Synthesis of optically active amphiphilic tetrathiafulvalene derivatives

Article abstract of DOI:10.1016/j.tet.2006.01.056

The synthesis and characterization of novel chiral tetrathiafulvalenes bearing two long alkyl chains at one end of the π-electron rich unit and different functional groups - ester, acid or thiolate - at the other extreme is described. The synthetic method requires the preparation of 1,3-dithiol derivatives with two stereogenic centers. Different routes and reaction conditions were explored to form these compounds, whose optimized synthesis involved the nucleophilic substitution of a chiral bromo methylene derivative with tetrabutylammonium bis(2-thioxo-1,3-dithiole-4,5-dithiolate)zincate. The tetrathiafulvalenes were prepared by coupling the 1,3-dithiol derivative with 4,5-bis(methoxycarbonyl)-1,3-dithiol-2-one or 4,5-bis(2-cyanotehylthio)-1,3- dithiol-2-thione. The products were fully characterized, including by circular dichroism spectroscopy, which confirmed their optical activity. They are promising candidates to be used as building blocks in supramolecular materials for molecular electronics, to produce systems with unique electrical, magnetic or optical properties that stem from their chirality.

Full text of DOI:10.1016/j.tet.2006.01.056

Tetrahedron 62 (2006) 3370–3379
Synthesis of optically active amphiphilic
tetrathiafulvalene derivatives
*
´
Elba Gomar-Nadal, Concepcio Rovira and David B. Amabilino
` ` `
Departament de Nanociencia Molecular i Materials Organics, Institut de Ciencia de Materials de Barcelona (ICMAB),
´
Consejo Superior de Investigaciones Cientıficas (CSIC), Campus Universitari, 08193 Bellaterra, Catalonia, Spain
Received 10 October 2005; revised 10 January 2006; accepted 17 January 2006
Available online 17 February 2006
Abstract—The synthesis and characterization of novel chiral tetrathiafulvalenes bearing two long alkyl chains at one end of the p-electron rich
unit and different functional groups—ester, acid or thiolate—at the other extreme is described. The synthetic method requires the preparation of
1,3-dithiol derivatives with two stereogenic centers. Different routes and reaction conditions were explored to form these compounds, whose
optimized synthesis involved the nucleophilic substitution of a chiral bromo methylene derivative with tetrabutylammonium bis(2-thioxo-1,3-
dithiole-4,5-dithiolate)zincate. The tetrathiafulvalenes were prepared by coupling the 1,3-dithiol derivative with 4,5-bis(methoxycarbonyl)-1,3-
dithiol-2-one or 4,5-bis(2-cyanotehylthio)-1,3-dithiol-2-thione. The products were fully characterized, including by circular dichroism
spectroscopy, which confirmed their optical activity. They are promising candidates to be used as building blocks in supramolecular materials for
molecular electronics, to produce systems with unique electrical, magnetic or optical properties that stem from their chirality.
q 2006 Elsevier Ltd. All rights reserved.
1. Introduction
nature, to ensure liquid crystallinity, solubility and
processing characteristics in general. To the best of our
knowledge, the synthetic routes to chiral TTFs reported to
date have not incorporated long alkyl chains. The efficiency
of the cyclic sulphate ester route to chiral TTFs suffers when
the size of the substituent on the cyclic sulphate is
increased.5,8 To overcome these problems, we envisaged
the preparation of TTFs of type 1 (see Scheme 1)
introducing directly two chiral chains (3) by reaction of
the readily available di-anion 2-thioxo-1,3-dithiole-4,5-
The stereochemistry of molecular components has signi-
ficant consequences for the properties of chemical systems
of which they form a part, such us magnetic and conducting
properties.1 Tetrathiafulvalene (TTF) derivatives2 are very
versatile electro-active molecules widely used as building
blocks to prepare organic metals, for supramolecular
functions3 and in molecular electronics.4 The preparation
of optically active compounds of this type offers, then, the
creation of new substances with novel characteristics. Some
chiral TTF derivatives have been previously reported.5–8
These compounds have been used to form chiral conducting
charge transfer complexes and salts mainly.5,7 However,
away from the constrictions of crystal space, they are also
interesting for preparing multifunctional materials in the
form of liquid crystals, thin films, self-assembled mono-
layers (SAMs), dendrimers and polymers for use in
molecular (opto)electronic devices with new properties
that arise from the chirality of the molecule, and in which
(more often than not) an amphiphilic character is present.
*R
S
S
R1
R2
S
S
S
S
1
*R
*R
*R
R1
R2
S
S
S
4
5
X
Y
S
S
S
In these systems it is often necessary to prepare components
with long alkyl chains, which provide the amphiphilic
S
S
S
S
*R
3
Z
Y
2
Keywords: Stereochemistry; Circular dichroism; Molecular electronics;
p-Donor.
Z = Leaving
group
*
Corresponding author. Tel.: C34 935801853; fax: C34 935805729;
e-mail: amabilino@icmab.es
Scheme 1.
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.01.056

E. Gomar-Nadal et al. / Tetrahedron 62 (2006) 3370–3379
3371
dithiolate (2), where a great body of literature exists for
achiral components with long alkyl chains,9 to give a 1,3-
dithiole derivative with general structure 4. Subsequently,
coupling of 1,3-dithio-l,2-ones (or -thiones) 4 and 5
with trialkyl phosphites10 would afford the desired
compounds 1.
The direct reaction of alcohols and zinc complexes has also
been reported using the Mitsunobu procedure.16 However,
treatment of the zinc complex with lactate 9 adding 4.1 equiv
of acetic acid (or without adding any acid) under these
conditionsdidnotleadtotheformationof6either,presumably
because of the strength of the chelate. Another route explored
to synthesize 6 was the mono-deprotection of 4,5-bis(2-
cyanotehylthio)-1,3-dithiol-2-thione17 with 1 equiv of CsOH
and subsequent reaction of the resulting thiolate salt with
lactate 9 under Mitsunobu conditions, but again no reaction
was observed. The lack of success in all these reactions is most
probably related to: (i) the role of the proton source12 in the
Mitsunobu reaction and (ii) the sterical impediment of the
stereogenic center hindering the reactivity with the bulky
(di)sulfide, a statement that was corroborated for the
experimental data presented in this article (see below) and
by Wallis and co-workers8 research.
Here, we describe the synthesis of new chiral TTFs of type 1
with two stereogenic centers in long alkyl chains at one
extreme of the p-electron rich unit, and functional groups at
the other that will help to incorporate the molecule into
chemical systems.
2. Results and discussion
2.1. Synthesis of enantiomeric 1,3-dithiol-2-thiones
To avoid the possible reactivity problems caused by the
proximity of the stereogenic carbon atom to the electrophilic
group, a synthetic route where the introduction of the chiral
‘tails’ took place through a nucleophilic substitution one atom
further from the chiral center was envisaged (Scheme 3). This
synthetic pathway started with the preparation of the chiral
acid 10 in two steps,18 conversion to ester 11 whose treatment
with LiAlH4 led to alcohol 12. Bromoderivative 13 was
prepared by two methods (Scheme 3). The first one consisted
of treating 12 with PBr3,19 which gave a mixture of the desired
product (13) and the characteristic intermediates of the
reaction,20 which, even after passing HBr, were not
completely transformed into the desired product, so very
low yields were attained (w10%, Table 1). Alternatively,
alcohol 12 was first tosylated and the functional group of the
resulting product (14) was subsequently exchanged for
bromide by reaction with LiBr in refluxing acetone, giving
13. The yield of the reaction depends strongly on the refluxing
time (Table 1). Long reaction times ensured a quantitative
conversion of 14 to 13. When NaBr was used, instead of LiBr,
the reaction did not take place.
