Dynamic NMR study of the rotation around "biphenyl-type" bonds in polycyclic sulfoxides

Article abstract of DOI:10.1021/jo010947z

In a recent paper, we reported on the base-catalyzed rearrangement of bis-propargylic sulfoxides that eventually leads to polycyclic products featuring an unsaturated, cyclic substituent such as cyclohexenyl or phenyl. Due to steric constraints, the latter is positioned roughly perpendicularly to the tricyclic core, and in most cases, two rotamers can be observed in the ground state. In the present work, we report on the synthesis and the products of both symmetrical and asymmetrical starting materials. We also measure, by NMR techniques, the rotation rate of the side chain for several such polycyclic sulfoxides. The barriers for this process, which is similar to a biphenyl rotation, are very strongly dependent on the nature of the substrate, ranging between <7 and 21.0 kcal·mol^-1 for sulfoxides with two five-membered rings and two seven-membered rings, respectively. These barriers can be successfully simulated by molecular-mechanics calculations, and the geometries of the transition states are discussed.

Full text of DOI:10.1021/jo010947z

J . Org. Chem. 2002, 67, 3277-3283
3277
Dyn a m ic NMR Stu d y of th e Rota tion a r ou n d “Bip h en yl-Typ e”
Bon d s in P olycyclic Su lfoxid es
Samuel Braverman, Yossi Zafrani, and Hugo E. Gottlieb*
Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel
gottlieb@mail.biu.ac.il
Received September 25, 2001
In a recent paper, we reported on the base-catalyzed rearrangement of bis-propargylic sulfoxides
that eventually leads to polycyclic products featuring an unsaturated, cyclic substituent such as
cyclohexenyl or phenyl. Due to steric constraints, the latter is positioned roughly perpendicularly
to the tricyclic core, and in most cases, two rotamers can be observed in the ground state. In the
present work, we report on the synthesis and the products of both symmetrical and asymmetrical
starting materials. We also measure, by NMR techniques, the rotation rate of the side chain for
several such polycyclic sulfoxides. The barriers for this process, which is similar to a biphenyl
rotation, are very strongly dependent on the nature of the substrate, ranging between <7 and 21.0
kcal‚mol-1 for sulfoxides with two five-membered rings and two seven-membered rings, respectively.
These barriers can be successfully simulated by molecular-mechanics calculations, and the
geometries of the transition states are discussed.
Sch em e 1
In tr od u ction
In the past decade, considerable attention has been
focused on cyclization reactions of diallenes or diacety-
lenes involving free-radical species.1 The trigger for
renewal of interest in this type of reaction was the
elegant mode of action of the naturally occurring ene-
diynes,2 whose biological activity involves a diradical
cycloaromatization.3 Recently, we became interested in
studying the effect of tandem cyclization and aromati-
zation of some novel sulfur- and selenium-bridged pro-
pargylic systems, which, besides their potential biological
activity, would also be of considerable mechanistic and
synthetic interest.4 During the course of our studies, we
found that π-conjugated bis-propargylic sulfoxides and
sulfones undergo facile isomerization to the correspond-
ing diallenes, followed by tandem cyclization and aro-
matization via a probable diradical intermediate, in the
presence of amine bases at room temperature (for the
case of sulfoxides, see Scheme 1). To test the generality
of the reactions reported in Scheme 1, we have examined
the reactivity of other dipropargylic compounds such as
4b.
as two broad signals of similar intensity (see Figure S1,
Supporting Information). This can be explained by pos-
tulating that, in the ground state, the cyclohexenyl ring
is roughly perpendicular to the plane of the aromatic ring.
Since the molecule contains a chiral sulfoxide moiety, this
arrangement constitutes a second chiral element, and
therefore, two diastereoisomers are possible. The latter
can interconvert via a process similar to the well-known
rotation of the aryl-aryl bond in biphenyls and can
therefore be called diastereorotamers (see Scheme 2).
A dynamic NMR experiment (EXSY, Figure S1) showed
that the barrier for this process is 18.1 kcal‚mol-1. We
prepared in a similar fashion the five-membered ring
equivalent 5a and were quite surprised to find that the
rotational barrier for this compound was too low to be
measured by NMR (<7 kcal‚mol-1). While the rotation
around the central bond in biphenyls has been well
studied,5 we could find only a few examples in the
literature6,7 for the equivalent process in simple olefin-
1
Interestingly, we found that in the H NMR spectrum
of polycyclic sulfoxide 5b, the olefinic proton appeared
(1) Selected reviews: (a) Nicolaou, K. C.; Smith, A. L. In Modern
Acetylene Chemistry; Stang, P. J ., Diedrich, F., Eds.; VCH: Weinheim,
1995; Chapter 7. (b) Grissom, J . W.; Gunawardena, G. U.; Klingberg,
D. Tetrahedron Report No. 399. Tetrahedron 1996, 52, 6453. (c) Wang,
K. K., Chem. Rev. 1996, 96, 207. (d) Maier, M. E. Synlett 1995, 13. (e)
Magnuse, P., Tetrahedron 1994, 50, 1397. (f) Nicolaou, K. C.; Dau, W.
M.; Tsay, S. C. Estevez, V. A. Science 1992, 256, 1172.
(2) For recent reviews, see: (a) Pogozelsky, W. K.; Tullius, T. D.
Chem. Rev. 1998, 98, 1089. (b) Maier, M. E.; Bosse, Folkert, Niestroj,
A. J . Eur. J . Org. Chem. 1999, 1, 1. (c) Thorson, J . S.; Shen, B.;
Whitwam, R. E.; Liu, W.; Li, Y.; Ahlert, J . Bioorg. Chem. 1999, 27,
172.
(3) Nicolaou, K. C.; Dai, W. M. Angew. Chem., Int. Ed. Engl. 1993,
32, 1387 and references cited therein.
(4) (a) Braverman, S.; Zafrani, Y.; Gottlieb, H. E. Tetrahedron Lett.
2000, 41, 2675. (b) Braverman, S.; Zafrani, Y.; Gottlieb, H. E.
Tetrahedron 2001, 57, 9177.
10.1021/jo010947z CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/12/2002

3278 J . Org. Chem., Vol. 67, No. 10, 2002
Braverman et al.
Sch em e 2
Sch em e 3a
substituted benzenes. This dramatic substitutional effect
encouraged us to investigate a series of unusual “biphe-
nyl-like” polycyclic sulfoxides substituted by aromatic (3,
18e, 19e), cyclic (5a -c, 18a , 19a ), and acyclic (19d )
groups (Schemes 2 and 5). The synthesis of polycyclic
sulfoxides such as 18a ,d ,e and 19a ,d ,e became possible
by the use of mixed propargylic sulfoxides that can cyclize
into two possible directions as shown in Scheme 5.
