Thiacyclophane cages and related bi- and tripodal molecules via transient polysulfenic acids

Article abstract of DOI:10.1021/jo070449b

(Chemical Equation Presented) A series of bis- and tris-bridged thiacyclophane S-oxides, as racemates or meso products, have been synthesized with a new procedure. Starting from the corresponding thiols, in three steps, transient polyarene-and polyarylmet

Full text of DOI:10.1021/jo070449b

Thiacyclophane Cages and Related Bi- and Tripodal Molecules via
Transient Polysulfenic Acids
Maria Chiara Aversa,† Anna Barattucci,*,† Paola Bonaccorsi,*,† Cristina Faggi,‡ and
Teresa Papalia†
Dipartimento di Chimica organica e biologica, UniVersita` degli Studi di Messina, Salita Sperone 31 (Vill.
S. Agata), 98166 Messina, Italy, and Centro Interdipartimentale di Cristallografia, UniVersita` degli Studi
di Firenze, Via della Lastruccia 3, 50019 Sesto Fiorentino, Firenze, Italy
paola.bonaccorsi@unime.it
ReceiVed March 5, 2007
A series of bis- and tris-bridged thiacyclophane S-oxides, as racemates or meso products, have been
synthesized with a new procedure. Starting from the corresponding thiols, in three steps, transient polyarene-
and polyarylmethane-sulfenic acids were generated in the presence of di- and triethynylbenzenes. The
thermal syn-addition of these sulfenic acids onto the triple bonds of the unsaturated acceptors was conducted
in CH2Cl2 at 40 °C. The concentration of sulfoxide precursors of sulfenic acid and the sulfoxide/acceptor
molar ratio addressed the syn-addition toward open-chain benzene sulfoxides or thiacyclophane S-oxides.
Complete stereochemical control was observed in some reactions between polysulfenic acids and
ethynylbenzenes, where the meso dithiacyclophane S,S′-dioxides were obtained exclusively, whereas
1:1 mixtures of meso/rac dithiacyclophanes S,S′-dioxides were isolated as products of other reactions. In
almost all the cases, the obtained compounds were separated by column chromatography. The structure
assignment of the new heterophanes was done on the basis of their diagnostic NMR spectra and X-ray
crystallographic analysis of some of them. Open-chain polysulfinyl and polysulfinylmethyl benzenes,
obtained as meso/rac mixtures, were separated and the products were fully characterized. Both synthesized
cages, including trithia[33](1,3,5)cyclophane S,S′,S′′-trioxides, and bi- and tripodal benzene sulfoxides,
appear promising in the field of coordination and material chemistry.
Introduction
suffer some limitations, such as long reaction times and yields
dependent on the structural features of the starting products,
which required slow addition of the reactants.5
Very recently, we envisaged that the syn-addition of poly-
arene- and poly-arylmethane-sulfenic acids onto the triple bonds
Bridged aromatic compounds, such as cyclophanes (CPs), are
potential building blocks in the design of molecules for catalytic
processes or electronic devices. The restricted conformational
mobility of these compounds, their intrinsic symmetry, and their
structural features, some of which are very exotic, addressed
the attention on the development of a number of synthetic
pathways.1 ThiaCPs2 represent significant components of the
CP family because the presence of sulfur atoms into the skeleton
of the cage allows a number of possible transformations of the
hetero function3 and some interesting conformational changes.4
Nevertheless, the methodologies developed for obtaining thiaCPs
(1) Tsukamoto, K.-i.; Sahade, D. A.; Taniguchi, M.; Sawada, T.;
Thiemann, T.; Mataka, S. Tetrahedron Lett. 1999, 40, 4691-4692. Wang,
H.; Wulff, W. D.; Rheingold, A. L. J. Am. Chem. Soc. 2000, 122, 9862-
9863. Gevorgyan, V.; Tsuboya, N.; Yamamoto, Y. J. Org. Chem. 2001,
66, 2743-2746. Christensen, C. A.; Batsanov, A. S.; Bryce, M. R.; Howard,
J. A. K. J. Org. Chem. 2001, 66, 3313-3320. Park, K. K.; Han, I. K.;
Park, J. W. J. Org. Chem. 2001, 66, 6800-6802. Camacho, D. H.; Salo, E.
V.; Guan, Z. Org. Lett. 2004, 6, 865-868. Kim, J.; Kim, Y. K.; Park, N.;
Hahn, J. H.; Ahn, K. H. J. Org. Chem. 2005, 70, 7087-7092. Birsa, M.
L.; Jones, P. G.; Braverman, S.; Hopf, H. Synlett 2005, 640-642. Hinrichs,
H.; Boydston, A. J.; Jones, P. G.; Hess, K.; Herges, R.; Haley, M. M.;
Hopf, H. Chem.sEur. J. 2006, 12, 7103-7115.
† Universita` degli Studi di Messina.
‡ Universita` degli Studi di Firenze.
10.1021/jo070449b CCC: $37.00 © 2007 American Chemical Society
Published on Web 05/16/2007
4486
J. Org. Chem. 2007, 72, 4486-4496

Cage and Bi/Tripodal Benzene Sulfoxides
SCHEME 1
of polyethynyl benzenes could represent an original and efficient
methodology for the construction of thiaCP S-oxides.
formation;6 (ii) it is possible to generate enantiopure sulfenic
acids by synthesizing their precursors with an enantiopure alkyl
or aryl residue;7 and (iii) the generation of sulfenic acids carrying
an aminoacidic or a glycosidic residue corresponds to a direct
strategy for the stereocontrolled preparation of sulfinyl molecules
possessing biological active residues.8
Sulfenic acids are implicated in a wide variety of relevant
chemical and biochemical reactions and, although the vast
majority of them are too unstable to be isolated, they cannot be
considered just casual intermediates in organic and biological
processes. For instance, the syn-addition of sulfenic acids onto
carbon-carbon triple bonds gives a reliable, easy way to obtain
vinyl sulfoxides in mild conditions without the need for acidic
or basic catalysis and with some stereo- and regio-selectivities
in the formation of the S-epimeric mixtures of sulfoxides,
induced by the structural features of the sulfenic acid and the
electronic ones of its unsaturated acceptor. This reaction and
its applications in organic synthesis have been widely studied
by us, showing that (i) it is possible to generate sulfenic acids
in three steps starting from the suitable thiols; in the thermolysis,
that represents the last step, with the sulfenic acid generated in
the presence of the unsaturated acceptor leading to sulfoxide
In this paper we describe the three-step generation of transient
diarenesulfenic acids and di- and triarylmethanesulfenic acids,9
starting from the corresponding thiols, and the results of their
additions onto the triple bonds of di- and triethynyl benzenes.
The presence of elements of symmetry, such as C2 and C3 axes,
in some of the aromatic polysulfenic acids and acceptors, the
formation of stereogenic sulfoxide sulfur atoms, the partner
choice in the addition sulfenic acid/triple bond, and the nature
and conditions of the syn-addition allowed the preparation of
π-electron-rich molecules, such as the predicted thiaCP S-oxides,
together with open-chain polysulfinyl and polysulfinylmethyl
benzenes, quite promising in the field of organic materials.
Results and Discussion
(2) (a) Sato, T.; Wakabayashi, M.; Hata, K.; Kainosho, M. Tetrahedron
1971, 27, 2737-2755. (b) Fujise, Y.; Nakasato, Y.; Itoˆ, S. Tetrahedron
Lett. 1986, 27, 2907-2908. (c) Bruhin, J.; Gerson, F.; Martin, W. B., Jr.;
Novotny, H. J. Am. Chem. Soc. 1988, 110, 6377-6384. (d) Laali, K. K.;
Okazaki, T.; Mitchell, R. H. J. Chem. Soc., Perkin Trans. 2 2001, 745-
748. (e) Yasutake, M.; Araki, K.; Zhou, M.; Nogita, R.; Shinmyozu, T.
Eur. J. Org. Chem. 2003, 1343-1351. (f) Nogita, R.; Matohara, K.; Yamaji,
M.; Oda, T.; Sakamoto, Y.; Kumagai, T.; Lim, C.; Yasutake, M.; Shimo,
T.; Jefford, C. W.; Shinmyozu, T. J. Am. Chem. Soc. 2004, 126, 13732-
13741.
Synthesis of the Precursors of Polysulfenic Acids 16-20.
Thiols 1-3 (Scheme 1) are commercially available, while thiols
(6) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Jafari,
S. M. A.; Jones, D. N. Tetrahedron Asymmetry 1992, 3, 701-704.
(7) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Jones,
D. N. J. Org. Chem. 1997, 62, 4376-4384.
(3) Mascal, M.; Kerdelhue´, J.-L.; Blake, A. J.; Cooke, P. A. Angew.
Chem., Int. Ed. 1999, 38, 1968-1971.
(8) (a) Aucagne, V.; Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.;
Giannetto, P.; Rollin, P.; Tatiboue¨t, A. J. Org. Chem. 2002, 62, 4376-
4384. (b) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Jones,
D. N. J. Org. Chem. 2005, 70, 1986-1992. (c) Aversa, M. C.; Barattucci,
A.; Bilardo, M. C.; Bonaccorsi, P.; Giannetto, P.; Rollin, P.; Tatiboue¨t, A.
J. Org. Chem. 2005, 70, 7389-7396.
(4) Mitchell, R. H. J. Am. Chem. Soc. 2002, 124, 2352-2357.
(5) Givens, R. S.; Olsen, R. J.; Wylie, P. L. J. Org. Chem. 1979, 44,
1608-1613. Mitchell, R. H.; Vinod, T. K.; Bodwell, G. J.; Bushnell, G.
W. J. Org. Chem. 1989, 54, 5871-5879. Chiu, J.; Hart, H.; Ward, D. L. J.
Org. Chem. 1993, 58, 964-966. Rajakumar, P.; Dhanasekaran, M.; Selvam,
S.; Aravindan, P. G.; Velmurugan, D. J. Org. Chem. 2005, 70, 3267-3270.
(9) Tripolt, R.; Nachbaur, E. Phosphorus, Sulfur Silicon Relat. Elem.
1992, 65, 173-176.
J. Org. Chem, Vol. 72, No. 12, 2007 4487

Aversa et al.
TABLE 1. Generation of Sulfenic Acids and Their syn-Addition to Alkyne Acceptors in Dichloromethane at Reflux
sulfoxide precursor
(sulfenic acid)
acceptor of
sulfenic acid
sulfox concn sulfox/acceptor
chromatographic eluant
(EtOAc/petrol)
entry
(mM)
molar ratio
adductsa (yield %)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
11 (16)
11 (16)
11 (16)
11 (16)
12 (17)
12 (17)
12 (17)
12 (17)
13 (18)
13 (18)
13 (18)
13 (18)
14 (19)
14 (19)
14 (19)
14 (19)
15 (20)
p(HCtC)2C6H4
m(HCtC)2C6H4
p(HCtC)2C6H4
m(HCtC)2C6H4
p(HCtC)2C6H4
m(HCtC)2C6H4
p(HCtC)2C6H4
m(HCtC)2C6H4
p(HCtC)2C6H4
p(HCtC)2C6H4
m(HCtC)2C6H4
m(HCtC)2C6H4
HCtCC6H5
60
60
10
10
60
60
10
10
10
60
10
60
60
60
60
10
10
1:4
1:4
1:1
1:1
1:4
1:4
1:1
1:1
1:1
1:4
1:1
1:4
1:9
1:9
1:9
1:1
1:1
21 (20) + 22 (20)
5:5
5:5
9:1
9:1
5:5
5:5 up to 8:2
8:2
23 (20) + 24 (20)
25 (30)
27 (15) + 26 (15)
34 (20) + 35 (20)
36 (10) + 37 (10) + 40 (10) + 39 (10)
38 (30)
40 (15) + 39 (15)
30 (15) + 31 (15)
30 (35) + 31 (35)
32 (15) + 33 (15)
32 (30) + 33 (30)
42 (5) + 43 (15)
44 (5) + 45 (12) + 48/49 (15)
46 (8) + 47 (20)
48/49 (20)
8:2
2.5:7.5
2.5:7.5
3:7
3:7
8:2
6:4 up to 10:0
8:2
10:0
sym(HCtC)3C6H3
p(HCtC)2C6H4
sym(HCtC)3C6H3
sym(HCtC)3C6H3
51 (10) + 52 (10)
10:0
a If more then one adduct is obtained, the products are reported in order of increasing retention times. Several products of sulfenic acid self-condensation
1
are always detected in the crudes by H NMR analysis.