Different strategies were considered for the preparation of
optically active 1,3-dithiol derivatives with two stereogenic
centers and long alkyl chains (4). The synthesis of the chiral
1,3-dithiol-2-thione 6 (Scheme 2) was attempted, taking
advantage of the stereoselectivity of the Mitsunobu11,12
reaction for the introduction of stereogenic centers in the
a-position to heteroatoms. A stable form of the synthon 2 is
tetrabutylammonium bis(2-thioxo-1,3-dithiole-4,5-dithio-
late)zincate13 (7, Scheme 2). The complex was treated
with dry hydrogen chloride in THF, and a change in color of
the solution was observed—from purple to yellow,
presumably resulting from decomplexation of the metal
ion and the formation of the unstable14 dithiol 8. After
bubbling nitrogen through the solution to eliminate the
excess of hydrogen chloride, treatment of the intermediate
with the lactate 9 under Mitsunobu reaction conditions11,12
did not give the desired product (6) despite the fact that this
type of coupling between alcohols and thiols has been
reported in the past.15
To optimize the reaction conditions to synthesize 4,5-
bis((S)-2-dodecyloxy-propanyl)-1,3-dithiol-2-thione (15,
Scheme 3), the synthesis of the analogous achiral thione
4,5-bis(decacyl)-1,3-dithiol-2-thione (16, Scheme 4) was
used as a reference. The nucleophilic substitution reaction
with the zinc complex 7 to form 16 gave higher yields using
1-bromodecane than tosylate 17 (Table 2). Addition of NaI
to interchange the tosylate group for iodine in situ increased
the yield of the reaction, which even so was lower than using
1-bromodecane as a starting material. Bromine and tosylate
are both very good leaving groups for nucleophilic
substitution reactions; so, the differences in yield observed
2-
S
S
S
Zn
S
S
S
S
S
+
2
NBu4
S
S
7
HCl(g)
THF
SH
S
S
8
S
SH
1) PPh3, THF,
2) DIAD, 0 ºC
3) rt., 16 h
21
are most likely due to steric impediment.
OC4H9
The same tendency was observed when the reactions were
done with the analogous chiral reactants (Table 2). The
efficiency of the reaction to form the chiral thione 15
(Scheme 3) was higher using the chiral bromide derivative
(13) than the corresponding chiral tosylate (14). Comparing
the reactions done under the same conditions for 15 and 16
the influence of the stereogenic carbon atom in the reaction
(mentioned before) was evident. Longer refluxing times
were necessary for the formation of the chiral 1,3-dithiol-2-
HO
9
O
O
S
S
6
O
S
O
S
S
O
Scheme 2.

3372
E. Gomar-Nadal et al. / Tetrahedron 62 (2006) 3370–3379
1) Ag2O, IC12H25, ∆
2) LiOH·H2O, MeOH, rt.
MeOH,
[H2SO4]cat.
O
O
O
OC12H25
OH
OC12H25
MeO
MeO
HO
50%
90%
11
10
LiAlH4,
Et2O, ∆
97%
TsCl, NEt3, DMAP,
CH2Cl2 ,rt.
OC12H25
S
S
S
7, CH3CN, ∆
OC12H25
OC12H25
TsO
HO
S
OC12H25
14
99%
12
36%
S
15
LiBr,
acetone, ∆
98%
10%
PBr3, Et2O
OC12H25
7, CH3CN, ∆
Br
13
98%
Scheme 3.
desorption–ionization mass spectrum showed a characte-
ristic peak corresponding to the addition of one of the alkyl
substituent fragment at the thiol to the thione sulphur atom.
Table 1. Reaction conditions tested to produce 13
Starting
material
Reaction conditions
Yield 13 (%)
12
14
(1) PBr3 in CCl4; (2) 20 min; (3) HBr
(1) PBr3 in Et2O; (2) 3 days; (3) HBr
(1) LiBr, acetone; (2) 2 h reflux
(1) NaBr, acetone; (2) 3 h reflux
(1) LiBr, acetone; (2) 20 h reflux
11
9
45
0
The preparation of 1,3-dithiol derivatives of type 4
(Scheme 1) which contain the stereogenic centers located
further from the TTF moiety was achieved (Scheme 5) by
reaction of the zinc complex 7 with (S)-(C)-citronellyl
bromide (18) and 19—that was obtained reducing 18 with
Adam’s catalyst. The chiral 1,3-dithiol-2-thiones 20 and 21
were formed in high yields (80–90%), which are compar-
able to the ones obtained with achiral bromides for the same
refluxing times (see e.g., reaction of 1-bromodecane with 7,
in Table 2). The presence of a stereogenic atom two atoms
away from the electrophilic carbon atom (one atom further
away than in the synthesis of 15) did not affect the yield of
the reaction. Hence, the position of the stereogenic atom
with respect to the atom on which the reaction takes place is
important and can dramatically affect the yield of the
reaction, to the point that we were unable to prepare
the compound where the stereogenic center is adjacent to
the electrophilic sulphur atoms.
98
17
TsOC10H21
7, MeCN, ∆
SC10H21
S
S
S
SC10H21
16
7, MeCN, ∆
BrC10H21
Scheme 4.
Br
18
Table 2. Comparison of the reactions condition examined to form 15 and 16
Starting
material
Reaction conditions
Product
Isolated
yield (%)
PtO2, H2
94%
77%
Br
19
17
7, MeCN, reflux 3 h 16
7, MeCN, NaI, reflux 3 h 16
7, MeCN, reflux 3 h
(1) 7, MeCN, reflux 2h;
(2) NaI, reflux 1h
3
60
87
12
BrC10H21
14
16
15
7, MeCN, ∆
7, MeCN, reflux 20 h
7, MeCN, reflux 20 h
15
15
36
98
R
R
S
S
13
89%
S
S
S
7, MeCN, ∆
thione (15) than for the comparable achiral thione (16) in
order to have the same yield, because of the steric
impediment created by the stereogenic center close to the
electrophilic carbon atom. The thione 15 gave NMR and IR
spectra in accord with the proposed structure. No evidence
of the presence of diastereomers was observable. The laser
20
21
R = –CH=C(CH3)2
R = –CH2CH(CH3)2
Scheme 5.

E. Gomar-Nadal et al. / Tetrahedron 62 (2006) 3370–3379
3373
2.2. Synthesis and characterisation of chiral TTF
derivatives
R
R
S
S
S
S
CN
CN
S
S
S
S
S
O
Coupling of the appropriate 1,3-dithio-2-thiones (or -ones)
with trimethyl phosphite10 allowed the preparation of chiral
TTF derivatives of type 1 directly (Scheme 1). Thus, the
cross-coupling reaction of 15 and 4,5-bis(methoxycarbonyl)-
1,3-dithiol-2-one (22)22 gave the chiral bisester TTF 23 in
about 40% yield (Scheme 6), a good result considering that
the symmetrical TTF derivatives are also formed during the
reaction.10 The redox properties of this TTF are those to
be expected of a compound of this type with two strongly
electron withdrawing ester groups at one extreme of the
molecule. The first oxidation process—from neutral to
cation radical—takes place at 683 mV, while further
oxidation to the dication occurs at 1055 mV (in CH2Cl2,
0.1 M [NBu4][PF6], Pt-electrodes and a Ag/AgCl electrode
as reference). Treatment of the bisester 23 with an excess
of LiBr in HMPA at 80 8C produced monodecarboxy-
methylation and basic hydrolysis of the resulting monoester
24 led to the chiral acid functionalized TTF 25 (Scheme 6).
Monoester 24 exhibited oxidation waves at 635 and
1051 mV (conditions as for 23).
20 R = –CH=C(CH3)2
26
R = –CH2CH(CH3)2
21
P(OMe)3, ∆
R
R
S
S
S
S
CN
CN
S
S
S
S
R = –CH=C(CH3)2
R = –CH2CH(CH3)2
27
29
68%
56%
R
R
S
S
R
S
S
S
S
S
S
R
R = –CH=C(CH3)2
R = –CH2CH(CH3)2
28
30
6%
7%
OC12H25
S
S
H3CO2C
H3CO2C
S
S
S
S
15
S
O
22
+
OC12H25
Scheme 7.
38%
P(OMe)3, ∆
type of coupling reaction. Cyclic voltammetry of 27 and 29
gave oxidation waves at identical positions, 650 and
1015 mV (in CH2Cl2, 0.1 M [NBu4][PF6], Pt-electrodes
and a Ag/AgCl electrode as reference).
