Combinatorial synthesis of oligo(phenylene ethynylene)s

Article abstract of DOI:10.1016/S0040-4020(02)01409-6

The combinatorial synthesis of oligo(phenylene ethynylene) tetramers, both in solution and on solid support, is described. These products are of interest for molecular electronics applications. An iterative sequence, coupling of aryl halides to alkynes under Sonogashira conditions, was used. Five monomers functionalized with electron-donating or electron-withdrawing groups were synthesized, and used to generate a library of 25 trimers in a solution-phase based process. A library of 24 tetramers was prepared by subsequent protodesilylation and coupling with the alligator clip 4-iodo-1-thioacetylbenzene. The solution-phase based sequence was successfully adapted to a higher yielding directed split-and-pool solid-phase process, with average yields of 78-86% for each step over seven steps. A triazene linker group was used to attach the starting monomer to the polymer beads. At the completion of the solid-phase-based process, traceless cleavage of trimers from the resin was achieved by sonication of the resin in 10% HCl/THF solution. The released products were then poised for the final step in the sequence, attachment of the alligator clip.

Full text of DOI:10.1016/S0040-4020(02)01409-6

Tetrahedron 58 (2002) 10387–10405
Combinatorial synthesis of oligo(phenylene ethynylene)s
*
Jiunn-Jye Hwang and James M. Tour
Department of Chemistry and Center for Nanoscale Science and Technology, MS-222, Rice University, 6100 Main Street,
Houston, TX 77005, USA
Received 15 August 2002; accepted 30 October 2002
Abstract—The combinatorial synthesis of oligo(phenylene ethynylene) tetramers, both in solution and on solid support, is described. These
products are of interest for molecular electronics applications. An iterative sequence, coupling of aryl halides to alkynes under Sonogashira
conditions, was used. Five monomers functionalized with electron-donating or electron-withdrawing groups were synthesized, and used to
generate a library of 25 trimers in a solution-phase based process. A library of 24 tetramers was prepared by subsequent protodesilylation and
coupling with the alligator clip 4-iodo-1-thioacetylbenzene. The solution-phase based sequence was successfully adapted to a higher yielding
directed split-and-pool solid-phase process, with average yields of 78–86% for each step over seven steps. A triazene linker group was used
to attach the starting monomer to the polymer beads. At the completion of the solid-phase-based process, traceless cleavage of trimers from
the resin was achieved by sonication of the resin in 10% HCl/THF solution. The released products were then poised for the final step in the
sequence, attachment of the alligator clip. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
metallic surfaces, can behave as molecular wires conducting
electrical currents, as devices showing negative differential
resistance (NDR), and/or as memory components retaining
electrical bits of information,6 depending on their function-
ality and structure.
Combinatorial chemistry is one of the fastest growing fields
in chemistry because combinatorial-based processes can
rapidly generate large libraries of small molecules.1 This
methodology has been extensively utilized2 for the synthesis
of potential drug candidates, but lately the combinatorial
approach has been applied to materials research,3 mainly on
inorganic solid-state materials, polymeric materials, and
catalytic systems, in order to speed discovery and develop-
ment. A combinatorial process coupled with effective
screening techniques can yield a great deal of information
concerning the activity of the synthesized compounds in the
desired application. Collection and analysis of large data
sets can produce structure–activity relationships (SAR) that
can lead to optimization of the molecular properties through
a feedback loop of synthesis and screening.
Most of the OPEs we have synthesized to date have been
‘trimers’ containing three aromatic rings.6 In the present
work, we report on our efforts to expand OPE space to
include a large group of tetramers (compounds with four
aromatic rings), synthesized using combinatorial chemistry.
2. Results and discussion
2.1. Monomer synthesis
Research in the field of molecular electronics4 is targeted to
the development of molecules that can function as wires or
switches, with the eventual goal of replacing present solid-
state-based devices. In 1974, Aviram and Ratner first
proposed5 that a single organic molecule could act as a
rectifier of electrical current. Since then, considerable effort
has been expended to synthesize and study a variety of
molecules as potential molecular electronics candidates.
Recently, we have been concentrating on the synthesis and
testing of conjugated oligo(phenylene ethynylene)s
(OPEs).6 OPEs, in self-assembled monolayers (SAMs) on
In order to develop SAR data, monomers with electron-
donating groups (EDGs), such as alkyl or alkoxy, or
electron-withdrawing groups (EWGs), such as F, CN, and
CF3, were designed and synthesized. The five scaffold
monomers were synthesized as shown in Scheme 1.
Sonogashira coupling7 of aniline derivatives 1a–e8 with
trimethylsilylacetylene (TMSA) in Et3N gave high yields of
the products 2a–e. Without further purification, 2a–e were
converted to the corresponding diazonium salts using the
method of Doyle et al.,9 followed by quenching with NaI
and I210 to give the desired monomers 3a–e in good yields.
2.2. Oligomer syntheses in solution
Keywords: tetramers; oligomer; molecular electronics.
*
Corresponding author. Tel.: 7133486246; fax: 7133486250;
e-mail: tour@rice.edu
Synthesis of a library of 25 tetramers of OPEs was carried
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01409-6

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J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
Scheme 1.
Scheme 2.
out by a combinatorial approach with the monomers 3a–e.
The solution phase synthesis of tetramers is outlined in
Scheme 2.
Sonogashira coupling five monomers 3a–e to phenyl-
acetylene afforded five corresponding dimers 4a–e in
excellent yield. Protodesilylation11,12 of the terminal
alkynes 4a–e with potassium carbonate in CH3OH and
CH2Cl2 gave 5a–e followed by a set of reactions in which
each of the five alkynes 5a–e was subjected to coupling
with the five monomers 3a–e to generate a library of 25
trimers. The coupling reaction of monomers bearing CF3 or
Et required higher temperatures and longer reaction times,
and they gave lower yields. The relatively lower yields in
this coupling may be caused by steric effects. The final step
in the process is the attachment of 1-iodo-4-thioacetylben-
zene 11,11 the alligator clip. A library of 24 potential
molecular devices 12b–e and 13a–e to 16a–e were
Table 1. Isolated yields of solution-phase synthesized trimers (6–10) and
tetramers (12–16)
R1¼H
R1¼F
R1¼CN
R1¼CF3
R1¼Et
R2¼H
R2¼F
6a (44%)
12aa
7a (86%)
8a (72%)
9a (75%)
13a (38%) 14a (58%) 15a (40%) 16a (46%)
10a (52%)
6b (66%) 7b (87%) 8b (88%) 9b (77%) 10b (70%)
12b (43%) 13b (41%) 14b (42%) 15b (36%) 16b (53%)
R2¼CN 6c (84%)
7c (97%)
8c (77%)
9c (70%)
10c (69%)
12c (41%) 13c (48%) 14c (42%) 15c (26%) 16c (46%)
R2¼CF3 6d (71%) 7d (62%) 8d (72%) 9d (51%) 10d (64%)
12d (47%) 13d (41%) 14d (30%) 15d (56%) 16d (51%)
R2¼Et
6e (55%)
12e (47%) 13e (48%) 14e (43%) 15e (21%) 16e (37%)
7e (54%)
8e (71%)
9e (68%)
10e (51%)
a
12a was not prepared because of low solubility of 6a.

J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
10389
Scheme 3. Retrosynthetic analysis.
obtained in moderate yields (Table 1). Unsubstituted
tetramer 12a was not prepared due to the low solubility of
trimer 6a. Tetramers bearing only one functional group in
the two central phenyl units exhibited low solubility in
organic solvents.
serve as a handle for further manipulation using standard
transition metal-catalyzed coupling conditions to add
additional monomeric units. The third method, traceless
cleavage using 10% HCl in THF,17 converts the triazene
linker into a C–H bond15a to give the corresponding arenes.
2.3. Oligomer syntheses on a solid support
The a priori retrosynthetic approach to the solid phase
combinatorial syntheses of the library of target OPEs is
outlined in Scheme 3. The tetramers would be synthesized
from the set of immobilized trimers by first cleaving the
trimers and then adding the alligator clip moiety. The
trimers would be synthesized using an iterative approach
where each monomer is derived from anilines 1a–e via the
appropriate chemical manipulations, which could be varied
depending on yields and other problems that might be
encountered during the synthesis. Anilines 1a–e were either
commercially available, or were obtainable via a short
synthesis from commercially available products.
The advantages of employing solid phase synthesis for the
preparation of conjugated oligomers instead of solution
phase synthesis have been demonstrated by many research
groups.12,13 Advantages include higher overall yields as
well as rapid purification processes, since time-consuming
chromatography, a bottleneck in conventional solution-
phase-based chemistry, is avoided. We hoped to quickly
adapt the optimized solution phase chemistry to the solid
phase synthesis of the same or similar library, which would
allow us to compare yields of the two processes.
An important issue in the design of a solid-phase
combinatorial synthesis is to choose the proper linker for
placing the starting monomer on the resin. The triazene
linkage has been used by us12 and other research
groups.14–16 The linker is stable under the various reaction
conditions encountered in the synthesis. The triazene linker
can be cleaved using a variety of conditions that yield
soluble products with different functionalities. Trifluoro-
acetic acid (TFA)15 cleavage gives the aromatic diazonium
salt, while cleavage using iodomethane12,14,16 produces the
corresponding aryl iodide. Each of these functionalities can
The first step in the solid phase synthesis of the OPEs was
attachment of the starting monomers to the resin. The
functionalized diazonium salts 17a–c were prepared9 in
high yields from the corresponding aniline derivatives 1a, c,
and d, respectively (Scheme 4).
Propylaminomethylate polystyrene 18 was prepared by
heating a suspension of Merrifield resin with n-propylamine
in a screw cap tube at 708C for 3–4 days.14 Functionalized
diazonium salts 17a–c were reacted with resin 18 in DMF–
THF solution in the presence of K2CO3 to form the

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J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
corresponding resin-immobilized triazene-linked monomers
19a–c, respectively (Scheme 5). The attachment procedure
was repeated to maximize the loading and a total of
2–3 equiv. of diazonium salts were used. Small portions of
resin were taken out and cleaved to give the corresponding
diiodobenzene derivatives 20a–c to monitor the loading. This
method was found to be more accurate than elemental analysis
or weight changes in calculating yields and loading.14,18
Scheme 4.
Treatment of resin-bound monomer 19a with iodomethane
in a screw cap tube at 1208C for 24 h liberated 1,4-
diiodobenzene 20a in 70% yield over three steps. This result
indicated that the first two steps were achieved in high
loadings. Unfortunately, cleavage of resin-bound monomer
19b in iodomethane at 1208C only gave 7–16% yields 20b
over three steps; various reaction times from 12 to 60 h
were screened but did not improve the yield. Slightly
higher yields (29–35%) were obtained by adding CH3CN
co-solvent. Similar low yields were obtained from the
liberation of resin-bound monomer 19c to give 20c. We
suspect that the ortho-EWG functional groups adjacent to
the triazene moiety caused the lower yields; steric hindrance
may also be a factor. We therefore sought to begin with a
scaffold in which the functionalized aromatic ring was
further removed from the triazene moiety.
As shown in the retrosynthetic analysis in Scheme 6, we
altered our synthetic pathway such that the two aromatic
rings containing the functionality were further removed
from the triazene linker. For the highest efficiency and
to take advantage of the easier handling afforded a solid
phase-based system, it was preferable to attach the alligator
Scheme 5.
Scheme 6. Retrosynthetic analysis.

J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
10391
the trimethylsilylethynyl group; 3317 cm21 (strong) alkynyl
carbon-hydrogen stretch; and 2106 cm21 (weak) alkyne
carbon–carbon stretch.
The preparation of resin-bound alkyne 23 was followed by a
parallel synthesis. The subsequent directed sort, split, and
pool synthesis of individual oligomers was performed in
small reactors constructed of polypropylene mesh flow-
through walls, specifically MacroKans,20 using a unique
identification system.21 Resin-bound monomer 23 sealed in
MacroKans were subjected to a Pd/Cu-catalyzed cross-
coupling with monomers 3a–e in Et3N. The catalyst
solution (Pd(dba)2/PPh3/CuI)12,14 was pre-mixed at 708C
for 2 h prior to use. The suspended MacroKans were heated
with the catalyst in a screw cap tube at 658C for 44–48 h.
At the completion of the coupling reaction, the MacroKans
were collected and washed according to a literature
procedure.12,14 The next step in the process was to pool
one (or more) of each resin-bound dimer 24a–e for another
split-and-pool combinatorial reaction with monomers 3a–e.
Resin-bound dimers 24a–e were deprotected with a
solution of TBAF in THF to give the corresponding resin-
bound alkynes, followed by a subsequent Pd/Cu-catalyzed
cross-coupling with monomers 3a–e to afford a library of
25 different polymer-supported trimers 25a–e to 29a–e.
Scheme 7.
clip before cleavage from the resin. Therefore, the last step
would be traceless cleavage. The success of this route
depended on the survival of the thiol protection group. Note
that if we were successful, this route would produce a set of
tetramers in which the functional groups were meta to the
alligator clip, a different set than that produced in the
solution phase work. Retrosynthetically, the procedure
would utilize the same monomers 1a–e as before.
The linker diazonium salt 21 was prepared in high yield
from diazotization of 4-(trimethylsilylethynyl)aniline (2a)
with NOBF4 (Scheme 7).
19
Diazonium salt 21 was then reacted with resin 18 in DMF–
THF solution in the presence of K2CO3 to give the
corresponding triazene monomer 22 (Scheme 8). The
terminal alkyne in resin 22 was revealed by treatment
with a solution of tetrabutylammonium fluoride (TBAF) in
THF to remove the TMS-protecting group and give the
corresponding resin-bound alkyne 23.12,14 Infrared analysis
was used as a simple, non-destructive method to monitor
oligomer synthesis. The IR spectra were assigned as
follows: 2153 cm21 (medium) carbon–carbon stretch of
In order to monitor resin loading, 24a and 24e were
liberated via traceless cleavage15a by sonication at 508C
using 10% HCl in THF solution (Scheme 9). The isolated
yields of 4a and 4e (over five steps from Merrifield resin)
Scheme 8.

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J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
Scheme 9.
were 37% and 43%, respectively. This result indicates that
high loadings and cleavage (.82%, on average) were
achieved in each step.
Since the alligator clip did not survive the cleavage reaction,
we decided to liberate the trimers prior to the coupling with
the alligator clip. The traceless cleavage method was
applied to the polymer-supported trimers 25a–e to 29a–e
to afford products 6a–e to 10a–e that we had previously
taken on to the tetramer stage in the solution phase.
(Scheme 11). The final isolated yields of trimers over seven
steps from commercially available Merrifield resin ranged
from 18 to 34%, an average of 78–86% yield over each step
(Table 2).
Before the cleavage to release the desired library of
products, the last step of the planned synthesis was to
attach alligator clip 11 (Scheme 10). Deprotection of 25c
using TBAF in THF gave the free alkyne that was
subsequently coupled with 11 under standard conditions to
give 30. Unfortunately, after exposure of the resin-bound 30
to 10% HCl in THF at 508C under sonication, the 1H NMR
spectra of crude liberation product 31 indicated a plethora of
products. One of the possible side-reactions would be
hydrolysis of the thioester to form intermediate sulfides that
would subsequently couple in the presence of oxygen to
form insoluble disulfides.
3. Summary
We demonstrated the combinatorial synthesis of oligo-
(phenylene ethynylene)s both in solution phase and on solid
Scheme 10.
Scheme 11.