4 and 5 were prepared following literature procedures.10 The
reaction of each of these compounds with diethyl isopropy-
lidenemalonate in the presence of benzyltrimethylammonium
hydroxide (Triton B), at -78 °C, led to the corresponding
sulfides 6-10 in good yields. Oxidation of these sulfides to
sulfoxides 11-15, respectively, was conducted in dichlo-
romethane, using m-CPBA as the oxidizing agent at -78 °C.
Sulfoxides 11-15, which represent the direct precursors of the
corresponding transient polysulfenic acids 16-20, were obtained
in almost quantitative yield, not needing further purification
before undergoing the thermolysis toward sulfenic acids.
The choice of such sulfinyl precursors 11-15 was done taking
into account previously disappointing experiments. At the
beginning of this investigation, we decided to thermolyze
2-cyanoethyl sulfoxides coming from the nucleophilic addition
of thiols 1-5 to acrylonitrile,11 followed by the oxidation to
sulfoxides. On the basis of our experience,8c 2-cyanoethyl
sulfoxides can be easier handled than (1,1-diethoxycarbonyl-
2-methyl)-2-propyl sulfoxides: 2-cyanoethyl sulfoxides can be
purified by column chromatography and left on the bench for
quite a long time. On the contrary, sulfoxides 11-15 must be
prepared and immediately used to avoid the spontaneous
formation of products coming from self-condensation of the
corresponding sulfenic acids. However, in the present case, the
crude mixtures of 2-cyanoethyl sulfoxides were found difficult
to treat for the high insolubility of the sulfoxide products, which
were detected by proton magnetic resonance, but could not be
easily separated and fully characterized. For these reasons, they
were discarded.
in 1:4 sulfoxide/acceptor molar ratio, 1,4-bis(sulfinylmethyl)-
benzenes 21-24 were obtained, each pair in 40% yield
(Scheme 2). Compounds 21/22 and 23/24 were 1:1 mixtures of
meso compound and racemate that could be easily separated
by column chromatography (Table 1, entries 1 and 2). A 1:1
molar ratio of sulfoxide 11 with each of the two diethynylben-
zenes and a reduced concentration of sulfenic acid precursor in
dichloromethane allowed the formation of dithiaCP S-oxides
25-27. The syn-addition of transient 1,4-benzenedimethane-
sulfenic acid (16) onto the triple bonds of p-diethynylbenzene
led to the obtainment, in 30% yield, of adduct 25 as the unique
product of the reaction (Table 1, entry 3) to which the meso
structure was unambiguously attributed by NMR (see section
below). ThiaCPs 26 and 27 were obtained, in a 1:1 ratio of
meso compound and racemate, respectively, from the reaction
of sulfenic acid 16 with m-diethynylbenzene (Table 1, entry
4). Subsequent oxidation of the 1:1 mixture of 26 and 27 gave
bis-sulfone 29 as a proof that the two diastereoisomers 26 and
27 differ only in the configuration at one sulfinyl sulfur atom,
while bissulfone 28 was the expected product of the m-CPBA
oxidation of paraCP 25.
The stereochemical outcome of the reactions between sulfenic
acid 16 and the two diethynylbenzenes for the preparation of
thiaCP S-oxides was quite unexpected; when p-diethynylbenzene
was the acceptor, a complete stereoselection was observed,
whereas in the addition of transient compound 16 to m-
diethynylbenzene, no stereoselection at all was pointed out. To
further explore these results, the generation of 1,3-benzene-
dimethanesulfenic acid (17) from the sulfinyl precursor 12 and
its addition onto the triple bonds of p- and m-diethynylbenzenes
were performed in the same conditions we have used for sulfenic
acid 16 (Scheme 3).
Synthesis of thiaCP S-Oxides 25-27, 38-40, 48, 49, 51,
52, and Open-Chain Bis and Tris Sulfinyl and Sulfinylmethyl
Benzenes 21-24, 30-37, 42-47. The reaction conditions
adopted for the generation of sulfenic acids 16-20 and their
syn-addition to alkyne acceptors are reported in Table 1.
When 1,4-benzenedimethanesulfenic acid (16) was generated
from sulfoxide 11 in the presence of p- or m-diethynylbenzene
Sulfoxide concentration and the sulfoxide/acceptor molar ratio
addressed the syn-addition toward the open-chain benzene
derivatives 34-37 (Table 1, entries 5 and 6) or the thiaCP
S-oxides 38-40 (Table 1, entries 7 and 8). Complete stereo-
chemical control was again observed in the reaction of sulfenic
acid 17 with the p-diethynylbenzene, where the meso
thiaCP S-oxide 38 was obtained in 30% yield. A 1:1 mixture
of the meso macrocycle 39 and the racemate 40 was obtained
in 30% total yield by the addition of the transient 17 to
(10) Houk, J.; Whitesides, G. M. J. Am. Chem. Soc. 1987, 109, 6825-
6836.
(11) For 3,3′-(m-phenylenedithio)dipropionitrile, see: Kuliev, A. M.;
Aliev, S. M. Zh. Org. Khim. 1967, 3, 1045-1047; Chem. Abstr. 1967, 67,
108360.
4488 J. Org. Chem., Vol. 72, No. 12, 2007

Cage and Bi/Tripodal Benzene Sulfoxides
SCHEME 2
SCHEME 3
m-diethynylbenzene, the two products were easily separated by
column chromatography and their mixture oxidized to sulfone
41.
followed by the intramolecular cyclization affording metaCPs
39/40 instead of the expected sole formation of open-chain
benzene derivatives 36/37. This can be ascribed to the favorable
geometrical contiguity of the reactive moieties in the second
step of the intramolecular cyclization toward CPs.
We have also prepared the precursors of 1,3-benzenedis-
ulfenic acid (18; Scheme 3) that was generated in the presence
of the two diethynylbenzene acceptors and gave in good yields
the open-chain sulfoxides 30-33 as 1:1 meso/rac mixtures,
separable by column chromatography (Table 1, entries 10 and
12). The same reactions were performed in diluted solutions
and sulfoxide/acceptor 1:1 molar ratio (Table 1, entries 9 and
11); again, sulfoxides 30-33 were obtained, but in reduced
yields.
These results, identical from a stereochemical point of view
to the ones observed for sulfenic acid 16, suggest a different
attack pathway for compounds 16 and 17 onto the electronically
different triple bonds of the two diethynylbenzenes. At the actual
level of our knowledge, indeed, the only difference we can
surely envisage is the widespread π-conjugation characterizing
p-diethynylbenzene, against the more localized triple bonds of
the m-diethynylbenzene. Noteworthy are the results shown in
Table 1 as entry 6 compared to the analogous results in entry
8; when the two partners of the double syn-addition are both
m-substituted, a relevant amount of CPs is obtained even if the
concentration of the sulfoxide precursor is the one identified as
more suitable to the formation of open-chain benzene deriva-
tives. We suggest that the attack of the one sulfenic function of
17 onto one triple bond in m-diethynylbenzene is preferably
Later we turned our attention to the synthesis of thiaCPs with
a “cylindrical” structure, because they appear as attractive cages,
able to participate in metal ion complexation.3 For this purpose,
we began with a model reaction and synthesized 1,3,5-tris-
J. Org. Chem, Vol. 72, No. 12, 2007 4489

Aversa et al.
SCHEME 4
(sulfinylmethyl)benzene 14 (Scheme 1) as the precursor of the
“three-branched” sulfenic acid 19, which was thermolyzed in
dichloromethane in the presence of phenylacetylene, with the
idea of trapping the three sulfenic functions and proving the
existence of the transient intermediate 19. Actually, a 1:3
mixture of tripodal sulfoxides 42 and 43 was obtained in 20%
total yield, as shown in Scheme 4 (Table 1, entry 13). The syn-
addition of sulfenic acid 19 to an equimolecular quantity of
1,3,5-triethynylbenzene in the reaction conditions reported in
Table 1 (entry 16) led to the formation of the thiaCP S-oxides
48 and 49, as two diastereomeric mixtures of racemates in about
1:1 ratio, respectively, that were converted into one sulfonyl
derivative 50 by oxidation with m-CPBA. The structural
differences between the cage 48, possessing a C3 axis of
symmetry, and the cage 49, where only two of the three sulfinyl
sulfur atoms show the same configuration, were clear once we
obtained the “thiacylindrophanes” 51 and 52 as an approximate
1:1 mixture. Compounds 48 and 49 were not completely
separable by column chromatography, while if the 48/49 mixture
was incompletely dissolved in ethyl acetate, the mother liquors
were enriched in 48 up to 90%. CPs 51 and 52, possessing three
methyl substituents in one of the two benzene rings, could be
separated and their spectra completely interpreted (see section
below). Cages 51 and 52 were the products of the syn-addition
of sulfenic acid 20 to 1,3,5-triethynylbenzene in the same
conditions of reaction adopted for the preparation of 48 and 49
(Table 1, entry 17). The mixture 51/52 was quantitatively
converted in sulfone 53.
the reaction of sulfenic acid 19 with p-diethynylbenzene
(Table 1, entry 15), while compounds 44 and 45 were the
products of the reaction between the transient 19 and the
symmetrical triethynylbenzene in the reaction conditions shown
in Table 1, entry 14. In this last reaction, an almost equal
quantity of the cages 48 and 49 was also obtained, analogously
to the results in entry 6.
Structure Assignments. The presence of two stereogenic
sulfinyl sulfur atoms into the thiaCP cage of compounds 25-
27 and 38-40, and in the open-chain benzene derivatives 21-
24 and 30-37, led to the formation of racemates and/or meso
products.
The structure assignment of dithiaCP S,S′-oxides, with at least
a p-substituted aromatic ring (25-27, 38), was easily done on
1
the basis of their diagnostic H NMR spectra. The meso CPs
25, 26, and 38 were unequivocally identified because their
spectra showed no ortho spin-spin couplings, owing to the
symmetry plane perpendicularly cutting the p-disubstituted
aromatic ring and bisecting its two HC/CH carbon-carbon
bonds. The corresponding Jortho ) 7.9 Hz was instead measured
for rac-1,12-dimethylene-2,11-dithia[3.3]parametacyclophane
2,11-dioxide (27).
The attribution of the structure to metaCP 39 was done by
means of X-ray crystallographic analysis (Figure 1). meso-1,-
12-Dimethylene-2,11-dithia[3.3]metametacyclophane 2,11-di-
oxide (39), with the two sulfinyl oxygen atoms pointing away
from the methylene moieties, shows a syn-chair-chair (Scc)
conformation, in line with the conformational studies already
conducted on this kind of molecule.4 In the solid state, the two
aromatic rings of 39 are not coplanar and their planes form an
angle of 28.74 (0.16)°, with the distance between the corre-
sponding two centroids being 3.677 Å.
The 1H NMR parameters are very similar for the open-chain
benzene derivatives 21-24 and 30-37, aside from their
stereochemistry of meso or racemate compounds. Again, the
configurational nature of rac-1,4-bis{[1-(4-ethynylphenyl)-
ethenylsulfinyl]methyl}benzene (21) was assigned on the basis
of the X-ray investigation. Figure 2 shows the asymmetric unit
Finally, we directed our interest toward the synthesis of other
tripodal molecules such as 44 and 45 and 46 and 47, shown in
Scheme 4. Similar compounds have demonstrated a certain
encapsulating tendency or stimulating coordination capabilities
due to the presence of the sulfinyl functions.12 Furthermore,
they possess carbon-carbon triple bonds that can be used for
subsequent syn-additions of arenesulfenic acids, thereby building
dendrimeric structures. Sulfoxides 46 and 47 were obtained in
(12) Yang, C.; Wong, W.-T. J. Mater. Chem. 2001, 11, 2898-2900. Li,
J.-R.; Bu, X.-H.; Zhang, R.-H. Eur. J. Inorg. Chem. 2004, 1701-1704.