OC12H25
H3CO2C
S
S
S
S
23
24
OC12H25
S
S
H3CO2C
All the TTF derivative compounds were identified clearly
by laser desorption–ionization time-of-flight mass spectro-
metry, which shows the molecular ion peaks as the most
abundant species in positive mode, with the exception of the
carboxylic acid derivatives, which decarboxylate under the
mass spectrometric conditions. The NMR spectra are also
fully consistent with the structures of the compounds.
75%
LiBr, HMPA, H2O
OC12H25
H3CO2C
S
S
S
S
S
S
OC12H25
88%
LiOH·H2O, THF
The optical activity of the TTF compounds was studied
by circular dichroism (CD) spectroscopy, which provides
direct information on the chromophores present in the
molecule. It was not possible to use polarimetry to
compare the optical activity because the ratio of
absorption to rotation is too high. The CD spectra
of representative examples of the two families of
compounds, with the different stereogenic centers, are
shown in Figure 1. Compound 23 shows a weak negative
Cotton effect at 400 nm and a stronger positive one at
300 nm, below which the absorption becomes too strong
to reliably measure the spectrum. The spectra of 24 and
25 are practically superimposable on this one. The TTF
derivative 29 shows just one broad Cotton effect centerd
on 350 nm. The slightly weaker Cotton effect in this
compound compared with 23 is most likely due to the
slightly larger distance between the stereogenic centre
and the chromophore.
OC12H25
S
S
HO2C
S
S
S
S
25
OC12H25
Scheme 6.
In the same way as for the preparation of 23, coupling of oxo
compound 26 with either thione 20 or 21 leads to excellent
yields of the corresponding TTFs 27 and 29, respectively
(Scheme 7), in which the stereogenic centers are one carbon
further away from the p-electron rich core than in 23, and
here the propionitrile protecting groups are incorporated.
This group can be sequentially removed using base,17 and
thus 27 and 29 are useful building blocks for a variety of
structures, including chiral phthalocyanine TTF composite
molecules.22 The yield of 27 (68%) is notably high for this

3374
E. Gomar-Nadal et al. / Tetrahedron 62 (2006) 3370–3379
OC12H25
OC12H25
a non-polished stainless steel sample plate from CH2Cl2
solution.
H3CO2C
H3CO2C
S
S
S
S
S
S
0.4
0.2
0.0
23
29
Infrared spectra were recorded on a Perkin Elmer FT-IR
Spectrum One spectrometer. 1H and 13C NMR spectra were
obtained using a Bruker Avance 250 spectrometer
with deuterated solvent as lock and tetramethylsilane as
internal reference. Polarimetry was performed using a Dr.
KrenchenCElectronik Propol polarimeter in a 1 cm cell
(20 mg/ml using as a solvent CH2Cl2). Cyclic voltammo-
grams were recorded with the conventional three-electrode
configuration in dry CH2Cl2 containing 0.1 M [NBu4][PF6],
as a supporting electrolyte, with Pt-electrodes and a Ag/
AgCl electrode as a reference one.
C
N
S
S
S
S
S
S
S
NC
S
ε
350
400
Wavelength/nm
450
4.1.1. (S)-2-Dodecyloxypropanoic acid (10). To a solution
of (K)-methyl L-lactate (2.0 ml, 21 mmol) and 1-iododo-
decane (12.0 ml, 49 mmol) was added silver (I) oxide
(6.53 g, 28 mmol). The mixture was sonicated for 10 min
before refluxing for 24 h in the dark. The suspension was
filtered through Celite, washed with diethyl ether, and the
solvent was removed under vacuum. To the remaining oil
(which contained the ester and by-products such as starting
material, iodoalkane, alkanol, and alkyl ether) was added
MeOH (70 ml), H2O (30 ml) and LiOH$H2O (2.80 g,
67 mmol), and the mixture was stirred overnight at room
temperature. After this time, NaOH (aqueous, 75 ml, 3.5%)
was added and the organic products were extracted with
diethyl ether. The aqueous phase, which contains the salt of
the chiral acid, was acidified with HCl (aqueous, 2 N). The
product was extracted with CH2Cl2 (3!100 ml) and dried
over MgSO4, and the solvent evaporated. The colorless
residue was purified by flash chromatography using hexane–
Figure 1. Circular dicroism spectra of 23 and 29 in THF.
3. Conclusion
In the synthesis of this series of chiral TTF derivatives using
the routes described here the yield of the thione precursors
depends critically on the position of the chiral center in the
lateral chains. Steric interactions between the thiolate
groups in 2-thioxo-1,3-dithiole-4,5-dithiolate and the
incoming chiral electrophile mean that at least one
methylene unit is necessary between the sulphur atom and
the stereogenic center. Once formed, the TTFs show all the
characteristics of this family of compounds, but also optical
activity. This fact and their inherent chirality—which has
important consequences during organization of
p-functional molecules—makes them, and related com-
pounds, very interesting for preparing multifunctional
materials with new properties that arise from the chirality
of the molecular building blocks.
EtOAc [9/1] mixture as eluent to obtain 2.60 g (50%) of a
25
546
transparent
oil.
[a]
(CH2Cl2,
20 mg/ml):
K4.05 deg cm2 gK1. FT-IR (NaCl discs): 3300–2500 (w,
OH), 2925 (s), 2855 (s), 1723 (s, C]O), 1462 (w), 1421
(w), 1371 (w), 1287 (w), 1241 (w), 1130 (m, C–O–C), 1013
(w), 932 (w), 828 (w), 721 (w), 658 (w), 561 (w), 523 (w),
489 (w) cmK1. 1H NMR (250 MHz, CDCl3): 9.60 (br s, 1H,
–OH), 3.99 (q, JZ6.8 Hz, 1H, –CH(CH3)), 3.60 (dt, JZ8.8,
6.6 Hz, 1H, –OCH2), 3.43 (dt, JZ8.8, 6.6 Hz, 1H, –OCH2),
1.61 (m, JZ6.8 Hz, 2H, –OCH2CH2), 1.45 (d, JZ6.8 Hz,
3H, –CH(CH3)), 1.40–1.20 (m, 18H, –(CH2)9CH3), 0.89 (t,
JZ6.6 Hz, 3H, –(CH2)9CH3) ppm. 13C NMR (62.8 MHz,
CDCl3): 178.4 (C]O), 74.5 (–CH(CH3)), 70.6 (–OCH2),
31.9 (–O(CH2)9CH2), 29.6 (–OCH2CH2), 29.6, 29.5, 29.4
and 29.3 (–O(CH2)3(CH2)6), 26.0 (–O(CH2)2CH2), 22.7
(–CH2CH3), 18.3 (–CH(CH3)), 14.0 (–(CH2)11CH3) ppm.
4. Experimental
4.1. Materials and methods
Tetrabutylammonium bis(2-thioxo-1,3-dithiole-4,5-dithio-
late)zincate (7),13 4,5-bis(methoxycarbonyl)-1,3-dithiol-2-
one (22)23 and 4,5-bis(2-cyanoethylthio)-1,3-dithiol-2-one
(26)24 were synthesized using procedures reported in the
literature. All other chemicals were commercial products
and were used as obtained. Tetrahydrofuran (THF) and
diethyl ether were distilled over sodium/benzophenone,
acetone over K2CO3, and CH2Cl2 and MeCN over P2O5.
Thin-layer chromatography (TLC) was performed on
aluminium plates coated with Merck Silica gel 60 F254.
Developed plates were air-dried and scrutinized under a UV
lamp except for compounds 10 and 11 that were visualized
by putting the plate in an iodine chamber. Silica gel 60
(35–70 mesh, SDS) was used for column chromatography.
