Synthesis of Well-Defined Tower-Shaped 1,3,5-Trisubstituted Adamantanes Incorporating a Macrocyclic Trilactam Ring System

Article abstract of DOI:10.1021/jo035640+

We describe the synthesis of two novel well-defined tower-shaped 1,3,5-trisubstituted adamantanes 30 and 33 that incorporate a macrocyclic trilactam ring system. Each nanoscale molecule has a broad tripodal base consisting of three identical sulfur-contai

Full text of DOI:10.1021/jo035640+

Syn th esis of Well-Defin ed Tow er -Sh a p ed 1,3,5-Tr isu bstitu ted
Ad a m a n ta n es In cor p or a tin g a Ma cr ocyclic Tr ila cta m Rin g System
Quan Li, Changshu J in, Pavel A. Petukhov, Aleksey V. Rukavishnikov, Tatiana O. Zaikova,
Avinash Phadke, Donald H. LaMunyon, Melissa D. Lee, and J ohn F. W. Keana*
Department of Chemistry, University of Oregon, Eugene, Oregon 97403-1253
jkeana@oregon.uoregon.edu
Received November 7, 2003
We describe the synthesis of two novel well-defined tower-shaped 1,3,5-trisubstituted adamantanes
30 and 33 that incorporate a macrocyclic trilactam ring system. Each nanoscale molecule has a
broad tripodal base consisting of three identical sulfur-containing termini as the tripod feet,
4-acetylsulfanylmethylphenyl units in the case of 30 and 3,5-bis(acetylsulfanylmethyl)phenyl units
in the case of 33. The sulfur atoms are designed to bind the molecules trivalently to the apex of a
gold-coated commercial AFM tip through formation of three S-Au bonds. The rigid adamantane-
derived head unit with a single hydrogen atom at the apex is designed to scan the sample. Molecules
30 and 33 are synthesized from 1,3,5-triethynyladamantane by a series of Sonogashira coupling
reactions involving terminal alkynes and aryl iodides. A macrocyclic trilactam unit is included for
added rigidity. We demonstrate that molecule 30 is sufficiently large and rigid to be visualized by
a conventional AFM tip. These nanoscale molecules may also find application as chemically well-
defined nanoscale objects for calibration of AFM tips.
In tr od u ction
recently, the synthesis of several related, tetrahedrally
shaped tripodal adamantane-based molecules 4 and 5
was completed. One terminus was differentiated as an
ester group while the other three termini contain sulfur
atoms for eventual binding to a gold-coated commercial
AFM tip.9 We also demonstrated that 38 and 49 (n ) 2)
are sufficiently large and rigid to be imaged by a
conventional AFM tip. Herein, we describe the synthesis
of two nanoscale molecules 30 and 33, which are much
larger versions of 1 and rationally designed to have a
more optimal aspect ratio when eventually attached to
a commercial AFM tip.
Tapered nanoscale molecules are potentially useful as
single-molecule atomic force microscopy (AFM) tips for
imaging both biological1 and nonbiological surfaces.2
Examples of such molecules include the tripodal3 oli-
gophenylene silanes described by Cai et al.4 and the
caltrop-shaped tetrasubstituted silanes described by Yao
and Tour.5 About the same time we described the
synthesis of a prototypic tower-shaped molecule 1 (Chart
1) as an inroad to a series of single molecule tips for AFM
applications.6,7 Subsequently, a series of tetrahedrally
shaped molecules was completed including 1,3,5,7-sym-
metrically substituted tetraphenyladamantane 2 and the
symmetrically substituted tetraphenylmethane 3.8 Most
Resu lts a n d Discu ssion
Molecu la r Design . Ideally, potential tip molecules
should be mechanically rigid and conformationally well
defined and include functional groups suitable for chemi-
cal attachment to the apex of a commercial tip. The base
of the molecular tip should be broad and the tip height
should be such that adjacent tip molecules bound to the
convex surface do not interfere with imaging by the apical
molecule (Figure 1). If the base of the tip molecule is too
small, then covering the commercial tip with tip mol-
ecules only increases the radius of curvature of the
molecular tip.
Each of the target molecules consists of four units. The
first unit is a rigid, trisubstituted adamantane head unit
with a single hydrogen atom at the apex and designed
to probe the sample. The second unit is the body consist-
ing of three rodlike phenylene-ethynylene units linked
(1) Atomic Force Microscopy in Cell Biology; J ena, B. P., Horber, H.
J . K., Eds.; Vol. 68, Methods in Cell Biology; 2002.
(2) Nanoscience and Technology. In Noncontact Atomic Force Mi-
croscopy; Morita, S., Wiesendanger, R., Meyer, E., Eds.; Springer-
Verlag: New York, 2002
(3) Recent examples of adamantane-, methane-, or silicon-based
tripodal molecules useful in other applications include the following:
(a) Piotrowiak, P.; Galoppini, E.; Wei, Q.; Meyer, G. J .; Wiewior, P. J .
Am. Chem. Soc. 2003, 125, 5278. (b) J ian, H.; Tour, J . M. J . Org. Chem.
2003, 68, 5091. (c) Hirayama, D.; Takimiya, K.; Aso, Y.; Otsubo, T.;
Hasobe, T.; Yamada, H.; Imahori, H.; Fukuzumi, S.; Sakata, Y. J . Am.
Chem. Soc. 2002, 124, 532. (d) Long, B.; Nikitin, K.; Fitzmaurice, D.
J . Am. Chem. Soc. 2003, 125, 5152.
(4) (a) Deng, X.; Mayeux, A.; Cai, C. J . Org. Chem. 2002, 67, 5279.
(b) Deng, X.; Cai, C. Tetrahedron Lett. 2003, 44, 815.
(5) Yao, Y.; Tour, J . M. J . Org. Chem. 1999, 68, 1968.
(6) Keana, J . F. W.; Petukhov, P. A.; Rukavishnikov, A. V.; Phadke,
A.; LaMunyon, D. H.; Lee, M. D. Abstract of Papers, 217th ACS
National Meeting, March 21-25, 1999, Anaheim CA; American
Chemical Society: Washington, DC, 1999; ORG 72.
(7) Rukavishnikov, A. V.; Phadke, A.; Lee, M. D.; LaMunyon, D. H.;
Petukhov, P. A.; Keana. J . F. W. Tetrahedron Lett. 1999, 40, 6353.
(8) Li, Q.; Rukavishnikov, A. V.; Petukhov, P. A.; Zaikova, T. O.;
Keana, J . F. W. Org. Lett. 2002, 21, 3631-3634.
(9) Li, Q.; Rukavishnikov, A. V.; Petukhov, P. A.; Zaikova, T. O.;
J in, C.; Keana, J . F. W. J . Org. Chem. 2003, 68, 4862.