Resu lts
a
Key: (a) THPOCH2CCH, n-BuLi, TMEDA, THF, -78 °C; (b)
Syn th esis of P olycyclic Su lfoxid es. The desired
mixed propargyl sulfoxide 14a , as well as symmetrical
sulfoxides 4a ,c, was prepared by the procedure shown
in Scheme 3. Thus, cycloalkanols 6a ,c were formed by
treatment of the appropriate cycloalkanone with the
lithiated tetrahydro-2-(3-propynyloxy)-2H-pyran and
deprotected under methanolic acid conditions followed by
tandem mesylation/elimination to afford 7a ,c in 78 and
61% overall yields, respectively. For symmetrical sulfox-
ides, these mesylates were treated with sodium bromide
to give the propargyl bromides 8a ,c (81 and 27% yields).
The latter were then reacted with sodium sulfide to
furnish the corresponding sulfides 9a ,c in 62 and 98%
yields, which were oxidized to sulfoxides 4a ,c (42% yield
each). Asymmetrical sulfoxides 14a ,d ,e were conve-
niently obtained by the reaction of the appropriate
substituted propargyl bromides with propargyl thioac-
etates in the presence of potassium hydroxide, followed
by oxidation with sodium periodate. Thus, reaction of
mesylate 7a with potassium thioacetate yielded propargyl
thioacetate 10a in 96% yield. In situ hydrolysis of the
latter and nucleophilic displacement by the released
thiolate anion on cyclohexenyl propargyl bromide af-
forded sulfide 11a in 85% yield. Oxidation of the latter
with sodium periodate gave sulfoxide 14a in 50% yield.
Similarly, sulfoxides 14d ,e were prepared in 29 and 39%
yields, respectively, using thioacetate 12 as a starting
material as shown in Scheme 4.
CSA, MeOH, 25 °C; (c) Et3N (3.5 equiv), CH3SO2Cl (2.5 equiv),
ether, 0 °C; (d) NaBr, CH3CN, 25 °C; (e) CH3COSK, MeOH, 25
°C; (f) 3-(cyclohex-1-enyl)propargyl mesylate, KOH, THF-MeOH,
25 °C; (g) NaIO4, H2O-MeOH, 0 °C; (h) Na2S‚9H2O, H2O-MeOH,
0 °C.
Sch em e 4
volved a benzyl radical (e.g., 15d ,e), the preference was
to recombine by intramolecular addition to a simple
double bond rather than to a benzene ring; the preference
is enhanced in a more polar solvent. Thus, reaction of
sulfoxide 14d with DBU in acetonitrile led exclusively
to the corresponding sulfoxide 18d in 74% yield, whereas
a 85:15 mixture of 18d and 19d was formed in a less
polar solvent, chloroform. Similarly, sulfoxide 14e, when
treated with DBU in chloroform, led to a 67:33 mixture
of 18e and 19e, but only 18e was obtained (89% yield)
with DBU in acetonitrile. The reaction of sulfoxide 14a
with DBU in acetonitrile at room temperature led to 18a
and 19a in a 16:84 ratio.
The ability to generate a variety of substituted cyclic
sulfoxides, from both symmetrical and asymmetrical
starting materials, allows us to investigate the changes
in the side-chain rotation barrier (Scheme 2) as a function
of different parameters, e.g., (a) the effect of ring size,
using policyclic sulfoxides 5a -c, which are derived from
symmetrical starting materials; (b) the effect of the
positioning of the different ring types (“fused” vs “per-
pendicular” rings) by examining sulfoxides 18a and 19a ,
Asymmetrical sulfoxides 14a ,d ,e undergo cyclization
(see Scheme 5) in both possible directions, presumably
as a function of the relative reactivity of diradicals
intermediates 15a ,d ,e. In general, when the latter in-
(5) Oki, M. Applications of Dynamic NMR Spectroscopy to Organic
Chemistry; VCH: Deerfield Beach, FL, 1985; Chapter 4.
(6) (a) Nasipuri, D.; Mukherjee, P. R. J . Chem. Soc., Perkin Trans.
2 1975, 464. (b) Nasipuri, D.; Bhattacharya, P. K.; Furst, G. T. J . Chem.
Soc., Perkin Trans. 2 1977, 356. (c) Nasipuri, D.; Konar, S. K. J . Chem.
Soc., Perkin Trans. 2 1979, 269.
(7) (a) Anderson, J . E.; Hazlehurst, C. J . J . Chem. Soc., Chem.
Commun. 1980, 1188. (b) Anderson, J . E.; Barkel, D. J .; Cooksey, C.
J . Tetrahedron Lett., 1983, 24, 1188.

“Biphenyl-Type” Bonds in Polycyclic Sulfoxides
J . Org. Chem., Vol. 67, No. 10, 2002 3279
Ta ble 1. Kin etic Resu lts Obta in ed fr om Exch a n ge
Sp ectr oscop y (EXSY)a
Sch em e 5
∆Gq (kcal
mol-1
∆Go (kcal
c
d
tm
Rb fusedb T (K) (s)
kmfM
(s-1
)
)
K
mol-1
)
19d Pr
19d Pr
Ph
Ph
Ph
6
277.2 0.25
298.8 0.03 13.0
299.1 1.00
296.3 1.00
326.3 5.00
2.5
15.7 ( 0.1 1.29
16.0 ( 0.1 1.13
17.8 ( 0.1 1.05
18.1 ( 0.1 1.18
0.12
0.07
0.03
0.10
0.01
19e
5b
6
6
7
0.60
0.38
5c
7
0.062 21.0 ( 0.1 1.01
a
b
In CDCl3. See text for explanation of convention. c Mixing
d
time. Rate constant for the conversion from the minor to the
major isomer.
Ta ble 2. Kin etic Resu lts Obta in ed fr om Lin esh a p e
An a lysis
T (K) kmfM (s-1
)
∆Gq (kcal mol-1
)
K
∆Go (kcal mol-1
)
a
19a : R ) 5, Fused ) 6;b,c Signals Used:
13CH2 R to SdO (ca. 59 ppm)
175.4
185.9
196.4
206.9
217.5
228.0
238.5
5
30
9.5 ( 0.3
9.5 ( 0.1
9.6 ( 0.1
9.7 ( 0.2
9.8 ( 0.2
9.9 ( 0.2
9.8 ( 0.3
1.25
1.15
0.08
0.05
90
240
600
1600
5000
18a : R ) 6, Fused ) 5;b,c Signals Used:
13CH2 R to SdO (ca. 59 ppm)
206.9
217.5
228.0
238.5
249.0
15
35
200
300
500
10.9 ( 0.2
11.0 ( 0.1
10.8 ( 0.2
11.2 ( 0.2
11.4 ( 0.2
1.10
1.20
1.06
0.04
0.08
0.03
18e: R ) Ph, Fused ) 6;b,d Signals Used:
Ortho and Meta 13CH’s of Phenyl Group (ca. 128 ppm)
327.5
339.8
344.3
349.8
361.0
4.8
9
18.2 ( 0.3
18.5 ( 0.2
18.4 ( 0.1
18.3 ( 0.1
18.3 ( 0.2
15
27
60
3: R ) Ph, Fused ) Ph;b,d Signals Used:
derived from the asymmetrical open-chain sulfoxide 14a ;
and (c) the effect of ring shape (planar or nonplanar), as
well as the effect of acyclic substituents, by investigating
sulfoxides 3, 18e, and 19d ,e.