J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
Table 2. Overall yields of solid-phase synthesized trimers
10393
R1¼H
R1¼F
R1¼CN
R1¼CF3
R1¼Et
R2¼H
6a, 30% (33 mg)
6b, 31% (36 mg)
6c, 33% (39 mg)
6d, 34% (44 mg)
6e, 27% (32 mg)
7a, 23% (26 mg)
7b, 33% (40 mg)
7c, 29% (35 mg)
7d, 31% (42 mg)
7e, 23% (28 mg)
8a, 32% (37 mg)
8b, 34% (42 mg)
8c, 25% (30 mg)
8d, 29% (40 mg)
8e, 26% (32 mg)
9a, 24% (41 mg)
9b, 33% (45 mg)
9c, 28% (39 mg)
9d, 32% (48 mg)
9e, 22% (30 mg)
10a, 27% (32 mg)
10b, 24% (30 mg)
10c, 18% (25 mg)
10d, 23% (28 mg)
10e, 18% (23 mg)
R2¼F
R2¼CN
R2¼CF3
R2¼Et
Yields are based on isolated products after chromatographic purification (amount shown in parentheses) and calculated according to the loading of original
resin.
supports. The construction of oligomers was accomplished
by following an iterative approach using the Sonogashira
coupling of aryl halides to alkynes as the capstone reaction.
Five monomers with electron-donating groups (H, Et) or
electron-withdrawing groups (F, CN, or CF3) were syn-
thesized and used to generate a library of 25 trimers by a
directed sortsplit-and-pool synthesis. The coupling reaction
with the monomers bearing CF3 or Et functional groups
required higher temperatures and longer reaction times, and
gave lower yields. A library of 24 tetramers bearing a
thioacetyl end group was synthesized from those 25 trimers.
We found that the solid-phase combinatorial synthesis
offered advantages over the conventional solution-phase
approach by maximizing overall yields and facilitating the
purification process through avoidance of time-consuming
chromatography. Functional groups ortho to the triazene
linkage group produced lower yields when the scaffold was
removed from the resin, necessitating an easy redesign of
the synthesis. Traceless cleavage from the resin was
effectively achieved via sonication of resin-bound oligomer
in 10% HCl in THF. An average yield of 78–86% (for each
step over seven steps in the solid-phase combinatorial
synthesis) was obtained. This study presents a fast
combinatorial synthesis of OPEs incorporating a diversity
of substituent groups. Testing of these diverse libraries in
molecular electronics applications will allow us to deduce
structure-activity relationships.
NaCl plate. After the beads were swollen with 2–3 drops of
CCl4, a second NaCl plate was pressed onto the beads, and
an FTIR spectrum was recorded.
4.2. General procedure for the coupling of aniline
derivatives with trimethylsilylacetylene
To a stirring solution in a septum-capped tube of the
aniline derivative was added at room temperature
bis(triphenylphosphine)palladium(II)
dichloride
(0.5 mol%), copper(I) iodide (1 mol%) in triethylamine,
and TMSA (1.07 equiv.). The tube was capped and the
solution was stirred overnight. The reaction mixture was
filtered and the filtrate was washed with ether. The
combined organic phase was then washed with NH4Cl
(2 M) (2£), brine and dried over Na2SO4 to give the desired
product.
4.2.1. 4-Trimethylsilylethynylaniline (2a).8b According
to the general procedure, 4-iodoaniline 1a (25.0 g,
114 mmol), bis(triphenylphosphine)palladium(II) dichloride
(400 mg, 0.57 mmol, 0.5 mol%), copper(I) iodide (217 mg,
1.14 mmol, 1 mol%), and TMSA (17.3 mL, 122 mmol,
1.07 equiv.) in triethylamine (200 mL) gave the desired
product (21.3 g, 113 mmol, 99%).
4.2.2.
2-Fluoro-4-trimethylsilylethynylaniline
(2b).
According to the general procedure, 1b (12.0 g,
50.6 mmol), bis(triphenylphosphine)palladium(II) dichloride
(178 mg, 0.253 mmol, 0.5 mol%), copper(I) iodide (96 mg,
0.506 mmol, 1 mol%) and TMSA (7.7 mL, 54.5 mmol,
1.07 equiv.) in triethylamine (120 mL) gave the desired
product (10.4 g, 50.1 mmol, 99%). IR (KBr) 3439, 3393,
4. Experimental
4.1. General procedure
1
All reactions were performed under an atmosphere of
nitrogen unless otherwise stated. Unless otherwise noted, all
chemicals were used as received without further purifi-
cation. Merrifield resin (1.1 mmol Cl2/g, 1% cross-linker
divinylbenzene copolymer, 70–90 mesh) was obtained
from Aldrich Chemical Co. MacroKans were obtained from
IRORI.20 The Pd/Cu couplings were conducted in a manner
analogous to that described by Suffert.7c THF and diethyl
ether were distilled from sodium benzophenone ketyl under
a nitrogen atmosphere. Triethylamine, N,N-diisopropyl-
ethylamine and acetonitrile were distilled over calcium
hydride under nitrogen. Column chromatography was
carried out using Silica gel (grade 60, 230–400 mesh
from EM Science). Thin layer chromatography (TLC) was
performed using glass-backed silica gel plates (40 F254
0.25 mm layer thickness, Merck). Infrared (IR) spectra
assignments have 2 cm21 resolution. FT-IR characteriz-
ations of the polymer-supported reactions were carried out
by placing ca. 10 mg of the polymer-supported material on a
2148 cm21; H NMR (400 MHz, CDCl3) d7.08–7.14 (m,
2H), 6.68(dd, J¼1.0, 8.2 Hz, 1H), 3.95(br s, 2H), 0.25(s, 9H);
13C NMR (100 MHz, CDCl3) d150.9 (d, JC–F¼239 Hz),
135.8 (d, JC–F¼12 Hz), 129.2 (d, JC–F¼3 Hz), 119.1 (d,
JC–F¼20 Hz), 116.5 (d, JC–F¼4 Hz), 113.1 (d, JC–F¼8 Hz),
105.1 (d, JC–F¼26 Hz), 92.6, 0.4; HRMS calcd for
C11H14FSi: 207.0880. Found: 207.0877.
4.2.3. 2-Amino-5-trimethylsilylethynylbenzonitrile (2c).
According to the general procedure, 1c (23.5 g,
104.5 mmol), bis(triphenylphosphine)palladium(II) dichloride
(338 mg, 0.48 mmol, 0.5 mol%), copper(I) iodide (183 mg,
0.96 mmol, 1 mol%) and TMSA (14.6 mL, 103 mmol,
1.07 equiv.) in triethylamine (200 mL) gave the desired
product (20.5 g, 95.6 mmol, 91%). IR (KBr) 3447, 3352,
1
2219, 2145 cm21; H NMR (400 MHz, CDCl3) d 7.53 (d,
J¼1.9 Hz, 1H), 7.42 (dd, J¼1.9, 8.6 Hz, 1H), 6.67 (d,
J¼8.6 Hz, 1H), 4.59 (br s, 2H), 0.25 (s, 9H); 13C NMR
(100 MHz, CDCl3) d 149.8, 137.8, 136.4, 117.2, 115.5,

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J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
113.1, 103.8, 96.1, 93.7, 0.4; HRMS calcd for C12H14N2Si:
214.0926. Found: 214.0924.
(28.2 mmol, 85%) of 3b was produced from 2b (6.9 g,
33.3 mmol). IR (neat) 2160 cm21 1H NMR (400 MHz,
;
CDCl3) d 7.69 (dd, J¼6.6, 8.1 Hz, 1H), 7.16 (dd, J¼1.7,
8.5 Hz, 1H), 7.00 (dd, J¼1.7, 8.6 Hz, 1H), 0.27 (s, 9H); 13C
NMR (100 MHz, CDCl3) d 161.2 (d, JC–F¼246 Hz), 139.1
4.2.4. 2-Trifluoromethyl-4-trimethylsilylethynylaniline
(2d). According to the general procedure, 1d (30.0 g,
104.5 mmol), bis(triphenylphosphine)palladium(II)dichloride
(367 mg, 0.52 mmol, 0.5 mol%), copper(I) iodide (199 mg,
1.04 mmol, 1 mol%) and TMSA (15.8 mL, 112 mmol,
1.07 equiv.) in triethylamine (200 mL) gave the desired
product (26.8 g, 104 mmol, 99%). IR (KBr) 3486, 3396,
2150 cm21; 1H NMR (400 MHz, CDCl3) d 7.58 (d, J¼1.8 Hz,
1H), 7.40(dd,J¼1.8,8.5 Hz, 1H), 6.66(d,J¼8.5 Hz, 1H),4.33
(br s, 2H), 0.25 (s, 9H); 13C NMR (100 MHz, CDCl3) d 144.9,
136.6, 131.0 (q, JC–F¼5 Hz), 124.8 (q, JC–F¼272 Hz), 117.2,
113.7 (q, JC–F¼30 Hz), 112.4, 104.8, 93.2, 0.4; HRMS calcd
for C12H14F3NSi: 257.0848. Found: 257.0845.
(d, JC–F¼2 Hz), 129.1 (d, JC–F¼3 Hz), 125.2 (d, JC–F
¼
8 Hz), 118.6 (d, JC–F¼25 Hz), 102.6 (d, JC–F¼3 Hz), 96.9,
81.8 (d, JC–F¼26 Hz), 20.2; HRMS calcd for C11H12FISi:
317.9737. Found: 317.9737.
4.3.3. 2-Iodo-5-trimethylsilanylethynylbenzonitrile (3c).
According to the general procedure, 9.6 g (29.5 mmol, 70%)
of 3c was produced from 2c (9.0 g, 42 mmol). IR (neat)
1
2233, 2151 cm21; H NMR (400 MHz, CDCl3) d 7.86 (d,
J¼8.3 Hz, 1H), 7.66 (d, J¼2.0 Hz, 1H), 7.31 (dd, J¼2.0,
8.3 Hz, 1H), 0.26 (s, 9H); 13C NMR (100 MHz, CDCl3) d
139.7, 137.1, 136.5, 124.2, 121.0, 118.7, 101.6, 99.1, 98.1,
20.1; HRMS calcd for C12H12INSi: 324.9784. Found:
324.9784.
4.2.5.
2-Ethyl-4-trimethylsilylethynylaniline
(2e).
According to the general procedure, 1e (7.4 g, 30 mmol),
bis(triphenylphosphine)palladium(II) dichloride (105 mg,
0.15 mmol, 0.5 mol%), copper(I) iodide (57 mg,
0.3 mmol, 1 mol%) and TMSA (4.5 mL, 31.8 mmol,
1.07 equiv.) in triethylamine (80 mL) gave the desired
product (6.5 g, 29.9 mmol, 99%). IR (neat) 3480,
4.3.4. (4-Iodo-3-trifluoromethylphenylethynyl)tri-
methylsilane (3d). According to the general procedure,
8.6 g (23.4 mmol, 67%) of 3d was produced from 2d (9.0 g,
;
35 mmol). IR (neat) 2164 cm21 1H NMR (400 MHz,
CDCl3) d 7.97 (d, J¼8.2 Hz, 1H), 7.74 (d, J¼1.8 Hz, 1H),
7.26 (dd, J¼1.8, 8.2 Hz, 1H), 0.28 (s, 9H); 13C NMR
(100 MHz, CDCl3) d 142.2, 135.7, 134.0 (q, JC–F¼31 Hz),
130.5 (q, JC–F¼6 Hz), 123.8, 122.9 (q, JC–F¼274 Hz),
102.6, 98.1, 91.0 (q, JC–F¼2 Hz), 20.4; HRMS calcd for
C12H12F3INSi: 367.9705. Found: 367.9702.
2140 cm21
;
1H NMR (400 MHz, CDCl3) d 7.19 (d,
J¼1.8 Hz, 1H), 7.14 (dd, J¼1.8, 8.1 Hz, 1H), 6.53 (d,
J¼8.1 Hz, 1H), 3.74 (br s, 2H), 2.43 (q, J¼7.5 Hz, 2H), 1.21
(t, J¼7.5 Hz, 3H), 0.23 (s, 9H); 13C NMR (100 MHz,
CDCl3) d 145.0, 132.6, 131.3, 127.9, 115.2, 113.0, 106.9,
91.5, 24.1, 13.1, 0.6; HRMS calcd for C13H19NSi:
217.1287. Found: 217.1285.
4.3.5. (3-Ethyl-4-iodophenylethynyl)trimethylsilane (3e).
According to the general procedure, 9.72 g (29.6 mmol,
86%) of 3e was produced from 2e (7.5 g, 34.5 mmol). IR
4.3. General procedure for the conversion of aniline
derivatives into iodoarenes through the diazonium salt22
1
(neat) 2160 cm21; H NMR (400 MHz, CDCl3) d 7.75 (d,
To a round-bottom flask fitted with an addition funnel and
nitrogen inlet was added boron trifluoride etherate (4 equiv.)
which was then chilled in a dry ice-acetone bath (2208C).
To the reaction flask was added dropwise over 5 min a
solution of the aniline derivative (1 equiv.) in dry ether,
followed by a solution of tert-butylnitrite (3.5 equiv.) in dry
ether over 30 min. The chilled mixture was stirred an
additional 10 min, and the cold bath was allowed to warm to
58C over 20 min. To the mixture was added diethyl ether,
and the mixture was chilled in an ice-bath for 15 min. The
solid was collected by filtration, washed with chilled
(0–58C) diethyl ether, and dried to give diazonium salt.
After briefly air-drying, the diazonium salt was dissolved in
CH3CN and then added dropwise via cannula to a solution
of NaI (1.1 equiv.) and I2 (0.1 equiv.) in CH3CN. The
mixture was stirred at rt for 1 h, then Na2S2O3 (aq) (2 M)
was added to the mixture. The mixture was extracted with
CH2Cl2 (3£), and the organic phase was washed with brine
and dried over Na2SO4. The crude product was purified by
column chromatography (silica gel) with hexane or a
hexane/EtOAc mixture to give the desired product.
J¼8.1 Hz, 1H), 7.33 (d, J¼8.1 Hz, 1H), 6.98 (dd, J¼2.0,
8.1 Hz, 1H), 2.71 (q, J¼7.5 Hz, 2H), 1.22 (t, J¼7.5 Hz, 3H),
0.27 (s, 9H); 13C NMR (100 MHz, CDCl3) d 147.1, 139.8,
132.2, 131.2, 123.9, 104.8, 101.3, 95.8, 34.5, 14.9, 0.5;
HRMS calcd for C13H17ISi: 328.0144. Found: 328.0142.
4.4. General procedure for the coupling of a terminal
alkyne with an aryl halide utilizing a palladium-copper
cross-coupling (Sonogashira protocol)
To a stirring solution of the aryl halide (1 equiv.),
bis(triphenylphosphine)palladium(II) dichloride (2 mol%),
copper(I) iodide (4 mol%), and addition triphenylphosphine
(only used at temperature .258C, 2 equiv. based on Pd) in
THF was added the terminal alkyne (1–2 equiv.) followed
by the amine (4 equiv. based on the aryl halide) at rt (unless
otherwise stated) under nitrogen in a screw cap tube. The
tube was flushed with nitrogen, capped, and allowed to stir
24 h. The reaction mixture was then subjected to an aqueous
workup and the aqueous layer extracted with dichloro-
methane. After drying the combined organic layers over
sodium sulfate, the solvent was removed in vacuo. The
crude product was purified by column chromatography
(silica gel) with hexanes or hexane/EtOAc mixtures to give
the desired product.
4.3.1. (4-Iodo-phenylethynyl)trimethylsilane (3a).23
According to the general procedure, 13.2 g (44 mmol,
78%) of 3a was produced from 2a (10.7 g, 56.5 mmol).
4.3.2. (3-Fluoro-4-iodophenylethynyl)trimethylsilane
(3b). According to the general procedure, 8.97 g
4.4.1. Trimethyl(4-phenylethynylphenylethynyl)silane
(4a).6b 3a (1.2 g, 4 mmol), phenylacetylene (0.48 mL,