4.1.2. Methyl (S)-2-dodecyloxypropanoate (11). A solu-
tion of (S)-2-dodecyloxypropanoic acid (10, 722 mg,
2.952 mmol) and sulphuric acid (three drops, 95–98%) in
MeOH (45 ml) was refluxed for 5 h. After this time, the
mixture was cooled to room temperature and NaHCO3
(5 ml, saturated aqueous solution) was added. The MeOH
was evaporated and the aqueous phase was extracted with
CH2Cl2 (3!20 ml). The organic phase was washed with
(3!100 ml) and dried over MgSO4, and the solvent
evaporated. The remaining oil (763 mg) was purified by
flash chromatography using hexane–EtOAc [19/1] mixture
as eluent to obtain 687 mg (90%) of a slightly yellow
transparent oil. Anal. Calcd for C16H32O3: C 70.54, H 11.84;
Melting points were determined using a Melting Point
SMP10, BIBBY Stuart Scientific instrument and are
uncorrected. LDI-TOF-MS were obtained using a Kratos
Kompact Maldi 2 K-probe (Kratos Analytical) operating
with pulsed extraction of the ions in positive and linear high
power mode. The samples were deposited directly onto

E. Gomar-Nadal et al. / Tetrahedron 62 (2006) 3370–3379
3375
25
546
Found: C 70.05, H 11.98. [a]
(CH2Cl2, 20 mg/ml):
converted phospite esters. Dry HBr gas was bubbled
through the ether solution at a slow rate for about 15 min
at room temperature. The diethyl ether solution was
carefully washed with H2O, NaHCO3 (saturated aqueous
solution), H2O, dried over MgSO4 and the solvent
evaporated. The remaining oil (150 mg) was purified by
flash chromatography using hexane–CH2Cl2 [1/1.5] mixture
as eluent to obtain 28 mg (10%) of a slightly yellow
transparent oil.
K45.43 deg cm2 gK1. FT-IR (NaCl discs): 2987 (w), 2925
(s), 2855 (s), 1758 (s, C]O), 1740 (m, C]O), 1460 (w),
1371 (w), 1330 (w), 1273 (w), 1202 (m, C–O), 1148 (m,
C–O–C), 1075 (w), 982 (w), 843 (w), 754 (w), 722 (w), 656
(w) cmK1. 1H NMR (250 MHz, CDCl3): 4.00 (q, JZ6.8 Hz,
1H, –CH(CH3)), 3.74 (s, 3H, –CO2CH3), 3.54 (dt, JZ8.9,
4.4 Hz, 1H, –OCH2), 3.35 (dt, JZ8.9, 4.4 Hz, 1H, –OCH2),
1.59 (qi, JZ7.0 Hz, 2H, –OCH2CH2), 1.39 (d, JZ6.9 Hz,
3H, –CH(CH3)), 1.40–1.20 (m, 18H, –(CH2)9CH3), 0.88 (t,
JZ6.5 Hz, 3H, –(CH2)11CH3) ppm. 13C NMR (62.8 MHz,
CDCl3): 173.9 (C]O), 74.9 (–CH(CH3)), 70.5 (–OCH2),
51.7 (–CO2CH3), 31.9(–CH2CH2CH3), 29.7 (–OCH2CH2),
29.7, 29.6, 29.6, 29.6, 29.4 and 29.3 (–(CH2)6(CH2)2CH3),
26.0 (–(CH2)2CH2), 22.7 (–CH2CH3), 18.6 (–CH(CH3)),
14.1 (–O(CH2)9CH3) ppm.
Method B. A solution of (S)-2-dodecyloxypropyl toluene-4-
sulphonate (14, 358 mg, 1.098 mmol) and LiBr (2.3 g,
26 mmol) in acetone (10 ml) was refluxed overnight. The
acetone was removed and diethyl ether (30 ml) was added.
The diethyl ether solution was washed with H2O, dried over
MgSO4 and the solvent evaporated. The remaining oil
(358 mg) was purified as in Method A to give a yield of
94%. Anal. Calcd for C15H31BrO: C 58.62, H 10.17; Found:
4.1.3. (S)-2-Dodecyloxypropan-1-ol (12). To a suspension
ofLiAlH4 (39 mg, 1.03 mmol)indrydiethylether(15 ml)was
added drop-wise a solution of methyl (S)-2-dodecyloxy-
propanoate (11, 288 mg, 1.11 mmol) in dry diethyl ether
(15 ml) during15 min. The mixture was refluxed for 1 h. After
this, the solution was cooled to room temperature and then to
0 8C introducing it in an ice bath, and H2O was added drop-
wise to eliminate the remaining LiAlH4. The reaction product
was filtered from the white sludge, the filtrate was dried over
MgSO4 and the solvent evaporated leaving a slightly yellow
transparent oil (270 mg). The sludge in the filter funnel was
dissolved in sulphuric acid (aqueous, 20%) and the resulting
solution was extracted with diethyl ether. The organic phase
was dried over MgSO4 and the solvent evaporated. The
residual oil obtained from the sludge treatment (85 mg) was
combined with the first oil and they were purified by flash
chromatography using hexane–EtOAc [3/1] mixture as eluent
to obtain 240 mg (94%) of a slightly yellow transparent oil.
25
C
59.08, H, 10.36. [a]
(CH2Cl2, 20 mg/ml):
546
C4.09 deg cm2 gK1. FT-IR (NaCl discs): 2925 (s), 2854
(s), 1466 (w), 1376 (w), 1326 (w), 1229 (w), 1196 (w), 1140
(w), 1099 (m, C–O–C), 920 (w), 722 (w), 671 (w) cmK1. 1H
NMR (250 MHz, CDCl3): 3.64 (sxd, JZ6.1, 1.2 Hz, 1H,
–CH(CH3)), 3.50 (t, JZ6.5 Hz, 2H, –OCH2), 3.41 (dd, JZ
23.3, 10.2 Hz, 1H, –CH2Br), 3.39 (dd, JZ23.3, 10.2 Hz,
1H, –CH2Br), 1.70–1.20 (m, 23H, –CH(CH3)OCH2(CH2)10-
CH3), 0.91 (t, JZ6.7 Hz, 3H, –O(CH2)11CH3) ppm. 13C
NMR (62.8 MHz, CDCl3): 76.6 (–CH(CH3)),
69.5 (–OCH2(CH2)10), 36.5 (–CH2Br), 32.0 (–CH2CH2-
CH3), 30.0 (–OCH2CH2), 29.7, 29.6, 29.5 and 29.4
(–(CH2)6(CH2)2CH3), 26.2 (–O(CH2)2CH2), 22.7
(–CH2CH3), 19.0 (–CH(CH3)), 14.1 (–O(CH2)11CH3) ppm.
4.1.5. (S)-2-Dodecyloxypropyl toluene-4-sulphonate (14).