10.1021/jo035640+ CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/15/2004
1010
J . Org. Chem. 2004, 69, 1010-1019

Well-Defined Tower-Shaped 1,3,5-Trisubstituted Adamantanes
CHART 1
together to form a rigidifying cage-like macrocycle con-
sisting of three 44-membered rings. The third unit is the
three legs, which radiate downward and outward from
the body and contribute to the height and width of the
molecule. Three identical, sulfur-containing termini con-
stitute the fourth unit, which serves as the feet of the
tripod. Given the high affinity that thiols,10 disulfides,10
or thiolacetates11 display toward gold, we included S
(10) The question of binding of disulfides and thiols to the gold
surface is complicated by thermodynamic stability of disulfide ring and
monolayer formation kinetics. See the discussion in: Schlenoff, J . B.;
Li, M.; Ly, H. J . Am. Chem. Soc. 1995, 117, 12528.
J . Org. Chem, Vol. 69, No. 4, 2004 1011

Li et al.
CHART 2. Mon om er Bu ild in g Block s
F IGURE 1. Schematic diagram of a commercial AFM tip
modified by attachment of tower-shaped molecules.
SCHEME 1a
Delimarskii and coauthors17 rather than the route used
by Stetter and Wulff18 or by Malik et al.16
The synthesis of monomers 9,13 10,13 11,13 13,19,20 14,13
and 1513 (Chart 2) followed the protocol of Moore and co-
workers.13 We elected to use iodoanilines instead of
bromoanilines for our Sonogashira coupling reactions in
view of the reported superior reactivity of aryl iodides.21,22
In our hands, pyrrolidinyl diazene 11 gave a better yield
of iodide 13 than did the corresponding N,N-diethyl
derivative used by Moore.19 In general, pyrrolidinyl
diazenes were used throughout our work. Monomer 12
was prepared by treatment of 11 with K2CO3 in MeOH/
CH2Cl2. Foot units 169,23 and 177 were prepared as
previously described by us.7,9
a
Reagents and conditions: (a) Br2, Fe; (b) vinyl bromide, AlCl3;
(c) t-BuOH, t-BuOK, heat.
atoms in the feet to anchor the molecular tip to a thin
film of gold placed on a conventional AFM tip.12 Thus, a
4-(acetylsulfanylmethy)phenyl unit and a 3,5-bis(acetyl-
sulfanylmethyl)phenyl unit were chosen as the feet of
molecules 30 and 33, respectively, for eventual anchoring
to conventional gold-coated AFM tip. Hydrolysis to the
corresponding more air-sensitive thiol groups remains a
possibility. The spacing of the trivalent tripodal tip
molecules may be modulated either by varying the
concentration of tip molecules in the application solution
and/or by including an appropriate concentration of
competing monovalent short-chain thiol molecules, which
can “fill in” the monolayer on the gold surface.
Syn th esis of Mon om er s. We adapted the elegant
convergent, stepwise synthesis of oligo(4-phenylene ethy-
nylenes) used by Moore13,14 and others15 for the synthesis
of our nanoscale, tower-shaped molecules. Triethyny-
ladamantane 8 (Scheme 1) was chosen as the head unit
owing to its rigid nature, well-defined geometry, and
anticipated reactivity in the Sonogashira coupling reac-
tion. Adamantane 8 was prepared from adamantane
generally along the lines of Malik and co-workers.16 1,3,5-
Tribromoadamantane was prepared as described by
Syn th esis of th e Ma cr ocyclic Tr ila cta m 26. Alkyne
19 was synthesized by a cross-coupling reaction between
monomers 13 and 15 to give 18, which was deprotected
with K2CO3 in MeOH/CH2Cl2 (Scheme 2). Alkyne 19 was
next cross-coupled with iodide 10 to give diazene 20,
which was heated in n-BuI to give iodide 21. Triester 23
was synthesized by coupling iodide 21 with 1,3,5-triethy-
nyladamantane 8. A small amount of diyne 22 was
obtained as a byproduct arising by a Glaser-type24,25
oxidative homocoupling reaction and identified by NMR
and MS. The TMS protecting groups in 23 were then
removed by n-Bu4NF to afford trialkyne 24. Alkaline
hydrolysis of 24 gave triacid 25. Treatment of 25 with
(17) Delimarskii, R. E.; Rodionov, V. N.; Yurchenko, A. G. Ukr.
Khimi. Zh. 1988, 54, 437.
(18) Stetter, H.; Wulff, C. Chem. Ber. 1960, 93, 1366.
(19) Moore, J . S.; Weinstein, E. J .; Wu, Z. Tetrahedron Lett. 1991,
32, 2465.
(20) Hsung, R. P.; Chidsey, C. E. D.; Sita, L. R. Organometallics
1995, 14, 4808.
(21) Cassar, L. J . Organomet. Chem. 1975, 93, 253.
(22) Thorand, S.; Krause, N. J . Org. Chem. 1998, 63, 8551.
(23) Gryko, T. T.; Clausen, C.; Roth, K. M.; Dontha, N.; Bocian, D.
F.; Kuhr, W. G.; Lindsey, J . S. J . Org. Chem. 2000, 65, 7345.
(24) (a) Ziener, U.; Godt, A. J . Org. Chem. 1997, 62, 6137. (b) Xu,
Z.; Moore, J . S. Angew. Chem., Int. Ed. Engl. 1993, 32, 246. (c) Wager,
R. W.; J ohnson, T. E.; Li, F.; Lindsey, J . S. J . Org. Chem. 1995, 60,
5266.
(11) Kim, S.; Park, S.-K.; Park, C.; J eon, I. C. J . Vac. Sci. Technol.
B 1996, 14, 1318.
(12) Tour, J . M.; J ones, L., II; Pearson, D. L.; Lamba, J . J . S.; Burgin,
T. P.; Whitesides, G. M.; Allara, D. L.; Parikh, A. N.; Atre, S. V. J .
Am. Chem. Soc. 1995, 117, 9529.
(13) Zhang, J .; Pesak, D. J .; Ludwick, J . L.; Moore, J . S. J . Am.
Chem. Soc. 1994, 116, 4227.
(14) See: Young, J . K.; Moore, J . S. Acetylenes in Nanostructures.
In Modern Acetylene Chemistry; Stang, P. J ., Diederich, F., Eds.;
VHC: New York, 1995.
(15) See for example: (a) J ones, L.; Schumm, J . S.; Tour, J . M. J .
Org. Chem. 1997, 62, 1388-1410. (b) Aujard, I.; Baltaze, J .-P.; Baudin,
J .-B.; Cogne, E.; Ferrage, F.; J ullien, L.; Perez, E.; Prevost, V.; Qian,
L. M.; Ruel, O. J . Am. Chem. Soc. 2001, 123, 8177.
(16) Malik, A. A.; Archibald, T. G.; Baum, K.; Unroe, M. R. J . Polym.