J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
10395
4.4 mmol), bis(triphenylphosphine)palladium(II) dichloride
(56 mg, 0.08 mmol), copper(I) iodide (30 mg, 0.16 mmol),
and N,N-diisopropylethylamine (2.8 mL, 16.0 mmol) in
THF (40 mL) for 1 d gave the desired product (0.99 g, 90%).
129.6, 128.8, 128.7, 123.8, 123.4, 105.5, 96.0, 95.0, 88.2,
28.0, 15.0, 0.4; HRMS calcd for C21H22Si: 302.1491.
Found: 302.1492.
4.5. General procedures for the desilylation of alkynes
4.4.2. (3-Fluoro-4-phenylethynylphenylethynyl)tri-
methylsilane (4b). 3b (2.65 g, 8.33 mmol), phenylacetylene
(0.87 mL, 7.92 mmol), bis(triphenylphosphine)palladium(II)
dichloride (56 mg, 0.08 mmol), copper(I) iodide (30 mg,
0.16 mmol), and N,N-diisopropylethylamine (5.5 mL,
31.6 mmol) in THF (40 mL) for 1 d gave the desired
product (2.05 g, 88%). IR (KBr) 2216, 2154 cm21;1H NMR
(400 MHz, CDCl3) d 7.56–7.59 (m, 2H), 7.46 (dd, J¼8,
8 Hz, 1H), 7.38–7.40 (m, 3H), 7.21–7.26 (m, 2H), 0.29 (s,
The silylated alkyne (1 equiv.) was dissolved in CH3OH or
CH2Cl2/CH3OH mixtures. Potassium carbonate (2 equiv.)
was added, and the reaction was stirred overnight.
The reaction mixture was then subjected to an aqueous
workup and the aqueous layer extracted with CH2Cl2. After
drying the combined organic layers over Na2SO4, the
solvent was removed in vacuo. The crude product was
purified by column chromatography (silica gel) with
hexanes or hexane/EtOAc mixtures to give the desired
product.
9H); 13C NMR (100 MHz, CDCl3) d 161.2 (d, JC–F
¼
252 Hz), 133.5 (d, JC–F¼2 Hz), 132.1, 129.8, 128.8, 128.1
(d, JC–F¼3 Hz), 125.1 (d, JC–F¼6 Hz), 123.1, 119.2 (d,
JC–F¼23 Hz), 112.8 (d, JC–F¼16 Hz), 103.7 (d, JC–F
¼
4.5.1. 1-Ethynyl-4-phenylethynylbenzene (5a). 4a (1.3 g,
4.7 mmol), CH3OH (20 mL), CH2Cl2 (20 mL), and potas-
sium carbonate (1.3 g, 9.4 mmol) afforded 0.92 g (96%) of
3 Hz), 97.8, 96.5 (d, JC–F¼4 Hz), 82.8, 0.2; HRMS calcd
for C19H17FSi: 292.1084. Found: 292.1082.
the title compound. IR (KBr) 3276 cm21
;
1H NMR
4.4.3. 2-Phenylethynyl-5-trimethylsilanylethynylbenzo-
nitrile (4c). 3c (2.14 g, 6.58 mmol), phenylacetylene
(0.69 mL, 6.28 mmol), bis(triphenylphosphine)palladium(II)
dichloride (44 mg, 0.06 mmol), copper(I) iodide (24 mg,
0.12 mmol), and N,N-diisopropylethylamine (4.4 mL,
25.2 mmol) in THF (30 mL) for 1 d gave the desired
product (1.52 g, 81%). IR (KBr) 2230, 2211, 2152 cm21; 1H
NMR (400 MHz, CDCl3) d 7.77 (d, J¼1.6 Hz, 1H), 7.62–
7.65 (m, 5H), 7.57 (d, J¼8.2 Hz, 1H), 7.36–7.43 (m, 3H),
0.29 (s, 9H); 13C NMR (100 MHz, CDCl3) d 136.1, 135.8,
132.5, 132.4, 129.9, 128.9, 127.0, 124.0, 122.2, 117.2,
115.9, 102.6, 99.5, 98.3, 86.0, 0.2; HRMS calcd for
C20H17NSi: 299.1130. Found: 299.1134.
(400 MHz, CDCl3) d 7.55–7.58 (m, 2H), 7.43–7.52 (m,
4H), 7.37–7.40 (m, 3H), 3.20 (s, 1H); 13C NMR (100 MHz,
CDCl3) d 132.6, 132.2, 132.0, 129.0, 128.9, 124.3, 123.4,
122.4, 91.9, 89.4, 83.8, 79.5; HRMS calcd for C16H10:
202.0782. Found: 202.0784.
4.5.2. 4-Ethynyl-2-fluoro-1-phenylethynylbenzene (5b).
4b (1.2 g, 4.1 mmol), CH3OH (15 mL), CH2Cl2 (15 mL),
and potassium carbonate (1.13 g, 8.2 mmol) afforded
0.748 g (83%) of the title compound. IR (KBr) 3267,
1
2216 cm21; H NMR (500 MHz, CDCl3) d 7.57–7.60 (m,
2H), 7.48 (dd, J¼7.6, 7.6 Hz, 1H), 7.37–7.41 (m, 3H),
7.24–7.28 (m, 2H), 0.29 (s, 9H); 13C NMR (125 MHz,
CDCl3) d 162.4 (d, JC–F¼253 Hz), 133.6, 132.2, 129.3,
128.8, 128.2 (d, JC–F¼4 Hz), 124.0 (d, JC–F¼9 Hz), 123.0,
119.4 (d, JC–F¼23 Hz), 113.3 (d, JC–F¼16 Hz), 96.7 (d,
JC–F¼4 Hz), 82.7, 82.5 (d, JC–F¼3 Hz), 80.2; HRMS calcd
for C16H9F: 220.0688. Found: 220.0690.
4.4.4. Trimethyl-(4-phenylethynyl-3-trifluoromethyl-
phenylethynyl)silane (4d). 3d (3.23 g, 8.77 mmol), phenyl
acetylene (1.06 mL, 9.65 mmol), bis(triphenylphosphine)-
palladium(II) dichloride (123 mg, 0.17 mmol), copper(I)
iodide (67 mg, 0.35 mmol), triphenylphosphine (92 mg,
0.35 mmol), and N,N-diisopropylethylamine (6.1 mL,
35.0 mmol) in THF (45 mL) at 408C for 3 d gave the
4.5.3. 5-Ethynyl-2-phenylethynylbenzonitrile (5c). 4c
(425 mg, 1.4 mmol), CH3OH (10 mL), CH2Cl2 (10 mL),
and potassium carbonate (392 mg, 2.8 mmol) afforded
295 mg (91%) of the title compound. IR (KBr) 3262,
desired product (2.61 g, 87%). IR (KBr) 2210, 2159 cm21
;
1H NMR (400 MHz, CDCl3) d 7.77 (m, 1H), 7.56–7.60 (m,
2H), 7.54–7.56 (m, 2H), 7.36–7.40 (m, 3H), 0.28 (s, 9H);
13C NMR (100 MHz, CDCl3) d 134.8, 134.0, 132.1, 132.0
(q, JC–F¼31 Hz), 129.9 (q, JC–F¼5 Hz), 129.4, 128.8,
2234, 2207 cm21 1H NMR (400 MHz, CDCl3) d 7.79
;
(d, J¼1.6 Hz, 1H), 7.66 (dd, J¼1.6, 8.2 Hz, 1H), 7.63–7.65
(m, 2H), 7.60 (d, J¼8.2 Hz, 1H), 7.39–7.45 (m, 3H),
3.30 (s, 1H); 13C NMR (100 MHz, CDCl3) d 136.3, 136.0,
132.5, 132.4, 129.9, 128.9, 127.6, 123.0, 122.2, 117.1,
116.1, 85.8, 81.5; HRMS calcd for C17H9N: 227.0735.
Found: 227.0737.
123.6 (q, JC–F¼274 Hz), 123.4, 122.9, 121.7 (q, JC–F
¼
2 Hz), 103.6, 98.5, 97.2 (q, JC–F¼2 Hz), 85.6, 0.2; HRMS
calcd for C20H17F3Si: 342.1051. Found: 342.1054.
4.4.5. (3-Ethyl-4-phenylethynylphenylethynyl)trimethyl-
silane (4e). 3e (2.65 g, 8.07 mmol), phenylacetylene
(0.93 mL, 8.47 mmol), bis(triphenylphosphine)palladium(II)
dichloride (93 mg, 0.16 mmol), copper(I) iodide (61 mg,
0.32 mmol), triphenylphosphine (212 mg, 0.81 mmol), and
N,N-diisopropylethylamine (5.6 mL, 32.1 mmol) in THF
(40 mL) at 408C for 3 d gave the desired product (2.01 g,
4.5.4. 4-Ethynyl-1-phenylethynyl-2-trifluoromethyl-
benzene (5d). 4d (1.23 g, 3.59 mmol), CH3OH (35 mL),
and potassium carbonate (0.99 g, 7.16 mmol) afforded 0.9 g
(93%) of the title compound. IR (KBr) 2218, 2197 cm21; 1H
NMR (400 MHz, CDCl3) d 7.82 (s, 1H), 7.60 (br s, 2H),
7.55–7.59 (m, 2H), 7.38–7.42 (m, 3H), 3.27 (s, 1H); 13C
NMR (100 MHz, CDCl3) d 135.1, 134.1, 132.2, 132.0 (q,
JC–F¼31 Hz), 130.0 (q, JC–F¼5 Hz), 122.8, 122.5 (q,
JC–F¼274 Hz), 122.4, 122.2 (q, JC–F¼2 Hz), 97.5 (q,
JC–F¼2 Hz), 85.5, 82.4, 80.8; HRMS calcd for C17H9F3:
270.0656. Found: 270.0652
1
82%). IR (KBr) 2210, 2157 cm21; H NMR (400 MHz,
CDCl3) d 7.53–7.56 (m, 2H), 7.45 (d, J¼7.9 Hz, 1H), 7.35–
7.40 (m, 4H), 7.30 (dd, J¼1.7, 7.9 Hz, 1H), 2.86 (q,
J¼7.6 Hz, 2H), 1.32 (t, J¼7.6 Hz, 3H), 0.28 (s, 9H); 13C
NMR (100 MHz, CDCl3) d 146.5, 132.4, 131.9, 131.8,

10396
J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
4.5.5. 2-Ethyl-4-ethynyl-1-phenylethynylbenzene (5e). 4e
(1.43 g, 4.7 mmol), CH3OH (25 mL), and potassium
carbonate (1.3 g, 9.4 mmol) afforded 1.02 g (94%) of the
(517 mL, 2.96 mmol) in THF (8 mL) at 508C for 7 d gave
the desired product (233 mg, 71%). IR (KBr) 2210,
1
2157 cm21; H NMR (400 MHz, CDCl3) d 7.82 (s, 1H),
title compound. IR (neat) 3292, 2202 cm21
;
1H NMR
7.51–7.60 (m, 8H), 7.36–7.41 (m, 3H), 0.33 (s, 9H); 13C
NMR (100 MHz, CDCl3) d 134.9, 134.0, 132.1, 132.0,
131.9 (q, JC–F¼31 Hz), 129.9 (q, JC–F¼5 Hz), 129.0,
128.8, 124.4, 123.7, 123.4, 123.3 (q, JC–F¼274 Hz),
122.6, 121.4 (q, JC–F¼2 Hz), 103.6, 98.7, 96.9, 92.2, 89.5,
87.4, 0.2; HRMS calcd for C28H21F3Si: 442.1365. Found:
442.1366.
(400 MHz, CDCl3) d 7.54–7.58 (m, 2H), 7.48 (d, J¼7.9 Hz,
1H), 7.37–7.42 (m, 4H), 7.34 (dd, J¼1.6, 7.9 Hz, 1H), 3.18
(s, 1H), 2.90 (q, J¼7.6 Hz, 2H), 1.33 (t, J¼7.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3) d 146.7, 132.5, 132.1, 132.0,
129.9, 128.9, 128.8, 123.7, 123.5, 122.4, 95.2, 88.2, 84.1,
78.9, 28.1, 15.0; HRMS calcd for C18H14: 230.1096. Found:
230.1093.
4.5.10. [3-Ethyl-4-(4-phenylethynylphenylethynyl)phe-
nylethynyl]trimethylsilane (6e). 5a (155 mg, 0.77 mmol),
3e (330 mg, 1.0 mmol), bis(triphenylphosphine)pal-
ladium(II) dichloride (11 mg, 0.016 mmol), copper(I)
iodide (6 mg, 0.032 mmol), triphenylphosphine (8 mg,
0.03 mmol), and N,N-diisopropylethylamine (517 mL,
2.96 mmol) in THF (8 mL) at 508C for 5 d gave the desired
4.5.6. Trimethyl[4-(4-phenylethynylphenylethynyl)phe-
nylethynyl]silane (6a). 5a (250 mg, 1.24 mmol), 3a
(742 mg, 2.47 mmol), bis(triphenylphosphine)palladium(II)
dichloride (17 mg, 0.024 mmol), copper(I) iodide (9 mg,
0.047 mmol), and N,N-diisopropylethylamine (860 mL,
4.94 mmol) in THF (8 mL) for 1 d gave the desired product
(205 mg, 44%). IR (KBr) 2152 cm21; 1H NMR (400 MHz,
CDCl3) d 7.52 (m, 7H), 7.45–7.51 (m, 3H), 7.37–7.41 (m,
3H), 0.28 (s, 9H); 13C NMR (125 MHz, CDCl3) d 132.3,
132.1, 132.0, 131.9, 131.8, 128.9, 128.8, 123.8, 123.6,
123.5, 123.4, 123.2, 105.0, 96.9, 91.8, 91.4, 89.4, 0.3;
HRMS calcd for C27H22Si: 374.1491. Found: 374.1488.
1
product (171 mg, 55%). IR (KBr) 2156 cm21; H NMR
(500 MHz, CDCl3) d 7.51–7.58 (m, 6H), 7.46 (d, J¼7.9 Hz,
1H), 7.37–7.41 (m, 4H), 7.31 (dd, J¼1.4, 7.9 Hz, 1H), 2.88
(q, J¼7.6 Hz, 2H), 1.33 (t, J¼7.6 Hz, 3H), 0.29 (s, 9H); 13C
NMR (125 MHz, CDCl3) d 146.5, 132.4, 132.1, 132.0,
131.9, 131.8, 129.7, 128.9, 128.8, 123.7, 123.6, 123.5,
123.4, 122.8, 105.4, 96.2, 94.7, 91.8, 90.1, 89.5, 28.0, 15.0,
0.4; HRMS calcd for C29H26Si: 402.1804. Found: 402.1798.
4.5.7. [3-Fluoro-4-(4-phenylethynylphenylethynyl)phe-
nylethynyl]trimethylsilane (6b). 5a (240 mg, 1.19
mmol), 3b (756 mg, 2.38 mmol), bis(triphenylphosphine)-
palladium(II) dichloride (17 mg, 0.024 mmol), copper(I)
iodide (9 mg, 0.047 mmol), and N,N-diisopropylethylamine
(830 mL, 4.76 mmol) in THF (8 mL) for 1 d gave the desired
4.5.11. [4-(3-Fluoro-4-phenylethynylphenylethynyl)phe-
nylethynyl]trimethylsilane (7a). 5b (185 mg, 0.84 mmol),
3a (252 mg, 0.84 mmol), bis(triphenylphosphine)pal-
ladium(II) dichloride (18 mg, 0.026 mmol), copper(I)
iodide (10 mg, 0.052 mmol), and N,N-diisopropylethyl-
amine (586 mL, 3.36 mmol) in THF (8 mL) for 1 d gave
the desired product (285 mg, 86%). IR (KBr) 2210,
1
product (310 mg, 66%). IR (KBr) 2211, 2152 cm21; H
NMR (500 MHz, CDCl3) d 7.53–7.58 (m, 6H), 7.46 (dd,
J¼7.6, 7.6 Hz, 1H), 7.37–7.40 (m, 3H), 7.21–7.26 (m, 2H),
0.28 (s, 9H); 13C NMR (125 MHz, CDCl3) d 162.4 (d,
JC–F¼252 Hz), 133.5, 132.1, 132.0, 129.9, 128.9, 128.8,
128.1 (d, JC–F¼3 Hz), 125.4, 125.3, 124.1, 123.4, 122.8,
119.2 (d, JC–F¼23 Hz), 112.5 (d, JC–F¼16 Hz), 103.6 (d,
JC–F¼3 Hz), 98.0, 96.2 (d, JC–F¼4 Hz), 91.9, 89.4, 84.6,
0.2; HRMS calcd for C27H21FSi: 392.1396. Found:
392.1394.
1
2154 cm21; H NMR (500 MHz, CDCl3) d 7.56–7.59 (m,
2H), 7.48 (dd, J¼7.6, 7.6 Hz, 1H), 7.38–7.40 (m, 3H),
7.24–7.28 (m, 2H), 0.26 (s, 9H); 13C NMR (125 MHz,
CDCl3) d 161.5 (d, JC–F¼252 Hz), 133.7, 132.4, 132.1,
131.9, 129.2, 128.8, 127.7 (d, JC–F¼3 Hz), 125.0 (d,
JC–F¼9 Hz), 123.9, 123.0 (d, JC–F¼11 Hz), 118.8 (d,
JC–F¼23 Hz), 112.8 (d, JC–F¼16 Hz), 104.9, 97.1, 96.6
(d, JC–F¼3 Hz), 92.0, 90.2 (d, JC–F¼4 Hz), 0.3; HRMS
calcd for C27H21FSi: 392.1396. Found: 392.1397.
4.5.8. 2-(4-Phenylethynylphenylethynyl)-5-trimethyl-
silanylethynylbenzonitrile (6c). 5a (150 mg, 0.74 mmol),
3c (241 mg, 0.74 mmol), bis(triphenylphosphine)pal-
ladium(II) dichloride (10 mg, 0.014 mmol), copper(I)
iodide (6 mg, 0.032 mmol), and N,N-diisopropylethylamine
(517 mL, 2.96 mmol) in THF (8 mL) for 1 d gave the desired
4.5.12. [3-Fluoro-4-(3-fluoro-4-phenylethynylphenyl-
ethynyl)phenylethynyl]-trimethylsilane (7b). 5b (150
mg, 0.68 mmol), 3b (217 mg, 0.68 mmol), bis(triphenyl-
phosphine)palladium(II) dichloride (10 mg, 0.014 mmol),
copper(I) iodide (5 mg, 0.026 mmol), and N,N-diisopropyl-
ethylamine (474 mL, 2.72 mmol) in THF (8 mL) for 1 d
gave the desired product (231 mg, 82%). IR (KBr) 2209,
product (248 mg, 84%). IR (KBr) 2230, 2210, 2149 cm21
;
1H NMR (400 MHz, CDCl3) d 7.77 (d, J¼1.2 Hz, 1H), 7.63
(dd, J¼1.7, 8.2 Hz, 1H), 7.58–7.61 (m, 2H), 7.52–7.57 (m,
5H), 7.37–7.40 (m, 3H), 0.29 (s, 9H); 13C NMR (100 MHz,
CDCl3) d 136.2, 135.9, 132.1, 132.0, 131.9, 129.0, 128.8,
126.8, 124.8, 124.2, 123.3, 121.9, 117.2, 115.9, 102.5, 99.8,
97.8, 92.4, 89.4, 87.6, 0.1; HRMS calcd for C28H21NSi:
399.1443. Found: 399.1436.
1
2153 cm21; H NMR (400 MHz, CDCl3) d 7.56–7.60 (m,
2H), 7.52 (dd, J¼7.6, 7.6 Hz, 1H), 7.45 (dd, J¼7.6, 7.6 Hz,
1H), 7.22–7.27 (m, 2H), 0.28 (s, 9H); 13C NMR (100 MHz,
CDCl3) d 162.5 (d, JC–F¼252 Hz), 162.4 (d, JC–F
¼
252 Hz), 133.7, 133.6, 133.5, 133.4, 132.2, 129.2, 128.8,
128.2 (d, JC–F¼4 Hz), 128.8 (d, JC–F¼4 Hz), 127.7 (d,
JC–F¼9 Hz), 124.6 (d, JC–F¼9 Hz), 123.0, 119.2 (d,
4.5.9. Trimethyl[4-(4-phenylethynylphenylethynyl)-3-
trifluoromethylphenyl-ethynyl]silane (6d). 5a (150 mg,
0.74 mmol), 3d (410 mg, 1.11 mmol), bis(triphenylphos-
phine)palladium(II) dichloride (10 mg, 0.014 mmol),
copper(I) iodide (6 mg, 0.032 mmol), triphenylphosphine
(8 mg, 0.03 mmol), and N,N-diisopropylethylamine
JC–F¼22 Hz), 118.9 (d, JC–F¼22 Hz), 113.1 (d, JC–F
¼
16 Hz), 112.1 (d, JC–F¼16 Hz), 103.5 (d, JC–F¼3 Hz),
98.3, 96.8 (d, JC–F¼3 Hz), 95.0 (d, JC–F¼3 Hz), 94.9 (d,
JC–F¼3 Hz), 85.4, 82.8, 0.2; HRMS calcd for C26H17F2Si:
410.1302. Found: 410.1302.