(S)-2-Dodecyloxypropan-1-ol (12, 195 mg, 0.853 mmol) is
dissolved in CH2Cl2 (25 ml) and cooled in an ice bath
(0 8C). NEt3 (0.130 ml, 0.938 mmol) and dimethylamino-
pyridine (DMAP, two small crystals) were then added,
followed by the addition of toluene–p-sulphonyl chloride
(TsCl, 179 mg, 0.938 mmol) in small portions with constant
stirring. The resulting solution was stirred overnight. Ice
(25 g), HCl (aqueous 10%, 5 ml) and H2O (36 ml) are added
and the mixture was stirred until the ice was melted. The
organic layer was washed with H2O (3!50 ml), dried over
MgSO4 and the solvent was evaporated. The remaining oil
was purified by flash chromatography using hexane–CH2Cl2
[1/3] mixture as eluent to obtain 267 mg (84%) of a slightly
yellow transparent oil. FT-IR (NaCl discs): 2925 (s), 2855
(s), 1919 (w), 1754 (w), 1599 (w), 1496 (w), 1457 (m), 1367
(s, –SO2–), 1307 (w), 1292 (w), 1210 (w), 1188 (s, –SO2–),
1178 (s, –SO2–), 1098 (m, C–O–C), 1020 (w), 988 (m), 820
(m), 814 (m), 792 (w), 722 (w), 706 (w), 688 (w), 667 (m),
575 (w), 555 (m) cmK1. 1H NMR (250 MHz, CDCl3): 7.81
(d, JZ8.4 Hz, 2H, CH3CCHarCHarC–), 7.35 (d, JZ8.4 Hz,
2H, CH3CCHarCHarC–), 3.97 (dd, JZ7.68, 3.28 Hz, 1H,
–CH2OTs), 3.93 (dd, JZ7.68, 3.28 Hz, 1H, –CH2OTs), 3.62
(sx, 1H, JZ6.2 Hz, –CH(CH3)), 3.43 (dt, JZ8.8, 6.6 Hz,
1H, –OCH2), 3.35 (dt, JZ8.8, 6.6 Hz, 1H, –OCH2), 2.46 (s,
3H, CH3CCHarCHarC–), 1.50–1.20 (m, 18H, –(CH2)9CH3),
1.12 (d, JZ6.2 Hz, 3H, –CH(CH3)), 0.89 (t, JZ6.4 Hz, 3H,
–O(CH2)11CH3) ppm. 13C NMR (62.8 MHz, CDCl3): 144.7
(CH3CCHarCHarC–), 133.4 (CH3CCHarCHarC–), 129.7
(CH3CCHarCHarC–), 127.9 (CH3CCHarCHarC–), 72.8
Anal. Calcd for C15H32O2$1/4H2O: C 72.38, H 13.16; Found:
25
546
C
72.43,
H
13.29. [a]
(CH2Cl2, 20 mg/ml):
C27.12 deg cm2 gK1. FT-IR (NaCl discs): 3700–3200 (w,
wide, OH), 2925 (s), 2855 (s), 1465 (w), 1374 (w), 1343 (w),
1147 (w), 1096 (m, C–O–C), 1048 (m), 989 (w), 915 (w), 834
(w), 721 (w) cmK1. 1H NMR (250 MHz, CDCl3): 3.65–3.35
(m, 5H, –CH2CH(CH3)OCH2), 2.38 (br s, 1H, –OH), 1.58 (m,
JZ6.9 Hz, 2H, –OCH2CH2), 1.45–1.20 (m, 18H,
–(CH2)9CH3), 1.40 (d, JZ6.1 Hz, 3H, –CH(CH3)O), 0.88 (t,
JZ6.6 Hz, 3H, –O(CH2)11CH3) ppm. 13C NMR (62.8 MHz,
CDCl3): 75.8 (–CH(CH3)), 68.9 (–CH2OH), 66.3 (–OCH2),
31.9 (–CH2CH2CH3), 30.1 (–OCH2CH2), 29.7, 29.60, 29.5,
29.4 and 29.3 (–O(CH2)3(CH2)6), 26.2 (–O(CH2)2CH2), 22.7
(–CH2CH3), 15.9 (–CH(CH3)), 14.1 (–(CH2)11CH3) ppm.
4.1.4. 1-((S)-2-Bromo-1-methyl-etoxy)-dodecane (13).
Method A. To a solution of (S)-2-dodecyloxy-propan-1-ol
(12, 221 mg, 0.967 mmol) in diethyl ether (5 ml) at 0 8C
under argon atmosphere was added drop-wise a solution of
PBr3 (0.100 ml, 1.064 mmol) in diethyl ether (5 ml) for 1 h.
The reaction was then stirred for 2 days. The excess PBr3
was destroyed with water, and the organic layer was
separated, washed successively with equal volumes of H2O,
orthophosphoric acid (aqueous 85%), and NaHCO3 (satu-
rated aqueous solution) and twice with H2O, and was dried
over MgSO4. The infrared spectrum of the residue obtained
after evaporating the solvent showed the peaks at 1250,
950–1000, and 2400 cmK1 characteristic of partially

3376
E. Gomar-Nadal et al. / Tetrahedron 62 (2006) 3370–3379
(–CH(CH3)), 72.7 (–CH2CH(CH3)), 69.6 (–OCH2CH2),
31.9 (–CH2CH2CH3), 29.9 (–OCH2CH2), 29.6, 29.6, 29.4
and 29.3 (–(CH2)6(CH2)2CH3), 26.0 (–O(CH2)2CH2), 22.6
(–CH2CH3), 21.6 (CH3CCHarCHarC–), 16.8 (–CH(CH3)),
14.1 (–(CH2)11CH3) ppm.
7.1 mmol) and [Zn(dmit)2][NBu4]2 (7, 1.6 g, 1.7 mmol) in
MeCN (30 ml) under nitrogen was refluxed for 4 h. After
this time, MeCN was added and the resulting solution was
extracted with hexane. The hexane phases were combined
and washed with MeCN, H2O and dried over MgSO4. The
remaining oil was purified by flash chromatography using
hexane–CH2Cl2 [3/1] mixture as eluent to obtain 1.5 g
(89%) of a yellow oil. LDI-TOF m/z (%): 614.3 (Adduct
4.1.6. 4,5-Bis((S)-2-dodecyloxypropanyl)-1,3-dithiol-2-
thione (15). A solution of the alkyl derivative (13 or 14
see Table 2 and text, 4.1 mmol) and [Zn(dmit)2][NBu4]2 (7,
1 mmol) in MeCN (5 ml for 100 mg of alkyl derivative) was
refluxed under nitrogen overnight. MeCN was added and the
resulting solution was extracted with hexane. The hexane
phases were combined and washed with MeCN, H2O and
dried over MgSO4, and the solvent was evaporated. The
remaining oil was purified by flash chromatography using
hexane–CH2Cl2 [1/2] mixture as eluent to obtain the
product as a yellow oil (yield of 36 and 88% starting from
13 and 14, respectively). LDI-TOF m/z (%): 877.7 (Adduct
[CycleZS–CH2CH(CH3)OC12H25]C, 100). Anal. Calcd for
[CycleS–R*]C, 100). Anal. Calcd for C23H38S5 C 58.17, H
25
8.07; Found: C 58.41, H 7.98. [a] (CH2Cl2, 20 mg/ml):
546
49.1 deg cm2 gK1. FT-IR (NaCl discs): 2962 (s), 2921 (s),
2853 (m), 1455 (m), 1378 (w), 1277 (w), 1069 (s, C]S),
886 (w), 515 (w) cmK1. 1H NMR (250 MHz, CDCl3): 5.08
(tsp, JZ7.03, 1.34 Hz, 2H, –CH]C(CH3)2), 2.88 (m, 4H,
–SCH2–), 1.96 (m, 4H, –CH2CH]C(CH3)2), 1.88–1.10 (m,
10H, –SCH2CH2CH(CH3)CH2–), 1.66 (d, JZ10.12 Hz,
12H, –CH]C(CH3)2), 0.91 (d, JZ6.35 Hz, 6H, –CH2-
CH(CH3)CH2–) ppm. 13C NMR (62.8 MHz, CDCl3): 211.6
(C]S), 136.2 (C]C), 131.4 (–CH]C(CH3)2), 124.3
(–CH]C(CH3)2), 36.7 (–S(CH2)2CH(CH3)CH2–), 36.6
(–SCH2CH2), 34.7 (–S(CH2)2CH(CH3)–), 31.7 (–SCH2–),
25.7 (–CH]C(CH3)trans(CH3)cis), 19.1 (–S(CH2)2-
CH(CH3)–), 17.65 (–CH]C(CH3)trans(CH3)cis) ppm.
C33H62O2S5: C 60.87, H 9.60; Found: C 61.39, H 9.86.
25
546
[a]
(CH2Cl2, 20 mg/ml):C36.6 deg cm2 gK1. FT-IR
(NaCl discs): 2925 (s), 2854 (s), 1464 (w), 1373 (w), 1328
(w), 1136 (w), 1070 (s, C]S), 829 (w), 721 (w), 515
(w) cmK1 1H NMR (250 MHz, CDCl3): 3.61 (sp, JZ
.
6.2 Hz, 2H, –CH(CH3)), 3.46 (dt, JZ8.8, 6.6 Hz, 2H,
–OCH2), 3.42 (dt, JZ8.8, 6.6 Hz, 2H, –OCH2), 3.05 (dd,
JZ15.6, 13.2 Hz, 2H, –SCH2), 2.93 (dd, JZ15.6, 13.2 Hz,
2H, –SCH2), 1.57 (c, JZ6.4 Hz, 4H, –CH2(CH2)7CH3),
1.40–1.20 (m, 42H, –CH(CH3)O(CH2)2(CH2)9CH3), 0.90 (t,
JZ6.4 Hz, 6H, –O(CH2)11CH3) ppm. 13C NMR (62.8 MHz,
CDCl3): 211.1 (C]S), 136.5 (C]C), 74.4 (–CH(CH3)-
OC12H25), 69.4 (–OCH2(CH2)10CH3), 42.7 (–CH2-
CH(CH3)OC12H25), 31.9 (–O(CH2)9CH2CH2CH3), 30.0
(–OCH2CH2(CH2)10), 29.7, 29.7, 29.5 and 29.4
(–O(CH2)3(CH2)6(CH2)2CH3), 26.2 (–O(CH2)2CH2(CH2)8-
CH3), 22.7 (–O(CH2)10CH2CH3), 19.3 (–CH(CH3)OC12-
H25), 14.1 (–O(CH2)11CH3) ppm.