Sci.: Part A: Polym. Chem. 1992, 30, 1747.
(25) Chow, H. F.; Wan, C. W.; Low, K. H.; Yeung, Y. Y. J . Org. Chem.
2001, 66, 1910.
1012 J . Org. Chem., Vol. 69, No. 4, 2004

Well-Defined Tower-Shaped 1,3,5-Trisubstituted Adamantanes
SCHEME 2a
a
Reagents and conditions: (a) Pd(PPh3)2Cl2, CuI, NEt3/THF; (b) K2CO3, CH2Cl2, MeOH; (c) n-BuI, heat; (d) n-Bu4NF, THF; (e) NaOH,
EtOH, H2O, CHCl3; (f) oxalyl chloride, DMF, benzene; (g) tris(2-aminoethyl)amine, chlorobenzene, DMA, high-dilution conditions.
oxalyl chloride in DMF and benzene cleanly gave the
corresponding trichloride, which was allowed to react
with tris(2-aminoethyl)amine employing high dilution
conditions26 to successfully give the triply bridged mac-
rocycle 26 in 14% yield. The structure of macrocycle 26
with an excess of 1,4-diiodobenzene in the presence of
Pd(PPh3)2Cl2 and CuI as catalysts giving iodide 29.
Target molecule 30 was obtained in 15% yield after a
rather difficult column chromatography following the
coupling of an excess of 29 with macrocycle 26 under
Sonogashira reaction conditions. The low yield likely was
a result of competing Glaser-type oxidative homocoupling
reactions of the tri(terminal alkynyl) macrocycle 26 to
the corresponding diyne or higher oligoynes despite
efforts to exclude oxygen from the reaction. The structure
1
was confirmed by H (Figure 2) and 13C NMR, FAB MS
(Figure 3), and elemental analysis. The main byproduct
in the tricondensation reaction was a solid substance of
low solubility, which was probably a mixture of amide
oligomers formed by intermolecular reactions between
partially reacted intermediates in the macrocyclization
reaction.
Syn th esis of Well-Defin ed Tow er -Sh a p ed Na n o-
sca le Molecu les 30 a n d 33. The “feet” 29 of tower 30
were synthesized as follows. Iodide 16 was coupled with
TMSA under Sonogashira conditions to give TMS deriva-
tive 27,23 which was deprotected with Bu4NF to give
alkyne 2823 (Scheme 3). Alkyne 28 was allowed to react
1
of tower 30 was confirmed by 500 MHz 1- and 2-D H
NMR, 13C NMR, and FAB MS (calculated and found for
M + 2, m/e 2126.2).
The UV-visible spectrum of 30 in CH2Cl2 showed an
absorption maximum at 328 nm (Figure 4 top). The
molecule is also fluorescent (Figure 4 bottom). The
excitation spectrum (dashed line) was taken with the
emission wavelength set at 372 nm while the emission
spectrum (solid line) was obtained when the excitation
was set at 328 nm.
(26) Stutte, P.; Kiggen, W.; Vo¨gtle, F. Tetrahedron 1987, 43, 2065.
J . Org. Chem, Vol. 69, No. 4, 2004 1013

Li et al.
F IGURE 2. Portion of the 500-MHz NMR spectrum of macrocycle 26 in CDCl3. Left: COSY spectrum confirming connectivity in
the amide region of the macrocycle. The spectrum shows that the NH proton at δ 6.8 is coupled to the adjacent CH2 at δ 3.6
(cross-peaks C), which in turn is coupled to the adjacent CH2 at δ 2.8 (cross-peaks B). Geminal coupling of the CH2 protons (δ 2.1
and 2.2) at the 2-, 4-, and 6-positions of the adamantane is apparent (cross-peaks A). Right: 1-D proton spectrum.
F IGURE 3. FAB MS of macrocycle 26. The calculated value for m/e (M + 2) is 1334.5.
Tower-shaped molecule 33 was synthesized as follows
(Scheme 4). Foot unit 17 was coupled to diazene 12 giving
diazene 31. Reaction of 31 with hot n-BuI gave iodide
32. Excess 32 was then allowed to react with macrocycle
26 under Sonogashira conditions to give 33.
Visu a liza t ion of In d ivid u a l Molecu les of 30
w ith Use of a Con ven tion a l AF M Tip . CH2Cl2 solu-
tions of 30 (0.25 and 1.0 µM) were spin-coated onto a
freshly cleaved mica surface and then imaged by AFM
in tapping mode with use of a conventional AFM tip.
Individual molecules of 30 are easily visualized (Figure
5). Comparing panels A and B in Figure 5, it is seen that
the images of 30 are concentration dependent. The height
of the dots is uniform and equal to 0.55 ( 0.15 nm (error
limits calculated at 80-85% confidence level) for both
images. The height determined by AFM is lower than
the calculated height based on molecular modeling. This
28
is consistent with similar differences for DNA27 and C60
and may be due to molecular deformation caused by the
AFM tip. As a control, a CH2Cl2 solution of leg/foot seg-
ment 349 (0.25 µM) was similarly spin- coated onto the
mica surface and examined by AFM (Figure 5C). Since
molecules of alkyne 34 are much smaller than those of
30 and can lay flat on the surface, they cannot be
distinguished from the mica surface itself by AFM.
In summary, two rigid, tower-shaped, tripodal nanos-
cale molecules 30 and 33 designed for AFM applications
have been synthesized and characterized. Molecules 30
(27) Rivetti, C.; Guthold, M.; Bustamante, C. J . Mol. Biol. 1996, 264,
919-932.
(28) Kobayashi, K.; Yamada, H.; Horiuchi, T.; Matsushige, K. Appl.
Surf. Sci. 1999, 140, 281.
1014 J . Org. Chem., Vol. 69, No. 4, 2004

Well-Defined Tower-Shaped 1,3,5-Trisubstituted Adamantanes
SCHEME 3a
a
Reagents and conditions: (a) TMSA, Pd(PPh3)2Cl2, CuI, NEt3/THF; (b) n-Bu4NF, THF; (c) Pd(PPh3)2Cl2, CuI, NEt3/THF, excess 1,4-
diiodobenzene; (d) Pd(PPh3)2Cl2, CuI, NEt3/THF.
for eventual attachment to a commercial AFM tip. The
modular nature of the synthetic route allows for inde-
pendent variation of each unit. We also demonstrate that
molecule 30 is of sufficient size and rigidity that it can
be visualized by AFM with use of a conventional tip.
