Soluble ferrocene conjugates for incorporation into self-assembled monolayers

Article abstract of DOI:10.1021/jo982392m

A series of phenylethynyl oligomers (I-V) possessing a ferrocene and thiol at each termini have been synthesized. These oligomers have been designed to overcome the inherent insolubility of this class of complexes by substitution at the phenyl groups with methyl and propoxy substituents. Several new reactions for preparing arenethiol-protected compounds are described. Interestingly, the generation of an arenethiol anion during base- or fluoride-catalyzed deprotection has been characterized.

Full text of DOI:10.1021/jo982392m

2070
J . Org. Chem. 1999, 64, 2070-2079
Solu ble F er r ocen e Con ju ga tes for In cor p or a tion in to
Self-Assem bled Mon ola yer s
C. J . Yu,* Yoochul Chong, J on Faiz Kayyem, and Michael Gozin
Clinical Micro Sensors Inc., 101 Waverly Drive, Pasadena, California 91105
Received December 7, 1998
A series of phenylethynyl oligomers (I-V) possessing a ferrocene and thiol at each termini have
been synthesized. These oligomers have been designed to overcome the inherent insolubility of
this class of complexes by substitution at the phenyl groups with methyl and propoxy substituents.
Several new reactions for preparing arenethiol-protected compounds are described. Interestingly,
the generation of an arenethiol anion during base- or fluoride-catalyzed deprotection has been
characterized.
Ch a r t 1
In tr od u ction
Recent work on long-range electron-transfer reactions
through DNA suggested that an electrochemical nucleic
acid sensor could be developed.1-14 During the coarse of
our investigations into the development of this class of
sensor, we have designed and synthesized a series of
conjugated arenethiol molecular wires that are chemi-
sorbed onto gold surfaces. In particular, we are interested
in the ferrocene-terminated oligo(phenylethynyl)arene-
thiols as target molecules for exploring conductivity of
molecular wires that bridge ferrocene complexes to
electrodes.
(1) Meade, T. J . In Interactions of Metal Ions with Nucleotides,
Nucleic Acids, and Their Constituents; Asigel, Sigel, H., Eds.; Marcel
Dekker: New York, 1996; Vol. 32, Metal Inons in Biological Systems
pp 453-478.
(2) Holmlin, R. E.; Danlike, P. J .; Barton, J . K. Angew. Chem., Int.
Ed. Engl. 1997, 36, 3714-2730.
(3) Meade, T. J .; Kayyem, J . F. Angew. Chem., Int. Ed. Engl. 1995,
34, 352-354.
(4) Wilson, E. K. Chem Eng. News 1998, May 25, 47-49.
(5) Armitage, B.; Yu, C. J .; Devadoss, C.; Schuster, G. B. J . Am.
Chem. Soc. 1994, 116, 9854-9859.
(6) Lewis, F. D.; Wu, T. F.; Zhang, Y. F.; Letsinger, R. L.; Greenfield,
S. R.; Wasielewski, M. R. Science 1997, 277, 673-676.
(7) Tour, J . M.; J ones, L.; 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, 9529-9534.
(8) Chidsey, C. E. D. Science 1991, 251, 919-922.
(9) For synthesis of conjugated oligomers, see: (a) Tour, J . M. Chem.
Rev. 1996, 96, 537-553, and references therein. (b) Wu, R.; Schumm,
J . S.; Pearson, D. L.; Tour, J . M. J . Org. Chem. 1996, 61, 6901-6921.
(c) Pearson, D., Tour, J . M. J . Org. Chem. 1997, 62, 1376-1387. (c)
J ones, L., II; Schemm, J . S.; Tour, J . M. J . Org. Chem. 1996, 62, 1388-
1410.
(10) (a) Cygan, M. T.; Dunbar, T. D.; Arnold, J . J .; Bumm, L. A.;
Shedlock, N. F.; Burgin, T. P.; J ones, L.; Allara, D. L.; Tour, J . M.;
Weiss, P. S. J . Am. Chem. Soc. 1995, 118, 2721-2732. (b) Sachs, S.
B.; Dudek, S. P.; Hsung, R. P.; Sita, L. R.; Smalley, J . F.; Newton, M.
D.; Feldberg, S. W.; Chidsey, C. E. D. J . Am. Chem. Soc. 1997, 119,
10563-10564. (c) Zehner, R. W.; Sita, L. R. Langmuir 1997, 13, 2973-
2979.
(11) (a) Young, J . K.; Nelson, J . C.; Moore, J . S. J . Am. Chem. Soc.
1994, 116, 10841. (b) Bharathi, P.; Patel, U.; Kawaguchi, T.; Peask,
D. J .; Moore, J . S. Macromolecules 1995, 28, 5955. (c) Nelson, J . C.;
Young, J . K.; Moore, J . S. J . Org. Chem. 1996, 61, 8160. (d) Devadoss,
C.; Bharathi, P.; Moore, J . S. J . Am. Chem. Soc. 1996, 118, 9635-
9644.
Molecular wires based on oligo(phenylethynyl) deriva-
tives have been extensively studied by several research
groups;7,9-13,17 especially, Tour and co-workers9 have
contributed significantly to the synthesis of asymmetric
arenethiol adsorbates. For closely related molecules, Sita
and co-workers12,13 have reported the synthesis of fer-
rocene-[CtC-C6H4]n-SAc (n ) 1, 2, 3, Ac ) acetyl) by
the palladium-catalyzed Heck reactions14-16 using acetyl
as a protecting group for arylthiols. To our knowledge,
there has not been any report of the preparation of a
phenylethynyl oligomer (n > 3) with the same structural
features, presumably because of the poor solubility of
unsubstituted oligomers and the high lability of the acetyl
group for arenethiols to the basic conditions and elevated
temperature, commonly used for the aryl coupling reac-
tions.
We report here the design and synthesis of a series of
conductive oligomers, I-V (Chart 1), by using novel
protecting groups for arenethiols, 2-(4-pyridinyl)ethyl and
(12) Hsung, R. P.; Chidsey, C. E. D.; Sita, L. R. Organometallics
1995, 14, 4808-4815.
(13) Hsung, R. P.; Babcock, J . R.; Chidsey, C. E. D.; Sita, L. R.
Tetrahedron Lett. 1995, 36, 4525-4528.
(14) Heck, R. F. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 4, pp 833-
863.
(15) Heck, R. F. Org. React. 1982, 27, 345.
(16) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 4467-4470.
10.1021/jo982392m CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/04/1999

Soluble Ferrocene Conjugates
Sch em e 1
J . Org. Chem., Vol. 64, No. 6, 1999 2071
Sch em e 2
was prepared from a Pummerer rearrangement of the
corresponding sulfoxide utilizing an adopted procedure,22
was reacted with p-vinylpyridine under refluxing condi-
tions to afford compound 2 with a yield of 46%. Although
compound 1 was previously reported12 to be synthesized
via the reduction of pipsyl chloride, the process could not
be successfully repeated in our lab. Apparently, the
synthesis route starting with 4-iodothioanisole is not
ideal due to low yield and multistep reactions. To get
better yield with fewer steps of the reactions, we em-
ployed the commercially available 4-bromothiophenol for
the same addition reaction in which compound 3 was
obtained in excellent yield (95%). To couple trimethyl-
silylacetylene to the iodo derivative 2 utilizing the mild
catalyst Pd(PPh3)2Cl2 is easy and straightforward and
proceeds with a high yield of 81%. However, many
attempts to run the same cross-coupling reaction starting
with bromo derivative 3 by varying different Pd catalysts,
combinations of solvents, temperatures, and reaction
times failed. After numerous trials, it was found that an
unusually high percentage (>10% in molarity relative to
3) of Pd(dba)2/PPh3, in combination with DMF/diisopro-
pylamine, high temperature (60 °C), and long reaction
time (at least 16 h), is crucial to successfully couple
compound 3 with trimethylsilylacetylene to form the
desired product 4, with a yield of 94%. The compound 5,
obtained from the desilylation of 4 by either fluoride in
CH2Cl2 or potassium carbonate in methanol, was used
as one of the possible thiol-protected starting units to
build the oligomers.
The 2-(trialkylsilyl)ethyl as protecting group for the
thiols can be introduced by the reaction of either tri-
methylvinylsilane or dimethyl-tert-butylvinylsilane with
4-bromothiophenol in the presence of a catalytic amount
of tert-butyl peroxide as free radical initiator (Scheme 2)
to afford the desired (â-addition) compound 6 (88%) or 7
(91%). In addition, the above reactions also produced a
very small amount (<3%) of the undesired (R-addition)
products (structures not shown), as indicated by GC-
MS. The observation here is consistent with that in the
literature.24 After halogen exchange, the iodo derivatives
8 and 9 were obtained in excellent yields (coincidentally,
83%). After coupling to trimethylsilylacetylene, followed
2-(trialkylsilyl)ethyl, that can tolerate a range of experi-
mental conditions and can still be easily removed under
very mild conditions whenever thiols are needed. In
addition, we report a method for introducing two different
substitution groups on benzene rings in the phenyl-
ethynyl groups for increasing solubility of the target
compounds. The electrochemical properties of monolayers
of these molecules on gold electrodes have been studied
and are described separately.18
Resu lts a n d Discu ssion
To successfully synthesize the soluble and asym-
metrical ferrocene-terminated phenylethynyl oligomers,
three key issues must be addressed. The first is to protect
the arenethiols with the right protecting groups, the
second is to introduce appropriate substituents onto the
phenyl groups, and the last is to construct the oligomers
with the right sequences.