J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
10397
4.5.13. 2-(3-Fluoro-4-phenylethynylphenylethynyl)-5-
trimethylsilanylethynyl-benzonitrile (7c). 5b (150 mg,
0.68 mmol), 3c (221 mg, 0.68 mmol), bis(triphenyl-
phosphine)palladium(II) dichloride (10 mg, 0.014 mmol),
copper(I) iodide (5 mg, 0.026 mmol), and N,N-diisopropyl-
ethylamine (474 mL, 2.72 mmol) in THF (8 mL) for 1 d
gave the desired product (275 mg, 97%). IR (KBr) 2231,
ethylamine (460 mL, 2.64 mmol) in THF (4 mL) for 22 h
gave the desired product (190 mg, 72%). IR (KBr) 2233,
2211, 2152 cm21 1H NMR (500 MHz, CDCl3) d 7.82
;
(d, J¼1.6 Hz, 1H), 7.69 (dd, J¼1.6, 8.2 Hz, 1H), 7.61–7.65
(m, 3H), 7.49 (br, 4H), 7.39–7.45 (m, 3H), 0.29 (s, 9H);
13C NMR (125 MHz, CDCl3) d 135.8, 135.5, 132.6,
132.5, 132.4, 132.0, 129.9, 128.9, 127.0, 124.3, 123.9,
122.5, 122.3, 117.2, 116.2, 104.8, 98.4, 97.4, 93.3, 89.1,
86.0, 0.3; HRMS calcd for C28H21NSi: 399.1443. Found:
399.1446.
1
2217, 2152 cm21; H NMR (400 MHz, CDCl3) d 7.77 (d,
J¼1.3 Hz, 1H), 7.62 (dd, J¼1.6, 8.2 Hz, 1H), 7.57–7.61 (m,
3H), 7.53 (dd, J¼7.4, 7.4 Hz, 1H), 7.37–7.41 (m, 4H), 7.34
(dd, J¼1.4, 9.5 Hz, 1H), 0.28 (s, 9H); 13C NMR (100 MHz,
CDCl3) d 161.8 (d, JC–F¼253 Hz), 135.6, 135.3, 133.2,
133.1, 131.9, 131.6, 128.7, 128.2, 127.6 (d, JC–F¼3 Hz),
125.6, 124.0, 123.0 (d, JC–F¼9 Hz), 122.3, 118.5 (d,
JC–F¼22 Hz), 116.4, 115.4, 113.2 (d, JC–F¼16 Hz),
101.8, 99.4, 96.6 (d, JC–F¼3 Hz), 95.8 (d, JC–F¼3 Hz),
87.6, 82.2, 20.4; HRMS calcd for C28H20FNSi: 417.1349.
Found: 417.1346.
4.5.17. 5-(2-Fluoro-4-trimethylsilanylethynylphenyl-
ethynyl)-2-phenylethynyl-benzonitrile (8b). 5c (180 mg,
0.79 mmol), 3b (252 mg, 0.79 mmol), bis(triphenyl-
phosphine)palladium(II) dichloride (11 mg, 0.016 mmol),
copper(I) iodide (6 mg, 0.032 mmol), and N,N-diisopropyl-
ethylamine (550 mL, 3.16 mmol) in THF (8 mL) for 1 d
gave the desired product (293 mg, 88%). IR (KBr) 2231,
2210, 2149 cm21; 1H NMR (400 MHz, CDCl3) d 7.84 (dd,
J¼1.7, 0.3 Hz, 1H), 7.72 (dd, J¼1.7, 8.2 Hz, 1H), 7.62–
7.66 (m, 3H), 7.46 (dd, J¼7.6, 7.6 Hz, 1H), 7.39–7.46 (m,
3H), 7.23–7.28 (m, 2H), 0.29 (s, 9H); 13C NMR (100 MHz,
CDCl3) d 162.5 (d, JC–F¼252 Hz), 135.8, 135.5, 133.6,
133.5, 132.6, 132.5, 129.9, 128.9, 128.2 (d, JC–F¼3 Hz),
127.3, 126.1 (d, JC–F¼9 Hz), 123.5, 122.2, 119.3 (d,
JC–F¼22 Hz), 117.2, 116.2, 111.6 (d, JC–F¼16 Hz), 103.4
(d, JC–F¼3 Hz), 98.7, 98.6, 93.8 (d, JC–F¼3 Hz), 86.7, 86.0,
0.2; HRMS calcd for C28H20FNSi: 417.1349. Found:
417.1349.
4.5.14. [4-(3-Fluoro-4-phenylethynylphenylethynyl)-3-
trifluoromethyl-phenylethynyl]trimethylsilane (7d). 5b
(150 mg, 0.68 mmol), 3d (251 mg, 0.68 mmol), bis(tri-
phenylphosphine)palladium(II)
dichloride
(10 mg,
0.014 mmol), copper(I) iodide (5 mg, 0.026 mmol), tri-
phenylphosphine (8 mg, 0.03 mmol), and N,N-diisopropyl-
ethylamine (474 mL, 2.72 mmol) in THF (8 mL) at 508C for
7 d gave the desired product (195 mg, 62%). IR (KBr) 2207,
2159 cm21
;
1H NMR (500 MHz, CDCl3) d 7.80 (d,
J¼0.4 Hz, 1H), 7.60–7.62 (m, 2H), 7.56–7.60 (m, 2H),
7.53 (dd, J¼7.5, 7.5 Hz, 1H), 7.38–7.42 (m, 3H), 7.30–7.34
(m, 2H), 0.30 (s, 9H); 13C NMR (125 MHz, CDCl3) d 162.5
(d, JC–F¼252 Hz), 134.9, 134.1, 133.8, 133.7, 132.2, 132.1
(q, JC–F¼31 Hz), 129.9 (q, JC–F¼5 Hz), 129.3, 128.8,
127.8 (d, JC–F¼3 Hz), 124.4, 124.3, 124.1, 123.5 (q,
JC–F¼274 Hz), 123.1, 120.9 (q, JC–F¼2 Hz), 118.9 (d,
JC–F¼22 Hz), 113.4 (d, JC–F¼16 Hz), 103.4, 99.0, 97.0 (d,
JC–F¼3 Hz), 95.5 (d, JC–F¼3 Hz), 88.0, 82.9, 0.2; HRMS
calcd for C28H20F4Si: 460.1270. Found: 460.1273.
4.5.18. 2-(3-Cyano-4-phenylethynylphenylethynyl)-5-tri-
methylsilanylethynyl-benzonitrile (8c). 5c (126 mg,
0.55 mmol), 3c (189 mg, 0.58 mmol), bis(triphenyl-
phosphine)palladium(II) dichloride (12 mg, 0.017 mmol),
copper(I) iodide (6 mg, 0.032 mmol), triphenylphosphine
(9 mg, 0.034 mmol), and N,N-diisopropylethylamine
(380 mL, 2.18 mmol) in THF (4 mL) at 408C for 3 d gave
the desired product (182 mg, 77%). IR (KBr) 2196,
1704 cm21 1H NMR (400 MHz, CDCl3) d 7.87 (dd,
;
4.5.15. [3-Ethyl-4-(3-fluoro-4-phenylethynylphenyl-
ethynyl)phenylethynyl]-trimethylsilane (7e). 5b (150
mg, 0.68 mmol), 3e (223 mg, 0.68 mmol), bis(triphenyl-
phosphine)palladium(II) dichloride (10 mg, 0.014 mmol),
copper(I) iodide (5 mg, 0.026 mmol), triphenylphosphine
(8 mg, 0.03 mmol), and N,N-diisopropylethylamine
(474 mL, 2.72 mmol) in THF (8 mL) at 508C for 4 d gave
the desired product (150 mg, 54%). IR (KBr) 2219, 2152,
J¼0.5, 1.7 Hz, 1H), 7.78 (dd, J¼1.7, 8.3 Hz, 1H), 7.76
(dd, J¼0.5, 1.7 Hz, 1H), 7.62–7.67 (m, 4H), 7.57 (dd,
J¼0.5, 8.1 Hz, 1H), 7.37–7.42 (m, 3H), 0.27 (s, 9H); 13C
NMR (100 MHz, CDCl3) d 136.2, 136.0, 135.9, 132.6,
132.5, 130.0, 128.9, 128.0, 125.7, 125.0, 122.6, 122.1,
117.0, 116.9, 116.3, 116.2, 102.3, 100.4, 99.0, 95.1, 89.3,
85.9, 0.1; HRMS calcd for C29H20N2Si: 424.1396. Found:
424.1391.
1
2131 cm21; H NMR (400 MHz, CDCl3) d 7.57–7.61 (m,
2H), 7.52 (dd, J¼7.5, 7.5 Hz, 1H), 7.46 (d, J¼7.9 Hz, 1H),
7.36–7.42 (m, 4H), 7.26–7.34 (m, 3H), 2.89 (q, J¼7.6 Hz,
2H), 1.33 (t, J¼7.6 Hz, 3H), 0.30 (s, 9H); 13C NMR
(100 MHz, CDCl3) d 162.5 (d, JC–F¼252 Hz), 133.7, 133.6,
132.5, 132.0, 129.7, 129.2, 128.8, 127.6 (d, JC–F¼3 Hz),
124.0, 123.1, 122.3, 118.6 (d, JC–F¼22 Hz), 112.6 (d,
JC–F¼16 Hz), 105.3, 96.6 (d, JC–F¼3 Hz), 96.5, 93.5 (d,
JC–F¼3 Hz), 90.9, 82.9, 28.0, 15.0, 0.4; HRMS calcd for
C29H25FSi: 420.1710. Found: 420.1711.
4.5.19. 2-Phenylethynyl-5-(2-trifluoromethyl-4-tri-
methylsilanylethynyl-phenylethynyl)benzonitrile (8d).
5c (130 mg, 0.57 mmol), 3d (220 mg, 0.6 mmol), bis(tri-
phenylphosphine)palladium(II) dichloride (12 mg, 0.017
mmol), copper(I) iodide (7 mg, 0.037 mmol), triphenyl-
phosphine (9 mg, 0.034 mmol), and N,N-diisopropylethyl-
amine (400 mL, 2.30 mmol) in THF (4 mL) at 408C for 2 d
gave the desired product (192 mg, 72%). IR (KBr) 2231,
2209, 2156 cm21; 1H NMR (400 MHz, CDCl3) d 7.81 (dd,
J¼0.5, 1.7 Hz, 1H), 7.80 (br s, 1H), 7.69 (dd, J¼1.7, 8.2 Hz,
1H), 7.62–7.65 (m, 5H), 7.37–7.42 (m, 3H), 0.28 (s, 9H);
13C NMR (100 MHz, CDCl3) d 135.8, 135.5, 135.0, 134.1,
4.5.16. 2-Phenylethynyl-5-(4-trimethylsilanylethynyl-
phenylethynyl)benzonitrile (8a). 5c (150 mg, 0.66
mmol),
phosphine)palladium(II) dichloride (9 mg, 0.013 mmol),
copper(I) iodide (5 mg, 0.026 mmol), and N,N-diisopropyl-
3a
(208 mg,
0.69 mmol),
bis(triphenyl-
132.6, 132.5, 132.2 (q, JC–F¼31 Hz), 130.0 (q, JC–F¼
5 Hz), 129.9, 127.6, 124.5, 123.4 (q, JC–F¼274 Hz), 123.3,
122.2, 120.4 (q, JC–F¼2 Hz), 117.1, 116.2, 103.3, 99.4,