4490 J. Org. Chem., Vol. 72, No. 12, 2007

Cage and Bi/Tripodal Benzene Sulfoxides
The proposed strategy allowed the obtainment of these cages
in mild reaction conditions. The key step of the synthetic process
is the thermal syn-addition sulfenic acid/carbon-carbon triple
bond. Because no acidic or basic conditions are required during
this reaction, a broad range of substituents can be present in
the structural skeleton of reactants. The easy access to the
starting materials, the precursors of polysulfenic acids on one
hand and the alkyne acceptors on the other, guarantees a wide
range of possible modulations for the synthesis. The presence
of stereogenic sulfinyl sulfur atoms into the thiaCP scaffold of
the products caused the formation of meso and racemic cages
but enabled in general the easy separation and characterization
of the diastereomeric mixtures of such molecules. The thiaCP
core holds methylene moieties in a favorable position for further
transformations. Thus, these CPs can be useful for investigating
new properties of this kind of cage and can also represent
versatile starting materials for building new polycyclic structures.
Finally, the significant structural features of tripodal molecules,
such as 42-47, forward investigations on their coordina-
ting properties as they are and/or after modifications of their
skeleton.
FIGURE 1. Molecular structure of 39; ellipsoids are drawn with 50%
probability; a chloroform molecule is cocrystallized.
Experimental Section
All reactions were monitored by TLC on commercially available
aluminum supported silica gel plates (F 254), and the products were
visualized with acidic vanillin solution. The NMR assignments are
fully supported by attached proton test (APT) and homodecoupling
experiments.
FIGURE 2. Molecular structure of racemate 21; ellipsoids are drawn
with 50% probability; a chloroform molecule is cocrystallized.
2,4,6-Trimethyl-1,3,5-benzenetrimethanethiol (5). Trithiol 514
was prepared according to Whitesides protocol.9 To commercially
available 1,3,5-tris(bromomethyl)-2,4,6-trimethylbenzene (5.0 g,
12.53 mmol) suspended in EtOH (55 mL), thiourea (2.8 g,
36.78 mmol) was added, and the reaction mixture was maintained
under stirring at rt overnight. The solvent was then removed under
vacuum, a NaOH solution (3.0 g, 75 mmol in 50 mL H2O) was
added, and the mixture was refluxed for 4 h. HCl (6 N) was added
to the mixture, which was cooled in an ice bath, up to pH 2. Finally,
the water phase was extracted with CHCl3 (4 × 30 mL), dried over
Na2SO4, and concd under vacuum to give trithiol 5 as a white solid
(2.9 g, 11.22 mmol, 90%). TLC Rf (petrol/EtOAc 8:2) 0.75; mp
of 21, where two independent enantiomeric molecules, un-
equivalent from a crystallographic point of view, cocrystallize
with a chloroform molecule. Noteworthy is the different
reciprocal orientations of the benzene rings in the two molecules,
both showing the oxygen atoms pointing one toward the other.
This last steric feature allows the foresight of effective coordina-
tion capabilities to electron-deficient species.13
All synthesized trisulfoxides 42-49, 51, and 52 show
typically different NMR spectra in dependence of their C3
symmetry or not. As an example, apart from aromatic (m, 7.6-
1
7.5 ppm) and alkyne (s, 3.18 ppm) absorptions, the H NMR
1
3
143 °C; H NMR (300 MHz, CDCl3) δ 3.79 (d, Jvic ) 6.5 Hz,
spectrum of C3sym-1,3,5-tris{[1-(3,5-diethynylphenyl)ethenyl-
sulfinyl]methyl}benzene (44) shows a simple pattern of signals
[δ 6.70 (s, 3H, H-2,4,6), 5.98, and 5.73 (two d, 6H,
3 × dCH2), 3.95 and 3.54 (AB system, 6H, 3 × SCH2)], which
divide into two 2:1 parts for noC3sym-1,3,5-tris{[1-(3,5-
diethynylphenyl)ethenylsulfinyl]methyl}benzene (45) [δ 6.78 (s,
2H) and 6.75 (s, 1H) (H-2,4,6), 6.00 and 5.90 (two d, 2H, d
CH2), 5.99 and 5.83 (two d, 4H, 2 × dCH2), 3.91 and 3.59
(AB system, 4H, 2 × SCH2), 3.87 and 3.61 (AB system, 2H,
SCH2)]. Even the 13C NMR spectrum of 45 shows signal
doubling for almost all the resonances (see Experimental
Section).
3
6H, 3 × CH2), 2.44 (s, 9H, 3 × Me), 1.59 (t, Jvic ) 6.5 Hz, 3H,
3 × SH); 13C NMR (75 MHz, CDCl3) δ 136.2 (C-1,3,5), 133.2
(C-2,4,6), 24.1 (3 × CH2), 15.6 (3 × Me); Elem anal. Calcd (%)
for C12H18S3 (258.47): C, 55.76; H, 7.02. Found: C, 55.96; H,
6.88.
General Procedure A. To a stirred solution of the thiol in anhyd
THF at -78 °C, Triton B (40 wt.% solution in MeOH) and, after
5 min, diethyl isopropylidenemalonate were added. The molar ratio
of thiol/Triton B/malonate was 1:0.3:6 for the synthesis of disulfides
6-8, and 1:0.45:9 for the synthesis of trisulfides 9 and 10. The
THF volume was related to the malonate amount as 0.5 mL THF/
malonate mmol. The mixture was allowed to reach rt spontaneously,
and when the reaction appeared complete by TLC (petrol/EtOAc
8:2), it was quenched by water addition. The crude product was
extracted three times with Et2O. The combined organic layers were
washed with brine and dried over Na2SO4. After filtration of the
inorganic solid, the solvent was removed under reduced pressure,
Finally, the nearly quantitave m-CPBA formation of sulfones
28, 29, 41, 50, and 53 confirmed the structures assigned to their
sulfoxide precursors 25, 26/27, 39/40, 48/49, and 51/52,
respectively.
(14) Ciba-Geigy A.-G., Switzerland, Jpn. Kokai Tokkyo Koho, JP
54058751, 1979; Chem. Abstr. 1979, 91, 141655. Ohwa, M.; Yamoto, H.;
Birbaum, J.-L.; Nakashima, H.; Matsumoto, A.; Oka, H., Ciba Speciality
Chemicals Holding Inc., Switzerland, Ger. Offen., DE 19753655, 1998;
Chem. Abstr. 1998, 129, 68148. Hirai, O.; Uchida, T.; Watanabe, I.;
Fujinawa, M.; Tsukagoshi, I.; Fukushima, N.; Kobayashi, K.; Muramatsu,
Y., Hitachi Chemical Co., Ltd., Japan, Jpn. Kokai Tokkyo Koho, JP
11130841, 1999; Chem. Abstr. 1999, 131, 6316.
Conclusions
We have described an original synthetic pathway for the
preparation of new members of the class of thiaCP S-oxides.2a,c,d
(13) Khiar, N.; Arau´jo, C. S.; Alcudia, F.; Ferna´ndez, I. J. Org. Chem.
2002, 67, 345-356.
J. Org. Chem, Vol. 72, No. 12, 2007 4491

Aversa et al.
3
and the oily residue containing the sulfide product was purified by
flash column chromatography on silica gel.
CMe2), 1.30 (t, Jvic ) 7.2 Hz, 18H, 6 × OCH2CH3); 13C NMR
(75 MHz, CDCl3) δ 167.2 (6 × CO), 136.1 (C-1,3,5), 130.9 (C-
2,4,6), 61.4 (6 × OCH2), 60.4 [3 × CH(CO2Et)2], 45.9 (3 × CMe2),
28.9 (3 × SCH2), 26.3 (3 × CMe2), 15.4 (3 × ArMe), 14.1 (6 ×
OCH2CH3); Elem anal. Calcd (%) for C42H66O12S3 (859.16): C,
58.71; H, 7.74. Found: C, 58.69; H, 7.44.
1,4-Bis{[(1,1-diethoxycarbonyl-2-methyl)-2-propylthio]methyl}-
benzene (6). Commercial dithiol 1 (1.0 g, 5.87 mmol) was subjected
to general procedure A. The reaction was completed after 0.5 h
stirring at rt. Chromatographic purification (petrol/EtOAc 9.5:0.5)
gave disulfide 6 (2.8 g, 4.91 mmol, 84%) as a white solid. TLC Rf
0.32; mp 70 °C; 1H NMR (300 MHz, CDCl3) δ 7.24 (s, 4H, ArH),
General Procedure B. m-CPBA (80%) was dissolved in CH2-
Cl2 (10 mL/m-CPBA mmol) and added dropwise to a solution of
the sulfide or sulfoxide in the same volume of CH2Cl2 at -78 °C
(1 mol of m-CPBA for every molar site to be oxidized in the
substrate). When the reaction appeared complete by TLC (EtOAc/
petrol 7.5:2.5), a 10% solution of Na2S2O3 was added. Almost all
experiments performed were concluded just after finishing the
addition of the oxidant. The separated organic layer was washed
twice with a saturated solution of NaHCO3 and then twice with
brine. Evaporation of the solvent gave the expected sulfoxide or
sulfone.
1,4-Bis{[(1,1-diethoxycarbonyl-2-methyl)-2-propylsulfinyl]-
methyl}benzene 11. Disulfide 6 (1.1 g, 1.93 mmol) was oxidized
following the general procedure B. Disulfoxide 11 (meso/racemate
1:1) was obtained as an oil (1.1 g, 1.82 mmol, 94%) not needing
any purification before its involvement in the next reaction steps.
3
4.21 (q, Jvic ) 7.1 Hz, 8H, 4 × OCH2), 3.79 (s, 4H, 2 × SCH2),
3.72 [s, 2H, 2 × CH(CO2Et)2], 1.58 (s, 12H, 2 × CMe2), 1.29 (t,
3Jvic ) 7.1 Hz, 12H, 4 × OCH2CH3); 13C NMR (75 MHz, CDCl3)
δ 167.1 (4 × CO), 136.1 (C-1,4), 129.3 (C-2,3,5,6), 61.3 (4 ×
OCH2), 60.3 [2 × CH(CO2Et)2], 46.2 (2 × CMe2), 33.0 (2 × SCH2),
26.6 (2 × CMe2), 14.1 (4 × OCH2CH3); IR (CHCl3) 1753 and
1727 cm-1 (CO); Elem anal. Calcd (%) for C28H42O8S2 (570.76):
C, 58.92; H, 7.42. Found: C, 58.66; H, 7.39.
1,3-Bis{[(1,1-diethoxycarbonyl-2-methyl)-2-propylthio]methyl}-
benzene (7). Commercial dithiol 2 (1.0 g, 5.87 mmol) was subjected
to general procedure A. The reaction was completed after 1 h of
stirring at rt. Chromatographic purification (petrol/EtOAc 9.5:0.5)
gave disulfide 7 (2.6 g, 4.56 mmol, 78%) as a white solid. TLC Rf
1
0.35; mp 55 °C; H NMR (300 MHz, CDCl3) δ 7.3-7.2 (m, 4H,
3
1
ArH), 4.22 (q, Jvic ) 7.1 Hz, 8H, 4 × OCH2), 3.80 (s, 4H, 2 ×
TLC Rf 0.19; H NMR (300 MHz, CDCl3) δ 7.35 (s, 4H, ArH),
SCH2), 3.72 [s, 2H, 2 × CH(CO2Et)2], 1.58 (s, 12H, 2 × CMe2),
1.29 (t, 3Jvic ) 7.1 Hz, 12H, 4 × OCH2CH3); 13C NMR (75 MHz,
CDCl3) δ 167.1 (4 × CO), 137.5 (C-1,3), 129.8 (C-2), 128.7 (C-
5), 127.9 (C-4,6), 61.3 (4 × OCH2), 60.2 [2 × CH(CO2Et)2], 46.2
(2 × CMe2), 33.2 (2 × SCH2), 26.6 (2 × CMe2), 14.1 (4 ×
OCH2CH3); MS (70 eV, EI) m/z (%) 570 (2) [M+], 336 (47), 209
(53), 201 (36), 155 (47), 105 (41), 99 (65), 44 (35), 28 (100); Elem
anal. Calcd (%) for C28H42O8S2 (570.76): C, 58.92; H, 7.42.