Ar en eth iol P r otection . The choice of the protection
groups for arenethiols is crucial for the successful syn-
thesis of soluble “molecular wires”. Typical arenethiol
protecting groups, such as methyl or ethyl group,12,13 bind
too strongly, while acetyl groups bind too weakly.9-13
Ideally, the best protecting groups should be stable under
a variety of many experimental conditions while being
easily removed under mild conditions. We introduce here
two new types of protecting groups with these charac-
teristics, 2-(4-pyridinyl)ethyl and 2-(trialkylsilyl)ethyl, as
described in (Scheme 1). While these protecting groups
are used in the literature,18-21 they have not been
previously been used to protect arenethiols for use in the
formation of SAMs. Compound 1, 4-iodothiophenol, which
(17) Hoger, S.; Enkelmann, V. Angew. Chem., Int. Ed. Engl. 1995,
34, 2713-2716.
(18) Creager, S.; Yu, C. J .; Bamdad, C.; O’Connor, S.; Maclean, T.;
Lam, E.; Chong, Y.; Kayyem, J . F.; Gozin, M. J . Am. Chem. Soc. 1999,
121, 1059-1064.
(19) Young, R. N.; Gauthier, J . Y.; Coombs, W. Tetrahedron Lett.
1984, 1753-1756.
(22) Koreeda, M.; Yang, W. J . Am. Chem. Soc. 1994, 116, 10793-
10794.
(23) Takeda, H.; Shimada, S.; Ohnishi, S.; Nakanishi, F.; Matsuda,
H. Tetrahedron Lett. 1998, 39, 3701-3704.
(24) Wetterlin, K. Acta Chem. Scand. 1964, 18, 899-903.
(20) Katritzky, A. R.; Khan, G. R.; Schwarz, O. A. Tetrahedron Lett.
1984, 1223-1226.
(21) Katritzky, A. R.; Takahashi, I.; Marson, C. M. J . Org. Chem.
1986, 51, 4914-4920.

2072 J . Org. Chem., Vol. 64, No. 6, 1999
Yu et al.
Sch em e 3
Sch em e 4
product and the undesired isomer (2-(iodo or bromo)-4-
methylacetophenone), which can be separated from the
1
desired isomer using a silica gel column. From H NMR
chemical shifts and integrals, the structures of 14 or 16
and their isomers can be assigned. In the case of
3-iodotoluene as starting material, the yield of the desired
product 14 is very low because of the severe deiodination
of either starting material or the product or both, so that
the synthesis route involving 3-bromotoluene is preferred,
even though it involves one additional step. The trans-
formation of 17 to 15 was predicted.
by desilylation, the compound 12 or 13 was obtained. The
advantage of 13 over 12 as the starting unit in preparing
elongated oligomers is that the dimethyl-tert-butylsilyl-
ethyl-terminated multiple-unit phenylethynyl oligomers
have better solubility in common organic solvents. The
study on deprotection of those groups will be discussed
in a later section.
Syn th esis of Su bstitu ted Mon om er s. A character-
istic property of the oligo(phenylethynyl) derivatives is
their high degree of symmetry and they can easily
crystallize, which accounts for their limited solubility. If
a substituent, is introduced onto one or more of the
benzene rings, the symmetry of the molecules is dis-
rupted and the solubility of the compounds in organic
solvents is greatly improved. On this basis, two types of
substituted groups were considered. The first is the
methyl group, which might help break the symmetry of
molecules, but hopefully has little or no effect on the
assembly of target compounds onto gold surfaces due to
its small size. The second is the propoxy group, which
might help increase dramatically the compounds’ solubil-
ity due to its flexibility.
The preparation of the second substituted monomer
was carried out, starting with the known compound
18.28,29 Compound 18 is partially coupled to trimethyl-
silylacetylene, followed by coupling to triisopropylsilyl-
acetylene to afford 20. The selective desilylation of 20
provided the asymmetrical monomer 21, which is very
useful for attaching different groups on both ends, as seen
in Scheme 3. A compound similar to 21 has been
synthesized in one pot by Hoger and Enkelmann.17
Bu ild in g Oligom er s. There are two possible strate-
gies9 for building multiunit unsymmetrical oligo(phenyl-
ethynyl) derivatives: (i) the stepwise iterative approach,
and (ii) the combination of the stepwise iterative ap-
proach for the small pieces and a convergent approach
for final assembly of a large piece. We have found that
the second strategy is much more efficient than the first
one, especially more so in the case in which a large
oligomer was coupled to a small monomer. In this regard,
it is logical to synthesize the iodo-terminated universal
three-unit oligomers with different protection groups for
arenethiols as basic units, as depicted in Scheme 4. The
syntheses of 28, 29, and 30 were accomplished in a
straightforward manner, with good yields, involving two
palladium-catalyzed Heck reactions and one desilylation
reaction.
The synthesis of the substituted monomer 15 is de-
scribed in Scheme 3 where the acylation of either
3-iodotoluene or 3-bromotoluene under standard Friedel-
Crafts conditions25,26 gave products 14 or 16 and their
isomers (structures not shown), which were converted to
the corresponding acetylene derivatives 15 or 17 using
the published procedure.27 The acylation of 3-iodotoluene
or 3-bromotoluene gave only two isomers, the desired
Once all building blocks are prepared, the target
compounds can be constructed. The synthesis of the first
oligomer I is depicted in Scheme 5, where ferrocenyl-
(25) Friedman, L.; Honour, R. J . J . Am. Chem. Soc. 1969, 91, 6344-
6349.
(28) Zhao, Q.; Swager, T. M. J . Am. Chem. Soc. 1995, 117, 12593-
(26) Olah, G. A.; Kobayashi, S. J . Am. Chem. Soc. 1971, 93, 6964-
6967.
12602.
(29) Zhao, Q.; Carroll, P.; Swager, T. M. J . Org. Chem. 1994, 59,
(27) Negishi, E.; King, A. O.; Tour, J . M. Org. Synth. 1985, 64, 44.
1294.

Soluble Ferrocene Conjugates
Sch em e 5
J . Org. Chem., Vol. 64, No. 6, 1999 2073
Sch em e 7
Sch em e 6
31, producing compound 38 with a low yield (25.8%).
Compound 39 with three units, obtained from the desi-
lylation of 38, was then coupled to compound 30 to form
oligomer V in a relatively poor yield. By investigating
the lengths of oligomers and their yields in the final
coupling, it is apparent that the more phenylethynyl
units the synthesized oligomers have, the more compli-
cated the syntheses are and the lower the yields are. The
common problem associated with the low yield is that
the terminal acetylenes dimerized themselves under the
Heck cross-coupling conditions. Despite these limitations,
the present reactions offer the best and only route thus
far described for preparing soluble, asymmetrically sub-
stituted arylthiol adsorbates of this size suitable for use
in preparing electroactive SAMs.
Rem ova l of P r otection Gr ou p s for Ar en eth iols.
The protection groups chosen in this work for arenethiols
are stable in the experimental conditions. For the 2-(4-
pyridinyl)ethyl group, the first step in deprotecting the
thiol is to convert the compounds to the corresponding
pyridinium iodides by reaction with iodomethane in
acetone as solvent. The formation of the pyridinium salts
actually is an activation process in which â-hydrogen of
the ethyl group becomes acidic due to the nitrogen cation
on the pyridine ring. When the salt products were stirred
with a base (either organic base, such as TEA and (CH3-
CH2)2NH, or inorganic base, such as K2CO3 and NaH-
CO3), in organic solvents, for example, acetone, DMF, or
THF, for 2 h, the salts were consumed and new products,
arenethiolate anions, were formed.
acetylene30,31 was coupled to compound 28 to give I in
excellent yield. For oligomers II and III, which have the
same length but different substituents on the benzene
rings in the phenylethynyl bridge, the first step was to
build one-unit ferrocene 31, which is prepared using the
literature procedure,12 and 33, which is prepared by
reacting ferrocenylacetylene to compound 19, followed by
desilylation using potassium carbonate. Oligomers II and
III were then constructed by reactions of 31 to 29 and
33 to 30 with good to excellent yields, as illustrated in
Scheme 5.
The strategy for oligomer IV is to synthesize an iodo-
terminated one-unit ferrocene 34 via the reaction of
ferrocenylacetylene to 1,4-diiodobenzene, and a four-unit
oligomer, 36, via the coupling of 21 to 28, followed by
desilylation. The subsequent coupling between 34 and
36 was catalyzed by the Pd(0) complex to form IV with a
relatively low yield, as seen in Scheme 6.
To provide the evidence for the generation of the
arenethiolate anion, a good electrophile, such as CH3I,
was used as a trapping reagent. As exemplified in
Scheme 8, the activated form, 40, of the oligomer I was
mixed with a suspension of potassium carbonate and
DMF, followed by addition of a large excess of methyl
iodide. The product was isolated and analyzed by 1H
The final target, oligomer V, has six phenylethynyl
units and is the most complicated and tedious to make,
involving many reaction steps. As illustrated in Scheme
7, the asymmetrical monomer 21 was coupled to 1,4-
diiodobenzene, followed by coupling to one-unit ferrocene
1
NMR and FAB mass spectra. H NMR spectra clearly
showed the disappearance of the 2-(4-pyridinyl)ethyl
group and formation of a new peak at 2.547 ppm assigned
to CH3 attached to sulfur. These data coupled with an
indicated mass of 546.11 identified the isolated product
as compound 41. The result of the trapping experiment
confirmed the generation of the arenethiolate anion.
The solvent systems that have been tested for the
deprotection of arenethiols include K2CO3/DMF, K2CO3/
(30) Rosenblum, M.; Brawn, N.; Papenmerier, J .; Applebaum, M.
J . Organomet. Chem. 1966, 6, 173-180.
(31) Doisneau, G.; Balavoine, G.; Fillebeen-Khan, T. J . Organomet
Chem. 1992, 425, 113-117.

2074 J . Org. Chem., Vol. 64, No. 6, 1999
Yu et al.