NMR Mea su r em en t of Rota tion a l Ra te Con sta n ts.
As mentioned above, the main purpose of the preparation
of the various cyclic sulfoxides was to compare the
rotational barriers for the rotation of their “biphenyl-
type” substituent. For the easier identification of these
substrates in Tables 1-3, we decided on the following
conventions:
Ortho and Meta 13CH’s of Phenyl Group (ca. 128 ppm)
339.8
344.3
349.8
361.0
371.5
6
9
15
31
60
18.8 ( 0.3
18.8 ( 0.2
18.7 ( 0.1
18.8 ( 0.1
18.9 ( 0.2
20: R ) 6, Fused ) 6, Sulfone;b,d Signals Used:
Benzylic CH2 in Six-Membered Ring (ca. 2.6 ppm, AB f A2)
332.0
337.4
348.2
359.0
369.6
4
6
12
40
65
18.6 ( 0.2
18.6 ( 0.2
18.7 ( 0.1
18.5 ( 0.1
18.7 ( 0.1
The “biphenyl-type” substituent is called R and is
abbreviated as 5, 6, or 7 for cyclopent-1-enyl, cyclohex-
1-enyl, or cyclohept-1-enyl, respectively, or as Pr for prop-
2-enyl. Ph is, of course, phenyl.
a
Rate constant for the conversion from the minor to the major
isomer. See text for explanation of convention. c In CD2Cl2. In
DMSO-d6.
b
d
The carbocyclic ring fused to the central benzene
moiety is abbreviated as 5, 6, or 7 for a five-, six-, or
seven-membered ring, respectively. “Ph” indicates a fused
benzene ring (i.e., the substrate is a substituted naph-
thalene).
As explained above, the cases in which R * Ph give
two sets of NMR signals at temperatures below coales-
cence. For several of these cyclic sulfoxides, we found that
the most convenient way of measuring the rate constant
for the rotation of the substituent is through the two-
dimensional technique known as EXSY (exchange spec-
troscopy).8 The resulting interferogram correlates via off-
diagonal peaks the signals of two protons connected by
an exchange process (Figures S1-S3, Supporting Infor-
mation); the relative integral of these peaks is a function
of an experimental parameter called “mixing time” and
of the rate of interconversion. This technique was used
for the olefinic proton signals of several of our diastereo-
rotameric pairs, and the results are shown in Table 1.
For other sulfoxides, namely 18a and 19a (see Table 2),
the rotation rates were measured by a line shape
analysis9 of the coalescence of one pair of methylenes
carbons R to the sulfur as a function of temperature.
The situation is different when R ) Ph: in this case
the rotamers are structurally identical. The pairs of ortho
and meta carbons of the phenyl substituent, however,
give separated signals in the low-temperature regime and
their coalescence process can be followed by line shape
analysis9 (Table 2, Figure S4).
(9) Sutherland, I. O. In Annual Reports in NMR Spectroscopy;
Mooney, E. F., Ed.; Academic Press: London, 1971; Vol. 4, p 80.
(8) Perrin, C. L.; Dwyer, T. J . Chem. Rev. 1990, 90, 935.

3280 J . Org. Chem., Vol. 67, No. 10, 2002
Braverman et al.
Ta ble 3. Com p a r ison of Exp er im en ta l a n d Molecu la r
Mech a n ics Ca lcu la ted Rota tion Ba r r ier s
For comparison purposes, we were interested in mea-
suring the rotation rate for a sulfone. We chose to use
20, the preparation of which has been reported previ-
ously.4 For this material, the only asymmetric element
is the “biphenyl-type” bond, and this implies that the
protons of methylenes are diastereotopic in the low-
temperature regime. Fast rotation of the cyclohexenyl
substituent causes these protons to become isochronous,
and this process also can be followed by line shape
analysis10 (Table 2).
An inspection of Table 2 suggests that ∆Gq values are,
by and large, independent of the temperature, i.e., ∆Sq
≈ 0. It is thus possible to compare ∆Gq for different
substrates, without taking into account the temperature
at which the measurement was made. The barrier for
sulfoxide 5a could not be measured, as even at the lowest
temperature we could reach with our instrument (170
K) only one set of unbroadened signals was observed in
the NMR spectra.
rotational barrier, kcal mol-1
Ra
fuseda
exptl
calcd
5a
19a
18a
19d
19e
5b
18e
20
3
5c
5
5
<7
6.2
10.1
12.4
13.2
15.6
17.7
16.7
18.3
14.5
20.4
21.6
5
6
9.7
6
5
11.0
15.8
17.8
18.1
18.3
18.6
18.8
21.0
Pr
6
Ph
Ph
6
6
Ph
6b
Ph
7
6
6b
Ph
7
8
8
a
b
See text for explanation of convention. Sulfone.
The calculated and experimental values of the barriers
are compared in Table 3 and Figure 1.
Discu ssion
Molecu la r Mech a n ics E st im a t es of R ot a t ion a l
Ba r r ier s. The free energies of activation for the rotation
of the “biphenyl-like” substituent R cover a large range:
from less than 7 kcal‚mol-1 for 5a to 21.0 kcal‚mol-1 for
5c. While the general trend might have been expected,
we were quite surprised by the magnitude of the differ-
ences in ∆Gq values and decided to investigate further
by estimating the rotational barriers via molecular
mechanics. We used the PCModel package11 (a MM2-
based program), employing extensively its GMMX sub-
routine for finding global minima and therefore taking
into account the various possible conformations of the
nonaromatic rings. For each compound, we adopted the
following procedure:
The effect of the substituents on the rotation barriers
seems to be mainly steric, with relative sizes in the order
5 , Pr < 6 < Ph < 7. We did not synthesize the
compound with two eight-membered rings, but calcula-
tion of its barrier (Table 3) suggests that the increase is
leveling off. The results also indicate that the nature of
the substituent R is more important than that of the
fused ring (e.g., the barriers are in the order 18a > 19a
and 18e > 19e). Sulfone 20 has a barrier only slightly
higher than its corresponding sulfoxide (5b).