4.1.9. 4,5-Bis((S)-3,7-dimethyloctylthio)-1,3-dithiole-2-
thione (21). A solution of the (S)-1-bromo-3,7-dimethyl-
octane (19, 2.1 g, 9.4 mmol) and [Zn(dmit)2][NBu4]2 (7,
2.20 g, 2.3 mmol) in MeCN (30 ml) under nitrogen was
refluxed for 3 h. After this time, MeCN was added and the
resulting solution was extracted with hexane. The hexane
phases were combined and washed with MeCN, H2O and
dried over MgSO4. The remaining oil was purified by flash
chromatography using hexane–CH2Cl2 [4/1] mixture as
eluent to obtain 1.7 g (77%) of a yellow oil. Anal. Calcd for
C23H42S5 C 57.68, H. 8.84; Found: C 57.75, H 8.63. LDI-
TOF m/z (%): 620.4 (Adduct [CycleS–R*]C, 100). [a]
25
546
(CH2Cl2, 20 mg/ml): 40.5 deg cm2 gK1. FT-IR (NaCl
discs): 2955 (s), 2926 (s), 2868 (m), 1463 (m), 1283 (w),
1070 (s, C]S), 919 (w), 881 (w), 815 (w), 715 (w), 623 (w),
4.1.7. (S)-1-Bromo-3,7-dimethyloctane (19). To a solution
of (S)-8-bromo-2,6-dimethyloct-2-ene ((S)-(C)-citronellyl
bromide, 18, 2 ml, 10 mmol) in EtOAc (15 ml) was added
Adam’s PtO2 catalyst (40 mg, 0.176 mmol). H2 gas was
bubbled through the solution slowly for about 30 min and
the reaction was left under H2 atmosphere overnight. The
suspension was filtered through Celite, washed with diethyl
ether, and the solvent was removed under vacuum, leaving
2.1 g (94%) of a colourless transparent oil. FT-IR (NaCl
discs): 2956 (s), 2928 (s), 2869 (m), 1465 (m), 1382 (w),
1366 (w), 1261 (w), 1217 (w), 1170 (w), 1011 (w), 933 (w),
575 (w), 516 (w), 470 (w) cmK1 1H NMR (250 MHz,
.
CDCl3): 2.87 (m, 4H, –SCH2–), 1.70–1.40 (m, 8H,
–SCH2CH2CH(CH3)(CH2)3CH(CH3)2), 1.30–1.00 (m,
12H, –CH2CH2CH2CH(CH3)2), 0.88 (d, 6H, JZ6.52 Hz,
–S(CH2)2CH(CH3)–), 0.85 (d, 12H, JZ6.68 Hz,
–CH(CH3)2) ppm. 13C NMR (62.8 MHz, CDCl3): 211.7
(C]S), 136.2 (C]C), 39.1 (–SCH2–), 36.7 (–CH2(CH2)2-
CH(CH3)2), 34.7 (–SCH2CH2–), 32.1 (–S(CH2)2CH(CH3)–),
27.9 (–CH(CH3)2), 24.6 (–CH2CH2CH(CH3)2), 22.7 and 22.6
(–CH(CH3)2), 19.20 (–S(CH2)2CH(CH3)–) ppm.
649 (w), 568 (w), 488 (w) cmK1 1H NMR (250 MHz,
.
CDCl3): 3.47 (m, 2H, –CH2Br), 1.87 (m, 1H, –CH(CH3)),
1.75–1.42 (m, 3H, –CH(CH3)CH2CH2Br), 1.35–1.15 (m,
6H, –(CH2)3CH(CH3)2), 0.88 (d, 3H, JZ6.35 Hz,
–CH(CH3)), 0.86 (d, 6H, 6.52 Hz, –CH(CH3)2) ppm. 13C
NMR (62.8 MHz, CDCl3): 40.14 (–CH2CH(CH3)2), 39.21
(–CH2CH2Br), 36.75 (–CH2CH(CH3)(CH2)2Br), 32.13
4.1.10. 2,3-Bis((S)-2-dodecyloxy-propanylthio)-6,7-bis-
(methoxycarbonyl)tetrathiafulvalene (23). A solution of
4,5-bis(methoxycarbonyl)-1,3-dithiol-2-one22 (22, 163 mg,
0.295 mmol) and 4,5-bis((S)-2-dodecyloxy-propanyl)-1,3-
dithiol-2-thione (15, 90 mg, 0.384 mmol) in freshly distilled
trimethyl phosphite (4 ml) was brought to reflux for 3 h under
an Ar atmosphere. The solvent is evaporated and the residual
oil was purified by flash chromatography using hexane–
CH2Cl2 [1/2] mixture as eluent to obtain 89 mg (38%) of 23
as a red oil. The symmetrical chiral TTF (18 mg, 8%) was
also obtained as a side product of the reaction. Compound 23:
Anal. Calcd for C40H68O6S6 C 57.37, H. 8.19; Found: C
56.96, H 8.43. LDI-TOF m/z (%): 836.2 (MC, 100) ppm.
(–CH(CH3)(CH2)2Br),
31.70
(–CH2Br),
27.98
(–CH(CH3)2), 24.58 (–CH2CH2CH(CH3)2), 22.70 and
22.60 (–CH(CH3)2) 18.99 (–CH(CH3)(CH2)2Br) ppm.
4.1.8.
4,5-Bis((S)-3,7-dimethyloct-6-enylthio)-1,3-
dithiole-2-thione (20). A solution of the (S)-8-bromo-2,6-
dimethyloct-2-ene ((S)-(C)-citronellyl bromide, 18, 1.4 ml,

E. Gomar-Nadal et al. / Tetrahedron 62 (2006) 3370–3379
3377
FT-IR (NaCl disk): 2924 (w), 2853 (m), 1733 (m, C]O),
1579 (w), 1434 (w), 1375 (w), 1255 (m, C–O), 1135 (w),
4.1.12. 2,3-Bis((S)-2-dodecyloxy-propanylthio)-6-(car-
boxy)tetrathiafulvalene (25). LiOH$H2O (500 mg,
12 mmol) in 5 ml H2O was added drop-wise to a stirred
solution of 2,3-bis((S)-2-dodecyloxy-propanyl)-6-methoxy-
carbonyltetrathiafulvalene (24, 617 mg, 0.792 mmol) in
THF (50 ml). After stirring for 12 h, the mixture was
diluted with ether (25 ml) and hydrochloric acid (0.5 M,
10 ml) was added. The dark organic phase was dried
(MgSO4) and the evaporation of the solvent gave 543 mg
(88%) of purple oily solid. Anal. Calcd for C37H64O4S6 C
58.07, H 8.43; Found: C 57.77, H 8.21. LDI-TOF m/z (%):
764.4 ([M]C, 40) and 720.3 ([MKCO2H]C, 100). FT-IR
(KBr): 2924 (s), 2854 (s), 1712 (m, C]O free), 1682 (m,
C]O bound), 1564 (m), 1531 (m), 1455 (m), 1417 (m),
1373 (m), 1289 (m), 1199 (w), 1135 (m), 1094 (m), 891 (w),
1
1091 (w, C–O–C), 1027 (w), 765 (w), 470 (w) cmK1. H
NMR (250 MHz, CDCl3): 3.86 (s, 6H, –CO2CH3), 3.57 (sx,
JZ6.1 Hz, 2H, –CH(CH3)), 3.50 (dt, 2H, –OCH2), 3.44 (dt,
2H, –OCH2), 3.03 (dd, JZ13.2, 6.0 Hz, 2H, –SCH2), 2.83
(dd, JZ13.2, 6.0 Hz, 2H, –SCH2), 1.57 (qi, JZ6.5 Hz, 4H,
–OCH2CH2), 1.40–1.20 (m, 42H, –CH(CH3)O(CH2)2
(CH2)9), 0.90 (t, JZ6.6 Hz, 6H, –CH2CH3) ppm. 13C NMR
(62.8 MHz, CDCl3): 159.9 (–CO2CH3), 132.0 and 128.10
(lateral C]C), 112.5 and 108.2 (central C]C), 74.6
(–CH(CH3)), 69.3 (–OCH2), 53.3 (–CO2CH3), 42.2
(–SCH2), 31.9 (–CH2CH2CH3), 30.1 (–OCH2CH2), 29.7,
29.7, 29.5 and 29.7 (–O(CH2)3(CH2)6(CH2)2CH3), 26.2
(–O(CH2)2CH2), 22.7 (–CH2CH3), 19.3 (–CH(CH3)), 14.1
(–CH2CH3). E1/2(0/%C)Z683 mV and E1/2(%C/2C)Z
1055 mV. Symmetrical chiral TTF: LDI-TOF m/z (%):
1236.7 (MC, 100). FT-IR (NaCl discs): 2924 (s), 2854 (s),
1455 (w), 1373 (w), 1136 (w), 1099 (w), 805 (w) cmK1. 1H
NMR (250 MHz, CDCl3): 3.58 (sx, JZ6.0 Hz, 4H,
–CH(CH3)), 3.51 (dt, 4H, –OCH2), 3.50 (dt, 4H, –OCH2),
3.04 (dd, JZ13.1, 7.0 Hz, 4H, –SCH2), 2.84 (dd, JZ13.1,
7.0 Hz, 4H, –SCH2), 1.57 (qi, 8H, –OCH2CH2), 1.40–1.20
(m, 84H, –CH(CH3)O(CH2)2(CH2)9), 0.90 (t, JZ6.7 Hz,
12H, –CH2CH3) ppm.
