12) Ogoshi, T.; Nishida, Y.; Yamagishi, T.-A.; Nakamoto, Y.
Macromolecules 2010, 43, 7068.
(13) (a) Zhang, Z.; Xia, B.; Han, C.; Yu, Y.; Huang, F. Org. Lett.
2010, 12, 3285. (b) Han, C.; Ma, F.; Zhang, Z.; Xia, B.; Yu, Y.; Huang, F.
Org. Lett. 2010, 12, 4360. (c) Li, C.; Zhao, L.; Li, J.; Ding, X.; Chen, S.;
Zhang, Q.; Yu, Y.; Jia, X. Chem. Commun. 2010, 46, 9016.
’ REFERENCES
(1) (a) Cram, D. J.; Cram, J. M. Science 1974, 183, 803. (b) Cram,
D. J. Angew. Chem., Int. Ed. 1998, 27, 1009. (c) Cram, D. J.; Cram, J. M.
Container Molecules and Their Guests; Royal Society of Chemistry:
Cambridge, U.K., 1994.
(2) (a) Cramer, F. Einschlussverbindungen; Springer-Verlag: Berlin, 1954.
(b) French, D. Adv. Carbohydr. Chem. 1957, 12, 189. (c) D’Sousa, V. T.;
Bender, M. L. Acc. Chem. Res. 1987, 20, 146. (d) Breslow, R. Science 1982,
218, 532. (e)Saenger, W. Angew. Chem., Int. Ed. Engl. 1980, 19, 344. (f) Szejtli,
J. Chem. Rev. 1998, 98, 1743. (g) Nepogodiev, S. A.; Stoddart, J. F. Chem. Rev.
1998, 98, 1959. (h) Harada, A. Acc. Chem. Res. 2001, 34, 456. (i) Tian, H.;
Wang, Q.-C. Cyclodextrin Materials: Photochemistry, Photophysics and Photo-
biology; Elsevier: Amsterdam, 2006; pp 285-301. (j) Wenz, G.; Han, B.-H.;
M€uller, A. Chem. Rev. 2006, 106, 782. (k) Harada, A.; Hashidzume, A.;
Yamaguchi, H.; Takashima, Y. Chem. Rev. 2009, 109, 5974.
(3) (a) Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 2495. (b)Truter, M. R.
Struct. Bonding 1973, 16, 71. (c) Pedersen, C. J. Angew. Chem., Int. Ed. 1998,
27, 1021. (d) Stoddart, J. F. Top. Stereochem. 1987, 17, 207. (e) Cantrill, S. J.;
Pease, A. R.; Stoddart, J. F. J. Chem. Soc., Dalton Trans. 2000, 21, 3715.
(4) (a) Gutsche, C. D. Calixarenes; Royal Society of Chemistry:
Cambridge, U.K., 1989. (b) Vanloon, J. D.; Verboom, W.; Reinhoudt,
D. N. Org. Prep. Proced. Int. 1992, 24, 437. (c) Shinkai, S. Tetrahedron
1993, 49, 8933. (d) B€ohmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34,
713. (e) Gutsche, C. D. Calixarenes Revisited; Monographs in Supramo-
lecular Chemistry, Vol. 6; Royal Society of Chemistry: Cambridge, U.
K., 1998. (f) Rebek, J., Jr. Chem. Commun. 2000, 637. (g) Baldini, L.;
Casnati, A.; Sansone, F.; Ungaro, R. Chem. Soc. Rev. 2007, 36, 254. (h)
McIldowie, M. J.; Mocerino, M.; Ogden, M. I. Supramol. Chem. 2010,
22, 13.
(5) (a) Freeman, W. A.; Mock, W. L.; Shih, N. Y. J. Am. Chem. Soc.
1981, 103, 7367. (b) Mock, W. L.; Shih, N. Y. J. Am. Chem. Soc. 1988,
110, 4706. (c) Kim, J.; Jung, I.-S.; Kim, S.-Y.; Lee, E.; Kang, J.-K.;
Sakamoto, S.; Yamaguchi, K.; Kim, K. J. Am. Chem. Soc. 2000, 122, 540.
(d) Kim, K. Chem. Soc. Rev. 2002, 31, 96. (e) Lee, J. W.; Samal, S.;
Selvapalam, N.; Kim, H.-J.; Kim, K. Acc. Chem. Res. 2003, 36, 621. (f)
Lagona, J.; Mukhopadhyay, P.; Chakrabarti, S.; Isaacs, L. Angew. Chem.,
Int. Ed. 2005, 44, 4844.
(6) (a) Allwood, B. L.; Spencer, N.; Shahriari-Zavareh, H.; Stoddart,
J. F.; Williams, D. J. J. Chem. Soc., Chem. Commun. 1987, 1064. (b)
Ashton, P. R.; Campbell, P. J.; Glink, P. T.; Philp, D.; Spencer, N.;
Stoddart, J. F.; Chrystal, E. J. T.; Menzer, S.; Williams, D. J.; Tasker, P. A.
Angew. Chem., Int. Ed. Engl. 1995, 34, 1865. (c) Calixarenes 2001; Asfari,
Z., Bohmer, V., Harrowfield, J., Vicens, J., Eds.; Kluwer Academic:
Dordrecht, The Netherlands, 2001. (d) Moonen, N. N. P.; Flood, A. H.;
Fernꢀandez, J. M.; Stoddart, J. F. Top. Curr. Chem. 2005, 262, 99. (e)
Schneider, H. J. Angew. Chem., Int. Ed. 2009, 48, 3924.
(14) Greim, H.; Bury, D.; Klimisch, H. J.; Oeben-Negele, M.;
Ziegler-Skylakakis, K. Chemosphere 1998, 36, 271.