(a) After a first preliminary minimization, the program
was allowed to find the low energy conformers with a
cutoff of 1 kcal‚mol-1. Up to seven conformers were found
for each of the rotamers. The energy difference between
the global minima of the rotamer pair was usually
smaller than 0.1 kcal‚mol-1 (in one case up to 0.18
kcal‚mol-1), in line with the observation that the experi-
mental equilibrium constants are very close to unity; see
Tables 1 and 2. Such differences are within the expected
error in the calculations, and indeed, no obvious correla-
tion could be seen between experimental and calculated
∆Go values; therefore, we do not wish to identify the
structure of the major and minor rotamers.
Table 3 and Figure 1 show that the molecular mechan-
ics calculations predict successfully the barriers for all
the compounds with only one aromatic ring. For com-
pounds with a second benzene moiety (18e, 19d , and
19e), the calculated barrier is ca. 2 kcal mol-1 smaller
than the experimental one; the position of the second ring
(R or fused) is not so significant. For 3, which has a third
aromatic ring, the deviation is approximately double. The
molecular mechanics parameters seem to underestimate
the energetic cost involved in the loss of aromaticity
introduced by deformation these rings in the transition
state (see last item, below).
To obtain a better understanding of the molecular
deformations involved in the rotation process, we in-
spected the calculated ground- and transition-state ge-
ometries of four representative cyclic sulfoxides (3 and
5a -c) comparing distances, planar angles (R1-R3), and
dihedral angles (ψ1-ψ5). Our observations (more details
can be found in Figure S5, Supporting Information) can
be summarized as follows:
(b) Starting from the low energy conformers for one of
the rotamers, we fixed the dihedral angle defined by four
sp2-hybridized carbons forming the “biphenyl-type” bond
to 0 and 180° (these are different when R * Ph) and
performed minimizations of the resulting structures.
Preliminary calculations had shown that in the energy
maxima these four carbons were within no more than a
couple of degrees of planarity. We could find no regularity
as to the preferred direction of rotation (0 or 180°). Often,
these two angles and various conformations of the
nonaromatic rings generated several maxima within a
few hundred cal‚mol-1 of the lowest energy one.
(c) The energy barrier for the rotation process was
finally taken as the difference between the lowest energy
transition state (found in step b) and the ground state of
the minor isomer (step a).
The “biphenyl-type” bond distance “r” (for this and the
other geometric parameters, see structure 5b, above) does
not lengthen during the rotation process; in fact, there
(10) Alexander, S. J . Chem. Phys. 1962, 37, 967.
(11) PCMODEL version 7.50.00, Serena Software, Bloomington, IN.

“Biphenyl-Type” Bonds in Polycyclic Sulfoxides
J . Org. Chem., Vol. 67, No. 10, 2002 3281
land9 (for two coalescing singlets) or of Alexander10 (for the
AB f A2 case).
3-(Cyclopen t-1-en yl)pr opar gyl Mesylate (7a). To a stirred
solution of tetrahydro-2-(2-propynyloxy)-2-H-pyran (2 g, 14.3
mmol) and TMEDA (1.65 g, 14.2 mmol) in dry THF (70 mL)
at -78 °C was added 10.7 mL of 1.6 M BuLi. The reaction
mixture was stirred for 30 min, and then a solution of
cyclopentanone (1.2 g, 14.3 mmol) in dry THF (20 mL) was
added. After 30 min of stirring at -78 °C, the solution was
warmed to room temperature and stirred for a further 3 h.
The reaction mixture was diluted with diethyl ether (300 mL)
and washed with water (5 × 100 mL). The organic phase was
dried over anhydrous MgSO4, filtered, and concentrated in
1
vacuo to give alcohol 6a as a yellow oil. H NMR (300 MHz,
CDCl3): δ 4.83 (t, J ) 3.0 Hz, 1H), 4.33 and 4.25 (ABq, J )
15.5 Hz, each 1H), 3.88-3.80 (m, 1H), 3.58-3.51 (m, 1H),
1.96-1.54 (m, 14H). 13C NMR (75.5 MHz, CDCl3): δ 96.7 (CH),
89.8 (C), 78.5 (C), 74.1 (C), 61.8 (CH2), 54.2 (CH2), 42.2
(2×CH2), 30.1 (CH2), 25.2 (CH2), 23.3 (2×CH2), 18.8 (CH2).
With no purification, a solution of alcohol 6a (2.5 g, 11.1
mmol) in methanol (100 mL) was treated by camphorsulfonic
acid (0.51 g, 2.2 mmol) and stirred for 4 h at room temperature.
The solution was neutralized by triethylamine (0.22 g, 2.2
mmol), and the solvent was removed under reduced pressure.
The crude diol product (1.5 g, 10.7 mmol) and triethylamine
(3.78 g, 37.5 mmol) were dissolved in dry diethyl ether (80 mL).
After the mixture was cooled to 0 °C, a solution of methane-
sulfonyl chloride (3.1 g, 27 mmol) in dry diethyl ether (20 mL)
was added, and the reaction mixture was stirred for 2 h before
it was warmed to room temperature and stirred for further
3.5 h. The reaction mixture was then transferred to a sepa-
ratory funnel, diluted with 100 mL of ether, and washed with
water (3 × 100 mL), 3% HCl (100 mL), 3% NaHCO3 (1 × 100
mL), and water (3 × 100 mL). After drying over anhydrous
MgSO4, filtration, and evaporation of the ether, the desired
mesylate 7a was obtained as a yellow oil (2.26 g, 78% overall
yield), which was purified by column chromatography (silica
gel, ethyl acetate-hexane, first 5:95 and then 20:80). 1H NMR
(300 MHz, CDCl3): δ 6.16 (m, 1H), 5.00 (s, 2H), 3.13 (s, 3H),
2.46 (m, 4H), 1.93 (m, 2H). 13C NMR (75.5 MHz, CDCl3): δ
140.7 (CH), 122.8 (C), 86.9 (C), 81.8 (C), 58.6 (CH2), 38.9 (CH3),
35.9 (CH2), 33.3 (CH2), 23.1 (CH2). MS(EI): m/z 200 (M+, 44.5),
137 (52.9), 123 (100). HRMS: calcd (C9H12O3S) 200.0507, obsd
200.0509.
F igu r e 1. Experimental vs molecular-mechanics calculated
rotation barriers. The squares and the triangle correspond to
molecules with one and two peripheral aromatic rings, respec-
tively, in which the calculation underestimates the barrier (see
text). The bar at the bottom left of the figure refers to 5a , for
which, experimentally, only an upper limit can be ascertained.
seems to be a very slight shortening of this bond in the
transition state (up to 0.02 Å for 5c).
The distances d1 and d2 are quite invariant at 3.06 (
0.04 and 2.94 ( 0.01 Å, respectively. These carbon-
carbon distances seem quite short, and our feeling is that
the molecules cannot accommodate any more crowding
of the four peri carbons.