These nanoscale molecules may also find application as
chemically well-defined, nanoscale objects for the calibra-
tion of AFM tips.
Exp er im en ta l Section
3-Iod o-5-tr im eth ylsila n yleth yn ylben zoic Acid Meth yl
Ester (10). 3-(Pyrrolidin-1-ylazo)-5-trimethylsilanylethynyl-
benzoic acid methyl ester (9, 500 mg, 1.51 mmol)13 was
dissolved in n-BuI (5 mL). The solution was refluxed for 24 h.
The solvent was evaporated in vacuo and the residue was
purified by chromatography on silica gel with 1:19 EtOAc/
hexanes as the eluent to give iodide 10 (465 mg, 86%) as a
1
yellow solid: mp 65-67 °C; H NMR δ 0.25 (s, 9H), 3.92 (s,
3H), 7.97 (t, J ) 1.65 Hz, 6H), 8.07 (t, J ) 1.35 Hz, 1H), 8.30
(t, J ) 1.65 Hz, 1H); 13C NMR δ -0.27, 52.48, 93.11, 97.10,
102.01, 125.33, 131.66, 132.16, 138.15, 144.26, 164.84; MS
calcd for C13H16IO2Si (M + 1) 359.0, found 359.0. Anal. Calcd
for C13H15IO2Si: C, 43.58; H, 4.22. Found: C, 43.55; H, 4.09.
(4-Eth yn ylph en yl)pyr r olidin -1-yldiazen e (12). TMS pro-
tected alkyne 11 (1.35 g, 5.00 mmol) was dissolved in CH2Cl2
(15 mL). The solution was diluted with MeOH (15 mL) and
powdered K2CO3 (0.40 g) was added. The suspension was
F IGUR E 4. Top: UV-visible spectrum of 30 (4 nM in
stirred for 3 h at room temperature and then evaporated. The
residue was purified by chromatography on silica gel with 2:8
EtOAc/hexanes as the eluent to give diazene 12 (0.86 g, 88%)
as yellow crystals, which were pure by TLC and NMR: mp
93-95 °C (lit.30 mp 90 °C); 1H NMR δ 2.03 (t, J ) 6.8 Hz, 4H),
3.07 (s, 1H), 3.80 (br s, 4H), 7.36 (dt, J 1 ) 2.0 Hz, J 2 ) 8.7 Hz,
2H), 7.45 (dt, J 1 ) 2.0 Hz, J 2 ) 8.4 Hz, 2H); 13C NMR δ 23.74,
76.69, 84.17, 118.19, 120.22, 132.85, 151.63; MS calcd for
CH2Cl2). Bottom: Excitation and emission spectra of molecule
30 (0.25 µM in CH2Cl2). The excitation spectrum (dashed line)
was taken with an emission wavelength of 372 nm and
excitation was at 328 nm for the emission spectrum (solid line).
The same sample of 30 was used for both spectra. Uncorrected
spectra were acquired at 25 °C with 5 and 10 nm excitation
and emission slit widths, respectively, using a 10 mm path
quartz cuvette.
and 33 are much larger versions of the prototypic mol-
ecule 1 and have a more optimal aspect ratio, important
(29) Ramachandran, T. R.; Baur, C.; Bugacov, A.; Madhukar, A.;
Koel, B. E.; Requicha, A.; Gazen, C. Nanotechnology 1998, 9, 237.
J . Org. Chem, Vol. 69, No. 4, 2004 1015

Li et al.
SCHEME 4a
a
Reagents and conditions: (a) Pd(PPh3)2Cl2, CuI, NEt3/THF; (b) n-BuI, reflux.
F IGURE 5. AFM images (1.00 × 1.00 µm) of freshly cleaved mica after spin-coating with the following: (A) 0.25 µM solution of
30 in CH2Cl2; (B) 1.00 µM solution of 30 in CH2Cl2; and (C) 0.25 µM solution of leg/foot segment 349 (Scheme 4). Note the dependence
of 30 image density on concentration (A vs B). Nanoscale features such as those seen in C are occasionally seen on certain regions
of the surface when imaging freshly cleaved mica and may represent mica particulates produced as the result of the cleavage.8,29
C12H14N3 (M + 1) 200.1, found 200.1. Anal. Calcd for
12H13N3: C, 72.33; H, 6.58; N, 21.09. Found: C, 72.15; H,
6.67; N, 21.15.
P y r r o lid in -1-y l[3-(4-t r im e t h y ls ila n y le t h y n y lp h e -
n yleth yn yl)p h en yl]d ia zen e (18). A mixture of iodide 13
(5.00 g, 16.7 mmol), alkyne 15 (3.08 g, 15.3 mmol), Pd(PPh3)2-
Cl2 (0.54 g, 0.77 mmol), and CuI (0.30 g, 0.15 mmol) in Et3N
(15 mL) and THF (65 mL) was heated with stirring at 60 °C
for 2 h and then at room temperature for 20 h. The reaction
mixture was filtered and the solids were washed with ether
(50 mL). The combined filtrate and wash were evaporated to
dryness. The residue was purified by chromatography on silica
gel with 1:9 EtOAc/hexanes as the eluent to give 18 (5.1 g,
89%) as colorless crystals, which were pure by TLC and
C
3-(E t h yn ylp h en yl)p yr r olid in -1-yld ia zen e (15). To a
solution of pyrrolidin-1-yl(4-trimethylsilanylethynylphenyl)-
diazene (14, 500 mg, 1.84 mmol)13 in THF (6 mL) was added
a 1 M solution of n-Bu4NF in THF (2.00 mL, 2.00 mmol) with
stirring at -20 °C. After 30 min the mixture was diluted with
water (30 mL) and extracted with CH2Cl2 (2 × 20 mL). The
combined extract was evaporated and the residue was purified
by chromatography on silica gel with 1:1 hexanes/CH2Cl2 as
the eluent to give diazene 15 (348 mg, 95%) as light yellow
crystals, which were pure by TLC and NMR: mp 60-62 °C;
1H NMR δ 1.98 (t, J ) 6.8 Hz, 4H), 3.01 (s, 1H), 3.75 (br s,
4H), 7.21-7.24 (m, 2H), 7.35-7.38 (m, 2H), 7.53 (s, 1H); 13C
NMR δ 23.73, 76.56, 83.91, 121.25, 122.38, 123.81, 128.63,
128.75, 151.31; MS calcd for C12H14N3 (M + 1) 200.1, found
200.2.
1
NMR: mp 140-142 °C; H NMR δ 0.25 (s, 9H), 2.01 (t, J )
6.5 Hz, 4H), 3.78 (br s, 4H), 7.24-7.31 (m, 2H), 7.37-7.43 (m,
5H), 7.58 (br s, 1H); 13C NMR δ -0.10, 23.75, 88.51, 91.69,
96.09, 104.67, 121.13, 122.68, 123.16, 123.28, 123.52, 128.14,
128.85, 131.36, 131.82, 151.36; MS calcd for C23H26N3Si (M +
1) 372.2, found 372.2.