10398
J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
98.8, 94.2, 89.2, 86.0, 0.2; HRMS calcd for C29H20F3NSi:
467.1317. Found: 467.1313.
for 1 d gave the desired product (182 mg, 70%). IR (KBr)
2231, 2210, 2154 cm21; 1H NMR (500 MHz, CDCl3) d 7.90
(s, 1H), 7.78 (d, J¼1.3 Hz, 1H), 7.75 (dd, J¼1.3, 8.1 Hz,
1H), 7.68 (d, J¼8.1 Hz, 1H), 7.64 (dd, J¼1.6, 8.1 Hz, 1H),
7.56–7.60 (m, 3H), 7.39–7.42 (m, 3H), 0.30 (s, 9H); 13C
NMR (125 MHz, CDCl3) d 136.2, 135.9, 135.0, 134.3,
4.5.20. 5-(2-Ethyl-4-trimethylsilanylethynylphenyl-
ethynyl)-2-phenylethynyl-benzonitrile (8e). 5c (180 mg,
0.79 mmol), 3e (260 mg, 0.79 mmol), bis(triphenyl-
phosphine)palladium(II) dichloride (11 mg, 0.016 mmol),
copper(I) iodide (6 mg, 0.032 mmol), triphenylphosphine
(8 mg, 0.03 mmol), and N,N-diisopropylethylamine
(550 mL, 3.16 mmol) in THF (7 mL) at 508C for 5 d gave
the desired product (242 mg, 71%). IR (KBr) 2230, 2215,
132.6, 132.3 (q, JC–F¼31 Hz), 132.2, 129.7 (q, JC–F
¼
5 Hz), 129.6, 128.9, 126.1, 124.8, 123.4 (q, JC–F¼274 Hz),
122.8, 122.7 (q, JC–F¼2 Hz), 122.0, 117.0, 116.1, 102.4,
100.2, 98.2, 96.2, 88.6, 85.6, 0.1; HRMS calcd for
C29H20F3NSi: 467.1317. Found: 467.1314.
2152 cm21
;
1H NMR (400 MHz, CDCl3) d 7.81 (d,
J¼1.6 Hz, 1H), 7.68 (dd, J¼1.6, 1.78.1 Hz, 1H), 7.61–
7.69 (m, 3H), 7.43 (d, J¼8.1 Hz, 2H), 7.40–7.43 (m, 4H),
7.32 (dd, J¼1.6, 7.9 Hz, 1H), 2.86 (q, J¼7.6 Hz, 2H), 1.32
(t, J¼7.6 Hz, 3H), 0.29 (s, 9H); 13C NMR (100 MHz,
CDCl3) d 146.8, 135.6, 135.3, 132.6, 132.5, 132.4, 132.0,
129.9, 129.8, 128.9, 126.8, 124.4, 124.2, 122.3, 121.9,
117.3, 116.2, 105.2, 98.4, 96.8, 92.4, 92.2, 86.0, 28.0, 15.0,
0.4; HRMS calcd for C30H25NSi: 427.1756. Found:
427.1747.
4.5.24. Trimethyl[4-(4-phenylethynyl-3-trifluoromethyl-
phenylethynyl)-3-trifluoromethylphenylethynyl]silane
(9d). 5d (225 mg, 0.83 mmol), 3d (260 mg, 0.79 mmol),
bis(triphenylphosphine)palladium(II) dichloride (17 mg,
0.024 mmol), copper(I) iodide (9 mg, 0.047 mmol), tri-
phenylphosphine (13 mg, 0.049 mmol), and N,N-diiso-
propylethylamine (580 mL, 3.32 mmol) in THF (5 mL) at
508C for 3 d gave the desired product (230 mg, 51%). IR
1
(KBr) 2202, 2158 cm21; H NMR (400 MHz, CDCl3) d
7.84 (br s, 1H), 7.79 (d, J¼0.7 Hz, 1H), 7.66 (d, J¼1.1 Hz,
2H), 7.61 (d, J¼1.1 Hz, 2H), 7.55–7.59 (m, 2H), 7.35–7.40
(m, 3H), 0.28 (s, 9H); 13C NMR (100 MHz, CDCl3) d 134.9,
134.6, 134.2, 134.1, 132.3 (q, JC–F¼31 Hz), 132.2 (q,
JC–F¼31 Hz), 132.1, 129.9 (q, JC–F¼5 Hz), 129.4 (q,
JC–F¼5 Hz), 128.9, 124.9, 124.8, 124.2, 123.6 (q,
JC–F¼274 Hz), 123.5 (q, JC–F¼274 Hz), 122.8, 122.7,
122.3 (q, JC–F¼2 Hz), 120.7 (q, JC–F¼2 Hz), 103.4, 99.1,
97.7, 95.2, 88.5, 85.6, 0.2; HRMS calcd for C29H20F6Si:
510.1238. Found: 510.1234.
4.5.21. Trimethyl[4-(4-phenylethynyl-3-trifluoromethyl-
phenylethynyl)-phenylethynyl]silane (9a). 5d (150 mg,
0.55 mmol), 3a (167 mg, 0.55 mmol), bis(triphenyl-
phosphine)palladium(II) dichloride (8 mg, 0.011 mmol),
copper(I) iodide (4 mg, 0.021 mmol), and N,N-diisopropyl-
ethylamine (387 mL, 2.22 mmol) in THF (6 mL) for 1 d
gave the desired product (185 mg, 75%). IR (KBr) 2211,
1
2149 cm21; H NMR (500 MHz, CDCl3) d 7.86 (s, 1H),
7.64–7.68 (m, 2H), 7.57–7.60 (m, 2H), 7.48–7.52 (m, 4H),
7.39–7.42 (m, 3H), 0.29 (s, 9H); 13C NMR (125 MHz,
CDCl3) d 134.5, 134.2, 132.4, 132.1 (q, JC–F¼31 Hz),
132.0, 129.5 (q, JC–F¼5 Hz), 129.4, 128.9, 124.1, 123.5 (q,
JC–F¼274 Hz), 123.4, 123.0, 122.9, 121.6 (q, JC–F¼2 Hz),
104.9, 97.4, 97.2, 92.6, 90.1, 85.7, 0.3; HRMS calcd for
C28H21F3Si: 442.1364. Found: 442.1364.
4.5.25. [3-Ethyl-4-(4-phenylethynyl-3-trifluoromethyl-
phenylethynyl)-phenylethynyl]trimethylsilane (9e). 5d
(180 mg, 0.67 mmol), 3e (219 mg, 0.67 mmol), bis(tri-
phenylphosphine)palladium(II) dichloride (9 mg, 0.013
mmol), copper(I) iodide (5 mg, 0.026 mmol), triphenyl-
phosphine (7 mg, 0.026 mmol), and N,N-diisopropylethyl-
amine (550 mL, 3.16 mmol) in THF (7 mL) at 508C for 4 d
gave the desired product (213 mg, 68%). IR (KBr) 2216,
4.5.22. [3-Fluoro-4-(4-phenylethynyl-3-trifluoromethyl-
phenylethynyl)-phenylethynyl]-trimethyl-silane (9b). 5d
(150 mg, 0.55 mmol), 3b (177 mg, 0.55 mmol), bis(tri-
phenylphosphine)palladium(II) dichloride (8 mg, 0.011
mmol), copper(I) iodide (4 mg, 0.021 mmol), and N,N-
diisopropylethylamine (387 mL, 2.22 mmol) in THF (8 mL)
for 1 d gave the desired product (198 mg, 77%). IR (KBr)
1
2154 cm21; H NMR (400 MHz, CDCl3) d 7.79 (s, 1H),
7.56–7.64 (m, 2H), 7.52–7.55 (m, 2H), 7.42 (d, J¼7.9 Hz,
1H), 7.34–7.38 (m, 4H), 7.27 (dd, J¼1.6, 7.9 Hz, 1H), 2.83
(q, J¼7.6 Hz, 2H), 1.28 (t, J¼7.6 Hz, 3H), 0.25 (s, 9H); 13C
NMR (125 MHz, CDCl3) d 146.7, 134.4, 134.2, 132.6,
132.3 (q, JC–F¼31 Hz), 132.2, 132.0, 129.7, 129.5, 129.3
1
2204, 2151 cm21; H NMR (400 MHz, CDCl3) d 7.86 (d,
J¼0.5 Hz, 1H), 7.64–7.69 (m, 2H), 7.55–7.59 (m, 2H),
7.46 (dd, J¼7.5, 7.5 Hz, 1H), 7.38–7.41 (m, 3H), 7.23–7.28
(m, 2H), 0.28 (s, 9H); 13C NMR (125 MHz, CDCl3) d 162.5
(d, JC–F¼252 Hz), 134.6, 134.2, 133.6, 133.5, 132.1 (q,
JC–F¼31 Hz), 129.5 (q, JC–F¼5 Hz), 129.5, 128.5, 128.1(d,
JC–F¼3 Hz), 126.0, 125.9, 123.5 (q, JC–F¼274 Hz), 123.0,
122.9, 122.1 (q, JC–F¼2 Hz), 119.3 (d, JC–F¼23 Hz), 112.0
(d, JC–F¼16 Hz), 103.5 (d, JC–F¼3 Hz), 98.4, 97.6, 94.7 (d,
JC–F¼3 Hz), 86.0, 85.7, 0.2; HRMS calcd for C28H20F4Si:
460.1270. Found: 460.1266.
(q, JC–F¼5 Hz), 128.9, 125.0, 123.6, 123.5 (q, JC–F¼
274 Hz), 122.9, 122.2, 121.5 (q, JC–F¼2 Hz), 105.2, 97.3,
96.6, 93.3, 91.4, 85.7, 28.0, 15.0, 0.4; HRMS calcd for
C30H25F3Si: 470.1678. Found: 470.1678.
4.5.26. [4-(3-Ethyl-4-phenylethynylphenylethynyl)-
phenylethynyl]trimethylsilane (10a). 5e (150 mg,
0.65 mmol), 3a (196 mg, 0.65 mmol), bis(triphenyl-
phosphine)palladium(II) dichloride (9 mg, 0.013 mmol),
copper(I) iodide (5 mg, 0.026 mmol), and N,N-diisopropyl-
ethylamine (454 mL, 2.60 mmol) in THF (8 mL) for 1 d
gave the desired product (136 mg, 52%). IR (KBr) 2201,
4.5.23. 2-(4-Phenylethynyl-3-trifluoromethylphenyl-
ethynyl)-5-trimethylsilanylethynylbenzonitrile (9c). 5d
(150 mg, 0.55 mmol), 3c (180 mg, 0.55 mmol), bis(tri-
phenylphosphine)palladium(II) dichloride (8 mg, 0.011
mmol), copper(I) iodide (4 mg, 0.021 mmol), and N,N-
diisopropylethylamine (387 mL, 2.22 mmol) in THF (6 mL)
1
2154 cm21; H NMR (500 MHz, CDCl3) d 7.55–7.58 (m,
2H), 7.51 (d, J¼7.9 Hz, 1H), 7.43–7.50 (m, 4H), 7.44 (d,
J¼1.3 Hz, 1H), 7.35–7.42 (m, 4H), 2.92 (q, J¼7.6 Hz, 2H),
1.35 (t, J¼7.6 Hz, 3H), 0.29 (s, 9H); 13C NMR (125 MHz,
CDCl3) d 146.7, 132.5, 132.3, 131.9, 131.8, 131.5, 129.3,

J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
10399
128.8, 123.7, 123.6, 123.4, 123.3, 123.1, 105.0, 96.8, 95.1,
91.8, 90.8, 88.2, 28.0, 15.0, 0.3; HRMS calcd for C29H26Si:
402.1804. Found: 402.1800.
(8 mg, 0.032 mmol), and N,N-diisopropylethylamine
(545 mL, 3.13 mmol) in THF (8 mL) at 508C for 4 d gave
the desired product (170 mg, 51%). IR (KBr) 2200,
1
2155 cm21; H NMR (400 MHz, CDCl3) d 7.54–7.58 (m,
4.5.27. [4-(3-Ethyl-4-phenylethynylphenylethynyl)-3-
fluorophenylethynyl]trimethyl-silane (10b). 5e (160 mg,
0.69 mmol), 3b (221 mg, 0.69 mmol), bis(triphenyl-
phosphine)palladium(II) dichloride (10 mg, 0.014 mmol),
copper(I) iodide (4 mg, 0.026 mmol), and N,N-diisopropyl-
ethylamine (484 mL, 2.78 mmol) in THF (8 mL) for 1 d
gave the desired product (206 mg, 70%). IR (KBr) 2205,
2H), 7.51 (d, J¼8.0 Hz, 1H), 7.45 (d, J¼8.4 Hz, 1H), 7.41–
7.43 (m, 2H), 7.35–7.40 (m, 4H), 7.35 (dd, J¼1.7, 8.0 Hz,
1H), 7.30 (dd, J¼1.7, 8.0 Hz, 1H), 2.91 (q, J¼7.6 Hz, 2H),
2.90 (q, J¼7.6 Hz, 2H), 1.35 (t, J¼7.6 Hz, 3H), 1.33 (t,
J¼7.6 Hz, 3H), 0.29 (s, 9H); 13C NMR (125 MHz, CDCl3) d
146.7, 146.5, 132.5, 132.4, 131.9, 131.8, 131.4, 129.7,
129.2, 128.8, 128.7, 123.8, 123.6, 123.5, 123.0, 122.9,
105.5, 96.2, 95.1, 95.0, 89.6, 89.3, 28.1, 28.0, 15.0, 14.9,
0.4; HRMS calcd for C31H30Si: 430.2117. Found: 430.2120.
1
2150 cm21; H NMR (400 MHz, CDCl3) d 7.59–7.59 (m,
2H), 7.53 (d, J¼7.9 Hz, 1H), 7.46–7.49 (m, 2H), 7.37–7.42
(m, 4H), 7.23–7.27 (m, 2H), 2.93 (q, J¼7.6 Hz, 2H), 1.37 (t,
J¼7.6 Hz, 3H), 0.31 (s, 9H); 13C NMR (100 MHz, CDCl3) d
162.4 (d, JC–F¼252 Hz), 146.7, 133.5, 132.5, 132.0, 131.6,
129.4, 128.8, 128.1 (d, JC–F¼3 Hz), 125.3, 125.2, 123.7,
4.6. General procedure for the preparation of tetramer
thioacetate
123.5, 122.9, 119.2 (d, JC–F¼23 Hz), 112.7 (d, JC–F
¼
The silylated alkyne was deprotected as described
previously. Without further purification, the trimer alkyne
was subjected to coupling with the alligator clip as follows:
To a stirring solution of the 1-iodo-4-thioacetylbenzene (11)
(1–2 equiv.), bis(triphenylphosphine)palladium(II) dichlor-
ide (3 mol%), and copper(I) iodide (6 mol%) in THF was
added the terminal alkyne followed by the amine (4 equiv.
based on the alkyne) at room temperature under nitrogen in
a screw cap tube. The tube was flushed with nitrogen,
capped, and allowed to stir 24 h. The reaction mixture was
then subjected to an aqueous workup and the aqueous layer
extracted with dichloromethane. After drying the combined
organic layers over sodium sulfate, the solvent was removed
in vacuo. The crude product was purified by column
chromatography (silica gel) with hexane/EtOAc mixtures to
give desired product.
16 Hz), 103.7 (d, JC–F¼3 Hz), 98.0, 96.6 (d, JC–F¼3 Hz),
88.2, 84.2, 28.0, 15.0, 0.2; HRMS calcd for C29H25FSi:
420.1710. Found: 420.1706.
4.5.28. 2-(3-Ethyl-4-phenylethynylphenylethynyl)-5-tri-
methylsilanylethynyl-benzonitrile (10c). 5e (175 mg,
0.76 mmol), 3c (247 mg, 0.76 mmol), bis(triphenyl-
phosphine)palladium(II) dichloride (11 mg, 0.016 mmol),
copper(I) iodide (6 mg, 0.032 mmol), and N,N-diisopropyl-
ethylamine (530 mL, 3.04 mmol) in THF (8 mL) for 1 d
gave the desired product (225 mg, 69%). IR (KBr) 2230,
2201, 2149 cm21; 1H NMR (400 MHz, CDCl3) d 7.78 (dd,
J¼0.6, 1.6 Hz, 1H), 7.62 (dd, J¼1.6, 8.2 Hz, 1H), 7.51–
7.58 (m, 5H), 7.43 (dd, J¼1.6, 7.9 Hz, 1H), 7.37–7.41 (m,
3H), 2.92 (q, J¼7.6 Hz, 2H), 1.36 (t, J¼7.6 Hz, 3H), 0.28 (s,
9H); 13C NMR (125 MHz, CDCl3) d 146.8, 136.2, 135.8,
132.6, 132.4, 132.0, 131.9, 129.7, 128.9, 128.8, 126.9,
124.2, 124.1, 123.6, 122.0, 117.2, 115.9, 102.6, 99.7, 98.3,
95.7, 88.1, 87.1, 28.0, 15.0, 0.1; HRMS calcd for
C30H25NSi: 427.1756. Found: 427.1755.
4.6.1. Thioacetic acid S-{4-[3-fluoro-4-(4-phenylethynyl-
phenylethynyl-phenylethynyl]phenyl} ester (12b). 75 mg
(43%) of 12b as yellow solid, mp 196–2028C, was
produced from 6b (145 mg, 0.37 mmol) and 11 (205 mg,
0.74 mmol). IR (KBr) 2204, 1700 cm21
;
1H NMR
4.5.29. [4-(3-Ethyl-4-phenylethynylphenylethynyl)-3-tri-
fluoromethylphenylethynyl]-trimethylsilane (10d). 5e
(180 mg, 0.78 mmol), 3d (432 mg, 1.17 mmol), bis(tri-
(500 MHz, CDCl3) d 7.53–7.59 (m, 8H), 7.52 (dd, J¼7.6,
7.6 Hz, 1H) 7.43 (d, J¼8.4 Hz, 2H), 7.37–7.41 (m, 3H),
7.28–7.34 (m, 2H), 2.47 (s, 3H); 13C NMR (125 MHz,
CDCl3) d 193.7, 162.5 (d, JC–F¼252 Hz), 134.7, 133.6,
132.6, 132.1, 132.0, 129.2, 128.9, 128.8, 127.8 (d,
JC–F¼3 Hz), 125.1, 125.0, 124.2, 124.1, 123.4, 122.8,
118.9 (d, JC–F¼23 Hz), 112.6 (d, JC–F¼16 Hz), 96.5, 96.3
(d, JC–F¼3 Hz), 92.0, 91.8, 89.9 (d, JC–F¼3 Hz), 89.4, 84.7,
30.7; HRMS calcd for C32H19FOS: 470.1140. Found:
470.1141.
phenylphosphine)palladium(II) dichloride
2
(11 mg,
0.016 mmol), copper(I) iodide (6 mg, 0.032 mmol), tri-
phenylphosphine (8 mg, 0.032 mmol), and N,N-diisopropyl-
ethylamine (545 mL, 3.13 mmol) in THF (8 mL) at 508C for
7 d gave the desired product (235 mg, 64%). IR (KBr) 2200,
1
2157 cm21; H NMR (500 MHz, CDCl3) d 7.79 (s, 1H),
7.58–7.62 (m, 2H), 7.55–7.57 (m, 2H), 7.51 (d, J¼7.9 Hz,
1H), 7.44 (dd, J¼0.5, 1.5 Hz, 1H), 7.37–7.40 (m, 4H), 2.93
(q, J¼7.6 Hz, 2H), 1.35 (t, J¼7.6 Hz, 3H), 0.30 (s, 9H); 13C
NMR (125 MHz, CDCl3) d 146.8, 134.9, 134.0, 132.6,
4.6.2. Thioacetic acid S-{4-[3-cyano-4-(4-phenylethynyl-
phenylethynyl)-phenylethynyl]phenyl} ester (12c). 72 mg
(41%) of 12c as yellow solid, mp 199–2018C, was produced
from 6c (148 mg, 0.37 mmol) and 11 (122 mg, 0.44 mmol).
132.1 (q, JC–F¼31 Hz), 132.0, 131.6, 129.6 (q, JC–F
¼
5 Hz), 129.5, 128.9, 128.8, 123.8, 123.7, 123.6 (q, JC–F
¼
274 Hz), 123.5, 122.8, 121.6 (q, JC–F¼2 Hz), 103.6, 98.6,
97.3, 95.5, 88.2, 86.9, 28.1, 15.0, 0.2; HRMS calcd for
C30H25F3Si: 470.1678. Found: 470.1681.
IR (KBr) 2223, 2209, 1706 cm21 1H NMR (400 MHz,
;
CDCl3) d 7.85 (d, J¼1.5 Hz, 1H), 7.71 (dd, J¼1.7, 8.2 Hz,
1H), 7.55–7.65 (m, 9H), 7.45 (d, J¼8.4 Hz, 1H), 7.37–7.41
(m, 3H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3) d 193.6,
135.8, 135.6, 134.7, 132.7, 132.5, 132.4, 132.1, 132.0,
129.6, 129.0, 128.8, 126.8, 124.9, 124.0, 123.7, 123.3,
121.9, 117.2, 116.1, 98.0, 93.0, 92.4, 89.4, 88.8, 87.7, 30.8;
HRMS calcd for C33H19NOS: 477.1187. Found:
477.1193.
4.5.30. [3-Ethyl-4-(3-ethyl-4-phenylethynylphenyl-
ethynyl)phenylethynyl]trimethyl-silane (10e). 5e (180
mg, 0.78 mmol), 3e (385 mg, 1.17 mmol), bis(triphenyl
phosphine)palladium(II) dichloride (11 mg, 0.016 mmol),
copper(I) iodide (6 mg, 0.032 mmol), triphenylphosphine