Sch em e 8
to bases upon activation or to the fluorides and are very
useful to protect the unsaturated thiols, such as are-
nethiols, alkenylthiols, and alkynylthiols.23
Exp er im en ta l Section
Ma ter ia ls. Diisopropylamine, diethylamine, 1,2-dichloro-
ethane, triethylamine (TEA), pyrrolidine, Pd(PPh3)2Cl2, copper
iodide, 3-chloroperoxybenoic acid (mCPBA), trifluoroacetic
anhydride, vinyltrimethylsilane, tert-butyl peroxide, 1.7 M tert-
butyllithium (t-BuLi) pentane solution, 3-iodotoluene, 3-bro-
motoluene, 2.0 M lithium diisopropylamide (LDA) THF solu-
tion, diethylchlorophosphate, and triisopropylsilylacetylene
were purchased from Aldrich and used as received. Methanol,
dichloromethane, hexane, ethyl acetate, benzene, sodium
thiosulfate, ether, and sodium sulfate were purchased from
EM Science and used as received. Triphenylphosphine, 1-bromo-
thiophenol, trimethylsilylacetylene, and iodine were purchased
from Lancaster and used as received. Dimethylformamide
(DMF), 4-vinylpyridine, tetrahydrofuran (THF), and trimethyl-
chlorosilane were purchased from Fluka and used as received.
Aluminum chloride and 4-iodothioanisol were purchased from
Acros and used as received. Edetate disodium (EDTA) was
purchased from J . T. Baker and used as received. Vinyl(tert-
butyl)dimethylsilane was purchased from Gelest and used as
received. Pd(dba)2 was prepared following the literature
procedure.30,31
Sch em e 9
In str u m en ta tion . Spectra were recorded with the following
spectrometers: GC/MS performed at 70 eV with a 50 m × 0.2
mm capillary column programmed at 140 °C for 1 min and
then 280 °C at 10 °C min-1, NMR (300 MHz, 1H; 75 MHz, 13C).
Mass spectrometry was provided by Mass Consortium at San
Diego using either electrospray or high-resolution FAB.
Gen er a l P r oced u r e for th e P a lla d iu m -Ca ta lyzed Cou -
p lin g Rea ction s. A solution of aryl iodides or aryl bromides,
terminal acetylenes, Pd(PPh3)2Cl2 or Pd(dba)2PPh3, and CuI
in either diethylamine or amine-containing mixtures, such as
THF/diethylamine, DMF/diethylamine, DMF/TEA, THF/di-
isopropylamine, DMF/diisopropylamine, and DMF/pyrrolidine,
as solvents was degassed well by argon and stirred at 25-60
°C for 3 h to overnight, depending on the specific reactions
performed. The conditions for each reaction are specified
herein by the catalyst, solvents, temperature, and reaction
time. After removing the solvents, the residue was used either
for column chromatography separation or for the treatment
in which the dichloromethane solution of the residue was
stirred with the saturated EDTA aqueous solution for 3 h to
overnight. This procedure effectively removed the copper
impurities that interfered with column separation in some
cases when the products contained pyridinyl and/or propoxy
groups. The solvent systems for purifying the products are
variable and are specified in the actual reactions.
acetone, TEA/acetone, TEA/CH3CH2OH, TEA/THF, and
TEA/CH2Cl2. It was interesting to note that the depro-
tection in TEA/CH2Cl2 gave the CH2Cl2-trapped product
in which CH2Cl2 acted as an electrophile. The mechanism
of formation for the thiolate anion is the base-catalyzed
â-elimination of sulfur in the pyridinium salt, which is
consistent with the literature result.20
Gen er a l P r oced u r e for Desilyla tion . Two reagents were
used to remove the silyl groups. For TBAF as desilylation
reagent, the procedure is as follows: A solution of the substrate
in dichloromethane was cooled in an ice-water bath. Into this
cold solution was added 1.2 equiv of 1.0 M TBAF THF solution.
The resulting solution was stirred at the same temperature
for another 1 h, washed once with water, dried over sodium
sulfate, and then concentrated on a rotavapor. The crude
product was used for column separation. When potassium
carbonate is used as desilylation reagent, the procedure is as
follows: To a mixture of 200-300 mL of 50% THF/methanol
were added the substrate and a certain amount of potassium
carbonate. The resulting suspension was stirred at room
temperature for 2-3 h and diluted by adding 400 mL of
dichloromethane and 400 mL of water. Upon shaking well, the
organic layer was separated, dried over sodium sulfate and
concentrated in vacuo. The crude product was used for column
purification.
For the 2-(trialkylsilyl)ethyl group, prior to deprotec-
tion, there is no activation process. Scheme 9 presents
the reaction of oligomer II with tetrabutylammonium
fluoride in THF, and the consequential trapping reaction
by methyl iodide. The product was also isolated and
1
characterized by H NMR and mass spectrometry. The
structure of the isolated product was assigned to 42, on
1
the basis of its H NMR and mass spectra. The isolation
of 42 also indicated the generation of the arylthiolate
anion from the fluoride-induced â-elimination of 2-(tri-
alkylsilyl)ethyl group, which is known in the litera-
ture.22,23
Oligomers III, IV, and V can be deprotected in the
same manner.34 The experimental results demonstrate
that both types of protection groups are quite labile either
(32) Takahashi, Y.; Ito, T.; Sakai, S.; Ishi. Y. Chem Commun. 1970,
1065-1066.
(33) Rettig, M. F.; Maitlis, P. M. Inorg. Synth. 1972, 134-136.
(34) In our studies on the electrochemical properties of these target
molecules, the oligomers I-V self-assemble onto gold surfaces by in
situ deprotection, published separately.18

Soluble Ferrocene Conjugates
J . Org. Chem., Vol. 64, No. 6, 1999 2075
Syn th esis of 4-Iod oth iop h en ol (1). A solution of 6.0 g
(24.00 mmol) of 4-iodothioanisole in 300 mL of CH2Cl2 was
cooled in an ice-water bath. To the cooled solution was added
6.05 g (35.05 mmol) of mCPBA. After stirring for 30 min, 3.0
g (40.49 mmol) of Ca(OH)2 was added and the resulting
precipitate was filtered. To the filtrate was added 7 mL (49.56
mmol) of (CF3CO)2O, and the solution was refluxed for 1.5 h.
After evaporating off the solvent, the residue was dissolved
in 200 mL of 50% methanol/TEA. The solvent was then
evaporated, and the residue was further dried. The compound
was used immediately for the next step without further
purification and analysis in order to avoid oxidation.
Syn th esis of 2-(4-P yr id in yl)eth yl-4′-iod op h en yl Su lfid e
(2). The dried residue (1) was dissolved in 70 mL of benzene
and the solution washed once with 60 mL of a saturated
ammonium chloride solution. The organic layer was separated,
and the aqueous layer was extracted once with 40 mL of
benzene. The combined organic extracts were dried over
sodium sulfate and filtered off. To the benzene solution was
added 7.7 mL (7.21 mmol) of 4-vinylpyridine, and the reaction
mixture was refluxed overnight. The benzene was evaporated,
and the residue was dissolved in CH2Cl2 for column chroma-
tography. The crude product was purified on a 150 g silica gel
column, packing with 20% ethyl acetate/hexane and eluting
with 20-60% ethyl acetate/hexane. The desired fractions were
pooled and concentrated to afford 3.4 g (41.5%) of the title
compound: 1H NMR (300 MHz, CDCl3) δ 2.93 (t, J ) 7.2 Hz,
2H), 3.19 (t, J ) 7.2 Hz, 2H), 7.11-7.71 (m, 6H), 8.69 (d, J )
7.7 Hz, 2H); GC-MS m/z (relative intensity) 341.
Syn th esis of 2-(4-P yr id yn yl)eth yl-4′-br om op h en yl Su l-
fid e (3). A solution of 14.0 g (74.06 mmol) of 1-bromothiophenol
and 11 mL (103.01 mmol) of 4-vinylpyridine in 200 mL of
benzene was refluxed overnight. The solvent was evaporated,
and the residue was dissolved in CH2Cl2 for column chroma-
tography. The crude product was purified on a 250 g silica gel
column, packing with 20% ethyl acetate/hexane and eluted
with 20-60% ethyl acetate/hexane. The desired fractions were
pooled and evaporated to afford 20.78 g (95.0%) of the title
product: 1H NMR (300 MHz, CDCl3) δ 2.91 (t, J ) 7.2 Hz,
2H), 3.19 (t, J ) 7.2 Hz, 2H), 7.15-7.48 (m, 6H), 8.56 (d, J )
7.7 Hz, 2H); GC-MS m/z (relative intensity) 295 (36).
Syn th esis of 2-(4-P yr id in yl)eth yl-4′-[(tr im eth ylsilyl)-
eth yn yl]p h en yl Su lfid e (4) fr om 2. Compound 4 was
prepared following the general procedure for the palladium-
catalyzed coupling reaction using 1.70 g (4.98 mmol) of 2, 100
mg (0.14 mmol) of Pd(PPh3)2Cl2, 100 mg (0.53 mmol) of CuI,
and 0.95 mL (6.72 mmol) of trimethylsilylacetylene in 35 mL
of diethylamine. The reaction mixture was stirred for 2 h at
55 °C and worked up. The crude product was purified on a
150 g silica gel column, packing with hexane and eluting with
0-50% ethyl acetate/hexane. The desired fractions were pooled
and concentrated to afford 1.27 g (81.4%) of the title com-
pound: 1H NMR (300 MHz, CDCl3) δ 0.26 (s, 9H), 2.91 (t, J )
7.2 Hz, 2H), 3.17 (t, J ) 7.2 Hz, 2H), 7.15-7.49 (m, 6H), 8.56
(br s, 2H); GC-MS m/z (relative intensity) 311 (100).