[3-(4-Eth yn ylp h en yleth n yl)p h en yl]p yr r olid in -1-yld ia -
zen e (19). Powdered K2CO3 (0.500 g, 3.62 mmol) was added
to a stirred solution of silyl derivative 18 (1.5 g, 4.0 mmol) in
(30) Godt, A. J . Org. Chem. 1997, 62, 7471.
1016 J . Org. Chem., Vol. 69, No. 4, 2004

Well-Defined Tower-Shaped 1,3,5-Trisubstituted Adamantanes
CH2Cl2 (20 mL) and MeOH (40 mL) at room temperature. After
2 h the solvent was removed and the residue was purified by
chromatography over a short column of silica gel. Elution with
1:10 ether/hexane gave alkyne 19 (3.81 g, 95%) as colorless
crystals, which were pure by TLC and NMR: mp 126-127
128.36, 130.72, 130.81, 131.61, 131.64, 132.33, 132.60, 134.76,
138.56, 165.60; MS calcd for C103H84O6Si3 (M + 2) 1500.5, found
1500.5. Anal. Calcd for C103H82O6Si3‚2H2O: C, 80.54; H, 5.64.
Found: C, 80.76; H, 5.37. Continued elution gave 22 (33 mg,
6%) as a white solid: 1H NMR δ 0.26 (s, 36H), 1.85-1.92 (m,
12H), 2.06-2.15 (m, 12H), 2.21 (m, 2H), 3.93 (s, 12H), 7.28 (t,
J ) 7.5 Hz, 4H), 7.35 (d, J ) 7.8 Hz, 4H), 7.44 (d, J ) 7.5 Hz,
4H), 7.50 (s, 16H), 7.57 (s, 4H), 7.79 (t, J ) 1.7 Hz, 4H), 8.08
(t, J ) 1.4 Hz, 4H), 8.12 (t, J ) 1.5 Hz, 4H); FAB MS, calcd
for C148H121O8Si4 (M + 3), 2137.8, found 2137.8.
1
°C; H NMR δ 2.03 (t, J ) 6.6 Hz, 4H), 3.17 (s, 1H), 3.80 (br
s, 4H), 7.27-7.33 (m, 2H), 7.38-7.42 (m, 1H), 7.47 (s, 4H),
7.60 (d, J ) 1.2 Hz, 1H); 13C NMR δ 23.77, 78.79, 83.30, 88.33,
91.78, 121.18, 121.65, 123.18, 123.22, 123.94, 128.18, 128.87,
131.45, 132.01, 151.39; MS calcd for C20H18N3 (M + 1) 300.1,
found 300.1. Anal. Calcd for C20H17N3: C, 80.24; H, 5.72; N,
14.04. Found: C, 80.13; H, 5.52; N, 13.88.
1,3,5-Tr is-{2-[3-({[4-(3-m e t h oxyca r b on yl-5-e t h yn yl-
ph en yl)eth yn yl]ph en yl}eth yn yl)ph en yl]eth yn yl}adam an -
ta n e (24). A 1 M solution of Bu4NF (0.600 mL, 0.600 mmol)
in THF was added dropwise to a stirred solution of TMS
derivative 23 (220 mg, 0.147 mmol) in THF (10 mL) at -20
°C and then the solution was stirred for 2 h. The solvent was
removed and the residue was dissolved in CH2Cl2 (30 mL) and
washed with water (20 mL) and brine (2 × 30 mL). The organic
layer was dried over anhydrous Na2SO4 and evap-
orated to dryness. The residue was purified by chromatography
with 3:7 CH2Cl2/hexanes as the eluent to give triester 24 (174
mg, 93%) as white crystals, which were pure by TLC and
NMR: mp 119-122 °C; 1H NMR δ 1.93 (br s, 6H), 2.16 (s,
6H), 2.25 (m, 1H), 3.16 (s, 3H), 3.94 (s, 9H), 7.29 (t, J ) 7.8
3-{4-[3-(P yr r olid in -1-yla zo)p h en yleth yn yl]p h en yleth y-
n yl}-5-tr im eth ylsila n yleth yn ylben zoic Acid Meth yl Es-
ter (20). A thick-walled reaction tube was charged with iodide
10 (301 mg, 0.840 mmol), alkyne 19 (277 mg, 0.942 mmol),
Pd(PPh3)2Cl2 (29.5 mg, 0.042 mmol), CuI (16 mg, 0.084 mmol),
THF (10 mL), and Et3N (5 mL). The suspension was flushed
with N2, capped, and then heated at 50-60 °C for 12 h. The
mixture was filtered and the residue was washed with
CH2Cl2 (20 mL). The combined filtrate and wash were evapo-
rated to dryness. The residue was chromatographed with 1:1
CH2Cl2/hexanes as the eluent to afford diazene 20 as a
colorless glass (400 mg, 90%), which was pure by TLC and
1
NMR: mp 137-139 °C; H NMR δ 0.26 (s, 9H), 2.04 (t, J )
Hz, 3H), 7.38 (dt, J 1 ) 7.8 Hz, J 2 ) 1.4 Hz, 3H), 7.44 (dt, J 1 )
6.75 Hz, 4H), 3.81 (br s, 4H), 3.94 (s, 3H), 7.31 (m, 2H), 7.40
(m, 1H), 7.50 (d, J ) 1.8 Hz, 4H), 7.60 (d, J ) 1.2 Hz, 1H),
7.80 (t, J ) 1.7 Hz, 1H), 8.13 (t, J ) 1.7 Hz, 1H); 13C NMR δ
-0.30, 23.62, 52.27, 88.39, 89.09, 90.52, 91.91, 96.13, 102.87,
121.06, 122.04, 123.10, 123.64, 123.70, 123.86, 128.03, 128.74,
130.54, 131.45, 132.17, 132.39, 138.38, 151.27, 165.44; MS
calcd for C33H32N3O2Si (M + 1) 530.2, found 530.2. Anal. Calcd
for C33H31N3O2Si ‚1/2H2O: C, 73.58; H, 5.99; N, 7.80. Found:
C, 73.80; H, 5.80; N 7.63.