10400
J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
4.6.3. Thioacetic acid S-{4-[4-(4-phenylethynylphenyl-
ethynyl)-3-trifluoromethyl-phenylethynyl]phenyl} ester
(12d). 88 mg (47%) of 12d as yellow solid, mp 2018C
(dec.), was produced from 6d (158 mg, 0.36 mmol) and 11
(142 mg, 0.51 mmol). IR (KBr) 2214, 1703 cm21; 1H NMR
(400 MHz, CDCl3) d 7.87 (br s, 1H), 7.68 (br s, 2H), 7.56–
7.61 (m, 8H), 7.44 (d, J¼8.4 Hz, 2H), 7.36–7.41 (m, 3H),
2.48 (s, 3H); 13C NMR (125 MHz, CDCl3) d 193.7, 134.7,
134.6, 134.2, 132.7, 132.2 (q, JC–F¼31 Hz), 132.21, 132.0,
129.6 (q, JC–F¼5 Hz), 129.3, 129.0, 128.8, 124.4, 124.0,
123.5 (q, JC–F¼274 Hz), 123.4, 123.3, 122.6, 121.5 (q,
JC–F¼2 Hz), 97.0, 92.3, 92.1, 89.8, 89.4, 87.4, 30.7; HRMS
calcd for C33H19F3OS: 520.1109. Found: 520.1109.
1958C, was produced from 7c (115 mg, 0.28 mmol) and 11
1
(76 mg, 0.27 mmol). IR (KBr) 2228, 2208, 1700 cm21; H
NMR (400 MHz, CDCl3) d 7.80 (d, J¼1.7 Hz, 1H), 7.68
(dd, J¼1.6, 8.2 Hz, 1H), 7.59 (d, J¼8.2 Hz, 1H), 7.52–7.56
(m, 4H), 7.50 (dd, J¼7.7, 7.7 Hz, 1H), 7.41 (d, J¼8.4 Hz,
2H), 7.31–7.37 (m, 5H), 2.43 (s, 3H); 13C NMR (100 MHz,
CDCl3) d 193.5, 162.5 (d, JC–F¼252 Hz), 135.9, 135.6,
134.7, 133.9, 133.8, 132.7, 132.6, 132.2, 129.7, 129.3,
128.8, 128.2 (d, JC–F¼3 Hz), 126.3, 124.4, 123.6 (d,
JC–F¼9 Hz), 123.0, 119.1 (d, JC–F¼23 Hz), 117.0, 116.3,
113.9 (d, JC–F¼16 Hz), 97.3 (d, JC–F¼3 Hz), 96.6 (d,
JC–F¼3 Hz), 93.3, 88.7, 88.2, 82.8, 30.8; HRMS calcd for
C33H18FNOS: 495.1093. Found: 495.1096.
4.6.4. Thioacetic acid S-{4-[3-ethyl-4-(4-phenylethynyl-
phenylethynyl)-phenylethynyl]phenyl} ester (12e). 72 mg
(47%) of 12e as yellow solid, mp 176–1848C, was produced
from 6e (128 mg, 0.32 mmol) and 11 (131 mg, 0.47 mmol).
IR (KBr) 2200, 1694 cm21; 1H NMR (400 MHz, CDCl3) d
7.50–7.60 (m, 9H), 7.45–7.46 (m, 1H), 7.43 (d, J¼8.4 Hz,
2H), 7.37–7.41 (m, 4H), 2.91 (q, J¼7.6 Hz, 2H), 2.47 (s,
3H), 1.34 (t, J¼7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) d
193.8, 146.7, 134.7, 132.6, 132.5, 132.1, 132.0, 131.9, 131.6,
129.4, 128.9, 128.8, 128.6, 124.8, 123.7, 123.5, 123.4, 122.9,
94.9,91.8, 91.5, 90.6, 90.2, 89.6,30.7, 28.1, 15.0;HRMScalcd
for C34H24OS: 480.1548. Found: 480.1457.
4.6.8. Thioacetic acid S-{4-[4-(3-fluoro-4-phenylethynyl-
phenylethynyl)-3-trifluoromethylphenylethynyl]phenyl}
ester (13d). 80 mg (41%) of 13d as yellow solid, mp 188–
1908C, was produced from 7d (166 mg, 0.36 mmol) and 11
1
(97 mg, 0.35 mmol). IR (KBr) 2210, 1700 cm21; H NMR
(500 MHz, CDCl3) d 7.86 (s, 1H), 7.63–7.67 (m, 2H),
7.59–7.61 (m, 4H), 7.53 (dd, J¼7.6, 7.6 Hz, 1H), 7.44 (d,
J¼8.3 Hz, 2H), 7.38–7.41 (m, 3H), 7.29–7.34 (m, 2H),
2.47 (s, 3H); 13C NMR (125 MHz, CDCl3) d 193.6, 162.5
(d, JC–F¼252 Hz), 134.7, 134.6, 134.2, 133.7, 133.6, 123.7,
132.3 (q, JC–F¼31 Hz), 132.2, 129.6 (q, JC–F¼5 Hz),
129.4, 128.8, 127.9 (d, JC–F¼3 Hz), 124.4, 124.3, 123.9,
123.8, 123.4 (q, JC–F¼274 Hz), 120.9 (q, JC–F¼2 Hz),
118.9 (d, JC–F¼22 Hz), 113.4 (d, JC–F¼16 Hz), 97.0 (d,
JC–F¼3 Hz), 96.6 (d, JC–F¼3 Hz), 92.5, 89.7, 88.1, 82.8,
30.7; HRMS calcd for C33H18F4OS: 538.1014. Found:
538.1014.
4.6.5. Thioacetic acid S-{4-[4-(3-fluoro-4-phenylethynyl-
phenylethynyl)-phenylethynyl]phenyl}
ester
(13a).
82 mg (38%) of 13a as yellow solid, mp 202–2058C, was
produced from 7a (180 mg, 0.46 mmol) and 11 (120 mg,
0.43 mmol). IR (KBr) 2212, 1692 cm21
;
1H NMR
(500 MHz, CDCl3) d 7.56–7.60 (m, 4H), 7.50–7.56 (m,
4H), 7.52 (dd, J¼7.6, 7.6 Hz, 1H) 7.44 (d, J¼8.4 Hz, 2H),
7.35–7.40 (m, 3H), 7.31–7.35 (m, 2H), 2.47 (s, 3H); 13C
NMR (125 MHz, CDCl3) d 193.8, 162.5 (d, JC–F¼252 Hz),
133.7, 133.6, 132.6, 132.2, 132.1, 132.0, 129.2, 128.8, 127.7
(d, JC–F¼4 Hz), 125.0 (d, JC–F¼9 Hz), 124.6, 123.7, 123.1,
118.8 (d, JC–F¼23 Hz), 112.8 (d, JC–F¼16 Hz), 96.6 (d,
JC–F¼3 Hz), 92.0, 91.2, 91.0, 90.4 (d, JC–F¼4 Hz), 82.9,
30.7; HRMS; HRMS calcd for C32H19FOS: 470.1140.
Found: 470.1143.
4.6.9. Thioacetic acid S-{4-[3-ethyl-4-(3-fluoro-4-phenyl-
ethynylphenylethynyl)-phenylethynyl]phenyl} ester
(13e). 62 mg (48%) of 13e as yellow solid, mp 150–
1528C, was produced from 7e (110 mg, 0.26 mmol) and 11
1
(68 mg, 0.24 mmol). IR (KBr) 2218, 1698 cm21; H NMR
(400 MHz, CDCl3) d 7.56–7.61 (m, 4H), 7.50–7.54 (m,
2H), 7.46 (br, 1H), 7.43 (d, J¼8.2 Hz, 2H), 7.36–7.42 (m,
4H), 2.91 (q, J¼7.6 Hz, 2H), 2.47 (s, 3H), 1.33 (t, J¼7.6 Hz,
3H); 13C NMR (100 MHz, CDCl3) d 193.8, 162.5 (d,
JC–F¼252 Hz), 146.9, 134.6, 133.7, 133.6, 132.7, 132.6,
132.2, 131.6, 129.4, 129.2, 128.8, 128.7, 127.6 (d, JC–F
3 Hz), 125.3, 125.2, 124.7, 123.8, 123.1, 122.4, 118.6 (d,
¼
4.6.6. Thioacetic acid S-{4-[3-fluoro-4-(3-fluoro-4-
phenylethynylphenylethynyl)-phenylethynyl]phenyl}
ester (13b). 30 mg (23%) of 13b as yellow solid, mp 203–
2078C, was produced from 7b (112 mg, 0.28 mmol) and 11
JC–F¼23 Hz), 112.6 (d, JC–F¼16 Hz), 96.6 (d, JC–F
¼
3 Hz), 93.7 (d, JC–F¼3 Hz), 91.4, 90.9, 90.7, 83.0, 30.7,
28.0, 15.0; HRMS calcd for C34H23FOS: 498.1454. Found:
498.1453.
1
(75 mg, 0.27 mmol). IR (KBr) 2208, 1700 cm21; H NMR
(500 MHz, CDCl3) d 7.57–7.60 (m, 4H), 7.52 (dd, J¼7.3,
14.8 Hz, 2H) 7.44 (d, J¼8.4 Hz, 2H), 7.37–7.41 (m, 3H),
7.30–7.37 (m, 4H), 2.47 (s, 3H); 13C NMR (125 MHz,
4.6.10. Thioacetic acid S-{4-[4-(3-cyano-4-phenyl-
ethynylphenylethynyl)-phenylethynyl]phenyl} ester
(14a). 105 mg (58%) of 14a as yellow solid, mp 204–
2058C, was produced from 8a (125 mg, 0.38 mmol) and 11
CDCl3) d 193.7, 162.6 (d, JC–F¼252 Hz), 162.5 (d, JC–F
¼
252 Hz), 134.7, 133.7, 132.7, 132.2, 129.2 (d, JC–F¼4 Hz),
128.9, 127.9 (d, JC–F¼4 Hz), 127.8, 125.5 (d, JC–F¼9 Hz),
1
(111 mg, 0.4 mmol). IR (KBr) 2228, 2213, 1700 cm21; H
124.4 (d, JC–F¼9 Hz), 124.1, 123.0, 119.0 (d, JC–F
¼
NMR (400 MHz, CDCl3) d 7.82 (d, J¼1.8 Hz, 1H), 7.70
(dd, J¼1.7, 8.2 Hz, 1H), 7.61–7.65 (m, 3H), 7.57 (d,
J¼8.4 Hz, 2H), 7.53–7.56 (m, 4H), 7.41 (d, J¼8.4 Hz, 2H),
7.40–7.42 (m, 3H), 0.27 (s, 9H); 13C NMR (100 MHz,
CDCl3) d 193.8, 135.8, 135.5, 134.7, 132.6, 132.5, 132.4,
132.2, 132.1, 129.9, 128.8, 127.0, 124.5, 124.1, 123.9,
122.6, 122.2, 117.2, 116.2, 98.4, 93.3, 91.4, 90.9, 89.2, 86.0,
30.7; HRMS calcd for C33H19NOS: 477.1187. Found:
477.1184.
22 Hz), 118.9 (d, JC–F¼22 Hz), 113.1 (d, JC–F¼16 Hz),
112.1 (d, JC–F¼16 Hz), 96.8 (d, JC–F¼3 Hz), 96.5, 95.1 (d,
JC–F¼3 Hz), 92.0, 89.8 (d, JC–F¼3 Hz), 85.4, 82.8, 30.7;
HRMS calcd for C32H18F2OS: 488.1046. Found: 488.1034.
4.6.7. Thioacetic acid S-{4-[3-cyano-4-(3-fluoro-4-
phenylethynylphenylethynyl)-phenylethynyl]phenyl}
ester (13c). 65 mg (48%) of 13c as yellow solid, mp 192–