Syn th esis of 2-(4-P yr id in yl)eth yl-4′-[(tr im eth ylsilyl)-
eth yn yl]p h en yl Su lfid e (4) fr om 3. Compound 4 was
prepared following the general procedure for the palladium-
catalyzed coupling reaction using 3.0 g (10.20 mmol) of 3, 2.45
mL (17.33 mmol) of trimethylsilylacetylene, 590 mg (1.01
mmol) of Pd(dba)2, 2.0 g (7.57 mmol) of triphenylphosphine,
300 mg (1.57 mmol) of CuI in 120 mL of DMF, and 30 mL of
diisopropylamine. The reaction mixture was stirred at 60 °C
overnight and worked up. The crude product was purified on
a 150 g silica gel column, packing with hexane and eluting
with 0-50% ethyl acetate/hexane. The desired fractions were
pooled and concentrated to afford 3.00 g (94.0%) of the title
compound. Characterization and analysis of this compound is
the same as above.
packing with 50% ethyl acetate/hexane, eluting with the same
solvents. The desired fractions were pooled and concentrated
to afford 1.87 g (94.1%) of the title compound: 1H NMR (300
MHz, CDCl3) δ 2.95 (t, J ) 7.2 Hz, 2H), 3.10 (s, 1H), 3.19 (t,
J ) 7.2 Hz, 2H), 7.15-7.40 (m, 6H), 8.56 (d, J ) 7.7 Hz, 2H);
GC-MS m/z (relative intensity) 239 (87).
Syn t h esis of 2-(Tr im et h ylsilyl)et h yl-4′-b r om op h en yl
Su lfid e (6). To a Schlenk tube was added 13.55 g (71.7 mmol)
of 4-bromothiophenol, 12.67 mL (82.20 mmol) of vinyltri-
methylsilane, and 1.88 mL (10.00 mmol) of tert-butyl peroxide
under argon. The reaction mixture was stirred at 100 °C for
10 h. The reaction mixture was diluted by adding 200 mL of
hexane, and the hexane solution was washed once with a 10%
sodium hydroxide aqueous solution. The organic layer was
separated, dried over sodium sulfate, and then concentrated
for column chromatography. The crude product was purified
on a 270 g silica gel column, packing and eluting with hexane.
The desired fractions were pooled and concentrated to afford
18.3 g (88.0%) of the title compound: 1H NMR (300 MHz,
CDCl3) δ 0.08 (s, 9H), 0.94-0.98 (m, 2H), 2.95-3.01 (m, 2H),
7.22 (d, J ) 8.4 Hz, 2H), 7.41 (d, J ) 8.4 Hz, 2H); GC-MS m/z
(relative intensity) 290 (4), 288 (3).
Syn th esis of 2-(ter t-Bu tyld im eth ylsilyl)eth yl-4′-br o-
m op h en yl Su lfid e (7). To a Schlenk tube was added 5.55 g
(29.36 mmol) of 4-bromothiophenol, 6.6 mL (35.05 mmol) of
vinyl(tert-butyl)dimethylsilane, and 0.5 mL (2.66 mmol) of tert-
butyl peroxide under argon. The reaction mixture was stirred
at 100 °C for 10 h. The reaction mixture was then diluted by
adding 200 mL of hexane, and the hexane solution washed
once with a 10% sodium hydroxide aqueous solution. The
organic layer was separated, dried over sodium sulfate, and
then concentrated for column chromatography. The crude
product was purified on a 250 g silica gel column, packing and
eluting with hexane. The desired fractions were pooled and
concentrated to afford 8.86 g (91.0%) of the title compound:
1H NMR (300 MHz, CDCl3) δ 0.03 (s, 6H), 0.91 (s, 9H), 0.94-
1.04 (m, 2H), 2.95-3.01 (m, 2H), 7.20 (d, J ) 8.7 Hz, 2H), 7.41
(d, J ) 8.7 Hz, 2H); GC-MS m/z (relative intensity) 275 (15),
273 (14).
Syn th esis of 2-(Tr im eth ylsilyl)eth yl-4′-iod op h en yl Su l-
fid e (8). A solution of 18.17 g (62.87 mmol) of compound 6 in
400 mL of dry ether was cooled to -78 °C in the presence of
argon. To this solution containing 6 was added 80 mL of 1.7
M t-BuLi pentane solution, and the reaction mixture was
stirred at -78 °C for 40 min. A second solution of 21.0 g (82.73
mmol) of iodine in 400 mL of dry ether was cooled to -78 °C
under argon, and the cooled iodine solution was then trans-
ferred into the cooled reaction mixture starting with 6. After
stirring for 10 min at -78 °C the reaction mixture was warmed
to 0 °C and stirring continued for another 30 min. The reaction
mixture was then washed with a sodium thiosulfate solution
until the iodine color disappeared. The ether layer was
separated, dried over sodium sulfate, and concentrated for
column chromatography. The crude product was purified on
a 250 g silica gel column, packing and eluting with hexane.
The desired fractions were pooled and concentrated to afford
17.4 g (83.0%) of the title compound: 1H NMR (300 MHz,
CDCl3) δ 0.09 (s, 9H), 0.0.94-0.98 (m, 2H), 2.97-3.02 (t, 2H),
7.07 (d, J ) 8.4 Hz, 2H), 7.62 (d, J ) 8.4 Hz, 2H); GC-MS m/z
(relative intensity) 336 (19).
Syn th esis of 2-(ter t-Bu tyld im eth yl)eth yl-4′-iod op h en yl
Su lfid e (9). A solution of 22.1 g (66.70 mmol) of 7 in 500 mL
of dry ether was cooled to -78 °C. To this cooled solution was
added 88 mL (149.60 mmol) of 1.7 M t-BuLi pentane solution
in the presence of argon, and then the reaction mixture was
stirred for 1 h. A separate solution of 22.0 g (86.68 mmol) of
iodine in 300 mL of dry ether was also cooled to -78 °C and
added to the reaction mixture starting with 7. This reaction
mixture was stirred for 10 min at -78 °C, and then stirring
continued for 30 min at 0 °C. The solution was then washed
with a sodium thiosulfate solution until the iodine color
disappeared. The ether layer was separated, dried over sodium
sulfate, and then concentrated for column chromatography.
The crude product was purified on a 230 g silica gel column,
packing and eluting with hexane. The desired fractions were
Syn th esis of 2-(4-P yr id in yl)eth yl-4′-(eth yn yl)p h en yl
Su lfid e (5). Compound 5 was prepared following the general
procedure for desilylation using 2.6 g (8.35 mmol) of 4 and 9
mL (9.00 mmol) of 1.0 M TBAF THF solution in 150 mL of
CH2Cl2. The reaction mixture was stirred for 1.5 h and worked
up. The crude product was purified on a 50 g silica gel column,

2076 J . Org. Chem., Vol. 64, No. 6, 1999
Yu et al.
pooled and concentrated to afford 21.1 g (83.0%) of the title
compound: 1H NMR (300 MHz, CDCl3) δ 0.03 (s, 6H), 0.93 (s,
9H), 0.94-1.00 (m, 2H), 2.95-3.01 (t, J ) 8.7 Hz, 2H), 7.06
(d, J ) 8.4 Hz, 2H), 7.62 (d, J ) 8.4 Hz, 2H); GC-MS m/z
(relative intensity) 378 (2).
2.48 (s, 3H), 2.56 (s, 3H), 7.39-7.65 (m, 3H); GC-MS m/z
(relative intensity) 260 (53).
Syn th esis of 2-(Tr im eth ylsilyl)eth yl-4-iod otolu en e (15)
fr om 14. To 25 mL of dry THF cooled to -78 °C was added 14
mL (28.00 mmol) 2.0 M LDA THF solution under argon. To
this mixture was added a solution of 6.34 g (24.38 mmol) of
(14) in 25 mL of THF dropwise. After the addition was
complete the reaction mixture was stirred at -78 °C for 1 h,
then 4 mL (27.68 mmol) of diethylchlorophosphate was added,
and stirring was continued for 15 min at -78 °C. The reaction
mixture was then allowed to warm to room temperature and
stirred for 3 h. The reaction mixture was cooled again to -78
°C, and 29 mL (56.0 mmol) of 2.0 M LDA THF was added
dropwise. Once addition of LDA was complete, the reaction
mixture was warmed to room temperature and stirred for an
additional 3 h. The reaction mixture was recooled to -20 °C,
9 mL (70.9 mmol) of trimethylsilyl chloride was added, and
the mixture was stirred at room temperature overnight. The
solution was then poured into 200 mL of 5% KHCO3 aqueous
solution and 300 mL of ether. The organic layer was separated,
and the aqueous phase was then extracted again with 300 mL
of ether. The combined ether extracts were dried over sodium
sulfate and concentrated for column chromatography. The
crude product was purified on a 250 g silica gel column,
packing and eluting with hexane. The desired fractions were
pooled and concentrated to afford 4.0 g (52.0%) of the title
compound: 1H NMR (300 MHz, CDCl3) δ 0.24 (s, 9H), 2.37 (s,
3H), 7.13 (d, J ) 8.4 Hz, 1H), 7.44-7.57 (m, 2H); GC-MS m/z
(relative intensity) 314 (53).
Syn th esis of 2-(Tr im eth ylsilyl)eth yl-4-iod otolu en e (15)
fr om 17. To a solution of 26.6 g (0.10 mol) of 17 in 400 mL of
ether cooled to -78 °C was added 128.7 mL (0.22 mol) of t-BuLi
pentane solution. The reaction mixture was stirred at -78 °C
for 30 min. Another solution of 33.2 g (0.13 mol) of I2 in 400
mL of ether was cooled to -78 °C and was added into the cold
reaction mixture starting with 17. The resulting mixture was
then allowed to warm to 0 °C, stirred for 10 min, and washed
with 10% sodium thiosulfate aqueous solution to remove any
excess iodine. The organic layer was then separated, dried over
sodium sulfate, and concentrated for column chromatography.
The crude product was purified on a 250 g silica gel column,
packing and eluting with hexane. The desired fractions were
pooled and concentrated to afford 27.6 g (88.1%) of the title
compound. Characterization and analysis of this compound is
the same as above.