Found: C, 58.90; H, 7.35.
4.23 (m, 8H, 4 × OCH2), 3.92 and 3.66 (AB system, 2Jgem ) 12.4
Hz, 4H, 2 × SCH2), 3.85 [s, 2H, 2 × CH(CO2Et)2], 1.55 (s, 12H,
3
2 × CMe2), 1.30 and 1.28 (two t, Jvic ) 7.1 Hz, 12H, 4 ×
OCH2CH3); 1H NMR (300 MHz, C6D6) δ 7.25 (s, 4H, ArH), 4.01
and 4.00 [two s, 2H, 2 × CH(CO2Et)2], 4.0-3.8 (m, 8H, 4 ×
2
OCH2), 3.43 and 3.38, 3.42 and 3.37 (two AB systems, Jgem
)
12.4 Hz, 4H, 2 × SCH2), 1.53 (s, 6H, CMe2 of meso-compound),
1.523 and 1.517 (two s, 6H, CMe2 of racemate), 0.87 and 0.86
3
(two t, Jvic ) 7.1 Hz, 12H, 4 × OCH2CH3).
1,3-Bis{[(1,1-diethoxycarbonyl-2-methyl)-2-propylsulfinyl]-
methyl}benzene 12. Disulfide 7 (0.8 g, 1.40 mmol) was oxidized
following the general procedure B. Disulfoxide 12 (meso/racemate
1:1) was obtained as an oil (0.8 g, 1.33 mmol, 95%), not needing
any purification before its involvement in the next reaction steps.
TLC Rf 0.20; 1H NMR (300 MHz, CDCl3) δ 7.4-7.3 (m, 4H, ArH),
4.24 (m, 8H, 4 × OCH2), 3.92 and 3.68 (or 3.66), 3.90 and 3.66
(or 3.68) (two AB systems, 2Jgem ) 12.6 Hz, 4H, 2 × SCH2), 3.85
[s, 2H, 2 × CH(CO2Et)2], 1.56, 1.55, and 1.54 (three s, 12H, 2 ×
CMe2), 1.30 and 1.27 (two t, 3Jvic ) 7.2 Hz, 12H, 4 × OCH2CH3).
1,3-Bis[(1,1-diethoxycarbonyl-2-methyl)-2-propylsulfinyl]ben-
zene 13. Disulfide 8 (1.0 g, 1.84 mmol) was oxidized following
the general procedure B. Disulfoxide 13 (meso/racemate 1:1) was
obtained as an oil (1.0 g, 1.74 mmol, 95%), not needing any
purification before its involvement in the next reaction steps. TLC
1,3-Bis[(1,1-diethoxycarbonyl-2-methyl)-2-propylthio]ben-
zene (8). Commercial 1,3-benzenedithiol (3; 1.0 g, 7.03 mmol) was
subjected to general procedure A. The reaction was completed after
24 h stirring at rt. Chromatographic purification (petrol/EtOAc 9:1)
gave disulfide 8 (2.9 g, 5.34 mmol, 76%) as a pale yellow oil.
1
4
TLC Rf 0.34; H NMR (300 MHz, CDCl3) δ 7.86 (t, Jmeta
)
3
4
1.7 Hz, 1H, H-2), 7.66 (dd, Jortho ) 7.6 Hz, Jmeta ) 1.7 Hz, 2H,
H-4,6), 7.36 (t, 3Jortho ) 7.6 Hz, 1H, H-5), 4.21 (q, 3Jvic ) 7.1 Hz,
8H, 4 × OCH2), 3.53 [s, 2H, 2 × CH(CO2Et)2], 1.49 (s, 12H, 2 ×
CMe2), 1.29 (t, Jvic ) 7.1 Hz, 12H, 4 × OCH2CH3); 13C NMR
3
(75 MHz, CDCl3) δ ) 167.0 (4 × CO), 146.9 (C-2), 138.5 (C-
4,6), 131.6 (C-1,3), 129.0 (C-5), 61.3 (4 × OCH2), 60.2 [2 × CH-
(CO2Et)2], 49.2 (2 × CMe2), 26.7 (2 × CMe2), 14.0 (4 ×
OCH2CH3); Elem anal. Calcd (%) for C26H38O8S2 (542.71): C,
57.54; H, 7.06. Found: C, 57.65; H, 7.35.
1
4
Rf 0.22; H NMR (300 MHz, CDCl3) δ 7.93 (t, Jmeta ) 1.5 Hz,
1,3,5-Tris{[(1,1-diethoxycarbonyl-2-methyl)-2-propylthio]-
methyl}benzene (9). Trithiol 4 (0.6 g, 2.77 mmol) was subjected
to general procedure A. The reaction was completed after 0.5 h
stirring at rt. Chromatographic purification (petrol/EtOAc 8.5:1.5)
gave trisulfide 9 (1.3 g, 1.59 mmol, 57%) as a white solid. TLC Rf
0.12; mp 46 °C; 1H NMR (300 MHz, CDCl3) δ 7.13 (s, 3H, ArH),
3
4
1H, H-2), 7.85 (dd, Jortho ) 7.7 Hz, Jmeta ) 1.5 Hz, 2H, H-4,6),
3
7.70 (t, Jortho ) 7.7 Hz, 1H, H-5), 4.3-4.2 (m, 8H, 4 × OCH2),
3.73 and 3.72 [two s, 2H, 2 × CH(CO2Et)2], 1.31 (m, 24H, 2 x
CMe2, 4 × OCH2CH3).
1,3,5-Tris{[(1,1-diethoxycarbonyl-2-methyl)-2-propylsulfinyl]-
methyl}benzene 14. Trisulfide 9 (0.8 g, 0.98 mmol) was oxidized
following the general procedure B. Trisulfoxide 14 (diastereomeric
mixture) was obtained as an oil (0.8 g, 0.92 mmol, 94%), not
needing any purification before its involvement in the next reaction
3
4.21 (split q, Jvic ) 7.1 Hz, 12H, 6 × OCH2), 3.77 (s, 6H, 3 ×
SCH2), 3.71 [s, 3H, 3 × CH(CO2Et)2], 1.57 (s, 18H, 3 × CMe2),
1.29 (t, 3Jvic ) 7.1 Hz, 18H, 6 × OCH2CH3); 13C NMR (75 MHz,
CDCl3) δ 167.1 (6 × CO), 137.8 (C-1,3,5), 128.6 (C-2,4,6), 61.3
(6 × OCH2), 60.3 [3 × CH(CO2Et)2], 46.2 (3 × CMe2), 33.1 (3 ×
SCH2), 26.6 (3 × CMe2), 14.1 (6 × OCH2CH3); IR (CHCl3) 1753
and 1728 cm-1 (CO); Elem anal. Calcd (%) for C39H60O12S3
(817.08): C, 57.33; H, 7.40. Found: C, 57.02; H, 7.44.
1
steps. TLC Rf 0.15; H NMR (300 MHz, CDCl3) δ 7.33 (m, 3H,
ArH), 4.3-4.2 (m, 12H, 6 × OCH2), 3.9-3.6 (m, 6H, 3 × SCH2),
3.85 [s, 3H, 3 × CH(CO2Et)2], 1.56, 1.55, and 1.53 (three s, 18H,
3
3
3 × CMe2), 1.30 (t, Jvic ) 7.2 Hz) and 1.28 (t, Jvic ) 7.0 Hz)
(18H, 6 × OCH2CH3); 13C NMR (75 MHz, CDCl3) δ 166.8 and
166.3 (6 × CO), 132.8 (C-1,3,5), 132.2 (C-2,4,6), 62.0 and 61.9
(6 × OCH2), 58.6 (3 × CMe2), 55.4 [3 × CH(CO2Et)2], 51.8 (3 ×
SCH2), 18.2 (3 × CMe2), 14.0 (6 × OCH2CH3).
1,3,5-Tris{[(1,1-diethoxycarbonyl-2-methyl)-2-propylthio]-
methyl}-2,4,6-trimethylbenzene (10). Trithiol 5 (3.2 g, 12.38
mmol) was subjected to general procedure A. The reaction was
completed after 18 h of stirring at rt. Chromatographic purification
(petrol/EtOAc 9:1) gave trisulfide 10 (5.5 g, 6.40 mmol, 52%) as
a white solid. TLC Rf 0.13; mp 73 °C; 1H NMR (300 MHz, CDCl3)
δ 4.23 (m, 12H, 6 × OCH2), 3.81 (s, 6H, 3 × SCH2), 3.75 [s, 3H,
3 × CH(CO2Et)2], 2.43 (s, 9H, 3 × ArMe), 1.64 (s, 18H, 3 ×
1,3,5-Tris{[(1,1-diethoxycarbonyl-2-methyl)-2-propylsulfinyl]-
methyl}-2,4,6-trimethylbenzene 15. Trisulfide 10 (0.8 g,
0.93 mmol) was oxidized following the general procedure B.
Trisulfoxide 15 (diastereomeric mixture) was obtained as an oil
4492 J. Org. Chem., Vol. 72, No. 12, 2007

Cage and Bi/Tripodal Benzene Sulfoxides
(0.8 g, 0.88 mmol, 95%), not needing any purification before its
involvement in the next reaction steps. TLC Rf 0.16; H NMR
(300 MHz, CDCl3) δ 4.3-3.8 [m, 21H, 6 × OCH2,3 × SCH2,3 ×
CH(CO2Et)2], 2.40 (m, 9H, 3 × ArMe), 1.63 and 1.60 (two s, 18H,
3 × CMe2), 1.29 (m, 18H, 6 × OCH2CH3).
CDCl3) δ 7.6-7.4 (m, 8H, 2 × H-2′,4′,5′,6′), 7.05 (s, 4H,
H-2,3,5,6), 5.94 and 5.76 (two s, 4H, 2 × dCH2), 3.96 and 3.58
tCH); 13C NMR (75 MHz, CDCl3) δ 150.4 (2 × CdCH2), 134.2
(2 × C-1,4), 133.0 (2 × C-4′), 130.3 (C-2,3,5,6), 130.1 (2 × C-2′),
129.4 (2 × C-1′), 129.3 (2 × C-5′), 126.9 (2 × C-6′), 123.3 (2 ×
C-3′), 119.1 (2 × dCH2), 82.6 (2 × CtCH), 78.5 (2 × tCH),
57.3 (2 × SCH2); Elem anal. Calcd (%) for C28H22O2S2 (454.61):
C, 73.98; H, 4.88. Found: C, 73.68; H, 4.75.
1
2
(AB system, Jgem ) 13.3 Hz, 4H, 2 × SCH2), 3.17 (s, 2H, 2 ×
General Procedure C. A solution of the sulfoxide and com-
mercial ethynyl acceptor in CH2Cl2 was maintained at reflux temp.
When the reaction appeared complete by TLC (disappearance of
starting sulfoxide required about one night), the solvent was
removed under reduced pressure and the reaction crude was purified
by flash column chromathography on silica gel (see Table 1).
rac-1,4-Bis{[1-(4-ethynylphenyl)ethenylsulfinyl]methyl}-
benzene (21). Compound 21 was prepared, together with its
diastereoisomer 22, from 1,4-diethynylbenzene and disulfoxide 11
[(via 1,4-benzenedimethanesulfenic acid 16)] following procedure
C (entry 1 in Table 1). The more mobile adduct 21 was isolated
after chromatographic separation as a white solid melting at
145 °C. Single crystals suitable for X-ray structure were obtained
by recrystallization from petrol/CHCl3 5:5. TLC Rf (EtOAc/petrol
7.5:2.5) 0.47; 1H NMR (300 MHz, CDCl3) δ 7.56 and 7.37
meso-1,12-Dimethylene-2,11-dithia[3.3]paraparacyclophane
2,11-Dioxide (25). Following procedure C (entry 3 in Table 1),
compound 25 was prepared from 1,4-diethynylbenzene and disul-
foxide 11 [(via 1,4-benzenedimethanesulfenic acid (16)] and isolated
after chromatographic purification as a white solid decomposing
at 135 °C. TLC Rf (EtOAc/petrol 7.5:2.5) 0.12; 1H NMR (300 MHz,
4
CDCl3) δ 7.29 and 6.79 (two split d, Jmeta ) 2.3 Hz, 4H, H-14,-
4
15,17,18), 7.14 and 6.46 (two split d, Jmeta ) 2.2 Hz, 4H,
H-5,6,8,9), 6.17 and 6.16 (two d, 2Jgem ) 1.0 Hz, 4H, 2 × dCH2),
2
4.60 and 3.76 (AB system, Jgem ) 11.6 Hz, 4H, H2-3,10); 13C
NMR (75 MHz, CDCl3) δ 152.6 (C-1,12), 136.1 and 129.8 (C-
4,7,13,16), 133.3, 128.8, 127.2, and 127.1 (C-5,6,8,9,14,15,17,18),
115.3 (2 × ) CH2), 65.0 (C-3,10); MS (70 eV, EI) m/z (%) 328
(1) [M+], 104 (4), 44 (3), 32 (20), 28 (100); Elem anal. Calcd (%)
for C18H16O2S2 (328.45): C, 65.82; H, 4.91. Found: C, 65.99; H,
5.02.