J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
10401
4.6.11. Thioacetic acid S-{4-[4-(3-cyano-4-phenyl-
ethynylphenylethynyl)-3-fluoro-phenylethynyl]phenyl}
ester (14b). 62 mg (42%) of 14b as yellow solid, mp 207–
2088C, was produced from 8b (125 mg, 0.3 mmol) and 11
28.0, 15.0; HRMS calcd for C35H23NOS: 505.1500. Found:
505.1501.
4.6.15. Thioacetic acid S-{4-[4-(4-phenylethynyl-3-tri-
fluoromethylphenylethynyl)-phenylethynyl]phenyl}
ester (15a). 60 mg (40%) of 15a as yellow solid, mp 192–
1948C, was produced from 9a (128 mg, 0.29 mmol) and 11
1
(78 mg, 0.28 mmol). IR (KBr) 2231, 2210, 1695 cm21; H
NMR (400 MHz, CDCl3) d 7.87 (d, J¼1.6 Hz, 1H), 7.74
(dd, J¼1.6, 8.2 Hz, 1H), 7.62–7.66 (m, 3H), 7.57 (dd,
J¼7.6, 7.6 Hz, 1H), 7.43 (d, J¼8.4 Hz, 2H), 7.41–7.43 (m,
3H), 7.30–7.35 (m, 2H), 2.47 (s, 3H); 13C NMR (100 MHz,
CDCl3) d 193.2, 162.2 (d, JC–F¼252 Hz), 135.1, 134.2,
133.3, 133.2, 132.2, 132.1, 132.0, 129.5, 128.9, 128.5, 127.5
(d, JC–F¼3 Hz), 126.9, 125.5 (d, JC–F¼9 Hz), 123.6, 123.1,
121.8, 118.5 (d, JC–F¼22 Hz), 116.7, 115.7, 111.3 (d,
JC–F¼16 Hz), 98.2, 93.5 (d, JC–F¼3 Hz), 91.8, 89.3 (d,
JC–F¼3 Hz), 86.3, 85.5, 30.3; HRMS calcd for
C33H18FNOS: 495.1093. Found: 495.1095.
1
(80 mg, 0.29 mmol). IR (KBr) 2212, 1697 cm21; H NMR
(500 MHz, CDCl3) d 7.87 (s, 1H), 7.67 (d, J¼1.1 Hz, 2H),
7.58–7.60 (m, 4H), 7.56 (br, 2H), 7.43 (d, J¼8.4 Hz, 2H),
7.39–7.5422 (m, 3H), 2.47 (s, 3H); 13C NMR (125 MHz,
CDCl3) d 193.8, 134.7, 134.5, 134.2, 133.5, 132.6, 132.3 (q,
JC–F¼31 Hz), 132.2, 132.1, 132.0, 129.6 (q, JC–F¼5 Hz),
129.5, 128.9, 124.6, 123.8, 123.5 (q, JC–F¼274 Hz), 123.4,
122.9, 121.7 (q, JC–F¼2 Hz), 97.4, 92.6, 91.3, 91.0, 90.2,
85.7, 30.7; HRMS calcd for C33H19F3OS: 520.1109. Found:
520.1107.
4.6.12. Thioacetic acid S-{4-[3-cyano-4-(3-cyano-4-
phenylethynylphenylethynyl)-phenylethynyl]phenyl}
ester (14c). 49 mg (42%) of 14c as yellow solid was
produced from 8c (100 mg, 0.24 mmol) and 11 (65 mg,
4.6.16. Thioacetic acid S-{4-[3-fluoro-4-(4-phenyl-
ethynyl-3-trifluoromethyl-phenylethynyl)phenyl-
ethynyl]phenyl} ester (15b). 56 mg (36%) of 15b as yellow
solid, mp 178–1808C, was produced from 9b (132 mg,
0.29 mmol) and 11 (77 mg, 0.28 mmol). IR (KBr) 2205,
1
0.23 mmol). IR (KBr) 2231, 2209, 1706 cm21; H NMR
(500 MHz, CDCl3) d 7.90 (d, J¼1.4 Hz, 1H), 7.86 (d,
J¼1.4 Hz, 1H), 7.80 (dd, J¼1.6, 8.2 Hz, 1H), 7.74 (dd,
J¼1.6, 8.2 Hz, 1H), 7.69 (d, J¼1.4 Hz, 1H), 7.65–7.69 (m,
4H), 7.59 (d, J¼8.4 Hz, 2H), 7.45 (d, J¼8.4 Hz, 2H), 7.40–
7.44 (m, 3H), 2.48 (s, 3H); 13C NMR (125 MHz, CDCl3) d
193.4, 136.0, 135.9, 135.8, 135.7, 134.7, 132.7, 132.6,
132.5, 130.0, 129.8, 128.9, 128.1, 125.8, 124.8, 123.5,
122.6, 122.1, 117.0, 116.9, 116.4, 116.3, 99.1, 95.3, 93.6,
89.3, 88.6, 86.0, 30.7; HRMS calcd for C34H18N2OS:
502.1140. Found: 502.1140.
1
1699 cm21; H NMR (500 MHz, CDCl3) d 7.89 (s, 1H),
7.69–7.72 (m, 2H), 7.58–7.60 (m, 4H), 7.53 (dd, J¼7.7,
7.7 Hz, 1H), 7.44 (d, J¼8.4 Hz, 2H), 7.40–7.42 (m, 3H),
7.34–7.35 (m, 1H), 7.30–7.33 (m, 1H), 2.47 (s, 3H); 13C
NMR (125 MHz, CDCl3) d 193.6, 162.6 (d, JC–F¼252 Hz),
134.7, 134.6, 134.2, 133.7, 132.7, 132.3 (q, JC–F¼31 Hz),
132.2, 129.6 (q, JC–F¼5 Hz), 129.5, 129.3, 128.9, 127.9 (d,
JC–F¼3 Hz), 125.7, 125.6, 124.1, 123.5 (q, JC–F¼274 Hz),
122.9, 122.8, 122.0, (q, JC–F¼2 Hz), 119.0 (d, JC–F
¼
23 Hz), 112.0 (d, JC–F¼16 Hz), 97.6, 94.8 (d, JC–F¼3 Hz),
92.1, 89.9 (d, JC–F¼3 Hz), 85.9, 85.6, 30.7; HRMS calcd
for C33H18F4OS: 538.1014. Found: 538.1013.
4.6.13. Thioacetic acid S-{4-[4-(3-cyano-4-phenyl-
ethynylphenylethynyl)-3-trifluoromethylphenyl-
ethynyl]phenyl} ester (14d). 32 mg (30%) of 14d as yellow
solid, mp 162–1648C, was produced from 8d (90 mg,
0.19 mmol) and 11 (53 mg, 0.19 mmol). IR (KBr) 2230,
4.6.17. Thioacetic acid S-{4-[3-cyano-4-(4-phenyl-
ethynyl-3-trifluoromethyl-phenylethynyl)phenyl-
ethynyl]phenyl} ester (15c). 35 mg (26%) of 15c as yellow
solid, mp 177–1768C, was produced from 9c (116 mg,
0.25 mmol) and 11 (68 mg, 0.24 mmol). IR (KBr) 2229,
2229, 1696 cm21; 1H NMR (400 MHz, CDCl3) d 7.90 (br s,
1H), 7.84 (d, J¼1.1 Hz, 1H), 7.75 (dd, J¼1.5, 8.1 Hz, 1H),
7.71 (dd, J¼1.6, 8.1 Hz, 1H), 7.68 (d, J¼8.1 Hz, 1H), 7.63
(d, J¼8.2 Hz, 1H), 7.56–7.58 (m, 4H), 7.43 (d, J¼8.4 Hz,
1H), 7.38–7.41 (m, 3H), 2.46 (s, 3H); 13C NMR (125 MHz,
CDCl3) d 193.5, 135.9, 135.6, 135.0, 134.7, 134.3, 132.7,
132.3 (q, JC–F¼31 Hz), 132.2, 129.7 (q, JC–F¼5 Hz),
1
2210, 1703 cm21; H NMR (500 MHz, CDCl3) d 7.88 (d,
J¼0.6 Hz, 1H), 7.84 (d, J¼1.5 Hz, 1H), 7.72 (dd, J¼1.7,
13.1 Hz, 1H), 7.69 (d, J¼1.4 Hz, 1H), 7.68 (s, 1H) 7.63–
7.66 (m, 3H), 7.60 (d, J¼8.4 Hz, 2H), 7.45 (d, J¼8.4 Hz,
2H), 7.38–7.44 (m, 3H), 2.48 (s, 3H); 13C NMR (125 MHz,
CDCl3) d 193.6, 135.9, 135.6, 134.7, 134.3, 132.7, 132.6,
132.5, 132.4 (q, JC–F¼31 Hz), 130.0, 129.7 (q, JC–F
¼
5 Hz), 129.5, 128.9, 127.6, 124.3, 123.9, 123.4 (q,
JC–F¼274 Hz), 123.3, 122.2, 120.5, 120.4 (q, JC–F
¼
2 Hz), 98.8, 94.4, 92.8, 89.5, 89.2, 86.0, 30.8; HRMS
calcd for C34H18F3NOS: 545.1061. Found: 545.1060.
129.6, 128.9, 126.1, 124.6, 123.6, 123.5 (q, JC–F
¼
274 Hz), 122.8, 122.8, 122.0, 117.0, 116.3, 98.0, 96.3,
93.4, 88.7, 88.6, 85.6, 30.8; HRMS calcd for C34H18F3NOS:
545.1061. Found: 545.1062.
4.6.14. Thioacetic acid S-{4-[4-(3-cyano-4-phenyl-
ethynylphenylethynyl)-3-ethyl-phenylethynyl]phenyl}
ester (14e). 61 mg (43%) of 14e as yellow solid, mp 144–
1468C, was produced from 8e (120 mg, 0.28 mmol) and 11
4.6.18. Thioacetic acid S-{4-[4-(4-phenylethynyl-3-tri-
fluoromethylphenylethynyl)-3-trifluoromethylphenyl-
ethynyl]phenyl} ester (15d). 125 mg (56%) of 15d as
yellow solid, mp 181–1838C, was produced from 9d
(195 mg, 0.38 mmol) and 11 (106 mg, 0.38 mmol). IR
1
(75 mg, 0.27 mmol). IR (KBr) 2229, 2212, 1706 cm21; H
NMR (400 MHz, CDCl3) d 7.84 (dd, J¼1.6, 0.4 Hz, 1H),
7.69 (dd, J¼1.6, 8.1 Hz, 1H), 7.64–7.68 (m, 3H), 7.60 (d,
J¼8.4 Hz, 2H), 7.53 (d, J¼8.0 Hz, 1H), 7.39 (m, 7H), 2.91
(q, J¼7.6 Hz, 2H), 2.49 (s, 3H), 1.37 (t, J¼7.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3) d 193.8, 147.0, 135.6, 135.3,
134.6, 132.8, 132.6, 132.5, 132.4, 132.3, 131.7, 129.9,
129.5, 128.9, 128.8, 126.9, 124.6, 124.2, 124.1, 122.3,
121.9, 117.3, 116.2, 98.4, 92.6, 92.3, 91.3, 91.0, 86.0, 30.7,
1
(KBr) 2206, 1699 cm21; H NMR (400 MHz, CDCl3) d
7.88 (d, J¼0.6 Hz, 1H), 7.86 (br s, 1H), 7.68–7.72 (m, 4H),
7.56–7.60 (m, 4H), 7.44 (d, J¼8.4 Hz, 2H), 7.39–7.42 (m,
3H), 2.48 (s, 3H); 13C NMR (100 MHz, CDCl3) d 193.6,
134.7, 134.6, 134.3, 134.2, 132.7, 132.4 (q, JC–F¼31 Hz),

10402
J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
132.3 (q, JC–F¼31 Hz), 132.2, 129.6 (q, JC–F¼5 Hz),
129.5, 129.4 (q, JC–F¼5 Hz), 128.9, 124.0, 123.9, 122.8,
122.7, 123.5 (q, JC–F¼274 Hz), 123.4 (q, JC–F¼274 Hz),
122.4 (q, JC–F¼2 Hz), 120.8 (q, JC–F¼2 Hz), 97.7, 95.3,
92.6, 89.6, 88.5, 85.6, 30.7; HRMS calcd for C34H18F6OS:
588.0982. Found: 588.0984.
(s, 3H), 1.36 (t, J¼7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 193.6, 146.8, 135.9, 135.6, 134.7, 132.7, 132.5,
132.0, 131.9, 129.8, 129.6, 128.9, 128.8, 126.9, 124.2,
123.9, 123.7, 123.6, 122.0, 117.2, 116.1, 98.4, 95.7, 93.0,
88.9, 88.1, 87.2, 30.8, 28.1, 15.0; HRMS calcd for
C35H23NOS: 505.1500. Found: 505.1497.
4.6.19. Thioacetic acid S-{4-[3-ethyl-4-(4-phenylethynyl-
3-trifluoromethyl-phenylethynyl)phenylethynyl]phenyl}
ester (15e). 34 mg (21%) of 15e as yellow solid, mp 167–
1728C, was produced from 9e (142 mg, 0.30 mmol) and 11
4.6.23. Thioacetic acid S-{4-[4-(3-ethyl-4-phenylethynyl-
phenylethynyl)-3-trifluoromethylphenylethynyl]phenyl}
ester (16d). 98 mg (51%) of 16d as yellow solid, mp 185–
1888C, was produced from 10d (165 mg, 0.35 mmol) and 11
1
1
(122 mg, 0.3 mmol). IR (KBr) 2219, 1696 cm21; H NMR
(80 mg, 0.29 mmol). IR (KBr) 2192, 1694 cm21; H NMR
(500 MHz, CDCl3) d 7.85 (s, 1H), 7.69–7.71 (m, 2H),
7.58–7.61 (m, 4H), 7.53 (d, J¼7.9 Hz, 1H), 7.47 (d,
J¼1.1 Hz, 1H), 7.44 (d, J¼8.4 Hz, 1H), 7.39–7.43 (m, 4H),
2.91 (q, J¼7.6 Hz, 2H), 2.47 (s, 3H), 1.36 (t, J¼7.6 Hz, 3H);
13C NMR (125 MHz, CDCl3) d 193.7, 146.9, 134.6, 134.4,
134.2, 132.7, 132.6, 132.4 (q, JC–F¼31 Hz), 132.2, 131.6,
129.4, 129.3 (q, JC–F¼5 Hz), 128.8, 128.7, 124.7, 123.9,
123.6, 123.5 (q, JC–F¼274 Hz), 123.0, 122.3, 121.6 (q,
JC–F F¼2 Hz), 97.3, 93.4, 91.4, 91.3, 90.8, 85.7, 30.7, 28.0,
15.0; HRMS calcd for C35H23F3OS: 548.1422. Found:
548.1423.
(500 MHz, CDCl3) d 7.87 (s, 1H), 7.68 (d, J¼1.0 Hz, 1H),
7.60 (d, J¼8.4 Hz, 2H), 7.55–7.59 (m, 2H), 7.52 (d,
J¼7.9 Hz, 1H), 7.42–7.46 (m, 3H), 7.37–7.41 (m, 4H),
2.92 (q, J¼7.6 Hz, 2H), 2.48 (s, 3H), 1.36 (t, J¼7.6 Hz, 3H);
13C NMR (125 MHz, CDCl3) d 193.6, 146.8, 134.7, 134.6,
134.2, 132.7, 132.5, 132.2 (q, JC–F¼31 Hz), 131.9, 131.6,
129.6 (q, JC–F¼5 Hz), 129.4, 129.3, 128.9, 128.8, 124.0,
123.7, 123.6, 123.5 (q, JC–F¼274 Hz), 123.3, 122.7, 121.6
(q, JC–F¼2 Hz), 97.4, 95.4, 92.2, 89.9, 88.2, 86.9, 30.7,
28.1, 15.0; HRMS calcd for C35H23OSF3: 548.1422. Found:
548.1423.
4.6.20. Thioacetic acid S-{4-[4-(3-ethyl-4-phenylethynyl-
phenylethynyl)-phenylethynyl]phenyl}
4.6.24. Thioacetic acid S-{4-[3-ethyl-4-(3-ethyl-4-phenyl-
ethynylphenylethynyl)-phenylethynyl]phenyl} ester
(16e). 48 mg (37%) of 16e as yellow solid, mp 141–
1448C, was produced from 10e (110 mg, 0.25 mmol) and 11
ester
(16a).
14 mg (12%) of 16a as yellow solid, mp 129–1318C, was
produced from 10a (98 mg, 0.24 mmol) and 11 (67 mg,
0.24 mmol). IR (KBr) 2203, 1708 cm21
;
1H NMR
(70 mg, 0.25 mmol). IR (KBr) 2199, 1692 cm21; H NMR
1
(400 MHz, CDCl3) d 7.50–7.60 (m, 9H), 7.43–7.46 (m,
3H), 7.36–7.41 (m, 4H), 2.92 (q, J¼7.6 Hz, 2H), 2.47 (s,
3H), 1.36 (t, J¼7.6 Hz, 3H); 13C NMR (125 MHz, CDCl3) d
193.4, 146.2, 134.2, 132.4, 132.2, 132.1, 132.0, 131.6,
131.58, 131.55, 131.5, 131.1, 128.9, 128.4, 128.3, 127.2,
124.3, 123.3, 122.8, 122.7, 122.6, 94.7, 91.5, 90.7, 90.5,
90.4, 87.8, 30.3, 27.6, 14.5; HRMS calcd for C34H24OS:
480.1548. Found: 480.1544.
(500 MHz, CDCl3) d 7.53–7.58 (m, 4H), 7.49 (dd, J¼9.9,
1.8 Hz, 2H), 7.38–7.44 (m, 4H), 7.34–7.37 (m, 5H), 2.90
(q, J¼7.6 Hz, 4H), 2.44 (s, 3H), 1.34 (t, J¼7.6 Hz, 6H); 13C
NMR (125 MHz, CDCl3) d 193.8, 146.8, 146.7, 134.6,
132.6, 132.5, 132.4, 131.9, 131.6, 131.4, 129.4, 129.2,
128.8, 128.6, 124.8, 123.8, 123.6, 123.3, 123.1, 123.0, 95.2,
95.1, 91.5, 90.5, 89.6, 88.3, 30.7, 28.1, 28.0, 15.1, 15.0;
HRMS calcd for C36H28OS: 508.1861. Found: 508.1860.
4.6.21. Thioacetic acid S-{4-[4-(3-ethyl-4-phenylethynyl-
phenylethynyl)-3-fluoro-phenylethynyl]phenyl} ester
(16b). 88 mg (53%) of 16b as yellow solid, mp 172–
1708C, was produced from 10b (140 mg, 0.33 mmol) and 11
4.7. General procedure for the diazonium formation
To a round-bottom flask fitted with an addition funnel and
nitrogen inlet was added boron trifluoride etherate (4 equiv.)
which was then chilled in a dry ice-acetone bath (2208C).
To the reaction flask was added dropwise over 5 min a
solution of the aniline derivative (1 equiv.) in dry THF,
followed by a solution of tert-butylnitrite (3.5 equiv.) in dry
THF over 30 min. The chilled mixture was stirred an
additional 10 min, and the cold bath was allowed to warm to
58C over 20 min. To the mixture was added diethyl ether,
and the mixture was chilled in an ice-bath for 15 min. The
solid was collected by filtration, washed with chilled
(0–58C) diethyl ether, and dried in vacuo to give the
desired product.
1
(88 mg, 0.32 mmol). IR (KBr) 2205, 1700 cm21; H NMR
(400 MHz, CDCl3) d 7.54–7.60 (m, 4H), 7.50–7.54 (m,
2H), 7.47 (d, J¼1.0 Hz, 1H), 7.44 (d, J¼8.4 Hz, 1H), 7.35–
7.40 (m, 4H), 7.29–7.33 (m, 2H), 2.91 (q, J¼7.6 Hz, 2H),
2.47 (s, 3H), 1.36 (t, J¼7.6 Hz, 3H); 13C NMR (125 MHz,
CDCl3) d 193.6, 162.5 (d, JC–F¼252 Hz), 146.7, 134.7,
133.7, 133.6, 132.7, 132.5, 131.9, 131.6, 129.4, 129.2,
128.8, 127.8 (d, JC–F¼3 Hz), 125.0, 124.9, 124.2, 123.7,
123.5, 122.9, 119.0 (d, JC–F¼23 Hz), 112.7 (d, JC–F
¼
16 Hz), 96.8 (d, JC–F¼3 Hz), 95.3, 91.7, 90.0 (d,
JC–F¼3 Hz), 88.2, 84.2, 30.7, 28.1, 15.0; HRMS calcd for
C34H23OSF: 498.1454. Found: 498.1456.
4.7.1. 4-Iodobenzenediazonium tetrafluoroborate
(17a).23 According to the general procedure, 7.0 g (96%)
of 17a was produced from 1a (5.0 g, 22.8 mmol).
4.6.22. Thioacetic acid S-{4-[3-cyano-4-(3-ethyl-4-
phenylethynylphenylethynyl)-phenylethynyl]phenyl}
ester (16c). 75 mg (46%) of 16c as yellow solid, mp 180–
1838C, was produced from 10c (138 mg, 0.32 mmol) and 11
(103 mg, 0.37 mmol). IR (KBr) 2228, 2197, 1696 cm21; 1H
NMR (400 MHz, CDCl3) d 7.85 (d, J¼1.6 Hz, 1H), 7.71
(dd, J¼1.6, 8.2 Hz, 1H), 7.63 (d, J¼9.7 Hz, 1H), 7.52–7.60
(m, 6H), 7.43–7.47 (m, 3H), 2.94 (q, J¼7.6 Hz, 2H), 2.48
4.7.2. 2-Cyano-4-iodobenzenediazonium tetrafluoro-
borate (17b). According to the general procedure, 6.5 g
(77%) of 17b was produced from 1c (6.0 g, 25.7 mmol). IR
1
(KBr) 2284, 2244 cm21; H NMR (400 MHz, CD3CN) d
8.76 (d, J¼1.7 Hz, 1H), 8.65 (dd, J¼1.7, 8.8 Hz, 1H), 8.42