The planar angles decrease to let the rotating R group
pass through. R1 and R3 are reduced by 2-4°, and in the
six- and seven-membered rings R2 is diminished by ca.
6°. It should be noted that, even in the ground state, these
angles are much smaller in five- (111-115°) than in six-
and seven-membered rings (120-123°). This explains
why the barrier for 5a is considerably lower than for the
other systems examined (Table 3).
The brunt of the deformation is reflected in dihedral
angles ψ2-ψ5. Typically, these are <2° in the ground
state but are much larger in the transition state. For 5a ,
the central aromatic ring shows distortions of up to 10°,
and the deviations of planarity reach 30° for 5c. The
resulting loss of aromaticity, in addition to the close
contacts of the peri carbons and their attached hydrogens,
are probably responsible for the high rotation barriers
in these cyclic sulfoxides.
3-(Cycloh ep t-1-en yl)p r op a r gyl m esyla te (7c) was ob-
tained by the procedure mentioned above using 6c, which was
1
obtained as a viscous oil. H NMR (300 MHz, CDCl3): δ 4.82
(t, J ) 3.3 Hz, 1H), 4.32 and 4.26 (ABq, J ) 15.5 Hz, each
1H), 3.86-3.78 (m, 1H), 3.57-3.50 (m, 1H), 2.02-1.96 (m, 2H),
1.85-1.50 (m, 16H). 13C NMR (75.5 MHz, CDCl3): δ 96.5 (CH),
90.8 (C), 78.9 (C), 71.5 (C), 61.8 (CH2), 54.2 (CH2), 42.9 (2 ×
CH2), 30.2 (CH2), 28.0 (2 × CH2), 25.3 (CH2), 22.1 (2 × CH2),
18.9 (CH2).
Compound 7c was obtained in 61% overall yield as viscous
oil after separation by column chromatography (silica gel, ethyl
acetate-hexane, first 5:95 and then 20:80). 1H NMR (300 MHz,
CDCl3): δ 6.38 (t, J ) 6.5 Hz, 1H), 4.97 (s, 2H), 3.12 (s, 3H),
2.34-2.30 (m, 2H), 2.22-2.20 (m, 2H), 1.76-1.72 (m, 2H),
1.58-1.51 (m, 4H). 13C NMR (75.5 MHz, CDCl3): δ 142.7 (CH),
125.3 (C), 92.9 (C), 77.9 (C), 58.8 (CH2), 38.9 (CH3), 33.6 (CH2),
31.8 (CH2), 29.1 (CH2), 26.3 (CH2), 26.2 (CH2). MS (CI): m/z
229 (MH+, 9.4), 133 (100). HRMS: calcd (C11H17O3S) 229.0898,
obsd 229.0913.
As far as we can tell, this is the first report on the
influence of ring size in the rotation around a “biphenyl-
type” bond.
Exp er im en ta l Section
Gen er a l Meth od s. Tetrahydrofuran was distilled from Na
and diethyl ether was dried over Na wires. Other commercially
available chemicals were used without further purification.
3-(Cyclop en t-1-en yl)p r op a r gyl Br om id e (8a ). A solution
of sulfonate 7a (1.9 g, 9.5 mmol) in acetonitrile (10 mL) was
slowly added to a magneticaly stirred suspension of NaBr in
acetonitrile (60 mL) at room temperature. After 48 h, the
reaction mixture was diluted with diethyl ether and the
organic layer was washed with water (3 × 100 mL) and dried
over anhydrous MgSO4. Removal of the solvent gave 1.43 g of
8a as a yellowish oil (81%). 1H NMR (300 MHz, CDCl3): δ
6.11 (m, 1H), 4.09 (s, 2H), 2.43 (m, 4H), 1.91 (m, 2H). 13C NMR
(75.5 MHz, CDCl3): δ 139.9 (CH), 123.8 (C), 85.4 (C), 84.4 (C),
1
NMR. H and 13C spectra were recorded in either CDCl3 or
other deuterated solvents (as indicated) and using TMS as
internal standard. Chemical shifts are reported in δ and
coupling constants in Hz. Sample temperatures were measured
with a calibrated digital thermometer and are assumed to be
correct to (0.5 K. Rate constants were calculated from the
volume integrals of the EXSY spectra with the equations of
Perrin and Dwyer.8 Line shape calculations were performed
using computer programs based on the equations of Suther-

3282 J . Org. Chem., Vol. 67, No. 10, 2002
Braverman et al.
36.2 (CH2), 33.4 (CH2), 23.3 (CH2), 15.8 (CH2). MS(EI): m/z
184 (M+, 18), 105 (100). HRMS: calcd (C8H9Br) 183.9887, obsd
183.9897.
Hz, 3H). 13C NMR (75.5 MHz, CDCl3): δ 131.7 (2 × CH), 128.2
(3 × CH), 126.4 (C), 122.8 (C), 122.0 (CH2), 84.6 (C), 83.5 (C),
83.2 (C), 70.1 (C), 23.4 (CH3), 20.0 (CH2), 19.9 (CH2). IR
(neat): 1611, 1490, 1355 cm-1. MS (CI): m/z 227 (MH+, 47.1),
193 (41.2), 115 (100). HRMS: calcd (C15H15S) 227.0894, obsd
227.0880.
3-(Cycloh ex-1-en yl)-3′-p h en yl dip r opa r gyl su lfid e (13e)
was prepared according to the above procedure in 62% yield
as viscous yellow oil, after separation by column chromatog-
raphy (silica gel, ethyl acetate-hexane 2:8). 1H NMR (300
MHz, CDCl3): δ 7.47-7.44 (m, 2H), 7.33-7.30 (m, 3H), 6.13
(quintet, J ) 1.8 Hz, 1H), 3.68 (s, 2H), 3.63 (s, 2H), 2.15-2.09
(m, 4H), 1.65-1.60 (m, 4H). 13C NMR (75.5 MHz, CDCl3): δ
134.9 (CH), 131.7 (CH), 131.6 (CH), 128.1 (2×CH), 128.07
(CH), 122.9 (C), 120.3 (C), 85.2 (C), 84.7 (C), 83.1 (C), 81.6 (C),
29.2 (CH2), 25.5 (CH2), 22.2 (CH2), 21.4 (CH2), 20.2 (CH2), 20.0
(CH2). IR (neat): 2212, 1435, 1348, 1066 cm-1. MS (CI): m/z
267 (MH+, 88.4), 233 (41.5), 119 (80.2), 115 (100). HRMS: calcd
(C18H19S) 267.1207, obsd 267.1183.