Syn th esis of 2-(Tr im eth ylsilyl)eth yl-4′-[(tr im eth ylsily)-
eth yn yl]p h en yl Su lfid e (10). Compound 10 was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 7.5 g (22.32 mmol) of 8, 469 mg (0.67
mmol) of Pd(PPh3)2Cl2, and 469 mg (2.46 mmol) of CuI in 300
mL of diethylamine. The reaction mixture was stirred at 50
°C for 1.5 h and worked up. The crude product was purified
on a 150 g silica gel column, packing with hexane and eluting
with 10-40% CH2Cl2/hexane. The desired fractions were
pooled and concentrated to afford 6.50 g (95.0%) of the title
compound: 1H NMR (300 MHz, CDCl3) δ 0.05 (s, 9H), 0.25 (s,
9H), 0.90-0.95 (m, 2H), 2.93-2.99 (m, 2H), 7.18 (d, J ) 8.4
Hz, 2H), 7.37 (d, J ) 8.4 Hz, 2H); GC-MS m/z (relative
intensity) 306 (7).
Syn th esis of 2-(ter t-Bu tyld im eth yl)eth yl-4′-[(tr im eth -
ylsilyl)eth yn yl]p h en yl Su lfid e (11). Compound 11 was
prepared following the general procedure for the palladium-
catalyzed coupling reaction using 10.0 g (26.43 mmol) of 9, 4.1
mL (29.01 mmol) of trimethylsilylacetylene, 0.43 g (0.61 mmol)
of Pd(PPh3)2Cl2, and 0.43 g (2.25 mmol) of CuI in 350 mL of
diethylamine. The reaction mixture was stirred at 55 °C for 1
h and then worked up. The crude product was purified on a
250 g silica gel column, packing and eluting with hexane. The
desired fractions were pooled and concentrated to afford 6.0 g
(65.5%) of the title compound: 1H NMR (300 MHz, CDCl3) δ
0.01 (s, 6H), 0.24 (s, 9H), 0.87 (s, 9H), 0.90-0.97 (m, 2H), 2.93-
2.99 (m, 2H), 7.16-7.38 (m, 4H); GC-MS m/z (relative
intensity) 348 (3).
Syn th esis of 2-(Tr im eth ylsilyl)eth yl-4′-(eth yn yl)p h en -
yl Su lfid e (12). Compound 12 was prepared following the
general procedure for desilylation using 14.67 g (47.92 mmol)
of 10 and 10.7 g (7.75 mmol) of potassium carbonate in 240
mL of 50% CH3OH/THF. The reaction mixture was stirred at
room temperature for 1 h and worked up. The crude product
was purified on a 150 g silica gel column, packing with hexane
and eluting with 10% CH2Cl2/hexane. The desired fractions
were pooled and concentrated to afford 10.23 g (98.0%) of the
title compound: 1H NMR (300 MHz, CDCl3) δ 0.04 (s, 9H),
0.91-0.97 (m, 2H), 2.97-3.00 (m, 2H), 3.10 (s, 1H), 7.20-7.41
(m, 4H); GC-MS m/z (relative intensity) 234 (9).
Syn th esis of 2-(ter t-bu tyld im eth yl)eth yl-4′-(eth yn yl)-
p h en yl Su lfid e (13). Compound 13 was prepared following
the general procedure for desilylation using 6.0 g (17.21 mmol)
of 11 and 10.0 g (7.25 mmol) of potassium carbonate in 200
mL of 50% CH3OH/THF. The reaction mixture was stirred at
room temperature for 1.5 h and worked up. The crude product
was purified on a 100 g silica gel column, packing and eluting
with hexane. The desired fractions were pooled and concen-
trated to afford 4.0 g (84.1%) of the title compound: 1H NMR
(300 MHz, CDCl3) δ 0.01 (s, 6H), 0.87 (s, 9H), 0.94-0.98 (m,
2H), 2.95-2.98 (m, 2H), 3.08 (s, 1H), 7.19-7.42 (m, 4H); GC-
MS m/z (relative intensity) 276 (1).
Syn th esis of 2-Meth yl-4-iod oa cetop h en on e (14). To a
suspension of 12.0 g (89.98 mmol) of AlCl3 in 200 mL of
dichloroethane was added 6.4 mL (0.19 mol) of acetyl chloride
under argon. When the suspension dissolved, a solution of 15
g (68.79 mmol) of 3-iodotoluene in 50 mL of dichloroethane
was added dropwise. After stirring at room temperature for 1
h and then at 50 °C for 2 h, the solution was diluted by adding
100 mL of CH2Cl2 and washed twice with a saturated am-
monium chloride solution and then with a 5% sodium bicar-
bonate solution. The organic layer was then separated, dried
over sodium sulfate, and concentrated for column chromatog-
raphy. The crude product was purified on a 240 g silica gel
column, packing with hexane and eluting with 500 mL of
hexane, 500 mL of 1% ether/hexane, 1.0 L of 2% ether/hexane,
and 2.5 L of 3% ether/hexane. Two isomers were formed. The
first peak from GC-MS analysis is the desired isomer. The
desired fractions were pooled and concentrated to afford 5.1 g
(28.5%) of the title compound: 1H NMR (300 MHz, CDCl3) δ
Syn th esis of 2-Meth yl-4-br om oa cetop h en on e (16). To
a suspension of 20.0 g (0.15 mol) of AlCl3 in 250 mL of CH2Cl2
was added 10.7 mL (0.15 mol) of acetyl chloride under argon.
After the suspension was dissolved, 20.0 g (0.12 mol) of
3-bromotoluene was added and the reaction mixture was
stirred overnight at room temperature. The reaction mixture
was washed twice with
a saturated ammonium chloride
solution. The organic layer was then separated, filtered
through Celite, and dried over sodium sulfate. The crude
product was purified on a 220 g silica gel column, packing with
hexane and eluting with 1 L of hexane, 500 mL of 10% CH2-
Cl2/hexane, 1.0 L of 20% CH2Cl2/hexane, and 2.5 L of 30% CH2-
Cl2/hexane. Two isomers were formed. The first peak from
GC-MS analysis is the desired isomer. The desired fractions
were pooled and concentrated to afford 13.4 g (53.8%) of the
title compound: 1H NMR (300 MHz, CDCl3) δ 2.50 (s, 3H),
2.58 (s, 3H), 7.38-7.58 (m, 3H); GC-MS m/z (relative inten-
sity) 214 (33), 212 (33).
Syn th esis of 2-(Tr im eth ylsilyl)eth yl-4-br om otolu en e
(17). To 50 mL of dry THF cooled to -78 °C was added 34 mL
(68.00 mmol) of 2.0 M LDA THF solution under argon. To this
mixture was added a solution of 13.3 g (62.41 mmol) of 16 in
50 mL of THF dropwise. After the addition of compound 16
solution was complete the reaction mixture was stirred at -78
°C for 1 h, then 11.9 mL (82.34 mmol) of diethylchlorophos-
phate was added, and stirring continued for 15 min at -78
°C. The reaction mixture was warmed to room temperature
and stirred for 3 h. The reaction mixture was recooled to -78
°C, and 69.0 mL (0.14 mol) of 2.0 M LDA THF solution was
added dropwise. Once addition of LDA solution was complete,

Soluble Ferrocene Conjugates
J . Org. Chem., Vol. 64, No. 6, 1999 2077
the reaction mixture was warmed to room temperature. After
stirring for 3 h, the reaction mixture was then cooled to -20
°C, 14.3 mL (0.11 mol) of trimethylsilyl chloride was added,
and stirring continued at room temperature overnight. The
solution was then poured into 400 mL of the saturated sodium
chloride aqueous solution and 1.0 L of ether. The organic layer
was separated, dried over sodium sulfate, and concentrated
for column chromatography. The crude product was purified
on a 300 g silica gel column, packing and eluting with hexane.
The desired fractions were pooled and concentrated to afford
9.03 g (54.0%) of the title compound: 1H NMR (300 MHz,
CDCl3) δ 0.27 (s, 9H), 2.42 (s, 3H), 7.20-7.37 (m, 3H); GC-
MS m/z (relative intensity) 268 (30), 266 (29).
Syn th esis of 2-Iod o-5-(tr im eth ylsily)eth yn yl-1,4-d ip r o-
p oxyben zen e (19). A solution of 6.46 g (14.51 mmol) of 18,
which was prepared from the literature procedure,26,27 2.15 mL
(15.21 mmol) of trimethylsilylacetylene, 600 mg (0.86 mmol)
of Pd(PPh3)2Cl2, and 300 mg (1.57 mmol) of CuI in 350 mL of
diisopropylamine was stirred at 70 °C for 2.5 h under argon.
The solvent was removed, and 300 mL of hexane was added
to the residue. The precipitated solids were filtered off, and
the solution was evaporated to dryness for column chroma-
tography. The crude product was purified on a 150 g silica gel
column, packing with hexane and eluting with 0-10% CH2-
Cl2/hexane. The desired fractions were pooled and evaporated
to afford 2.33 g (39.0%) of the title product: 1H NMR (300
MHz, CDCl3) δ 0.25 (s, 9H), 1.07 (t, J ) 7.2 Hz, 6H), 1.78-
1.86 (m, 4H), 3.91 (t, J ) 6.3 Hz, 4H), 6.84 (s, 2H); GC-MS
m/z (relative intensity) 416 (79).
Syn th esis of 2-(Tr iisop r op ylsilyl)eth yn yl-5-(tr im eth -
ylsily)eth yn yl-1,4-d ip r op oxyben zen e (20). Compound 20
was prepared following the general procedure for the pal-
ladium-catalyzed coupling reaction using 1.5 g (3.61 mmol) of
19, 0.79 g (4.33 mmol) of triisopropylsilylacetylene, 150 mg
(0.26 mmol) of Pd(dba)2, 500 mg (1.91 mmol) of PPh3, and 1.0
g (5.25 mmol) of CuI in 80 mL of THF and 80 mL of
diisopropylamine. The reaction mixture was stirred at 60 °C
for 3 h and worked up. The crude product was purified on a
100 g silica gel column, packing with hexane eluting with
0-10% CH2Cl2/hexane. The desired fractions were pooled and
concentrated to afford 1.5 g (88.0%) of the title compound.