3-[4-(3-Iod op h en yleth yn yl)p h en yleth yn yl]-5-tr im eth -
ylsila n yleth yn ylben zoic Acid Meth yl Ester (21). Diazene
20 (300 mg, 0.566 mmol) was dissolved in n-BuI (6 mL) and
then heated at 135-145 °C for 12 h. The mixture was evap-
orated to dryness. The residue was purified by chromatography
with 1:4 CH2Cl2/hexanes as the eluent to afford iodide 21 (268
mg, 85%) as a viscous colorless oil, which was pure by TLC
and NMR: 1H NMR δ 0.26 (s, 9H), 3.94 (s, 3H), 7.10 (t, J )
7.8 Hz, 1H), 7.48 (m, 1H), 7.50 (s, 4H), 7.68 (m, 1H), 7.80 (t, J
) 1.5 Hz, 1H), 7.90 (t, J ) 1.5 Hz, 1H), 8.08 (t, J ) 1.7 Hz,
1H), 8.13 (t, J ) 1.7 Hz, 1H); 13C NMR δ -0.21, 52.45, 89.47,
89.66, 90.21, 90.37, 93.71, 96.31, 102.88, 122.73, 123.04,
123.72, 124.04, 125.00, 129.87, 130.69, 131.64, 132.35, 132.65,
137.47, 138.58, 140.13, 165.67; MS calcd for C29H22IO2Si (M
- 1) 557.05, found 557.0. Anal. Calcd for C29H23IO2Si: C, 62.37;
H, 4.15. Found: C, 62.49; H, 4.11.
7.5 Hz, J 2 ) 1.5 Hz, 3H), 7.51 (s, 12H), 7.60 (m, 3H), 7.80 (t,
J 1 ) 1.5 Hz, 3H), 8.10 (t, J ) 1.5 Hz, 3H), 8.15 (t, J ) 1.5 Hz,
3H); 13C NMR δ 28.09, 30.66, 40.55, 46.40, 52.48, 78.84, 79.81,
81.70, 89.18, 89.33, 90.62, 90.78, 96.27, 122.40, 122.98, 123.06,
123.42, 123.89, 123.93, 128.37, 130.80, 131.60, 131.64, 132.72,
132.75, 134.74, 138.69, 165.53; MS calcd for C94H57O6 (M - 1)
1281.4, found 1281.4. Anal. Calcd for C94H58O6‚2H2O: C, 85.56;
H, 4.74. Found: C, 85.51; H, 4.45.
1,3,5-Tr is-{2-[3-({[4-(3-car boxy-5-eth yn ylph en yl)eth yn yl]-
p h en yl}eth yn yl)p h en yl]eth yn yl}a d a m a n ta n e (25). A so-
lution of 25% aqueous NaOH (0.30 mL, 1.9 mmol) was added
to a solution of triester 24 (168 mg, 0.131 mmol) in CHCl3 (2.5
mL) and ethanol (3 mL). The mixture was stirred at room
temperature for 2 h and then an additional portion of ethanol
(5 mL), CHCl3 (0.8 mL), water (1.8 mL), and 25% aqueous
NaOH (0.5 mL) was added to make the reaction mixture
homogeneous. The solution was stirred for an additional 2 h
at room temperature and then evaporated to dryness. The
residue was treated with water (8 mL) and the suspension was
acidified with 1 M HCl. The mixture was extracted with ether
(3 × 10 mL) and the combined extracts were washed with brine
and dried over Na2SO4. Removal of the solvent gave triacid
25 (133 mg, 82%) as a light yellow solid, which was pure by
TLC and NMR: dec ∼160-200 °C (PHB, yellow to brown
1
solid); H NMR (300 MHz, DMSO-d6) δ 1.91 (br s, 6H), 2.12
(br s, 6H), 2.20 (m, 1H), 4.43 (s, 3H), 7.45 (s, 6H), 7.56-7.64
(m, 18H), 7.90 (s, 3H), 7.96 (s, 3H), 8.06 (s, 3H); 13C NMR (125
MHz, DMSO-d6) δ 27.49, 30.12, 45.62, 79.37, 81.49, 82.60,
89.35, 89.43, 90.38, 90.58, 96.66, 121.99, 122.46, 122.65,
122.87, 123.18, 123.43, 129.17, 130.92, 131.69, 131.85, 132.08,
132.16, 132.30, 134.11, 137.77, 165.65; MS calcd for C91H52O6
(M) 1240.4, found 1240.4. Anal. Calcd for C91H52O6‚2H2O: C,
85.56, H, 4.42. Found: C, 85.19; H, 4.04.
Ma cr ocyclic Tr ila cta m 26. Oxalyl chloride (1 mL) was
added dropwise to a stirred solution of triacid 25 (200 mg,
0.161 mmol) in dry benzene (10 mL). Two drops of DMF were
added and the mixture was stirred at room temperature for
24 h. Evaporation of the volatiles gave crude triacid chloride,
which was dissolved in chlorobenzene (10 mL) and DMA (400
µL) and placed in a syringe. A second syringe was filled with
tris(2-aminoethyl)amine (46 µL, 0.314 mmol) dissolved in
chlorobenzene (10 mL). The contents of the two syringes were
simultaneously added dropwise at a rate of 1 mL/h to vigor-
ously stirred chlorobenzene (150 mL) at room temperature in
a 250-mL three-necked flask under a N2 atmosphere with the
aid of a syringe pump. Additions were complete after 10 h and
the reaction mixture was allowed to stir at room temperature
1,3,5-Tr is-{2-[3-({[4-(3-m et h oxyca r b on yl-5-t r im et h yl-
sila n yleth yn ylp h en yl)eth yn yl]p h en yl}eth yn yl)p h en yl]-
eth yn yl}a d a m a n ta n e (23). A thick-walled reaction tube was
charged with iodide 21 (508 mg, 0.910 mmol), triethynylada-
mantane 8 (51 mg, 0.245 mmol), Pd(PPh3)2Cl2 (26 mg, 0.037
mmol), CuI (14 mg, 0.074 mmol), Et3N (5 mL), and THF (10
mL). The mixture was flushed with N2 and sealed with a
Teflon screwcap. The mixture was heated with stirring at 55-
60 °C for 24 h. The suspension was filtered and the residue
was washed with ether (20 mL) and CH2Cl2 (20 mL). The
combined filtrate and wash were evaporated to dryness. The
residue was purified by chromatography with 3:7 CH2Cl2/
hexanes as the eluent to give crude triester 23, which was
further purified by chromatography. Elution with 20:79.5:0.5
CH2Cl2/hexanes/CH3OH gave ester 23 (230 mg, 62%) as
colorless crystals, which were pure by TLC and NMR: mp
154-156 °C; 1H NMR δ 0.26 (s, 27H), 1.93 (br s, 6H), 2.16 (br,
7H), 3.91 (s, 9H), 7.28 (dd, J ) 7.8, 7.8 Hz, 1H), 7.38 (d, J )
7.8 Hz, 1H), 7.44 (d, J ) 7.8 Hz, 1H), 7.50 (s, 4H), 7.62 (s,
1H), 7.78 (s, 1H), 8.07 (s, 1H), 8.10 (s, 1H); 13C NMR δ -0.15,
28.21, 30.72, 40.64, 46.49, 52.40, 79.42, 89.42, 90.51, 90.82,
96.31, 102.98, 122.54, 123.15, 123.41, 123.79, 124.00, 124.05,
J . Org. Chem, Vol. 69, No. 4, 2004 1017

Li et al.