Bis[3-(cyclop en t-1-en yl)p r op a r gyl] Su lfoxid e (4a ). To
a magnetically stirred solution of NaIO4 (0.176 g, 0.82 mmol)
in 20 mL of water was added a solution of 9a (0.2 g, 0.82 mmol)
at 0 °C for 2 h. The mixture was warmed to room temperature
and allowed to stir for 1 week. The solution was diluted with
chloroform, washed with water (3 × 50 mL) and saturated
NaCl, and then dried over MgSO4. Evaporation of the solvent
gave a mixture of products that was separated by column
chromatography (silica gel, ethyl acetate-hexane 1:1) to give
85 mg of yellowish oil (42%). 1H NMR (300 MHz, CDCl3): δ
6.12 (quintet, J ) 2.1 Hz, 2H), 3.98 and 3.81 (ABq, J ) 16.0
Hz, each 2H), 2.47-2.42 (m, 8H), 1.90 (dquintet, J ) 7.5, 0.5
Hz, 4H). 13C NMR (75.5 MHz, CDCl3): δ 139.6 (CH), 123.3
(C), 85.4 (C), 77.9 (C), 42.0 (CH2), 36.0 (CH2), 33.1 (CH2), 23.0
(CH2). IR (neat): 1448, 1345, 1061 cm-1. MS (CI): m/z 259
(MH+, 20.1), 209 (15.8), 153 (8), 137 (36.8), 105 (100). HRMS:
calcd (C16H19OS) 259.1157, obsd 259.1162.
Bis[3-(cycloh ep t-1-en yl)p r op a r gyl] su lfoxid e (4c) was
prepared from 9c by the procedure mentioned above and
obtained in 42% yield as a yellowish viscous oil, after separa-
tion by column chromatography (silica gel, ethyl acetate-
hexane 1:2). 1H NMR (300 MHz, CDCl3): δ 6.35 (t, J ) 6.6
Hz, 2H), 3.93 and 3.76 (ABq, J ) 16.0 Hz, each 2H), 2.34-
2.30 (m, 4H), 2.21-2.16 (m, 4H), 1.75-1.72 (m, 4H), 1.57-
1.49 (m, 8H). 13C NMR (75.5 MHz, CDCl3): δ 141.6 (CH), 125.8
(C), 91.6 (C), 74.0 (C), 42.1 (CH2), 33.9 (CH2), 31.9 (CH2), 29.1
(CH2), 26.4 (CH2), 26.3 (CH2). IR (neat): 1446, 1067 cm-1. MS
(CI): m/z 315 (MH+, 92.4), 299 (100), 265 (60.8), 133 (91.2).
HRMS: calcd (C20H27OS) 315.1782, obsd 315.1760.
3-(Cycloh ep t-1-en yl)p r op a r gyl br om id e (8c) was ob-
tained by the reaction of sulfonate 7b with NaBr according to
the above procedure, purified by column chromatography
(silica gel ethyl acetate-hexane 5:95) as a colorless oil in 27%
1
yield. H NMR (300 MHz, CDCl3): δ 6.33 (t, J ) 6.9 Hz, 1H),
4.08 (s, 2H), 2.33-2.29 (m, 2H), 2.21-2.17 (m, 2H), 1.74-1.71
(m, 2H), 1.59-1.49 (m, 4H). 13C NMR (75.5 MHz, CDCl3): δ
141.9 (CH), 126.1 (C), 90.5 (C), 81.6 (C), 33.9 (CH2), 32.1 (CH2),
29.3 (CH2), 26.6 (CH2), 26.5 (CH2), 16.2 (CH2). MS(EI): m/z
212 (M+, 17.9), 133 (100). HRMS: calcd (C10H13Br) 212.0200,
obsd 212.0194.
3-(Cyclop en t-1-en yl)p r op a r gyl Th ioa ceta te (10a ). To a
vigorously stirred solution of mesylate 7a (1.5 g, 7.47 mmol)
in methanol (50 mL) was added potassium thioacetate (1.7 g,
14.5 mmol) at room temperature. The reaction mixture was
stirred for 30 min, diluted with diethyl ether, and washed with
water (3 × 100 mL). After drying over anhydrous MgSO4,
filtration, and evaporation of the ether, the desired thioacetate
10a was obtained as a yellow oil (1.3 g, 96%). 1H NMR (300
MHz, CDCl3): δ 6.02 (m, 1H), 3.81 (s, 2H), 2.43-2.36 (m, 4H),
2.35 (s, 3H), 1.90-1.85 (m, 2H). 13C NMR (75.5 MHz, CDCl3):
δ 194.0 (C), 138.2 (CH), 123.9 (C), 84.8 (C), 80.1 (C), 36.1 (CH2),
33.1 (CH2), 30.1 (CH3), 23.1 (CH2), 18.6 (CH2). MS(EI): m/z
181 (MH+, 100), 147 (48.3), 105 (51.9). HRMS: calcd (C10H13
OS) 181.0687, obsd 181.0682.
-
Bis[3-(cyclop en t-1-en yl)p r op a r gyl] Su lfid e (9a ). A solu-
tion of Na2S‚9H2O (0.57 g, 2.37 mmol) in water (20 mL) was
slowly added to a magnetically stirred solution of 8a (0.59 g,
3.19 mmol) in methanol (30 mL) at 0 °C. After 2 h, the solution
was warmed to room temperature and stirred for a further 2
h before ether was added. The organic layer was separated,
washed with water (3 × 100 mL), and dried over MgSO4. The
solvent was evaporated to give 0.24 g of pure yellow oil (62%).
1H NMR (300 MHz, CDCl3): δ 6.03 (m, 2H), 3.57 (s, 4H), 2.42
(m, 8H), 1.90 (dq, J ) 7.5, 0.5 Hz, 4H). 13C NMR (75.5 MHz,
CDCl3): δ 137.9 (CH), 124.1 (C), 85.6 (C), 80.6 (C), 36.3 (CH2),
33.1 (CH2), 23.2 (CH2), 20.2 (CH2). IR (neat): 2221, 1435 cm-1
.
MS (CI): m/z 243 (MH+, 35.9), 209 (45), 137 (41.4), 105 (100).
HRMS: calcd (C16H19S) 243.1207, obsd 243.1200.
Bis[3-(cycloh ep t -1-en yl)p r op a r gyl] su lfid e (9c) was
prepared according to the above procedure as a yellow oil
(98%). 1H NMR (300 MHz, CDCl3): δ 6.26 (t, J ) 6.9 Hz, 2H),
3.53 (s, 4H), 2.33-2.29 (m, 4H), 2.20-2.14 (m, 4H), 1.75-1.70
(m, 4H), 1.58-1.50 (m, 8H). 13C NMR (75.5 MHz, CDCl3): δ
140.0 (CH), 126.6 (C), 86.8 (C), 81.8 (C), 34.3 (CH2), 32.2 (CH2),
29.2 (CH2), 26.58 (CH2), 26.57 (CH2), 20.3 (CH2). MS (CI): m/z
299 (MH+, 62.3), 265 (22), 165(29.4), 133 (100). HRMS: calcd
(C20H27S) 299.1833, obsd 299.1800.