Characterization and analysis of this compound will be
reported after desilylation.
Syn th esis of 2-(Tr iisop r op ylsilyl)eth yn yl-5-eth yn yl-
1,4-d ip r op oxyben zen e (21). Compound 21 was prepared
following the general procedure for desilylation using 1.8 g
(3.83 mmol) of 20 and 4.5 g of potassium carbonate in 200 mL
of 50% CH3OH/THF. The reaction mixture was stirred at room
temperature for 1.5 h and worked up. The crude product was
purified on a 100 g silica gel column, packing with 10% CH2-
Cl2/hexane and eluting with 10-20% of CH2Cl2/hexane. The
desired fractions were pooled and concentrated to afford 1.3 g
(85.5%) of the title compound: 1H NMR (300 MHz, CDCl3) δ
1.03 (t, J ) 7.5 Hz, 3H), 1.05 (t, J ) 7.5 Hz, 3H), 1.14 (br s,
21H), 1.74-1.89 (m, 4H), 3.32 (s, 1H), 3.90 (t, J ) 6.6 Hz, 2H),
3.95 (t, J ) 6.6 Hz, 2H), 6.91 (s, 2H); GC-MS m/z (relative
intensity) 398 (100).
was stirred at 60 °C for 2 h and worked up. The crude product
was purified on a 200 g silica gel column, packing with hexane
and eluting with 0-20% CH2Cl2/hexane. The desired fractions
were pooled and concentrated to afford 11.0 g (70.0%) of the
title compound: 1H NMR (300 MHz, CDCl3) δ 0.17 (s, 9H),
0.71 (s, 9H), 0.92-1.05 (m, 2H), 2.48 (s, 3H), 3.01-3.07 (m,
2H), 7.24-7.47 (m, 7H). Anal. Calcd for (C25H32SSi2 + Na)+:
443.18. Found: 445.
Syn th esis of Com p ou n d 24. Compound 24 was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 640 mg (1.11 mmol) of Pd(dba)2, 1.25
g (4.77 mmol) of PPh3, 640 mg (3.36 mmol) of CuI, 6.2 g (26.48
mmol) of 12, and 7.32 g (23.29 mmol) of 15 in 150 mL of DMF
and 200 mL of diisopropylamine. The reaction mixture was
stirred at 60 °C for 2.5 h and worked up. The crude product
was purified on a 220 g silica gel column, packing with hexane
and eluting with 0-10% CH2Cl2/hexane. The desired fractions
were pooled and concentrated to afford 8.06 g (77.4%) of the
title compound: 1H NMR (300 MHz, CDCl3) δ 0.05 (s, 6H),
0.31 (s, 9H), 0.92 (s, 9H), 0.93-1.05 (m, 2H), 2.46 (s, 3H), 3.00-
3.06 (m, 2H), 7.26-7.48 (m, 7H). Anal. Calcd for (C28H38SSi2
+ Na)+: 485.22. Found: 485.
Syn th esis of Com p ou n d 25. Compound 25 was prepared
following the general procedure for desilylation using 0.74 g
(1.74 mmol) of 22 and 2.2 mL (2.2 mmol) of a 1.0 M TBAF
THF solution and 150 mL of CH2Cl2. The reaction mixture was
stirred for 30 min and worked up. The crude product was
purified on a 50 g silica gel column, packing with 50% ethyl
acetate/CH2Cl2 and eluting with the same solvents. The
desired fractions were pooled and concentrated to afford 0.5 g
(81.3%) of the title compound: 1H NMR (300 MHz, CDCl3) δ
2.49 (s, 3H), 2.98 (t, J ) 7.8 Hz, 2H), 3.25 (t, J ) 7.8 Hz, 2H),
3.41 (s, 1H), 7.20-7.50 (m, 9H), 8.60 (br s, 2H). Anal. Calcd
for (C24H19NS + H)+: 354.12. Found: 354.
Syn th esis of Com p ou n d 26. Compound 26 was prepared
following the general procedure for desilylation using 11.0 g
(26.17 mmol) of 23 and 10.0 g (72.5 mmol) of potassium
carbonate in 240 mL of 50% THF/CH3OH. The reaction
mixture was stirred for 1.5 h and worked up. The crude
product was purified on a 200 g silica gel column, packing with
hexane and eluting with a 0-10% CH2Cl2/hexane. The desired
fractions were pooled and concentrated to afford 8.85 g (97.0%)
of the title compound: 1H NMR (300 MHz, CDCl3) δ 0.13 (s,
9H), 0.92-1.05 (m, 2H), 2.48 (s, 3H), 3.01-3.07 (m, 2H), 3.44
(s, 1H), 7.24-7.47 (m, 7H). Anal. Calcd for (C22H24SSi +
Na)+: 371.14. Found: 373.
Syn th esis of Com p ou n d 27. Compound 27 was prepared
following the general procedure for desilylation using 8.0 g
(17.28 mmol) of 24 and 10.0 g (72.5 mmol) of potassium
carbonate in 80 mL of THF and 150 mL of methanol. The
reaction mixture was stirred for 2 h and worked up. The crude
product was purified on a 220 g silica gel column, packing with
hexane and eluting with a 0-15% CH2Cl2/hexane. Then
desired fractions were pooled and concentrated to afford 6.60
g (97.6%) of the title compound: 1H NMR (300 MHz, CDCl3)
δ 0.041 (s, 6H), 0.92 (s, 9H), 1.00-1.03 (m, 2H), 2.49 (s, 3H),
3.03-3.06 (m, 2H), 3.41 (s, 1H), 7.26-7.48 (m, 7H). Anal. Calcd
for (C25H30SSi + K)+: 429.18. Found: 429.
Syn th esis of Com p ou n d 28. Compound 28 was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 350 mg (0.61 mmol) of Pd(dba)2, 1.0 g
(3.82 mmol) of PPh3, and 260 mg (1.37 mmol) of CuI, 2.4 g
(6.79 mmol) of 25, and 13.5 g (40.92 mmol) of diiodobenzene
in 200 mL of diisopropylamine and 200 mL of THF. The
reaction mixture was stirred at 60 °C for 16 h and worked up,
followed by the treatment of EDTA solution. The crude product
was purified on a 100 g silica gel column, packing with CH2-
Cl2 and eluting with 0-30% ethyl acetate/CH2Cl2. The desired
fractions were pooled and concentrated to afford 3.04 g (81.0%)
of the title compound: 1H NMR (300 MHz, CDCl3) δ 2.53 (s,
3H), 2.99 (t, J ) 7.2 Hz, 2H), 3.26 (t, J ) 7.2 Hz, 2H), 7.18-
7.49 (m, 11H), 7.74 (d, J ) 8.4 Hz, 2H), 8.58 (d, J ) 6.0 Hz,
2H). Anal. Calcd for (C30H22INS + H)+: 556.05. Found: 556.
Syn th esis of Com p ou n d 29. Compound 29 was prepared
following the general procedure for the palladium-catalyzed
Syn th esis of Com p ou n d 22. Compound 22 was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 252 mg (0.44 mmol) of Pd(dba)2, 700
mg (2.67 mmol) of PPh3, and 800 mg (4.20 mmol) of CuI, 1.5
g (6.35 mmol) of 5, and 2.2 g (7.00 mmol) of 15 in 60 mL of
diisopropylamine and 15 mL of THF. The reaction mixture was
stirred at 60 °C for 4 h and worked up. The crude product was
purified on a 100 g silica gel column, packing with CH2Cl2 and
eluting with 0-20% ethyl acetate/CH2Cl2. The desired frac-
tions were pooled and concentrated to afford 1.89 g (71.0%) of
the title compound. Characterization and analysis of this
compound will be reported after desilylation.
Syn th esis of Com p ou n d 23. Compound 23 was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 428 mg (0.74 mmol) of Pd(dba)2, 878
mg (3.35 mmol) of PPh3, and 428 mg (2.25 mmol) of CuI, 8.7
g (37.15 mmol) of 12, and 11.7 g (37.26 mmol) of 15 in 200 mL
of diisopropylamine and 100 mL of DMF. The reaction mixture

2078 J . Org. Chem., Vol. 64, No. 6, 1999
Yu et al.
coupling reaction using 210 mg (0.37 mmol) of Pd(dba)2, 431
mg (1.65 mol) of PPh3, and 200 mg (1.05 mmol) of CuI, 3.0 g
(8.6 mmol) of 26, and 12.0 g (36.0 mmol) of diiodobenzene in
175 mL of DMF and 125 mL of pyrrolidine. The reaction
mixture was stirred at 60 °C for 16 h and worked up. The crude
product was purified on a 250 g silica gel column, packing with
hexane and eluting with of 0-20% CH2Cl2/hexane. The desired
fractions were pooled and concentrated to afford 2.48 g (53.0%)
of the title compound: 1H NMR (300 MHz, CDCl3) δ 0.10 (s,
9H), 0.94-1.02 (m, 2H), 2.53 (s, 3H), 3.01-3.08 (m, 2H), 7.27-
mixture was stirred at 60 °C for 16 h and worked up, followed
by the treatment of EDTA solution. The crude product was
purified on a 50 g silica gel column, packing in CH2Cl2 and
eluting with 0-30% ethyl acetate/CH2Cl2. The desired frac-
tions were pooled and concentrated to afford 0.98 g (86.6%) of
the title compound. Characterization and analysis of this
compound will be reported after desilylation.