3
(AA′BB′system, Jortho ) 8.3 Hz, 8H, 2 x H-2′,3′,5′,6′), 7.01 (s,
4H, H-2,3,5,6), 5.92 and 5.70 (two s, 4H, 2 × ) CH2), 3.97 and
3.56 (AB system, 2Jgem ) 13.2 Hz, 4H, 2 × SCH2), 3.19 (s, 2H, 2
× tCH); 13C NMR (75 MHz, CDCl3) δ ) 150.4 (2 × CdCH2),
134.1 (C-1,4), 132.9 (2 × C-3′,5′), 130.2 (C-2,3,5,6), 129.1 (2 ×
C-1′), 126.4 (2 × C-2′,6′), 123.4 (2 × C-4′), 119.0 (2 × dCH2),
82.7 (2 × CtCH), 79.1 (2 × tCH), 56.9 (2 × SCH2); IR (CHCl3)
1502, 1054, 929, 844 cm-1; Elem anal. Calcd (%) for C28H22O2S2
(454.61): C, 73.98; H, 4.88. Found: C, 73.65; H, 5.11.
rac-1,12-Dimethylene-2,11-dithia[3.3]parametacyclophane 2,-
11-Dioxide (27). Racemate 27 was prepared, together with its meso-
isomer 26, from 1,3-diethynylbenzene and disulfoxide 11 [(via 1,4-
benzenedimethanesulfenic acid (16)] following procedure C (entry
4 in Table 1). The more mobile 27 was isolated after chromato-
graphic purification as a white solid decomposing at 110 °C. TLC
Rf (EtOAc/petrol 7.5:2.5) 0.13; 1H NMR (300 MHz, CDCl3) δ 7.22
(t, 3Jortho ) 9.2 Hz, 1H, H-15), 7.21 (AB dd, 3Jortho ) 9.2 Hz, 4Jmeta
) 0.5 Hz, 1H) and 7.16 (AB dd, 3Jortho ) 9.2 Hz, 4Jmeta ) 1.7 Hz,
meso-1,4-Bis{[1-(4-ethynylphenyl)ethenylsulfinyl]methyl}-
benzene (22). Compound 22 was prepared, together with its
diastereoisomer 21, from 1,4-diethynylbenzene and disulfoxide 11
[(via 1,4-benzenedimethanesulfenic acid (16)] following procedure
C (entry 1 in Table 1). The less mobile adduct 22 was isolated
after chromatographic separation as a white solid melting at
170 °C. TLC Rf (EtOAc/petrol 7.5:2.5) 0.45; 1H NMR (300 MHz,
CDCl3) δ 7.56 and 7.37 (AA′BB′system, 3Jortho ) 8.5 Hz, 8H, 2 ×
H-2′,3′,5′,6′), 7.04 (s, 4H, H-2,3,5,6), 5.94 and 5.77 (two s, 4H,
2 × dCH2), 3.95 and 3.57 (AB system, 2Jgem ) 13.2 Hz, 4H, 2 ×
SCH2), 3.19 (s, 2H, 2 × tCH); 13C NMR (75 MHz, CDCl3) δ
150.6 (2 × CdCH2), 134.2 (C-1,4), 132.9 (2 × C-3′,5′), 130.2 (C-
2,3,5,6), 129.4 (2 × C-1′), 126.4 (C-2′,6′), 123.3 (2 × C-4′), 118.9
(2 × dCH2), 82.7 (2 × CtCH), 79.1 (2 × tCH), 57.4 (2 ×
SCH2); IR (CHCl3) 1503, 1053, 928, 844 cm-1; Elem anal. Calcd
(%) for C28H22O2S2 (454.61): C, 73.98; H, 4.88. Found: C, 73.94;
H, 4.94.
3
4
1H) (H-14,16), 6.80 and 6.68 (two AB dd, Jortho ) 7.9 Hz, Jmeta
4
) 1.7 Hz, 4H, H-5,6,8,9) 5.98 (dd, Jmeta ) 1.7 and 0.5 Hz, 1H,
H-18), 6.12 and 5.96 (two s, 4H, 2 × ) CH2), 4.74 and 3.70 (AB
system, 2Jgem ) 12.2 Hz, 4H, H2-3,10); 13C NMR (75 MHz, CDCl3)
δ 152.4 (C-1,12), 135.5 and 130.3 (C-4,7,13,17), 129.9, 129.3, and
127.4 (C-5,6,8,9,14,16), 127.9 (C-15), 123.8 (C-18), 118.0 (2 ×
dCH2), 64.4 (C-3,10); MS (70 eV, EI) m/z (%) 328 (53) [M+],
310 (17), 279 (31), 262 (16), 261 (20), 229 (21), 128 (16), 127
(16), 104 (100), 103 (19); Elem anal. Calcd (%) for C18H16O2S2
(328.45): C, 65.82; H, 4.91. Found: C, 65.54; H, 4.96.
meso-1,12-Dimethylene-2,11-dithia [3.3]parametacyclophane
2,11-Dioxide (26). meso-Compound 26 was prepared, together with
its racemate isomer 27, from 1,3-diethynylbenzene and disulfoxide
11 [(via 1,4-benzenedimethanesulfenic acid (16)] following pro-
cedure C (entry 4 in Table 1). The less mobile CP 26 was isolated
after chromatographic purification as a white solid decomposing
at 100 °C. TLC Rf (EtOAc/petrol 7.5:2.5) 0.12; 1H NMR (300 MHz,
More Mobile 1,4-Bis{[1-(3-ethynylphenyl)ethenylsulfinyl]-
methyl}benzene 23. Compound 23 was prepared, together with
its diastereoisomer 24, from 1,3-diethynylbenzene and disulfoxide
11 [(via 1,4-benzenedimethanesulfenic acid (16)] following pro-
cedure C (entry 2 in Table 1). The more mobile adduct 23 was
isolated after chromatographic separation as a white solid melting
at 100 °C. TLC Rf (EtOAc/petrol 7.5:2.5) 0.46; 1H NMR (300 MHz,
CDCl3) δ 7.6-7.4 (m, 8H, 2 × H-2′,4′,5′,6′), 7.04 (s, 4H,
H-2,3,5,6), 5.93 and 5.73 (two s, 4H, 2 × dCH2), 3.97 and 3.58
3
CDCl3) δ 7.18 (t, Jortho ) 7.8 Hz, 1H, H-15), 7.03 and 6.43 (two
3
4
split s, 4H, H-5,6,8,9) 6.99 (dd, Jortho ) 7.8 Hz, Jmeta ) 1.5 Hz,
2H, H-14,16), 6.21 and 5.95 (two s, 4H, 2 × dCH2), 6.02 (t, 4Jmeta
) 1.5 Hz, 1H, H-18), 4.92 and 3.42 (AB system, 2Jgem ) 11.8 Hz,
4H, H2-3,10); 13C NMR (75 MHz, CDCl3) δ 153.5 (C-1,12), 136.3
and 130.8 (C-4,7,13,17), 130.1, 128.5 and 128.1 (C-5,6,8,9,14,-
16), 128.2 (C-15), 127.5 (C-18), 117.7 (2 × dCH2), 66.3 (C-3,-
10); Elem anal. Calcd (%) for C18H16O2S2 (328.45): C, 65.82; H,
4.91. Found: C, 65.84; H, 4.89.
2
(AB system, Jgem ) 13.3 Hz, 4H, 2 × SCH2), 3.17 (s, 2H, 2 ×
tCH); 13C NMR (75 MHz, CDCl3) δ 150.4 (2 × CdCH2), 134.2
(2 × C-1,4), 133.0 (2 × C-4′), 130.3 (C-2,3,5,6), 130.0 (2 × C-2′),
129.3 (2 × C-5′), 129.2 (2 × C-1′), 126.9 (2 × C-6′), 123.3 (2 ×
C-3′), 119.1 (2 × dCH2), 82.6 (2 × CtCH), 78.5 (2 × tCH),
57.1 (2 × SCH2); Elem anal. Calcd (%) for C28H22O2S2 (454.61):
C, 73.98; H, 4.88. Found: C, 73.86; H, 4.68.
1,12-Dimethylene-2,11-dithia[3.3]paraparacyclophane 2,2,11,-
11-Tetraoxide (28). Disulfoxide 25 (0.2 g, 0.61 mmol) was
oxidized following the general procedure B. Disulfone 28 was
obtained as a white solid (0.2 g, 0.58 mmol, 95%) decomposing at
Less Mobile 1,4-Bis{[1-(3-ethynylphenyl)ethenylsulfinyl]-
methyl}benzene 24. Compound 24 was prepared, together with
its diastereoisomer 23, from 1,3-diethynylbenzene and disulfoxide
11 [(via 1,4-benzenedimethanesulfenic acid (16)] following pro-
cedure C (entry 2 in Table 1). The less mobile adduct 24 was
isolated after chromatographic separation as a white solid melting
at 105 °C. TLC Rf (EtOAc/petrol 7.5:2.5) 0.44; 1H NMR (300 MHz,
1
190 °C. TLC Rf 0.82; H NMR (300 MHz, CDCl3) δ 7.40 (s, 4H,
H-14,15,17,18), 7.10 (s, 4H, H-5,6,8,9), 6.61 and 6.17 (two s, 4H,
2 × dCH2), 4.30 (s, 4H, H2-3,10); 13C NMR (75 MHz, CDCl3) δ
148.9 (C-1,12), 131.5 (C-5,6,8,9), 129.8 (C-4,7,13,16), 129.6 (C-
J. Org. Chem, Vol. 72, No. 12, 2007 4493

Aversa et al.
14,15,17,18), 126.8 (2 × dCH2), 63.6 (C-3,10); Elem anal. Calcd
(%) for C18H16O4S2 (360.45): C, 59.98; H, 4.47. Found: C, 59.92;
H, 4.49.
after chromatographic purification as a white solid decomposing
at 110 °C. TLC Rf (EtOAc/petrol 7.5:2.5) 0.09; 1H NMR (300 MHz,
CDCl3) δ 7.53 and 6.48 (two split d, 4Jmeta ) 2.3 Hz, 4H, H-14,15,
2
17,18), 7.31 (m, 3H, H-5-7), 6.11 and 6.00 (two d, Jgem
)
1,12-Dimethylene-2,11-dithia[3.3]parametacyclophane 2,2,11,-
11-Tetraoxide (29). A 1:1 mixture of disulfoxides 26 and 27
(0.2 g, 0.61 mmol) was oxidized following the general procedure
B. Disulfone 29 was obtained as a white solid (0.2 g, 0.58 mmol,
0.7 Hz, 4H, 2 × dCH2), 5.42 (br s, 1H, H-9), 4.06 and 3.90 (AB
system, 2Jgem ) 12.6 Hz, 4H, H2-3,10); 13C NMR (75 MHz, CDCl3)
δ 154.3 (C-1,12), 135.0 and 132.1 (C-4,8,13,16), 129.4, 129.3, and
126.6 (C-5,7,14,15,17,18), 129.2 and 128.7 (C-6,9), 115.8 (2 ×
dCH2), 63.7 (C-3,10); Elem anal. Calcd (%) for C18H16O2S2
(328.45): C, 65.82; H, 4.91. Found: C, 65.90; H, 4.95.