J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
10403
(d, J¼8.8 Hz, 1H); 13C NMR (100 MHz, CD3CN) d 146.8,
146.2, 135.2, 116.6, 115.3, 114.7, 111.3; FAB HRMS calcd
for (M - BF-4) C7H3N3I: 255.9372. Found: 255.9379.
4.8.3. 1-(2-Trifluoromethyl-4-iodophenyl)-3-propyl-3-
(benzyl-supported) triazene (19c). According to the
general procedure, resin 18 (3.00 g), potassium carbonate
(0.83 g, 6 mmol), and 2-trifluoromethyl-4-iodo-benzene-
diazonium tetrafluoroborate (17c) (1.16 g, 3 mmol) in
DMF–THF (25 mL–25 mL) gave desired polymer beads
3.60 g.
4.7.3. 2-Trifluoromethyl-4-iodobenzenediazonium tetra-
fluoroborate (17c). According to the general procedure,
3.83 g (95%) of 17c was produced from 1d (3.0 g,
;
10.4 mmol). IR (KBr) 2290 cm21 1H NMR (400 MHz,
CD3CN) d 8.71 (d, J¼1.6 Hz, 1H), 8.66 (dd, J¼1.6, 8.7 Hz,
4.9. General procedure for the cleavage of polymer-
supported triazene using iodomethane
1H), 8.46 (d, J¼8.7 Hz, 1H); 13C NMR (125 MHz, CD3CN)
d 146.3, 141.1 (q, JC–F¼4 Hz), 136.2, 130.5 (q, JC–F
¼
36 Hz), 120.9 (q, JC–F¼275 Hz), 115.7, 111.8; FAB HRMS
calcd for (M2BF24 ) C7H3N2IF3: 298.9293. Found:
298.9292.
A thick-walled oven-dried screw cap tube was charged with
a suspension of the polymer-supported triazene and
iodomethane. The tube was flushed with nitrogen, capped,
and heated to 1208C for 24 h without stirring. The reaction
mixture was cooled and passed through a fritted filter before
the resin was introduced to hot CH2Cl2 (3£) to extract any
residual product trapped in the polymer matrix. The product
was purified by chromatography with hexane or a
hexane/EtOAc mixture to give the product.
4.7.4. Propylaminomethylated polystyrene (1% cross-
linked divinylbenzene copolymer, 7–90 mesh) (18).14
A
suspension of chloromethyl polystyrene: 1% divinyl-
benzene copolymer beads (54 g, 1.1 mequiv./g of chlorine,
70–90 mesh) and n-propylamine (350 mL) were degassed
and heated at 708C with stirring for 4 d in a screw cap tube.
The polymer was transferred to a coarse sintered glass filter
using CH2Cl2 and washed with CH2Cl2 (500 mL). The resin
was thoroughly washed with the following protocol to
remove noncovalently-bound material: the resin was stirred
slowly with dioxane/2N NaOH (1/1, v/v, 500 mL) at 708C
for 30 min, and the solvent was removed by aspiration
through a coarse sintered glass filter. This was repeated once
more with dioxane/2N NaOH (1/1, v/v, 500 mL), twice each
with dioxane/H2O (1/1, v/v, 500 mL), DMF (500 mL),
CH3OH (500 mL), and finally benzene (500 mL). The resin
was then washed with hot CH3OH (800 mL), hot benzene
(800 mL), hot CH3OH (800 mL), hot CH2Cl2 (800 mL) and
400 mL of CH3OH and dried in vauco to a constant mass to
give 53.97 g.
4.9.1. 1,4-Diiodobenzene (20a). According to the general
procedure, 1-(4-iodophenyl)-3-propyl-3-(benzyl-supported)
triazene (19a) (300 mg) in iodomethane (4.5 mL) gave the
product (62 mg, 70% yield over three steps from Merrifield
resin 1.1 mequiv./g).
4.9.2. 2-Cyano-1,4-diiodobenzene (20b). According to the
general procedure, 1-(2-cyano-4-iodophenyl)-3-propyl-3-
(benzyl-supported) triazene (19b) (300 mg) in CH3I–
CH3CN (2.5 mL–2.5 mL) at 1208C for 18 h gave the
product (33 mg, 35% yield over three steps from Merrifield
resin 1.1 mequiv./g). IR (KBr) 2230 cm21
;
1H NMR
(400 MHz, CDCl3) d 7.89 (d, J¼2.0 Hz, 1H), 7.62 (d,
J¼8.4 Hz, 1H), 7.57 (dd, J¼2.0, 8.4 Hz, 1H), 13C NMR
(100 MHz, CDCl3) d 143.2, 142.8, 141.2, 123.0, 118.2,
98.0, 93.1; HRMS calcd for C7H3NI2: 354.8355. Found:
354.8352.
4.8. General procedure for the polymer-supported
triazene formation
To a chilled (08C) suspension of propylaminomethyl
polystyrene resin (18) and finely ground potassium
carbonate (2 equiv.) in DMF–THF was added the diazo-
nium salt with stirring at 08C for 5 min and rt for 1 h. The
suspension was transferred to a fritted filter using DMF and
washed sequentially with 120 mL of the following solvents:
CH3OH, H2O, CH3OH, THF, CH3OH. The loading
procedure was repeated twice and the resin was dried in
vacuo to a constant mass to give desired functional polymer
beads.
4.9.3.
2-Trifluoromethyl-1,4-diiodobenzene
(20c).
According to the general procedure, 1-(2-trifluoromethyl-
4-iodophenyl)-3-propyl-3-(benzyl-supported) triazene (19c)
(300 mg) in CH3I–CH3CN (2.5 mL–2.5 mL) at 1108C for
24 h gave the product (37 mg, 36% yield over three steps
1
from Merrifield resin 1.1 mequiv./g). H NMR (400 MHz,
CDCl3) d 7.95 (d, J¼2.0 Hz, 1H), 7.74 (d, J¼8.2 Hz, 1H),
7.53 (dd, J¼2.0, 8.2 Hz, 1H); 13C NMR (125 MHz, CDCl3)
d 143.8, 142.3, 136.8 (q, JC–F¼6 Hz), 135.8 (q, JC–
¼31 Hz), 122.0 (q, JC–F¼274 Hz), 93.4, 90.7; HRMS
F
calcd for C7H3F3I2: 397.8276. Found: 397.8272.
4.8.1. 1-(4-Iodo-phenyl)-3-propyl-3-(benzyl-supported)
triazene (19a). According to the general procedure, resin
18 (3.00 g), potassium carbonate (0.83 g, 6 mmol), and
4-iodo-benzenediazonium tetrafluoroborate (17a) (0.954 g,
3 mmol) in DMF–THF (25 mL–25 mL) gave desired
polymer beads 3.72 g.
4.9.4. 4-(Trimethylsilyl)ethynylbenzenediazonium tetra-
fluoroborate (21). To a cooled solution of NOBF4 (5.75 g,
49 mmol, 1.05 equiv.) in 50 mL CH3CN at 2408C was
added dropwise over 15 min 2a (8.86 g, 46.8 mmol) in
60 mL CH3CN, and the mixture was stirred at 2408C for
another 50 min. Ether was added to this mixture to
precipitate the product. The precipitate was collected by
filtration, washed with chilled ether, and dried in vacuo to
give the product (11.5 g, 85%), a yellow solid. IR (KBr)
4.8.2. 1-(2-Cyano-4-iodophenyl)-3-propyl-3-(benzyl-sup-
ported) triazene (19b). According to the general procedure,
resin 18 (4.00 g), potassium carbonate (1.1 g, 8 mmol), and
2-cyano-4-iodo-benzenediazonium tetrafluoroborate (17b)
(1.37 g, 4 mmol) in DMF–THF (25 mL–25 mL) gave
desired polymer beads 4.89 g.
2290 cm21 1H NMR (400 MHz, CD3CN) d 8.46 (d,
;
J¼9.2 Hz, 2H), 7.90 (d, J¼9.2 Hz, 2H), 0.32 (s, 9H); 13C
NMR (100 MHz, CD3CN) d 137.3, 135.4, 133.8, 114.2,

10404
J.-J. Hwang, J. M. Tour / Tetrahedron 58 (2002) 10387–10405
109.6, 102.6, 20.5; FAB HRMS calcd for (M2BF24 )
C11H13N2SiI: 201.0848. Found: 201.0850.
4.12. Polymer-supported trimer formation
The above Macrokans were re-split into five new groups by
combining two Macrokans from each of the previous
groups. Each of the five new groups was subjected to
coupling with the previous five aryl halides (3a–e) by
following the previous general procedure.
4.9.5. 1-(4-(2-(Trimethylsilyl)ethynyl)phenyl)-3-propyl-
3-(benzyl-supported) triazene (22). According to the
general procedure, 4-(trimethylsilyl)ethynyl-benzenediazo-
nium tetrafluoroborate 21 (5.65 g, 19.6 mmol), potassium
carbonate (5.4 g, 39.1 mmol), and resin 18 (19.6 g) in
DMF–THF (80 mL–80 mL) were allowed to react; the
loading procedure was repeated twice (2.8 and 1.6 g of 21
were used, respectively) and the product was dried in vacuo
to a constant mass to give desired polymer beads 22,
4.13. Traceless cleavage of resin
A suspension of polymer-supported trimer 25a–e to 29a–e
in 4 mL of 10% conc. HCl/THF solution was treated with
ultrasound in a sonicator bath at 508C for 10 min. The
resulting slurry was filtered and the resin residue was
washed with EtOAc and THF. The organic phase was then
washed with H2O (2£), brine, and dried over Na2SO4. The
crude product was purified by column chromatography
(silica gel) with hexanes or a hexane/EtOAc mixture to give
the desired product.
23.96 g. IR 2153 cm21
.
4.9.6. 1-(4-Ethynyl)phenyl)-3-propyl-3-(benzyl-sup-
ported) triazene (23). To a suspension of polymer-
supported aryl(trimethylsilyl)alkyne 22 (23.96 g) and THF
(9 mL/g of polymer) in an Erlenmeyer flask was added a
solution of TBAF (50 mL, 50 mmol, 1.0 M in THF). The
suspension was swirled periodically for 25 min. The
polymer was then transferred to a pre-weighed fritted filter
using THF, washed sequentially (ca. 30 mL/g polymer) with
THF followed by CH3OH, and dried to constant mass in a
vacuum oven at 608C for 36 h to give desired polymer beads
4.13.1. Trimethyl-(4-phenylethynylphenylethynyl)silane
(4a).6b 30 mg (37% yield over five steps from Merrifield
resin) of product was obtained. The yield was calculated
according to the loading of original resin.
22.11 g. IR 3317, 2106 cm21
.
4.13.2. (3-Ethyl-4-phenylethynylphenylethynyl)tri-
methylsilane (4e). 36 mg (41% yield over five steps from
Merrifield resin) of product was obtained. The yield was
calculated according to the loading of original resin.
Macrokans loading. Resin 23 was distributed into 50
Macrokans (300 mg each). The Macrokans were then split
into five groups each containing 10 Macrokans. Each
group was subjected to coupling with the corresponding
aryl halides (3a–e) (Scheme 8) under the following
procedure.
Acknowledgements
4.10. General procedure for cross-coupling of resin-
bound terminal alkyne with aryl halide monomers
We thank DARPA administered by the Office of Naval
Research (ONR); the ONR Polymer Program; and the US
Department of Commerce, National Institute of Standards
and Technology, for financial support. We thank IRORI for
their generous academic lease program that allowed us to
use the AccuTag-100 Combinatorial Chemistry System at a
reduced cost, and for providing free samples of MacroKans
and various resins. We also thank Dr I. Chester of FAR
Laboratories for providing (trimethylsilyl)acetylene.
To a heavy-walled flask equipped with a nitrogen inlet was
added 10 Macrokans. The flask was evacuated and back-
filled with dry nitrogen 3£. In a separate flask, a catalyst
solution consisting of tris(dibenzylideneacetone)dipalla-
dium(0) (138 mg, 0.24 mmol), copper(I) iodide (46 mg,
0.24 mmol), and triphenylphosphine (252 mg, 0.96 mmol)
in dry triethylamine (50 mL) was degassed and stirred at
708C for 2 h. The supernatant from this catalyst solution was
transferred via cannula to the reaction flask containing the
Macrokans. To the mixture was added one of the aryl
halides 3a–e (15 mmol). The flask was sealed and kept at
658C for 44 h with stirring. The Macrokans were collected
and washed sequentially with 100 mL of the following
solvents: CH2Cl2, DMF, 0.05 M solution of sodium diethyl
dithiocarbamate in 99/1 DMF/diisopropylethylamine,
DMF, CH2Cl2, CH3OH, and dried in vacuo.
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To a suspension of 10 Macrokans containing polymer-
supported aryl(trimethylsilyl)alkyne 24 and THF (50 mL) in
an Erlenmeyer flask was added a solution of TBAF (20 mL,
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sequentially (100 mL) with THF followed by CH3OH, and
dried in vacuo.
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