775 (w), 729 (m), 662 (d), 496 (d) cmK1 1H NMR
.
(250 MHz, CDCl3): 7.48 (br s, 1H, C]CH), 4.8 (br s,
–OH), 3.60 (m, 2H, –CH(CH3)), 3.49 (m, 4H, –OCH2), 3.60
(dd, JZ12.9, 7.0 Hz, 2H, –SCH2), 2.85 (m, 2H, –SCH2),
1.58 (m, 4H, –OCH2CH2) 1.40–1.20 (m, 19H, –CH(CH3)-
OCH2(CH2)10), 0.91 (t, JZ6.5 Hz, 3H, –CH2CH3) ppm. 13
C
NMR (62.8 MHz, CDCl3): 163.2 (C]O), 134.4, 128.5,
130.0 and 127.5 (lateral C]C), 112.1 and 110.3 (central
C]C), 74.7 (–CH(CH3)), 69.4 (–OCH2), 42.0 (–SCH2),
32.0, 30.1, 29.7, 29.6 and 29.4 (–O(CH2)3(CH2)6(CH2)2-
CH3), 26.2 (–O(CH2)2CH2), 22.7 (–CH2CH3), 19.4
(–CH(CH3)), 14.1 (–CH2CH3) ppm. E1/2(0/%C)Z586 mV
and E1/2(%C/2C)Z1050 mV.
4.1.11. 2,3-Bis((S)-2-dodecyloxy-propanylthio)-6-meth-
oxycarbonyltetrathiafulvalene (24). A solution of 2,3-
bis((S)-2-dodecyloxy-propanylthio)-6,7-bis(methoxycar-
bonyl)tetrathiafulvalene (23, 194 mg, 0.262 mmol) and
LiBr (289 mg, 3.327 mmol) in HMPA (3 ml) with a drop
of H2O was heated to 80 8C, causing evolution of gas
(CH3Br). When no more gas was evolved, the mixture was
cooled to room temperature, H2O (10 ml) was added and the
aqueous phase was extracted successively with hexane until
the organic phase was colorless. The combined organic
fractions were washed with H2O and were dried over
MgSO4, filtered, and evaporated to dryness, leaving an
orange oil, which was purified by column chromatography
on alumina using as eluent hexane–CH2Cl2 [1/1] mixture
obtaining 134 mg (75%) of an orange oil. Anal. Calcd for
C38H66O4S6 C 58.56, H. 8.54; Found: C 58.17, H 8.73. LDI-
TOF m/z (%): 778.4 (MC, 100). FT-IR (NaCl disk): 2925
(s), 2854 (s), 1716 (m, C]O), 1566 (w), 1538 (w), 1456
(w), 1374 (w), 1327 (w), 1284 (m, C–O), 1251 (m, C–O),
1199 (w), 1095 (m, C–O–C), 1060 (w, C–O–O), 890 (w),
761 (w), 727 (w) cmK1. 1H NMR (250 MHz, CDCl3): 7.38
(s, 1H, C]CH), 3.84 (s, 3H, –CO2CH3), 3.58 (sx, JZ
6.0 Hz, 1H, –CH(CH3)), 3.57 (sx, JZ6.0 Hz, 1H,
–CH(CH3)), 3.51–3.44 (m, 4H, –OCH2), 3.04 (dd, JZ
13.2, 6.0 Hz, 2H, –SCH2), 2.85 (dd, JZ13.2, 7.1 Hz, 1H,
–SCH2), 2.83 (dd, JZ13.2, 7.1 Hz, 1H, –SCH2), 1.58 (qi,
JZ7.0 Hz, 4H, –OCH2CH2) 1.40–1.20 (m, 42H,
–CH(CH3)OCH2CH2(CH2)9), 0.91 (t, JZ6.6 Hz, 6H,
–CH2CH3) ppm. 13C NMR (62.8 MHz, CDCl3): 159.77
(C]O), 131.8, 128.4, 128.2 and 127.6 (lateral C]C), 112.6
and 109.7 (central C]C), 74.6 (–CH(CH3)), 69.3 (–OCH2),
52.7 (–CO2CH3), 42.1 (–SCH2), 32.0, 30.4, 30.1, 30.1, 29.9,
29.7, 29.7, 29.6 and 29.4 (–O(CH2)3(CH2)6(CH2)2CH3),
26.3 (–O(CH2)2CH2), 22.7 (–CH2CH3), 19.4 (–CH(CH3)),
14.1 (–CH2CH3) ppm. E1/2(0/%C)Z593 mV and E1/2
(%C/2C)Z998 mV.
4.1.13.
2,3-Bis(2-cyanoethylthio)-6,7-bis((S)-3,7-
dimethyloct-6-enylthio)tetrathiafulvalene (27).
A
solution of 4,5-bis(2-cyanoethylthio)-1,3-dithiol-2-one24
(26, 125 mg, 0.441 mmol) and 4,5-bis((S)-3,7-dimethyloct-
6-enylthio)-1,3-dithiole-2-thione (20, 190 mg, 0.400 mmol)
in freshly distilled trimethyl phosphite (4 ml) was brought to
reflux for 7 h under an Ar atmosphere. Evaporation of
solvent and purification of the residual oil by flash
chromatography using hexane–CH2Cl2 [1/4] mixture as
eluent gave 197 mg (68%) of 27 as an orange solid. The
symmetrical chiral TTF 28 (18 mg, 6%) was also obtained as
a side product of the reaction as an oily material. Compound
27: mp: 64–65 8C. Anal. Calcd for C32H46N2S8 C 53.74, H.