3-(P r op -2-en yl)-3′-p h en yl d ip r op a r gyl su lfoxid e (14d )
was prepared from 13d by the procedure mentioned above and
obtained in 29% yield as a yellowish viscous oil, after separa-
tion by column chromatography (silica gel, ethyl acetate-
hexane 1:1). 1H NMR (300 MHz, CDCl3): δ 7.48-7.44 (m, 2H),
7.33-7.30 (m, 3H), 5.38 (m, 1H), 5.30 (quintet, J ) 2.1 Hz,
1H), 4.06 and 3.89 (ABq, J ) 16.0 Hz, each 1H), 4.01 and 3.84
(ABq, J ) 16.0 Hz, each 1H), 1.90 (dd, J ) 1.5, 1.0 Hz, 3H).
13C NMR (75.5 MHz, CDCl3): δ 131.8 (2 × CH), 128.8 (CH),
128.2 (3 × CH), 125.6 (C), 123.4 (CH2), 121.7 (C), 89.3 (C), 88.1
(C), 77.0 (C), 75.9 (C), 42.0 (CH2), 41.9 (CH2), 23.1 (CH3). IR
(neat): 1602, 1490, 1442, 1063 cm-1. MS (CI): m/z 243 (MH+,
21.6), 115 (100). HRMS: calcd (C15H15OS) 243.0843, obsd
243.0856.
3-(Cyclop en t-1-en yl)-3′-(cycloh ex-1-en yl) Dip r op a r gyl
Su lfid e (11a ). A solution of KOH (0.52 g, 9.3 mmol) in
methanol (10 mL) was slowly added to a magnetically stirred
solution of tihioacetate 10a (0.84 g, 4.6 mmol) and 3-(cyclo-
hexen-1-enyl)propargyl mesylate (1 g, 4.6 mmol) in tetrahy-
drofuran (30 mL) at room temperature. After 40 min, the
reaction mixture was diluted with diethyl ether (100 mL) and
washed with water (3 × 100 mL). The organic phase was dried
over anhydrous MgSO4, filtered, and concentrated in vacuo to
1
give 16c as a yellowish oil (1.02 g, 85%). H NMR (300 MHz,
CDCl3): δ 6.01 (quintet, J ) 2.1 Hz, 1H), 5.95 (m, 1H), 3.49
(s, 2H), 3.47 (s, 2H), 2.38-2.34 (m, 4H), 2.04-2.02 (m, 4H),
1.82 (quintet, J ) 7.5 Hz, 2H), 1.54-1.51 (m, 4H). 13C NMR
(75.5 MHz, CDCl3): δ 137.7 (CH), 134.8 (CH), 124.1 (C), 120.2
(C), 85.6 (C), 85.0 (C), 81.6 (C), 80.4 (C), 36.3 (CH2), 33.0 (CH2),
29.1 (CH2), 25.4 (CH2), 23.1 (CH2), 22.1 (CH2), 21.3 (CH2), 20.0
(2 × CH2). IR (neat): 2212, 1628, 1435 cm-1. MS (CI): m/z
257 (MH+, 100), 223 (80.6), 119 (96.7), 105 (79.6). HRMS: calcd
(C17H21S) 257.1363, obsd 257.1352.
3-(P r op -2-en yl)-3′-p h en yl d ip r op a r gyl su lfid e (13d ) was
prepared according to the above procedure in 82% yield as a
viscous yellow oil. 1H NMR (300 MHz, CDCl3): δ 7.45-7.41
(m, 2H), 7.30-7.28 (m, 3H), 5.29 (m, 1H), 5.22 (quintet, J )
1.5 Hz, 1H), 3.65 (s, 2H), 3.60 (s, 2H), 1.89 (dd, J ) 1.5, 1.0
3-(Cycloh ex-1-en yl)-3′-p h en yl d ip r op a r gyl su lfoxid e
(14e) was prepared from 13e by the procedure mentioned
above and obtained in 39% yield as a yellowish viscous oil,
after separation by column chromatography (silica gel, ethyl
acetate-hexane 1:1). 1H NMR (300 MHz, CDCl3): δ 7.48-7.45
(m, 2H), 7.34-7.31 (m, 3H), 6.18 (quintet, J ) 1.8 Hz, 1H),
4.06 and 3.89 (ABq, J ) 16.0 Hz, each 1H), 4.00 and 3.83 (ABq,
J ) 16 Hz, each 1H), 2.12-2.04 (m, 4H), 1.65-1.57 (m, 4H).
13C NMR (75.5 MHz, CDCl3): δ 136.7 (CH), 131.9 (2 × CH),
128.8 (CH), 128.3 (2 × CH), 121.9 (C), 119.7 (C), 90.2 (C), 88.1
(C), 77.2 (C), 74.0 (C), 42.3 (CH2), 42.0 (CH2), 28.9 (CH2), 25.6
(CH2), 22.1 (CH2), 21.3 (CH2). IR (neat): 1489, 1442, 1066 cm-1
.

“Biphenyl-Type” Bonds in Polycyclic Sulfoxides
J . Org. Chem., Vol. 67, No. 10, 2002 3283
MS (CI): m/z 283 (MH+, 21), 234 (35.6), 119 (100), 115 (87.8).
HRMS: calcd (C18H19OS) 283.1157, obsd 283.1166.
together with 18d (48%) as an inseparable mixture that was
purified by column chromatography (silica gel, ethyl acetate-
hexane 1:1, then ethyl acetate 100%). Due to the small amount
of this product in the mixture, only partial NMR data are
presented; the olefinic signals were well separated enough for
3-(Cyclop en t-1-en yl)-3′-(cycloh ex-1-en yl) d ip r op a r gyl
su lfoxid e (14a ) was prepared from 11a by the procedure
mentioned above and obtained in 50% yield as a yellowish
viscous oil, after separation by column chromatography (silica
gel, ethyl acetate-hexane 1:1). 1H NMR (300 MHz, CDCl3): δ
6.17 (m, 1H), 6.12 (m, 1H), 3.98 and 3.80 (ABq, J ) 16 Hz,
each 1H), 3.95 and 3.78 (ABq, J ) 16 Hz, each 1H), 2.46-2.43
(m, 4H), 2.13-2.09 (m, 4H), 1.90 (quintet, J ) 7.5 Hz, 2H),
1.64-1.60 (m, 4H). 13C NMR (75.5 MHz, CDCl3): δ 139.6 (CH),
136.5 (CH), 123.4 (C), 119.6 (C), 90.0 (C), 85.4 (C), 78.0 (C),
74.0 (C), 42.0 (2 × CH2), 36.1 (CH2), 33.1 (CH2), 28.8 (CH2),
25.5 (CH2), 23.1 (CH2), 22.0 (CH2), 21.2 (CH2). IR (neat): 1431,
1060 cm-1. MS (CI): m/z 273 (MH+, 12.9), 255 (18.3), 223
(25.5), 119 (100), 105 (52). HRMS: calcd (C17H21OS) 273.1313,
obsd 273.1303.