Syn th esis of Com p ou n d 36. Compound 36 was prepared
following the general procedure for desilylation using 0.98 g
(1.19 mmol) of 35 and 1.5 mL (1.50 mmol) of 1.0 M TBAF THF
and 50 mL of CH2Cl2. The reaction mixture was stirred for 1
h and worked up. The crude product was purified on a 30 g
silica gel column, packing with CH2Cl2 and eluting with 0-30%
ethyl acetate/CH2Cl2. The desired fractions were pooled and
concentrated to afford 0.74 g (93.6%) of the title compound:
1H NMR (300 MHz, CDCl3) δ 1.08-1.18 (m, 6H), 1.83-1.95
(m, 4H), 2.56 (s, 3H), 2.98 (t, J ) 7.8 Hz, 2H), 3.25 (t, J ) 7.8
Hz, 2H), 3.40 (s, 1H), 4.00-4.05 (m, 4H), 7.03-7.55 (m, 15H),
8.57 (d, J ) 5.4 Hz, 2H). Anal. Calcd for (C46H39NO2S + Na)+:
692.27. Found: 692.
Syn th esis of Com p ou n d 37. Compound 37 was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 140 mg (0.24 mmol) of Pd(dba)2, 280
mg (1.07 mmol) of triphenylphosphine, 140 mg (0.74 mmol) of
CuI, 1.2 g (3.01 mmol) of 21, and 9.93 g (30.10 mmol) of
diiodobenzene in 300 mL of DMF and 140 mL of diisopropyl-
amine. The reaction mixture was stirred at 60 °C for 4 h and
worked up. The crude product was purified on a 200 g silica
gel column, packing with hexane, eluting with hexane until
the diiodobenzene is out of the column, and then eluting with
0-30% CH2Cl2/hexane. The desired fractions were pooled and
concentrated to afford 0.65 g (36.1%) of the title compound:
1H NMR (300 MHz, CDCl3) δ 1.09 (t, J ) 7.2 Hz, 3H), 1.13 (t,
J ) 7.2 Hz, 3H), 1.18 (br s, 21H), 1.81-1.94 (m, 4H), 3.97 (t,
J ) 6.6 Hz, 2H), 4.02 (t, J ) 6.6 Hz, 2H), 6.98 (s, 2H), 7.28 (d,
J ) 8.4 Hz, 2H), 7.78 (d, J ) 8.4 Hz, 2H). Anal. Calcd for
(C31H41IO2S + Na)+: 623.19. Found: 623.
Syn th esis of Com p ou n d 38. Compound 38 was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 100 mg (0.17 mmol) of Pd(dba)2, 200
mg (0.77 mmol) of triphenylphosphine, 100 mg (0.53 mmol) of
CuI, 0.47 g (1.51 mmol) of 31, which is prepared in the
literature procedure,12 and 0.60 g (1.00 mmol) of 37 in 250 mL
of DMF and 150 mL of diisopropylamine. The reaction mixture
was stirred at 60 °C for 16 h and worked up, followed by the
treatment of EDTA solution. The crude product was purified
on a 50 g silica gel column, packing with hexane and eluting
with of 0-40% CH2Cl2/hexane. The desired fractions were
pooled and concentrated to afford 200 mg (25.8%) of the title
compound: 1H NMR (300 MHz, CDCl3) δ 1.07 (t, J ) 7.2 Hz,
3H), 1.15 (t, J ) 7.2 Hz, 3H), 1.19 (br s, 21H), 1.83-1.95 (m,
4H), 3.98 (t, J ) 6.6 Hz, 2H), 4.03 (t, J ) 6.6 Hz, 2H), 4.30-
4.56 (m, 9H), 6.99 (br s, 2H), 7.51-7.54 (m, 8H). Anal. Calcd
for (C51H54FeO2Si + Na)+: 805.32. Found: 805.
7.53 (m, 9H), 7.74 (d, J ) 8.1 Hz, 2H). Anal. Calcd for (C28H27
-
ISSi + H)+: 551.06. Found: 551.
Syn th esis of Com p ou n d 30. Compound 30 was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 350 mg (0.61 mmol) of Pd(dba)2, 670
mg (2.56 mmol) of PPh3, and 350 mg (1.83 mmol) of CuI, 4.0
g (10.23 mmol) of (27), and 33.8 g (0.10 mol) of diiodobenzene
in 600 mL of DMF and 300 mL of diisopropylamine. The
reaction mixture was stirred at 60 °C for 3 h and worked up,
followed by the treatment of EDTA solution. The crude product
was purified on a 240 g silica gel column, packing with hexane
and eluting with 0-20% CH2Cl2/hexane. The desired fractions
were pooled and concentrated to afford 3.98 g (65.8%) of the
title compound: 1H NMR (300 MHz, CDCl3) δ 0.04 (s, 6H),
0.92 (s, 9H), 0.98-1.03 (m, 2H), 2.53 (s, 3H), 3.02-3.07 (m,
2H), 7.27-7.51 (m, 9H), 7.74 (d, J ) 8.4 Hz, 2H). Anal. Calcd
for (C31H33ISSi + H)+: 593.11. Found: 593.
Syn th esis of Com p ou n d 32. Compound 32 was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 70 mg (0.12 mmol) Pd(dba)2, 140 mg
(0.53 mmol) of triphenylphosphine, 70 mg (0.37 mmol) of CuI,
1.0 g (2.4 mmol) of 19, and 0.61 g (2.9 mmol) of ferrocenyl-
acetylene in 75 mL of DMF and 75 mL of diisopropylamine.
The reaction mixture was stirred at 55 °C for 3 h and worked
up, followed by the treatment of the EDTA solution. The crude
product was purified on a 100 g silica gel column, packing with
hexane and eluting with 0-30% CH2Cl2/hexane. The desired
fractions were pooled and concentrated to afford 0.53 g (44.5%)
of the title compound. Characterization and analysis of this
compound will be reported after desilylation.
Syn th esis of Com p ou n d 33. Compound 33 was prepared
following the general procedure for desilylation using 0.53 g
(1.06 mmol) of 32 and 8.0 g (57.88 mmol) of potassium
carbonate in 100 mL of 50% THF/CH3OH. The reaction
mixture was stirred at room temperature for 2 h and worked
up. The crude product was purified on a 50 g silica gel column,
packing with hexane and eluting with 0-50% CH2Cl2/hexane.
The desired fractions were pooled and concentrated to afford
0.41 g (91.1%) of the title compound: 1H NMR (300 MHz,
CDCl3) δ 1.10 (t, J ) 7.2 Hz, 3H), 1.17 (t, J ) 7.2 Hz, 3H),
1.81-1.96 (m, 4H), 3.38 (s, 1H), 4.00 (t, J ) 6.6 Hz), 4.01(t, J
) 6.6 Hz, 2H), 4.30-4.56 (m, 9H), 6.99 (d, J ) 3.3 Hz, 2H).
Anal. Calcd for (C26H26FeO + Na)+: 449.13. Found: 449.
Syn th esis of Com p ou n d 34. Compound 34 was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 230 mg (0.40 mmol) of Pd(dba)2, 442
mg (1.69 mmol) of triphenylphosphine, 200 mg (1.05 mmol) of
CuI, 3.1 g (14.76 mmol) of ferrocenylacetylene, and 16.0 g
(48.50 mmol) of diiodobenzene in 150 mL of THF and 100 mL
of diisopropylamine. The reaction mixture was stirred at 60
°C for 16 h and worked up. The crude product was purified on
a 300 g silica gel column, packing in hexane, eluting with
hexane until all diiodobenzene is out, and eluting then with
20% CH2Cl2/hexane. The desired fractions were pooled and
concentrated to afford 3.76 g (73.4%) of the title compound:
1H NMR (300 MHz, CDCl3) δ 4.24-4.50 (m, 9H), 7.20 (d, J )
8.4 Hz, 2H), 7.65 (d, J ) 8.4 Hz). Anal. Calcd for (C18H13Fe +
H)+ and (C18H13Fe - H)-: 412.94 and 411.94. Found: 412 and
410.
Syn th esis of Com p ou n d 39. Compound 39 was prepared
following the general procedure for desilylation using 200 mg
(0.25 mmol) of 38 and 0.31 mL (0.31 mmol) of 1.0 M TBAF
THF solution in 50 mL of THF. The reaction mixture was
stirred at room temperature for 2 h and worked up. The crude
product was purified on a 50 g silica gel column, packing with
hexane and eluting with 0-30% CH2Cl2/hexane. The desired
fractions were pooled and concentrated to afford 130 mg
(81.8%) of the title compound: 1H NMR (300 MHz, CDCl3) δ
1.10 (t, J ) 6.9 Hz, 3H), 1.14 (t, J ) 6.9 Hz, 3H), 1.825-1.97
(m, 4H), 3.40 (s, 1H), 4.01 (t, J ) 6.6 Hz, 2H), 4.03 (t, J ) 6.6
Hz, 2H), 4.30-4.56 (m, 9H), 7.03 (s, 1H), 7.04 (s, 1H), 7.52 (br
s, 4H), 7.55 (br s, 4H). Anal. Calcd for (C42H34FeO2 + Na)+
and (C42H34FeO2 - H)-: 649.19 and 625.19. Found: 649 and
625.
Syn th esis of Com p ou n d 35. Compound 35 was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 56 mg (0.01 mmol) of Pd(dba)2, 108
mg (0.41 mmol) of triphenylphosphine, 50 mg (0.26 mmol) of
CuI, 0.63 g (1.57 mmol) of 21, and 0.76 g (1.37 mmol) of 28 in
50 mL of THF and 50 mL of diisopropylamine. The reaction
Syn th esis of Com p ou n d 40. A solution of 0.93 g (1.46
mmol) of I and 2 mL (3.21 mmol) of iodomethane in 200 mL
of acetone was stirred at room temperature overnight. The
solution was concentrated to half its volume and diluted by
adding 200 mL of hexane. The yellow precipitate was formed,
filtered off, and dried to afford 0.60 g (53.0%) of the title

Soluble Ferrocene Conjugates
J . Org. Chem., Vol. 64, No. 6, 1999 2079
compound: 1H NMR (300 MHz, CD2Cl2) δ 2.15 (s, 3H), 2.56
(s, 3H), 3.29 (t, J ) 6.3 Hz, 2H), 3.40 (t, J ) 6.3 Hz, 2H), 4.30-
4.60 (m, 9H), 7.36-7.56 (m, 11H), 7.91 (d, J ) 6.6 Hz, 2H),
9.02 (d, J ) 6.6 Hz, 2H). Anal. Calcd for (C43H34FeSN)+:
652.17. Found: 652.
δ 0.10 (s, 9H), 0.94-1.02 (m, 2H), 2.53 (s, 3H), 3.01-3.08 (m,
2H), 4.29-4.57 (m, 9H), 7.27-7.78 (m, 15H). HRMS calcd for
(C48H40FeSSi + H)+: 733.2048. Found: 733.2021.