(15) World Anti-Doping Agency. The 2011 Prohibited List, Inter-
national Standard, Montreal, Canada, 2011; http://www.wada-ama.
org/en/ (accessed Dec 19, 2010).
(16) Llop, A.; Pocurull, E.; Borrull, F. J. Chromatogr., A 2010, 1217, 575.
(17) The interaction of aliphatic amines with the cavity of DMpillar-
[5]arene is expected to be driven at least partially by hydrophobic
forces,13 as observed with complexes of cucurbiturils and alkylammo-
nium salts.5 However, the solubility of DMpillar[5]arene is low in polar
solvents at the concentrations necessary to perform 1H NMR spectro-
scopic titrations, so the initial binding studies were performed in CDCl3.
(18) Under the same conditions, the chemicalshifts of the inner protons
of octane moved slightly upfield (0.05 ppm) upon the addition of 1.0 equiv
of the host. The difference in binding of n-octylamine and octane with
DMpillar[5]arene in CDCl3 suggests that hydrogen bonding between the
primary amino groups on the guest and the methoxyl groups that line the rim
of the host contribute to the stabilization of the host-guest complex.
(19) The formation of pseudorotaxanes by DMpillar[5]arene and
both 1,8-diaminooctane and n-octylamine was supported by 2D NOESY
experiments (see the SI).
(20) The low yield can be attributed in part to the solvent mixture
[4:1 (v/v) THF/H2O] used in the [2]rotaxane synthesis. This mixed
solvent system was expected to support complexation between 1,8-
diaminooctane and DMpillar[5]arene (the [2]rotaxane was not de-
tected when the synthesis was attempted in CHCl3), despite its having a
negative influence on imine bond formation during the template-
directed synthesis of the [2]rotaxane.
(21) (a) D’Alessandro, F.; Gulino, F. G.; Impellizzeri, G.; Pappalardo,
G.; Rizzarelli, E.; Sciotto, D.; Vecchio, G. Tetrahedron Lett. 1994, 35, 629.
(b) Janshoff, A.; Steinem, C.; Michalke, A.; Henke, C.; Galla, H. J. Sens.
Actuators, B 2000, 70, 243. (c) Corradini, R.; Paganuzzi, C.; Marchelli, R.;
Pagliari, S.; Sforza, S.; Dossena, A.; Galaverna, G.; Duchateau, A. Chirality
2003, 15, S30. (d) Trellenkamp, T.; Ritter, H. Macromolecules 2010,
43, 5538.
(22) During the peer-review process, it was reported that Zhang et al.
independently conceived a similar synthetic approach and used it to
prepare a monooctyl-substituted pillar[5]arene that forms supramole-
cular polymers. Further functionalization of this compound was not
attempted. See: Zhang, Z.; Luo, Y.; Chen, J.; Dong, S.; Yu, Y.; Ma, Z.;
Huang, F. Angew. Chem., Int. Ed. 2011, 50, 1397.
(7) (a) Freeman, W. Acta. Crystallogr., Sect. B 1984, 40, 382. (b)
Diederich, F. Angew. Chem., Int. Ed. Engl. 1988, 27, 362. (c) Atwood,
J. L.; Barbour, L. J.; Raston, C. L.; Sudria, I. B. N. Angew. Chem., Int. Ed.
1998, 37, 981. (d) Purse, B. W.; Rebek, J., Jr. Proc. Natl. Acad. Sci. U.S.A.
2005, 102, 10777. (e) Lagona, J.; Wagner, B. D.; Isaacs, L. J. Org. Chem.
2006, 71, 1181.
(8) (a) Beer,P.D. Acc. Chem. Res. 1998, 31,71.(b)Beer,P.D.;Gale,P.A.
Angew. Chem., Int. Ed. 2001, 40, 486. (c) Sessler, J. L.; Camiolo, S.; Gale, P. A.
Coord. Chem. Rev. 2003, 240, 17. (d)Vickers, M. S.;Beer, P. D.Chem. Soc. Rev.
2007, 36, 211. (e) Hua, Y.; Flood, A. H. Chem. Soc. Rev. 2010, 39, 1262.
(9) (a) Zadmard, R.; Schrader, T. J. Am. Chem. Soc. 2005, 127, 904. (b)
Hayashida, O.; Uchiyama, M. Org. Biomol. Chem. 2008, 6, 3166. (c) Zhou,
Y.-Y.; Yang, J.; Liu, M.; Wang, S.-F.; Lu, Q. J. Lumin. 2010, 130, 817.
(10) Ogoshi, T.; Kanai, S.; Fujinami, S.; Yamagishi, T.-A.; Nakamoto,
Y. J. Am. Chem. Soc. 2008, 130, 5022.
(23) (a) Huisgen, R.; Szeimies, G. N.; M€obius, L. Chem. Ber. 1967,
100, 2494. (b) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless,
K. B. Angew. Chem., Int. Ed. 2002, 41, 2596. (c) Tornøe, C. W.;
Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057.
(24) An additional 1.0 equiv of 1,4-dimethoxybenzene was added to
avoid the formation of di- and trifunctionalized derivatives.
(25) Schultz, D. M.; Prescher, J. A.; Kidd, S.; Marona-Lewicka, D.;
Nichols, D. E.; Monte, A. Biorg. Med. Chem. 2008, 16, 6242.
(26) Meldal, M.; Tornøe, C. W. Chem. Rev. 2008, 108, 2952.
(27) (a) de Silva, A. P.; Rupasinghe, R. A. D. D. J. Chem. Soc., Chem.
Commun. 1985, 1669. (b) Lakowicz, J. R. Principles of Fluorescence
Spectroscopy, 3rd ed.; Springer: New York, 2006.
5671
dx.doi.org/10.1021/ja111418j |J. Am. Chem. Soc. 2011, 133, 5668–5671