for another 10 h. The cloudy reaction mixture was filtered
through a glass filter to give a clear colorless solution, which
was concentrated to dryness. The residue was purified by
chromatography with 5:95 CH3OH/CHCl3 as the eluent to give
crude 26. Further purification by radial chromatography on
silica gel with 4:96 CH3OH/CHCl3 as the eluent gave macro-
cycle 26 (13 mg, 14%) as a white solid, which was pure by NMR
and TLC: dec ∼218 °C (PHB, yellow solid); 1H NMR (500 MHz)
δ 1.91 (br s, 6H), 2.16 (d, J ) 13 Hz, 3H), 2.25 (d, J ) 13 Hz,
3H), 2.24-2.27 (m, 1H), 2.86 (br t, 6H), 3.13 (s, 3H), 3.60 (br
q, 6H), 6.82 (t, 3H, disappeared after D2O exchange), 7.28 (t,
J ) 8.0 Hz, 3H), 7.33 (d, J ) 8.0 Hz, 3H), 7.40 (d, J ) 7.5 Hz,
3H), 7.49 (d, J ) 8.0 Hz, 6H), 7.52 (d, J ) 8.5 Hz, 6H), 7.67 (s,
3H), 7.69 (s, 3H), 7.77 (s, 3H), 7.86 (s, 3H); 13C NMR δ 27.98,
30.98, 38.19, 39.38, 47.67, 53.96, 77.20, 78.96, 80.41, 81.88,
89.50, 89.59, 90.64, 90.94, 96.83, 122.54, 123.05, 123.14,
123.42, 123.80, 123.94, 128.43, 129.87, 130.18, 130.55, 131.61,
131.65, 134.87, 137.04, 137.60, 166.56; FAB MS calcd for
mL). The mixture was flushed with N2 and sealed with a
Teflon screwcap. The mixture was heated with stirring at 55-
60 °C for 18 h. The suspension was filtered and the filtrate
was evaporated to dryness. The residue was purified by
chromatography with 3:7 CH2Cl2/hexanes as the eluent to give
diazene 31 (221 mg, 82%) as white crystals, which were pure
by TLC and NMR: mp 90-92 °C; 1H NMR δ 2.04 (t, J ) 6.75
Hz, 4H), 2.37 (s, 6H), 3.81 (br s, 4H), 4.07 (s, 4H), 7.14 (m,
1H), 7.32 (d, J ) 1.5 Hz, 2H), 7.39 (d, J ) 8.7 Hz, 2H), 7.47 (d,
J ) 9.0 Hz, 2H); 13C NMR δ 23.75, 30.32, 32.86, 88.50, 90.47,
119.11, 120.28, 124.25, 128.89, 130.65, 132.37, 138.25, 151.28,
194.86; MS calcd for C24H26N3O2S2 (M + 1) 452.14, found 452.2.
Anal. Calcd for C24H25N3O2S2: C, 63.83; H, 5.58; N, 9.30.
Found: C, 63.82; H, 5.48; N 9.14.
4-[3,5-B i s (a c e t y ls u lfa n y m e t h y l)p h e n y le t h y n y l]-
iod oben zen e (32). A solution of diazene 31 (200 mg, 0.443
mmol) in n-BuI (8 mL) was heated at 120 °C for 48 h. The
solvent was removed and the residue was purified by chro-
matography with 3:7 CH2Cl2/hexane as the eluent to give
diazene 32 (171 mg, 80%) as white crystals, which were pure
by TLC and NMR: mp 120-121.5 °C; 1H NMR δ 2.37 (s, 6H),
4.07 (s, 4H), 7.17 (s, 1H), 7.23 (d, J ) 8.4 Hz, 2H), 7.33 (d, J
) 1.5 Hz, 2H), 7.69 (d, J ) 8.4 Hz, 2H); 13C NMR δ 30.28,
32.79, 88.83, 90.10, 94.28, 122.49, 123.56, 129.41, 130.73,
133.05, 137.49, 138.45, 194.68; MS calcd for C20H17IO2S2Na
(M + Na) 503.0, found 503.0. Anal. Calcd for C20H17IO2S2: C,
50.00; H, 3.57. Found: C, 49.95; H 3.49.
Tow er -Sh a p ed Molecu le 33. A mixture of macrocyclic
trilactam 26 (96.1 mg, 0.0721 mmol), iodide 32 (111 mg, 0.2307
mmol), Pd(PPh3)2Cl2 (5.4 mg, 0.0077 mmol), and CuI (4.4 mg,
0.0231 mmol) in a solution of Et3N (8 mL) and THF (6 mL)
was heated at 115 °C for 8 h. The solvent was evaporated and
the residue was purified by chromatography over a short
column of silica gel. Elution with 3:97 MeOH/CHCl3 gave crude
33, which was further purified by radial chromatography (2
mm disk). Elution with 1:50 MeOH/CHCl3 gave 33 (24.2 mg,
14%) as an off-white solid, which was pure by NMR and TLC:
1H NMR δ 1.91 (br s, 6H), 2.17 (d, J ) 12 Hz, 3H), 2.26 (d, J
) 12 Hz, 3H), 2.24-2.28 (m, 1H), 2.37 (s, 18H), 2.89 (br, 6H),
3.64 (br, 6H), 4.07 (s, 12H), 6.96 (br s, 3H), 7.18 (s, 3H), 7.25-
7.52 (m, 45H), 7.68 (s, 3H), 7.72 (m, 3H), 7.94 (br s, 3H); FAB
MS calcd for C157H112N4O9S6 (M) 2389, found 2389.
Atom ic F or ce Micr oscop y Exp er im en ts. AFM measure-
ments were carried out with a Nanoscope IIIa Multimode AFM
(Digital Instruments, Santa Barbara, CA), using a 10 µm
scanner. Tapping mode AFM (TM AFM) scans were performed
in air with NANOSENSORS silicon cantilevers/tips: type
NCH, cantilever resonance frequency f0 ) 289-332 kHz and
force constant 24.0-37.0 N/m.
The instrument was operated at frequencies slightly lower
than the natural resonance frequency in air. All data were
recorded in height mode. Set point values were chosen so that
the interaction of the tip and sample provided a good compro-
mise between stability and resolution, without damaging the
tip or the sample. Scan rates ranged from 1 to 3 Hz. Images
were taken at a 512 × 512-pixel resolution to increase the
detail in the images. All TM AFM studies were carried out on
freshly cleaved muscovite mica, grade V-4 (Structure Probe,
Inc.).