Syn th esis of Com p ou n d III. Compound III was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 100 mg (0.17 mmol) of Pd(dba)2, 200
mg (0.76 mmol) of triphenylphosphine, 100 mg (0.53 mmol) of
CuI, 0.65 g (1.10 mmol) of 30, and 0.41 g (0.97 mmol) of 33 in
100 mL of DMF, 60 mL of THF, and 100 mL of diisopropyl-
amine. The reaction mixture was stirred at 60 °C for 4 h and
worked up, followed by the treatment of EDTA solution. The
crude product was purified on a 110 g silica gel column,
packing with hexane and eluting with 0-50% CH2Cl2/hexane.
The desired fractions were pooled and concentrated to afford
0.40 g (46.5%) of the title compound: 1H NMR (300 MHz,
CDCl3) δ 0.07 (s, 6H), 0.89 (s, 9H), 0.94-1.00 (m, 2H), 1.15 (t,
J ) 7.5 Hz, 3H), 1.17 (t, J ) 7.5 Hz, 3H), 1.79-1.93 (m, 4H),
2.52 (s, 3H), 2.99-3.05 (m, 2H), 4.03 (t, J ) 6.3 Hz, 2H), 4.04
(t, J ) 6.3 Hz, 2H), 4.25 (s, 5H), 4.27 (t, J ) 1.8 Hz, 2H), 4.51
(t, J ) 1.8 Hz, 2H), 6.98 (s, 1H), 7.01 (s, 1H), 7.24-7.55 (m,
Syn th esis of Com p ou n d 41. To 60 mL of DMF was added
0.18 g (0.22 mmol) of (40) under argon. To this solution was
added 2.0 g (14.47 mmol) of potassium carbonate and 1.5 mL
of water. After stirring at room temperature for 1.2 h, 6 mL
(96.38 mmol) of iodomethane was added and stirring continued
for 40 min. The reaction mixture was diluted by adding 600
mL of CH2Cl2 and washed once with 400 mL of water. After
separating the organic layer, the aqueous layer was extracted
twice with 200 mL of CH2Cl2. The combined organic extracts
were washed once with water, dried over sodium sulfate, and
concentrated for column chromatography. The crude product
was purified on a 88 g silica gel column, packing with hexane
and eluting with 20-50% CH2Cl2/hexane. The desired fractions
were pooled and concentrated to afford 58.5 mg (48.7%) of the
title compound: 1H NMR (300 MHz, CDCl3) δ 2.547 (s, 3H),
2.553 (s, 3H), 4.29-4.56 (m, 9H), 7.24-7.52 (m, 11H). HRMS
calcd for C36H26FeS: 546.1104. Found: 546.1100.
11H). HRMS calcd for
890.3241.
C57H58FeO2SSi: 890.3276. Found:
Syn th esis of Com p ou n d 42. To 40 mg (0.06 mmol) of II
was added 5.0 mL (5.00 mmol) of TBAF THF solution under
argon, and the resulting red solution was stirred for 45 min.
To this reaction mixture was added 1.5 mL (24.09 mmol) of
iodomethane, and the mixture was stirred another 20 min. The
solution was diluted by adding 60 mL of dichloromethane and
10 mL of water. Upon shaking well, the organic layer was
separated, dried over sodium sulfate, and concentrated for
column chromatography. The crude product was purified on
a 53 g silica gel column, packing with hexane and eluting with
50% CH2Cl2/hexane. The desired fractions were pooled and
concentrated. The yellow product was then precipitated from
hexane to afford 22 mg (61.9%) of the title compound: 1H NMR
(300 MHz, CDCl3) δ 2.548 (s, 3H), 2.557 (s, 3H), 4.29-4.56
(m, 9H), 7.24-7.56 (m, 15H). Anal. Calcd for (C44H30FeS +
K)+, (C44H30FeS + Na)+, (C44H30FeS - H)-: 685.24, 669.13,
645.13. Found 685, 669, 645.
Syn th esis of Com p ou n d IV. Compound IV was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 30 mg (0.05 mmol) of Pd(dba)2, 58 mg
(0.22 mmol) of triphenylphosphine, 30 mg (0.16 mmol) of CuI,
0.40 g (0.60 mmol) of 36, and 0.50 g (0.98 mmol) of 34 in 60
mL of DMF and 40 mL of diisopropylamine. The reaction
mixture was stirred at 65 °C for 4 h and worked up, followed
by the treatment of EDTA solution. The crude product was
purified on a 35 g silica gel column, packing with CH2Cl2 and
eluting with 0-25% ethyl acetate/CH2Cl2. The desired frac-
tions were pooled and concentrated to afford 0.20 g (35.0%) of
the title compound: 1H NMR (300 MHz, CDCl3) δ 1.16 (t, J )
7.5 Hz, 6H), 1.94 (sextet, J ) 6.6 Hz, 4H), 2.56 (s, 3H), 2.99 (t,
J ) 7.8 Hz, 2H), 3.26 (t, J ) 7.8 Hz, 2H), 4.06 (t, J ) 7.2 Hz,
4H), 4.30(br s, 7H), 4.56 (s, 2H), 7.07 (s, 2H), 7.21-7.56 (m,
17H), 8.61 (br s, 2H). HRMS calcd for (C64H51FeNO2S + H)+:
954.3068. Found: 954.3036.
Syn th esis of Com p ou n d I. Compound I was prepared
following the general procedure for the palladium-catalyzed
coupling using 55 mg (0.0.96 mmol) of Pd(dba)2, 112 mg (0.43
mmol) of triphenylphosphine, 55 mg (0.29 mmol) of CuI, 1.06
g (1.91 mmol) of 28, and 0.5 g (2.4 mmol) of ferrocenylacetylene
in 75 mL of DMF and 75 mL of pyrrolidine. The reaction
mixture was stirred for 16 h at 60 °C and worked up, followed
by the treatment of EDTA solution. The crude product was
purified on a 60 g silica gel column, packing with CH2Cl2 and
eluting with 0-20% ethyl acetate/CH2Cl2. The desired frac-
tions were pooled and concentrated to afford 0.91 g (74.6%) of
the title compound: 1H NMR (300 MHz, CD2Cl2) δ 2.55 (s, 3H),
3.01 (t, J ) 7.2 Hz, 2H), 3.27 (t, J ) 7.2 Hz, 2H), 4.29-4.60
(m, 9H), 7.18-7.56 (m, 13H), 8.53 (d, J ) 5.7 Hz, 2H). HRMS
calcd for (C42H31FeNS + H)+: 638.1605. Found: 638.1622.
Syn th esis of Com p ou n d II. Compound II was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 47 mg (0.08 mmol) of Pd(dba)2, 90 mg
(0.34 mmol) of triphenylphosphine, 35 mg (0.18 mmol) of CuI,
0.34 g (1.09 mmol) of 31, which is prepared in the literature
procedure,12 and 0.45 g (0.82 mmol) of 29 in 50 mL of DMF
and 25 mL of pyrrolidine. The reaction mixture was stirred at
60 °C for 4 h and worked up, followed by the treatment of
EDTA solution. The crude product was purified on a 120 g
silica gel column, packing with hexane and eluting with 0-20%
CH2Cl2/hexane. The desired fractions were pooled and con-
centrated to afford 0.60 g (95.0%) of the title compound. The
desired fractions were pooled and concentrated to afford 2.48
g (53.0%) of the title compound: 1H NMR (300 MHz, CDCl3)
Syn th esis of Com p ou n d V. Compound V was prepared
following the general procedure for the palladium-catalyzed
coupling reaction using 100 mg (0.17 mmol) of Pd(dba)2, 200
mg (0.76 mmol) of triphenylphosphine, 100 mg (0.53 mmol) of
CuI, 130 mg (0.20 mmol) of 39, and 162 mg (0.27 mmol) of 30
in 50 mL of DMF and 50 mL of pyrrolidine. The reaction
mixture was stirred at 60 °C for 16 h and worked up, followed
by the treatment of EDTA solution. The crude product was
purified on a 60 g silica gel column, packing with hexane and
eluting with 0-30% CH2Cl2/hexane. The desired fractions were
pooled and concentrated to 50 mg (27.2%) of the title com-
pound: 1H NMR (300 MHz, CDCl3) δ 0.01 (s, 6H), 0.89 (s, 9H),
0.94-1.00 (m, 2H), 1.12 (t, J ) 7.5 Hz, 6H), 1.90 (sextet, J )
6.6 Hz, 4H), 2.52 (s, 3H), 2.97-3.03 (m, 2H), 4.02 (t, J ) 6.6
Hz, 4H), 4.27-4.52 (m, 9H), 7.03 (s, 2H), 7.23-7.52 (m, 19H).
HRMS calcd for (C73H66FeO2SSi + H)+: 1091.3980. Found:
1091.4018.
Ack n ow led gm en t. We thank Professor Tom Meade
of the California Institute of Technology, Professor
Stephen Creager of Clemson University, and Dr. Gary
F. Blackburn and Dr. Dan Farkas at CMS for careful
reading and helpful comments on the manuscript.
Su p p or tin g In for m a tion Ava ila ble: Proton NMR spectra
of all new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O982392M