6.48; Found: C 53.48, H 6.64. LDI-TOF m/z (%): 714.1
([M]C, 100). FT-IR (KBr): 2956 (s), 2923 (s), 2851 (s), 2249
(w, CN), 1473 (m), 1416 (m), 1379 (m), 1294 (w), 1264
(w), 1232 (w), 1127 (w), 891 (w), 800 (w), 771 (w), 728
(w) cmK1. H NMR (250 MHz, CDCl3): 5.08 (tt, 2H, JZ
1
7.02, 1.30 Hz, –CH]C(CH3)2), 3.08 (t, 4H, JZ7.35 Hz,
–CH2CH2CN), 2.82 (m, 4H, –SCH2CH2CH(CH3)–), 2.73 (t,
4H, JZ7.35 Hz, –CH2CH2CN), 1.96 (sx, 4H, JZ7.02 Hz,
(–CH2CH]CCH3)2), 1.70–1.00 (m, 10H, –SCH2CH2-
CH(CH3)CH2–), 1.65 (d, 12H, JZ11.25 Hz, –C(CH3)2),
0.90 (d, 6H, JZ6.35 Hz, –S(CH2)2CH(CH3)–) ppm. 13C
NMR (62.8 MHz, CDCl3): 131.6 (C]C(CH3)2), 128.3,
128.1 (outer TTF C]C), 124.9 (C]C(CH3)2), 117.9 (CN),
114.6, 107.1 (central TTF C]C), 37.1, 37.0 (–SCH2–), 34.5
(–SCH2CH2–), 32.0 (–CH2CH(CH3)CH2–), 31.6 (–CH2
CH2CHC(CH3)2), 26.1 (–CH(CH3)), 25.8 (CH2CHC
(CH3)2), 19.6 (CH2CN), 19.3, 18.1 (C(CH3)2) ppm.
E1/2(0/%C)Z650 mV and E1/2(%C/2C)Z1015 mV. Com-
pound 28: Anal. Calcd for C46H76S8 C 62.38, H. 8.65;
Found: C 62.43, H 8.50. LDI-TOF m/z (%): 884.4 ([M]C,
100). FT-IR (KBr): 2956 (m), 2923 (s), 2853 (m), 1455 (w),

3378
E. Gomar-Nadal et al. / Tetrahedron 62 (2006) 3370–3379
1377 (w), 1221 (w), 1073 (w), 825 (w), 772 (w) cmK1. H
NMR (250 MHz, CDCl3): 5.08 (tt, 4H, JZ7.18, 1.50 Hz,
–CH]C(CH3)2), 2.82 (m, 8H, –SCH2CH2CH(CH3)–),
1.97 (m, 8H, (–CH2CH]CCH3)2), 1.80–1.00 (m,
20H, –SCH2CH2CH(CH3)CH2–), 1.64 (d, 24H, JZ
19.75 Hz, –C(CH3)2), 0.90 (d, 12H, JZ6.35 Hz, –S(CH2)2-
CH(CH3)–) ppm. 13C NMR (62.8 MHz, CDCl3): 131.6
(C]C(CH3)2), 128.3 (outer TTF C]C), 124.9
(C]C(CH3)2), 109.4 (central TTF C]C), 37.1 (–SCH2–),
34.4 (–SCH2CH2–), 32.0 (–CH2CH(CH3)CH2–), 31.7
(–CH2CH2CHC(CH3)2), 26.1 (–CH(CH3)), 25.8 (CH2-
CHC(CH3)2), 19.4, 18.1 (C(CH3)2) ppm. E1/2(0/%C)Z
510 mV and E1/2(%C/2C)Z978 mV.
Ciencia y Tecnologıa (Spain), under the project BQU2003-
00760, DGR, Catalonia (Project 2005SGR00591), and the
European Integrated Project project NAIMO (NMP4-CT-
2004-500355). E.G.-N. is grateful to the Generalitat de
Catalunya for a predoctoral grant.
1
´
References and notes
1. (a) Decurtins, S.; Schmalle, H. W.; Schneuwly, P.; Ensling, J.;
Gu¨tlich, P. J. Am. Chem. Soc. 1994, 116, 9521–9528. (b)
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4.1.14.
2,3-Bis(2-cyanoethylthio)-6,7-bis((S)-3,7-
dimethyloctylthio)tetrathiafulvalene (29). A solution of
4,5-bis(2-cyanoethylthio)-1,3-dithiol-2-one24 (26, 858 mg,
3.03 mmol) and 4,5-bis((S)-3,7-dimethyloctylthio)-1,3-
dithiole-2-thione (21, 1.44 g, 3.03 mmol) in freshly distilled
trimethyl phosphite (10 ml) was brought to reflux for 4 h
under an atmosphere of argon. After this time, the solvent
was evaporated and the residual oil was purified by flash
chromatography using CH2Cl2 as eluent to obtain 1.20 g
(56%) of 29 as an orange solid. The symmetrical chiral TTF
30 (151 mg, 7%) was also obtained as a side product of the
reaction. Compound 29: mp: 76–77 8C. Anal. Calcd for
C32H50N2S8 C 53.43, H. 7.01; Found: C 53.35, H 6.99. LDI-
TOF m/z (%): 718.2 ([M]C, 100). FT-IR (KBr): 2956 (s),
2923 (s), 2851 (m), 2249 (w, CN), 1473 (m), 1416 (m), 1380
(m), 1293 (w), 1264 (w), 1232 (w), 1126 (w), 891 (w),
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¨
Fanghanel, E. Sulfur Reports 2003, 24, 1–190. (e) TTF
Chemistry: Fundamentals and Applications of Tetrathiafulva-
lene; Yamada, J.-I., Sugimoto, T., Eds.; Springer: Berlin,
2004. (f) Gorgues, A. J. Phys. IV 2004, 114, 405–410. (g)
Chem. Rev. 2004, 104. Special issue “Molecular Conductors”
no. 11. (h) Herranz, M. A.; Sanchez, L.; Martin, N.
Phosphorus, Sulfur Silicon Relat. Elem. 2005, 180,
1133–1148. (i) Sarhan, A.W.-W.A.O. Tetrahedron 2005, 61,
3889–3932.
800 (w), 770 (w), 728 (w) cmK1 1H NMR (250 MHz,
.
CDCl3): 3.06 (t, 4H, JZ7.06 Hz, –CH2CH2CN), 2.82
(m, 4H, –SCH2CH2CH(CH3)–), 2.72 (t, 4H, JZ7.06 Hz,
–CH2CN), 1.70–1.35 (m, 8H, –CH2CH(CH3)(CH2)3-
CH(CH3)2), 1.30–1.05 (m, 12H, –(CH2)3CH(CH3)2), 0.87
(d, 6H, JZ5.58 Hz, –CH2CH(CH3)CH2–), 0.84 (d, 12H,
JZ6.70 Hz, –CH(CH3)2) ppm. 13C NMR (62.8 MHz,
CDCl3): 128.5, 128.2 (outer C]C), 117.9 (CN),
114.9, 107.0 (central C]C), 39.1, 37.3 (–SCH2–),
34.7 (–SCH2CH2–), 32.5 (–CH2CH(CH3)CH2–), 31.7
(–CH2(CH2)2CH(CH3)2), 28.4 (–CH(CH3)2), 25.1 (–CH2-
CH2CH(CH3)2), 23.2 (–CH2CH(CH3)2), 23.1 (–CH(CH3)),
19.8 (CH2CN) and 19.4 (CH(CH3)2) ppm. E1/2(0/%C)Z
650 mV and E1/2(%C/2C)Z1015 mV. Compound 30:
Anal. Calcd for C46H84S8 C 61.82, H. 9.47; Found: C
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Beverly, K.; Sampaio, J.; Raymo, F.; Stoddart, J. F.; Heath,
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1
62.08, H 9.18. LDI-TOF m/z (%): 892.4 ([M]C, 100). H
NMR (250 MHz, CDCl3): 2.81 (m, 8H, –SCH2CH2-
CH(CH3)–), 1.70–1.35 (m, 16H, –CH2CH(CH3)(CH2)3-
CH(CH3)2), 1.30–1.05 (m, 24H, –(CH2)3CH(CH3)2), 0.88
(d, 12H, JZ5.03 Hz, –CH2CH(CH3)CH2–), 0.86 (d, 24H,
JZ6.68 Hz, –CH(CH3)2) ppm. 13C NMR (62.8 MHz,
CDCl3): 128.3 (outer C]C), 109.4 (central C]C) 38.9,
(–SCH2–), 34.6 (–SCH2CH2–), 32.5 (–CH2CH(CH3)CH2–),
31.8 (–CH2(CH2)2CH(CH3)2), 28.3 (–CH(CH3)2), 25.1
(–CH2CH2CH(CH3)2), 23.2 (–CH2CH(CH3)2), 23.1
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506 mV and E1/2(%C/2C)Z980 mV.
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Acknowledgements
This work was supported by the Programa General de
´ ´
Conocimento of the Direccion General de Investigacion,

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