Sa m p le P r ep a r a tion . Spectroscopic grade solvents were
used for sample preparation. Molecule 30 on mica: One drop
of a 0.25 or 1.0 µM solution of 30 in CH2Cl2 was spin-coated
onto freshly cleaved mica (cleaved with Scotch tape) for 15-
20 s under ambient conditions at a speed of 2000 rpm.
Scanning of the sample by AFM began immediately after
completion of the spin-coating step. A control image was
recorded under similar conditions by spin-coating a 0.25 µM
solution of leg/foot segment 34 onto freshly cleaved mica. In
this case only the mica surface was visible.
C
97H66N4O3 (M + 2) 1334.5, found 1334.5. Anal. Calcd for
C97H64N4O3‚2H2O: C, 85.06; H, 5.00; N, 4.09. Found: C, 85.29;
H, 4.68; N, 3.79.
Th ioa cet ic Acid S-[4-(4-Iod op h en ylet h yn yl)b en zyl]
Ester (29). A mixture of thioester 28 (300 mg, 1.58 mmol),
1,4-diiodobenzene (2.00 g, 6.32 mmol), Pd(PPh3)2Cl2 (55 mg,
0.079 mmol), CuI (30 mg, 0.16 mmol), Et3N (8 mL), and THF
(8 mL) in a thick-walled reaction tube was flushed with N2
and sealed with a Teflon screwcap. The mixture was heated
with stirring at 50-60 °C for 20 h. The suspension was filtered
and the residue was washed with CH2Cl2 (30 mL). The
combined filtrate and wash were evaporated to dryness. The
residue was purified by chromatography with 3:7 CH2Cl2/
hexanes as the eluent to give iodide 29 (410 mg, 67%) as yellow
crystals, which were pure by NMR and TLC: mp 120-122
1
°C; H NMR δ 2.38 (s, 3H), 4.13 (s, 2H), 7.25 (d, J ) 8.4 Hz,
2H), 7.29 (d, J ) 8.4 Hz, 2H), 7.46 (d, J ) 8.4 Hz, 2H), 7.69 (d,
J ) 8.4 Hz, 2H); 13C NMR δ 30.28, 33.17, 88.65, 90.45, 94.12,
121.75, 122.62, 128.85, 131.74, 133.01, 137.43, 138.16, 194.81;
MS calcd for C17H13IOSNa (M + Na) 415.0, found 415.0. Anal.
Calcd for C17H13IOS: C, 52.05; H, 3.34. Found: C, 52.18; H,
3.06.
Tow er -Sh a p ed Molecu le 30. A thick-walled reaction tube
was charged with macrocyclic trilactam 26 (16.0 mg, 0.0120
mmol), iodide 29 (18.8 mg, 0.0480 mmol), Pd(PPh3)2Cl2 (1.3
mg, 0.0018 mmol), CuI (0.7 mg, 0.004 mmol), THF (12 mL),
and Et3N (12 mL). The mixture was flushed with N2 and sealed
with a Teflon screwcap. The mixture was heated at 50-60 °C
for 20 h and then allowed to stir at room temperature for 24
h. The suspension was filtered and the residue was washed
with CH2Cl2 (20 mL) and Et2O (10 mL). The combined filtrate
and wash were evaporated to dryness. The residue was
purified by chromatography. Elution with CH2Cl2 followed by
3:97 MeOH/CH2Cl2 gave crude 30, which was further purified
by radial chromatography (1 mm disk). Elution with 1:50
CH3OH/CHCl3 gave molecule 30 (4.5 mg, 15%) as light yellow
crystals, which were pure by NMR and TLC: 1H NMR (500
MHz) δ 1.90 (br s, 6H), 2.16 (d, J ) 14 Hz, 3H), 2.25 (d, J )
13 Hz, 3H), 2.23-2.26 (m, 1H), 2.36 (s, 9H), 2.86 (br t, 6H),
3.62 (br q, 6H), 4.11 (s, 6H), 7.00 (m, 3H, disappeared after
D2O exchange), 7.24-7.56 (m, 42H), 7.65-7.69 (m, 12H), 7.89
(s, 3H); 13C NMR (125 MHz) δ 27.98, 30.33, 30.99, 33.27, 38.07,
38.38, 47.74, 53.61, 80.44, 89.34, 89.62, 89.70, 90.46, 90.74,
90.89, 91.15, 96.85 (overlap of an alkynyl carbon), 121.95,
122.46, 122.65, 123.17, 123.36, 123.74, 123.95, 124.02, 128.44,
128.54, 128.88, 129.25, 129.92, 130.15, 131.49, 131.61, 131.87,
132.04, 132.11, 132.92, 135.02, 136.93, 137.02, 138.12, 166.86,
194.87; UV/vis (CH2Cl2) λmax ) 328 nm; FAB MS calcd for
C
148H102N4O6S3 (M + 2) 2126.7, found 2126.7.
N -P y r r o li d i n o {4-[3,5-b i s (a c e t y ls u lfa n y m e t h y l)-
p h en yleth yn yl]p h en yl}d ia zen e (31). A thick-walled reac-
tion tube was charged with iodide 17 (226 mg, 0.595 mmol),
alkyne 12 (129 mg, 0.648 mmol), Pd(PPh3)2Cl2 (21 mg, 0.030
mmol), CuI (11 mg, 0.058 mmol), Et3N (2 mL), and THF (10
Ack n ow led gm en t. We thank Margret Ryan for
measuring the fluorescence spectrum of 30. We thank
1018 J . Org. Chem., Vol. 69, No. 4, 2004

Well-Defined Tower-Shaped 1,3,5-Trisubstituted Adamantanes
27-29, 31-33; 1H NMR (500 MHz) spectra for 26 and 30; 13
C
the National Institute of Biomedical Imaging and
Bioengineering EB002051 (formerly GM27137) for gen-
erous support of this research.
NMR (75 MHz) spectra for 8, 10-13, 15-21, 23, 24, 26-29,
31, and 32; 13C NMR (125 MHz) spectra for 25, 26, and 30;
2D NMR (500 MHz) spectra for 26 and 30; FAB MS for 22,
26, and 30. This material is available free of charge via the
Internet at http://pubs.acs.org.
Su p p or tin g In for m a tion Ava ila ble: General experimen-
tal details and spectral and analytical data for 8, 11, 13, 16,
1
17, 27, 28; H NMR (300 MHz) spectra for 8, 10-13, 15-25,
J O035640+
J . Org. Chem, Vol. 69, No. 4, 2004 1019