1
95%) decomposing at 190 °C. TLC Rf 0.80; H NMR (300 MHz,
CDCl3) δ 7.54 (dd, 3Jortho ) 7.9 Hz, 4Jmeta ) 1.8 Hz, 2H, H-14,16),
3
7.23 (t, Jortho ) 7.9 Hz, 1H, H-15), 7.00 (s, 4H, H-5,6,8,9), 6.56
4
and 5.99 (two s, 4H, 2 × dCH2), 5.90 (t, Jmeta ) 1.8 Hz, 1H,
rac-1,12-Dimethylene-2,11-dithia[3.3]metametacyclophane 2,-
11-Dioxide (40). Racemate 40 was prepared, together with its meso-
isomer 39, from 1,3-diethynylbenzene and disulfoxide 12 [(via 1,3-
benzenedimethanesulfenic acid (17)] following procedure C (entry
8 in Table 1). The more mobile 40 was isolated after chromato-
graphic purification as a white solid decomposing at 60 °C. TLC
Rf (EtOAc/petrol 7.5:2.5) 0.12; 1H NMR (300 MHz, CDCl3) δ 7.2-
7.0 (m, 6H, H-5-7,14-16), 6.80 (s, 1H, H-18), 6.20 (br s, 1H,
H-9), 6.10 and 6.01 (two s, 4H, 2 × dCH2), 4.28 and 3.92 (AB
system, 2Jgem ) 13.1 Hz, 4H, H2-3,10); 13C NMR (75 MHz, CDCl3)
δ 152.6 (C-1,12), 135.0 and 130.4 (C-4,8,13,17), 132.8, 129.6,
129.2, 129.0 and 127.1 (C-5-7,9,14-16,18), 117.4 (2 × dCH2),
63.2 (C-3,10); MS (70 eV, EI) m/z (%) 328 (1) [M+], 105 (6), 104
(4), 84 (3), 77 (5), 49 (3), 44 (7), 40 (6), 32 (100), 29 (6); Elem
anal. Calcd (%) for C18H16O2S2 (328.45): C, 65.82; H, 4.91.
Found: C, 65.72; H, 4.85.
H-18), 4.42 (s, 4H, H2-3,10); 13C NMR (75 MHz, CDCl3) δ 149.0
(C-1,12), 133.2 and 128.9 (C-4,7,13,17), 140.4, 140.0, 129.1, 129.0,
and 127.2 (C-5,6,8,9,14-16,18), 121.0 (2 × dCH2), 64.5 (C-3,-
10); Elem anal. Calcd (%) for C18H16O4S2 (360.45): C, 59.98; H,
4.47. Found: C, 60.25; H, 4.53.
More Mobile 1,3-Bis{[1-(4-ethynylphenyl)ethenylsulfinyl]-
methyl}benzene 34. Compound 34 was prepared, together with
its stereoisomer 35, from 1,4-diethynylbenzene and disulfoxide 12
[(via 1,3-benzenedimethanesulfenic acid (17)] following procedure
C (entry 5 in Table 1). The more mobile adduct 34 was isolated
after chromatographic separation as a white solid. TLC Rf (EtOAc/
petrol 7.5:2.5) 0.52; 1H NMR (300 MHz, CDCl3) δ 7.56 (AA′BB′
3
3
d, Jortho ) 8.5 Hz, 4H, 2 × H-3′,5′), 7.42 (AA′BB′ d, Jortho
)
8.5 Hz, 4H, 2 × H-2′,6′), 7.4-7.0 (m, 3H, H-4-6), 6.76 (br s, 1H,
H-2), 5.97 and 5.74 (two s, 4H, 2 × dCH2), 3.95 and 3.54 (AB
system, 2Jgem ) 13.4 Hz, 4H, 2 × SCH2), 3.20 (s, 2H, 2 × tCH);
Elem anal. Calcd (%) for C28H22O2S2 (454.61): C, 73.98; H, 4.88.
Found: C, 74.00; H, 4.68.
meso-1,12-Dimethylene-2,11-dithia[3.3]metametacyclophane
2,11-Dioxide (39). meso-Compound 39 was prepared, together with
its racemate isomer 40, from 1,3-diethynylbenzene and disulfoxide
12 [(via 1,3-benzenedimethanesulfenic acid (17)] following pro-
cedure C (entry 8 in Table 1). The less mobile CP 39 was isolated
after chromatographic purification as a white solid decomposing
at 115 °C. Single crystals suitable for X-ray structure were obtained
by recrystallization from CHCl3. TLC Rf (EtOAc/petrol 7.5:2.5)
Less Mobile 1,3-Bis{[1-(4-ethynylphenyl)ethenylsulfinyl]-
methyl}benzene 35. Compound 35 was prepared, together with
its stereoisomer 34, from 1,4-diethynylbenzene and disulfoxide 12
[(via 1,3-benzenedimethanesulfenic acid (17)] following procedure
C (entry 5 in Table 1). The less mobile adduct 35 was isolated
after chromatographic separation as a white solid. TLC Rf (EtOAc/
petrol 7.5:2.5) 0.51; 1H NMR (300 MHz, CDCl3) δ 7.55 (AA′BB′
1
0.10; H NMR (300 MHz, CDCl3) δ 7.1-6.9 (m, 8H, H-5-7,9,-
14-16,18), 6.21 and 6.06 (two d, 2Jgem ) 0.5 Hz, 4H, 2 × dCH2),
3
3
2
d, Jortho ) 8.6 Hz, 4H, 2 × H-3′,5′), 7.40 (AA′BB′ d, Jortho
)
4.54 and 3.83 (AB system, Jgem ) 12.3 Hz, 4H, H2-3,10); 13C
8.6 Hz, 4H, 2 × H-2′,6′), 7.3-7.0 (m, 3H, H-4-6), 6.82 (br s, 1H,
H-2), 5.98 and 5.82 (two s, 4H, 2 × dCH2), 3.92 and 3.56 (AB
system, 2Jgem ) 13.3 Hz, 4H, 2 × SCH2), 3.20 (s, 2H, 2 × tCH);
Elem anal. Calcd (%) for C28H22O2S2 (454.61): C, 73.98; H, 4.88.
Found: C, 73.67; H, 4.94.
NMR (75 MHz, CDCl3) δ 153.4 (C-1,12), 135.6 and 130.2
(C-4,8,13,17), 129.7, 129.5, 128.8, and 127.2 (C-5-7,9,14-16,-
18), 117.1 (2 × dCH2), 64.4 (C-3,10); IR (CHCl3) 3031, 1047
(SO), 908 cm-1; MS (70 eV, EI) m/z (%) 328 (2) [M+], 263 (3),
229 (3), 105 (3), 104 (10), 103 (4), 78 (4), 32 (18), 28 (100); Elem
anal. Calcd (%) for C18H16O2S2 (328.45): C, 65.82; H, 4.91.
Found: C, 65.75; H, 4.95.
More Mobile 1,3-Bis{[1-(3-ethynylphenyl)ethenylsulfinyl]-
methyl}benzene 36. Compound 36 was obtained, together with
its diastereoisomer 37 and phanes 39/40, from 1,3-diethynylbenzene
and disulfoxide 12 [(via 1,3-benzenedimethanesulfenic acid (17)]
following procedure C (entry 6 in Table 1). The more mobile adduct
36 was isolated after chromatographic separation as an oil. TLC Rf
1,12-Dimethylene-2,11-dithia[3.3]metametacyclophane 2,2,-
11,11-Tetraoxide (41). A 1:1 mixture of disulfoxides 39 and 40
(0.1 g, 0.30 mmol) was oxidized following the general procedure
B. Disulfone 41 was obtained as a white solid (0.1 g, 0.28 mmol,
1
1
(EtOAc/petrol 7.5:2.5) 0.51; H NMR (300 MHz, CDCl3) δ 7.6-
93%) decomposing at 185 °C. TLC Rf 0.80; H NMR (300 MHz,
CDCl3) δ 7.53 (dd, 3Jortho ) 7.9 Hz, 4Jmeta ) 1.8 Hz, 2H, H-14,16),
6.8 (m, 12H, ArH), 5.96 and 5.82 (two s, 4H, 2 × dCH2), 3.92
2
4
and 3.59 (AB system, Jgem ) 13.2 Hz, 4H, 2 × SCH2), 3.15 (s,
7.44 (t, Jmeta ) 1.7 Hz, 1H, H-18), 7.3-7.1 (m, 4H, H-5-7,15),
2H, 2 × tCH); Elem anal. Calcd (%) for C28H22O2S2 (454.61):
6.57 and 6.07 (two s, 4H, 2 × dCH2), 6.50 (br s, 1H, H-9), 4.28
(s, 4H, H2-3,10); 13C NMR (75 MHz, CDCl3) δ 149.0 (C-1,12),
133.3 and 128.4 (C-4,8,13,17), 134.0, 132.9, 131.5, 129.8, 129.1
and 128.5 (C-5-7,9,14-16,18), 127.2 (2 × dCH2), 62.2 (C-3,-
10); MS (70 eV, EI) m/z (%) 360 (14) [M+], 231 (33), 217 (86),
216 (70), 202 (73), 192 (33), 191 (33), 127 (55), 28 (100); Elem
anal. Calcd (%) for C18H16O4S2 (360.45): C, 59.98; H, 4.47.
Found: C, 59.67; H, 4.16.
C, 73.98; H, 4.88. Found: C, 74.01; H, 4.95.
Less Mobile 1,3-Bis{[1-(3-ethynylphenyl)ethenylsulfinyl]-
methyl}benzene 37. Compound 37 was obtained, together with
its diastereoisomer 36 and phanes 39/40, from 1,3-diethy-
nylbenzene and disulfoxide 12 [(via 1,3-benzenedimethane-
sulfenic acid (17)] following procedure C (entry 8 in Table 1). The
less mobile 1,3-bis{[1-(3-ethynylphenyl)ethenylsulfinyl]methyl}-
benzene adduct 37 was isolated after chromatographic separation
as an oil. TLC Rf (EtOAc/petrol 7.5:2.5) 0.50; 1H NMR (300 MHz,
CDCl3) δ 7.6-6.7 (m, 12H, ArH), 5.95 and 5.75 (two s, 4H, 2 ×
More Mobile 1,3-Bis[1-(4-ethynylphenyl)ethenylsulfinyl]-
benzene 30. Compound 30 was prepared, together with its
stereoisomer 31, from 1,4-diethynylbenzene and disulfoxide 13 [(via
1,3-benzenedisulfenic acid (18)] following procedure C (entries 9
and 10 in Table 1). The more mobile adduct 30 was isolated after
chromatographic separation as a light yellow solid melting at
164 °C. TLC Rf (EtOAc/petrol 7.5:2.5) 0.72; 1H NMR (300 MHz,
2
dCH2), 3.95 and 3.56 (AB system, Jgem ) 13.0 Hz, 4H, 2 ×
SCH2), 3.16 (s, 2H, 2 × tCH); Elem anal. Calcd (%) for
C28H22O2S2 (454.61): C, 73.98; H, 4.88. Found: C, 74.03; H, 4.90.
meso-1,12-Dimethylene-2,11-dithia[3.3]metaparacyclophane
2,11-Dioxide (38). Following procedure C (entry 7 in Table 1),
compound 38 was prepared from 1,4-diethynylbenzene and disul-
foxide 12 [(via 1,3-benzenedimethanesulfenic acid (17)] and isolated
CDCl3) δ 7.52 (t, 4Jmeta ) 1.7 Hz, 1H, H-2), 7.41 (AA′ m, 3Jortho
)
)
3
4
8.5 Hz, 4H, 2 × H-3′,5′), 7.34 (m, Jortho ) 8.5 Hz, Jmeta
3
4
1.7 Hz, 1H) and 7.33 (m, Jortho ) 6.5 Hz, Jmeta ) 1.7 Hz, 1H,
4494 J. Org. Chem., Vol. 72, No. 12, 2007

Cage and Bi/Tripodal Benzene Sulfoxides
H-4,6), 7.25 (dd, 3Jortho ) 8.5 and 6.5 Hz, 1H, H-5), 7.05 (BB′ m,
C3sym-1,3,5-Tris{[1-(phenyl)ethenylsulfinyl]methyl}-
benzene (42). Compound 42 was prepared, together with its
diastereoisomer 43, from phenylacetylene and trisulfoxide 14 [(via
1,3,5-benzenetrimethanesulfenic acid (19)] following procedure C
(entry 13 in Table 1). The more mobile adduct 42 was isolated
after chromatographic separation as a light yellow low-melting solid.
TLC Rf (EtOAc/petrol 9:1) 0.46; H NMR (300 MHz, CDCl3) δ
7.5-7.4 (m, 15H, 3 × H-2′-6′), 6.79 (s, 3H, H-2,4,6), 5.97 and
2
3Jortho ) 8.5 Hz, 4H, 2 × H-2′,6′), 6.16 and 5.86 (two d, Jgem
)
0.9 Hz, 4H, 2 × dCH2), 3.17 (s, 2H, 2 × tCH); 1H NMR
4
(400 MHz, C6D6) δ 7.62 (t, Jmeta ) 1.6 Hz, 1H, H-2), 7.12 (AA′
3
3
m, Jortho ) 8.4 Hz, 4H, 2 x H-3′,5′), 6.95 (dd, Jortho ) 7.7 Hz,
4Jmeta ) 1.6 Hz, 2H, H-4,6), 6.58 (BB′ m, Jortho ) 8.4 Hz, 4H,
3
3
1
2 × H-2′,6′), 6.39 (t, Jortho ) 7.7 Hz, 1H, H-5), 6.12 and 5.36
(two s, 4H, 2 × dCH2), 2.68 (s, 2H, 2 × tCH); 13C NMR (75
MHz, CDCl3) δ 153.3 (2 × CdCH2), 144.3 (C-1,3), 133.4 (2 ×
C-1′), 132.3 (2 × C-3′,5′), 129.3 (C-5), 127.3 and 127.2 (C-4,6,
2 × C-2′,6′), 123.1 (2 × C-4′), 120.8 (C-2), 117.1 (2 × dCH2),
82.6 (2 × CtCH), 79.1 (2 × tCH); MS (70 eV, EI) m/z (%) 426
(0.1) [M+], 300 (10), 129 (12), 128 (12), 127 (100), 126 (16), 101
(10), 77 (16), 51 (10); Elem anal. Calcd (%) for C26H18O2S2
(426.55): C, 73.21; H, 4.25. Found: C, 73.58; H, 4.58.
2
5.70 (two s, 6H, 3 × dCH2), 3.95 and 3.48 (AB system, Jgem
)
13.3 Hz, 6H, 3 × SCH2); 13C NMR (75 MHz, CDCl3) δ 150.9
(3 × CdCH2), 133.9 (C-1,3,5), 132.6 (C-2,4,6), 129.5 (3 × C-4′),
129.4 (3 × C-1′), 129.3 (3 × C-3′,5′), 126.6 (3 × C-2′,6′), 118.4
(3 × dCH2), 56.8 (3 × SCH2); Elem anal. Calcd (%) for
C33H30O3S3 (570.78): C, 69.44; H, 5.30. Found: C, 69.52; H, 5.68.
noC3sym-1,3,5-Tris{[1-(phenyl)ethenylsulfinyl]methyl}-
benzene (43). Compound 43 was prepared, together with its
diastereoisomer 42, from phenylacetylene and trisulfoxide 14 [(via
1,3,5-benzenetrimethanesulfenic acid (19)] following procedure C
(entry 13 in Table 1). The less mobile adduct 43 was isolated after
chromatographic separation as a light yellow low-melting solid.
Less Mobile 1,3-Bis[1-(4-ethynylphenyl)ethenylsulfinyl]benzene
31. Compound 31 was prepared, together with its stereoisomer 30,
from 1,4-diethynylbenzene and disulfoxide 13 [(via 1,3-benzene-
disulfenic acid (18)] following procedure C (entries 9 and 10 in
Table 1). The less mobile adduct 31 was isolated after chromato-
graphic separation as a light yellow solid melting at 125 °C. TLC
Rf (EtOAc/petrol 7.5:2.5) 0.69; 1H NMR (300 MHz, CDCl3) δ 7.60
1
TLC Rf (EtOAc/petrol 9:1) 0.45; H NMR (300 MHz, CDCl3) δ
7.5-7.4 (m, 15H, 3 × H-2′-6′), 6.84 (s, 2H) and 6.78 (s, 1H) (H-
4
3
2,4,6), 5.98 and 5.82 (two s, 2H, dCH2), 5.97 and 5.74 (two s,
(t, Jmeta ) 1.6 Hz, 1H, H-2), 7.38 (AA′ m, Jortho ) 8.5 Hz, 4H,
2
3
4H, 2 × CH2), 3.91 and 3.51 (AB system, Jgem ) 13.2 Hz, 4H,
2 × H-3′,5′), 7.4-7.3 (m, 2H, H-4,6), 7.27 (dd, Jortho ) 8.7 and
2 × SCH2), 3.89 and 3.55 (AB system, 2Jgem ) 12.8 Hz, 2H, SCH2);
13C NMR (75 MHz, CDCl3) δ 151.7 and 151.2 (3 × CdCH2),
133.9 (C-1,3,5), 132.2 and 132.1 (C-2,4,6), 130.3 and 130.0 (3 ×
C-1′), 129.5 (3 × C-4′), 129.3 (3 × C-3′,5′), 126.6 (3 × C-2′,6′),
118.3 and 118.1 (3 × dCH2), 58.1 and 57.3 (3 × SCH2); Elem
anal. Calcd (%) for C33H30O3S3 (570.78): C, 69.44; H, 5.30.
Found: C, 69.38; H, 5.45.
6.4 Hz, 1H, H-5), 7.07 (BB′ m, 3Jortho ) 8.5 Hz, 4H, 2 × H-2′,6′),
2
6.21 and 5.93 (two d, Jgem ) 0.8 Hz, 4H, 2 × dCH2), 3.15 (s,
2H, 2 × tCH); 13C NMR (75 MHz, CDCl3) δ 153.0 (2 × Cd
CH2), 144.2 (C-1,3), 133.2 (2 × C-1′), 132.3 (2 × C-3′,5′), 129.5
(C-5), 127.5 and 127.3 (C-4,6, 2 × C-2′,6′), 123.1 (2 × C-4′), 121.6
(C-2), 118.6 (2 × dCH2), 82.6 (2 × CtCH), 79.0 (2 × tCH);
Elem anal. Calcd (%) for C26H18O2S2 (426.55): C, 73.21; H, 4.25.
Found: C, 73.18; H, 4.50.
(R*,R*,R*)- and (R*,R*,S*)-1,12,19-Trimethylene-2,11,20-
trithia[33](1,3,5)cyclophane 2,11,20-Trioxides (48) and (49). C3-
Symmetrical 48 was prepared, together with its stereoisomer 49,
from 1,3,5-triethynylbenzene and trisulfoxide 14 [(via 1,3,5-
benzenetrimethanesulfenic acid (19)] following procedure C (entry
16 in Table 1). After chromatographic purification, various mixtures
of the cage compounds 48/49 as white solids were obtained; TLC
Rf (EtOAc/petrol 9:1) 0.03; Elem anal. Calcd (%) for C21H18O3S3
(414.56): C, 60.84; H, 4.38. Found: C, 60.72; H, 4.30. The
following NMR data come from suitably enriched mixtures: 1H
NMR of (R*,R*,R*)-1,12,19-trimethylene-2,11,20-trithia[33](1,3,5)-
cyclophane 2,11,20-trioxide (48; 300 MHz, CDCl3) δ 7.11 and 6.92
More Mobile 1,3-Bis[1-(3-ethynylphenyl)ethenylsulfinyl]-
benzene 32. Compound 32 was prepared, together with its
stereoisomer 33, from 1,3-diethynylbenzene and disulfoxide 13 [(via
1,3-benzenedisulfenic acid (18)] following procedure C (entries 11
and 12 in Table 1). The more mobile adduct 32 was isolated after
chromatographic separation as a light yellow solid melting at
1
78 °C. TLC Rf (EtOAc/petrol 7.5:2.5) 0.72; H NMR (300 MHz,
CDCl3) δ 7.52 (t, 4Jmeta ) 1.5 Hz, 1H, H-2), 7.45 (dt, 3Jortho ) 7.7,
4Jmeta ) 1.4 Hz, 2H, 2 × H-4′ or H-6′), 7.3-7.2 (m, 3H, H-4-6),
3
4
7.27 (t, Jortho ) 7.7 Hz, 2H, 2 × H-5′), 7.22 (t, Jmeta ) 1.4 Hz,
3
4
2H, 2 × H-2′), 7.07 (dt, Jortho ) 7.7, Jmeta ) 1.4 Hz, 2H, 2 ×
2
2
(two br s, 6H, ArH), 6.21 and 6.04 (two d, Jgem ) 0.6 Hz, 6H,
H-4′ or H-6′), 6.14 and 5.83 (two d, Jgem ) 0.8 Hz, 4H, 2 × d
3 × dCH2), 4.62 and 3.77 (AB system, 2Jgem ) 12.1 Hz, 6H, H2-
3,10,21). 1H NMR of (R*,R*,S*)-1,12,19-trimethylene-2,11,20-
trithia[33](1,3,5)cyclophane 2,11,20-trioxide (49; 300 MHz, CDCl3)
δ 7.2-6.6 (m, 6H, ArH), 6.2-6.0 (m, 6H, 3 × dCH2), 4.5-3.8
(m, 6H, H2-3,10,21).
CH2), 3.13 (s, 2H, 2 × tCH); 13C NMR (75 MHz, CDCl3) δ 153.3
(2 × CdCH2), 144.3 (C-1,3), 133.5 (2 × C-1′), 132.8 (2 × C-4′),
130.9 (2 × C-2′), 129.3 (C-5), 128.8, 127.8, and 127.2 (C-4,6, 2 ×
C-5′,6′), 122.9 (2 × C-3′), 120.7 (C-2), 117.4 (2 × dCH2), 82.5
(2 × CtCH), 78.5 (2 × tCH); Elem anal. Calcd (%) for
C26H18O2S2 (426.55): C, 73.21; H, 4.25. Found: C, 73.34; H, 4.16.
Less Mobile 1,3-Bis[1-(4-ethynylphenyl)ethenylsulfinyl]benzene
33. Compound 33 was prepared, together with its stereoisomer 32,
from 1,3-diethynylbenzene and disulfoxide 13 [(via 1,3-benzene-
disulfenic acid (18)] following procedure C (entries 11 and 12 in
Table 1). The less mobile adduct 33 was isolated after chromato-
graphic separation as a light yellow solid melting at 130 °C. TLC
Rf (EtOAc/petrol 7.5:2.5) 0.69; 1H NMR (300 MHz, CDCl3) δ 7.62
1,12,19-Trimethylene-2,11,20-trithia[33](1,3,5)cyclophane 2,2,-
11,11,20,20-Hexaoxide (50). A mixture of trisulfoxides 48 and 49
(0.1 g, 0.24 mmol) was oxidized following the general procedure
B. Trisulfone 50 was obtained as a white solid (0.1 g, 0.22 mmol,
1
92%) decomposing at 250 °C. TLC Rf 0.78; H NMR (300 MHz,
CDCl3) δ 7.78 and 7.50 (two s, 6H, ArH), 6.69 and 6.09 (two s,
6H, 3 × dCH2), 4.39 (s, 6H, 3 × SCH2); MS (70 eV, EI) m/z (%)
462 (7) [M+], 270 (29), 239 (23), 104 (31), 57 (25), 55 (21), 44
(93), 43 (35), 41 (21), 32 (100); Elem anal. Calcd (%) for
C21H18O6S3 (462.56): C, 54.53; H, 3.92. Found: C, 54.31; H, 4.00.
(R*,R*,R*)-5,7,9-Trimethyl-1,12,19-trimethylene-2,11,20-trithia-
[33](1,3,5)cyclophane 2,11,20-Trioxide (51). Cage 51 was pre-
pared, together with its diastereoisomer 52, from 1,3,5-triethynyl-
benzene and trisulfoxide 15 [(via 2,4,6-trimethyl-1,3,5-
benzenetrimethanesulfenic acid (20)] following procedure C (entry
17 in Table 1). The more mobile adduct 51 was isolated after
chromatographic separation as a white solid decomposing at
4
3
4
(t, Jmeta ) 1.8 Hz, 1H, H-2), 7.42 (dt, Jortho ) 7.6, Jmeta
)
1.5 Hz, 2H, 2 × H-4′ or H-6′), 7.35 (m, 2H, H-4,6), 7.27 (dd, 3Jortho
4
) 8.7 and 6.4, 1H, H-5), 7.24 (t, Jmeta ) 1.5 Hz, 2H, 2 × H-2′),
3
3
7.23 (t, Jortho ) 7.6 Hz, 2H, 2 × H-5′), 7.06 (dt, Jortho ) 7.6,
4Jmeta ) 1.5 Hz, 2H, 2 × H-4′ or H-6′), 6.21 and 5.92 (two d,
2Jgem ) 0.8 Hz, 4H, 2 × dCH2), 3.10 (s, 2H, 2 × tCH); 13C
NMR (75 MHz, CDCl3) δ 153.0 (2 × CdCH2), 144.2 (C-1,3),
133.3 (2 × C-1′), 132.9 (2 × C-4′), 131.0 (2 × C-2′), 129.4 (C-5),
128.7, 127.9, and 127.7 (C-4,6, 2 × C-5′,6′), 122.8 (2 × C-3′),
121.6 (C-2), 118.6 (2 × dCH2), 82.6 (2 × CtCH), 78.4 (2 ×
tCH); Elem anal. Calcd (%) for C26H18O2S2 (426.55): C, 73.21;
H, 4.25. Found: C, 73.19; H, 4.60.
1
180 °C. TLC Rf (EtOAc/petrol 9:1) 0.05; H NMR (300 MHz,
CDCl3) δ 7.24 (s, 3H, ArH), 6.20 and 6.10 (two s, 6H, 3 ×
2
dCH2), 4.60 and 4.17 (AB system, Jgem ) 12.6 Hz, 6H, H2-3,-
J. Org. Chem, Vol. 72, No. 12, 2007 4495

Aversa et al.
10,21), 2.40 (s, 9H, 3 × Me); Elem anal. Calcd (%) for C24H24O3S3
(456.64): C, 63.13; H, 5.30. Found: C, 63.26; H, 5.65.
13C NMR (75 MHz, CDCl3) δ 151.0 and 150.4 (3 × CdCH2),
134.1 (C-1,3,5), 133.0 (3 × C-3′,5′), 132.3 and 132.1 (C-2,4,6),
130.1 and 129.8 (3 × C-1′), 126.6 and 126.5 (3 × C-2′,6′), 123.4
(3 × C-4′), 119.2 and 118.9 (3 × dCH2), 82.7 (3 × CtCH), 79.1
(3 × tCH), 58.1 and 57.1 (3 × SCH2); Elem anal. Calcd (%) for
C39H30O3S3 (642.85): C, 72.87; H, 4.70. Found: C, 72.62; H, 4.85.
C3sym-1,3,5-Tris{[1-(3,5-diethynylphenyl)ethenylsulfinyl]-
methyl}benzene (44). Compound 44 was prepared, together with
its diastereoisomer 45 and the cages 48/49, from 1,3,5-triethynyl-
benzene and trisulfoxide 14 [(via 1,3,5-benzenetrimethanesulfenic
acid (19)] following procedure C (entry 14 in Table 1). The more
mobile adduct 44 was isolated after chromatographic separation as
a yellow solid melting at 94 °C. TLC Rf (EtOAc/petrol 9:1) 0.80;
1H NMR (300 MHz, CDCl3) δ 7.6-7.5 (m, 9H, 3 × H-2′,3′,5′),
3 × dCH2), 3.95 and 3.54 (AB system, 2Jgem ) 13.2 Hz, 6H, 3 ×
SCH2), 3.18 (s, 6H, 6 × tCH); 13C NMR (75 MHz, CDCl3) δ
149.2 (3 × CdCH2), 136.2 (3 × C-4′), 134.6 (C-1,3,5), 132.6
(3 × C-2′,6′), 130.3 (C-2,4,6), 129.0 (3 × C-1′), 123.6 (3 × C-3′.5′),
120.4 (3 × dCH2), 81.7 (3 × CtCH), 79.3 (3 × tCH), 56.5
(3 × SCH2); Elem anal. Calcd (%) for C45H30O3S3 (714.92): C,
75.60; H, 4.23. Found: C, 75.66; H, 4.55.
(R*,R*,S*)-5,7,9-Trimethyl-1,12,19-trimethylene-2,11,20-trithia-
[33](1,3,5)cyclophane 2,11,20-Trioxide (52). Cage 52 was pre-
pared, together with its diastereoisomer 51, from 1,3,5-triethynyl-
benzene and trisulfoxide 15 [(via 2,4,6-trimethyl-1,3,5-
benzenetrimethanesulfenic acid (20)] following procedure C (entry
17 in Table 1). The less mobile adduct 52 was isolated after
chromatographic separation as a white solid decomposing at
1
180 °C. TLC Rf (EtOAc/petrol 9:1) 0.04; H NMR (300 MHz,
CDCl3) δ 7.6-6.9 (m, 3H, ArH), 6.30, 6.19, 6.13, 6.12, 6.08, and
6.05 (six s, 6H, 3 × dCH2), 4.8-4.0 (m, 6H, H2-3,10,21), 2.72,
2.11, and 2.05 (three s, 9H, 3 × Me); Elem anal. Calcd (%) for
C24H24O3S3 (456.64): C, 63.13; H, 5.30. Found: C, 63.10; H, 5.37.
5,7,9-Trimethyl-1,12,19-trimethylene-2,11,20-trithia[33](1,3,5)-
cyclophane 2,2,11,11,20,20-Hexaoxide (53). A mixture of trisul-
foxides 51 and 52 (0.2 g, 0.44 mmol) was oxidized following the
general procedure B. Trisulfone 53 was obtained as a white solid
(0.2 g, 0.40 mmol, 91%), decomposing at 250 °C. TLC Rf 0.80;
1H NMR (300 MHz, CDCl3) δ 8.10 (s, 3H, ArH), 6.71 and 6.19
2
6.70 (s, 3H, H-2,4,6), 5.98 and 5.73 (two d, Jgem ) 0.6 Hz, 6H,
2
(two d, Jgem ) 0.8 Hz, 6H, 3 × dCH2), 4.73 (s, 6H, 3 × SCH2),
2.50 (s, 9H, 3 × Me); Elem anal. Calcd (%) for C24H24O6S3
(504.64): C, 57.12; H, 4.79. Found: C, 57.31; H, 4.55.
noC3sym-1,3,5-Tris{[1-(3,5-diethynylphenyl)ethenylsulfinyl]-
methyl}benzene (45). Compound 45 was prepared, together with
its diastereoisomer 44 and the cages 48/49, from 1,3,5-triethynyl-
benzene and trisulfoxide 14 [(via 1,3,5-benzenetrimethanesulfenic
acid (19)] following procedure C (entry 14 in Table 1). Compound
45 was isolated after chromatographic separation as a yellow solid
melting at 110 °C. TLC Rf (EtOAc/petrol 9:1) 0.76; 1H NMR
C3sym-1,3,5-Tris{[1-(4-ethynylphenyl)ethenylsulfinyl]methyl}-
benzene (46). Compound 46 was prepared, together with its
diastereoisomer 47, from 1,4-diethynylbenzene and trisulfoxide 14
[(via 1,3,5-benzenetrimethanesulfenic acid (19)] following proce-
dure C (entry 15 in Table 1). The more mobile adduct 46 was
isolated after chromatographic separation as a yellow solid melting
1
at 95 °C. TLC Rf (EtOAc/petrol 9:1) 0.77; H NMR (300 MHz,
(300 MHz, CDCl3) δ 7.6-7.5 (m, 9H, 3 × H-2′,3′,5′), 6.78 (s,
3
2
CDCl3) δ 7.57 and 7.48 (AA′BB′ system, Jortho ) 8.5 Hz, 12H,
2H) and 6.75 (s, 1H) (H-2,4,6), 6.00 and 5.90 (two d, Jgem
)
2
3 × H-2′,3′,5′,6′), 6.73 (s, 3H, H-2,4,6), 6.02 and 5.69 (two s, 6H,
3 × ) CH2), 3.93 and 3.47 (AB system, 2Jgem ) 13.3 Hz, 6H, 3 ×
SCH2), 3.21 (s, 3H, 3 × tCH); 13C NMR (75 MHz, CDCl3) δ
149.8 (3 × CdCH2), 134.1 (C-1,3,5), 133.0 (3 × C-3′,5′), 132.8
(C-2,4,6), 128.9 (3 × C-1′), 126.5 (3 × C-2′,6′), 123.4 (3 × C-4′),
119.4 (3 × dCH2), 82.8 (3 × CtCH), 79.1 (3 × tCH), 56.3
(3 × SCH2); MS (FAB) m/z (%) 643 (9) [M + 1], 391 (19), 155
(46), 149 (27), 139 (21), 138 (54), 137 (100), 120 (19), 107 (32),
89 (29), 77 (25); Elem anal. Calcd (%) for C39H30O3S3 (642.85):
C, 72.87; H, 4.70. Found: C, 73.26; H, 4.68.
0.6 Hz, 2H, )CH2), 5.99 and 5.83 (two d, Jgem ) 0.8 Hz, 4H,
2
2 × dCH2), 3.91 and 3.59 (AB system, Jgem ) 13.2 Hz, 4H,
2 × SCH2), 3.87 and 3.61 (AB system, 2Jgem ) 13.1 Hz, 2H, SCH2),
3.18 (s, 6H, 6 × tCH); 13C NMR (75 MHz, CDCl3) δ 150.0 and
149.6 (3 × CdCH2), 136.2 (3 × C-4′), 134.6 (C-1,3,5), 132.4 and
132.0 (3 × C-2′,6′), 130.4 and 130.3 (C-2,4,6), 129.8 and 129.7
(3 × C-1′), 123.63 and 123.61 (3 × C-3′,5′), 120.3 (3 × dCH2),
81.7 (3 × CtCH), 79.3 (3 × tCH), 58.0 and 57.4 (3 × SCH2);
Elem anal. Calcd (%) for C45H30O3S3 (714.92): C, 75.60; H, 4.23.
Found: C, 75.42; H, 4.33.
noC3sym-1,3,5-Tris{[1-(4-ethynylphenyl)ethenylsulfinyl]-
methyl}benzene (47). Compound 47 was prepared, together with
its diastereoisomer 46, from 1,4-diethynylbenzene and trisulfoxide
14 [(via 1,3,5-benzenetrimethanesulfenic acid (19)] following
procedure C (entry 15 in Table 1). The less mobile adduct 47 was
isolated after chromatographic separation as a yellow solid melting
Acknowledgment. We thank the Universita` degli Studi di
Messina for financial support (PRA project) and Prof. S.
Pappalardo (Universita` degli Studi di Catania, Italy) for helpful
discussion.
Supporting Information Available: Experimental details of
X-ray crystallographic analyses, crystallographic data, and CIF files
of compounds 21 and 39 and 1H and 13C NMR spectra of all new
compounds. This material is available free of charge via the Internet
at http://pubs.acs.org.
1
at 97 °C. TLC Rf (EtOAc/petrol 9:1) 0.73; H NMR (300 MHz,
CDCl3) δ 7.6-7.4 (m, 12H, 3 × H-2′,3′,5′,6′), 6.80 (s, 2H) and
6.75 (s, 1H) (H-2,4,6), 6.02 and 5.86 (two s, 2H, )CH2), 6.00 and
2
5.77 (two s, 4H, 2 × CH2), 3.90 and 3.51 (AB system, Jgem
)
)
2
13.1 Hz, 4H, 2 × SCH2), 3.87 and 3.54 (AB system, Jgem
13.1 Hz, 2H, SCH2), 3.21 (s, 2H, 2 × tCH), 3.20 (s, 1H, tCH);
JO070449B
4496 J. Org. Chem., Vol. 72, No. 12, 2007