Gen er a l P r oced u r e for th e Rea ction of Su lfu r -Br id ged
P r op a r gylic System s w ith DBU. To a solution of the desired
sulfur-bridged propargylic system (1 mmol) in 10 mL of
acetonitrile were added 1.5 equiv of DBU. After the mixture
was stirred at room temperature for the appropriate time,
chloroform was added, and the solution was washed with water
(3 × 50 mL). The organic layer was dried over anhydrous
MgSO4 and the solvent removed under reduced pressure. The
data for all cyclization products are listed below.
4-(Cyclop en t-1-en yl)-3,5,6,7-tetr a h yd r o-1H-2-th ia -s-in -
d a cen e 2-oxid e (5a ) was obtained from 4a by the general
procedure in 64% yield as a yellowish viscous oil, after
separation by column chromatography (silica gel, ethyl acetate-
methanol 12:1). 1H NMR (300 MHz, CDCl3): δ 7.09 (s, 1H),
5.68 (quintet, J ) 1.5 Hz, 1H), 4.26 and 4.10 (ABq, J ) 15.0
Hz, each 1H), 4.22 and 4.06 (ABq, J ) 15.0 Hz, each 1H), 2.89
(t, J ) 9.0 Hz, 2H), 2.82 (t, J ) 9.0 Hz, 2H), 2.54-2.48 (m,
4H), 2.08-2.01 (m, 4H). 13C NMR (75.5 MHz, CDCl3): δ 145.2
(C), 142.8 (C), 141.3 (C), 134.1 (C), 132.9 (C), 130.6 (CH), 130.5
(C), 120.6 (CH), 58.8 (CH2), 58.2 (CH2), 35.9 (CH2), 33.0 (CH2),
32.8 (CH2), 32.2 (CH2), 25.6 (CH2), 24.0 (CH2). IR (neat): 1637,
1448, 1038 cm-1. MS (CI): m/z 259 (MH+, 59.5), 209 (100).
HRMS: calcd (C16H19OS) 259.1157, obsd 259.1169.
4-(Cycloh ep t -1-en yl)-3,5,6,7,8,9-h exa h yd r o-1H -2-t h ia -
cycloh ep ta [f]in d en e-2 oxid e (5c) was obtained from 4c by
the general procedure in 33% yield as a yellowish viscous oil,
after separation by column chromatography (silica gel, ethyl
acetate 100%). These data refer to a mixture of two stable
diastereorotamers which are easily distinguishable by the
appearance of two aromatic singlets and two olefinic triplets,
resulting from the orientation of the cycloheptenyl double bond
with respect to the sulfinyl oxygen (see text). 1H NMR (300
MHz, CDCl3): δ 6.98 and 6.97 (2 × s, each 0.5H), 5.72 and
5.61 (2 × t, J ) 6.3 Hz, each 0.5H), 4.29, 4.28, 4.15, 4.11, 4.10
and 3.99 (3 × ABq, J ) 16.0 Hz, each 0.5H), 4.18 (s, 1H), 2.81-
2.77 (m, 4H), 2.30-2.26 (m, 4H), 1.85-1.57 (m, 12H). 13C NMR
(75.5 MHz, CDCl3): δ 144.6 (C), 143.1 (C), 142.4 (C), 140.6
(C), 132.1 (CH), 131.7 (CH), 131.5 (C), 131.3 (C), 124.9 (CH),
124.8 (CH), 59.6 (CH2), 59.5 (CH2), 59.1 (CH2), 36.6 (CH2), 35.2
(CH2), 35.1 (CH2), 32.4 (CH2), 32.1 (CH2), 31.9 (CH2), 31.4
(CH2), 28.8 (CH2), 28.7 (CH2), 28.1 (CH2), 27.8 (CH2), 27.2
(CH2), 27.1 (CH2), 26.8 (CH2), 26.7 (CH2). IR (neat): 1445, 1041
cm-1. MS (CI): m/z 315 (MH+, 88), 299 (100), 265 (97.5).
HRMS: calcd (C20H27OS) 315.1782, obsd 315.1761.
1
a successful EXSY experiment (see text). H NMR (600 MHz,
CDCl3): δ 7.91 (m, 1H), 7.82-7.80 (m, 1H), 7.76 (br s, 1H),
7.49-7.48 (m, 2H), 5.55, 5.09 and 5.53, 4.99 (4 × s, each 0.5H),
4.46, 4.43, 4.41, 4.37, 4.35, 4.28, 4.18 and 4.05 (4 × ABq, J )
16.0 Hz, each 0.5H), 2.17 and 2.11 (2 × s, each 1.5H).
4-P h e n yl-1,3,5,6,7,8-h e xa h yd r on a p h t h o[2,3-c]t h io-
p h en e 2-oxid e (18e) was obtained from 14e by the general
procedure in 89% yield as an orange viscous oil, after separa-
tion by column chromatography (silica gel, ethyl acetate-
hexane 4:1). 1H NMR (300 MHz, CDCl3): δ 7.45-7.32 (m, 3H),
7.23-7.20 (m, 1H), 7.12-7.08 (m, 2H), 4.29 and 4.13 (ABq, J
) 16.0 Hz, each 1H) 3.95 and 3.75 (ABq, J ) 16.0 Hz, each
1H), 2.83 (t, J ) 6.3 Hz, 2H), 2.41 (t, J ) 6.3 Hz, 2H), 1.79-
1.63 (m, 4H). 13C NMR (75.5 MHz, CDCl3): δ 140.3 (C), 139.2
(C), 138.0 (C), 135.3 (C), 131.7 (C), 131.2 (C), 128.8 (CH), 128.7
(CH), 128.5 (CH), 128.4 (CH), 127.3 (CH), 126.1 (CH), 59.2
(CH2), 58.7 (CH2), 30.0 (CH2), 27.9 (CH2), 23.1 (CH2), 22.6
(CH2). IR (neat): 1448, 1036 cm-1. MS (CI): m/z 283 (MH+,
100), 233 (68.6). HRMS: calcd (C18H19OS) 283.1156, obsd
283.1166.
Compound 19e was prepared by the procedure mentioned
above using chloroform as solvent and obtained in 14% yield
together with 18e (30%) as an inseparable mixture that was
purified by column chromatography (silica gel, ethyl acetate-
hexane 1:1, then ethyl acetate 100%). Due to the small amount
of this product in the mixture, only partial NMR data are
presented; the olefinic signals were well separated enough for
1
a successful EXSY experiment (see text). H NMR (600 MHz,
CDCl3): δ 7.93-7.89 (m, 1H), 7.83-7.80 (m, 1H), 7.76 (br s,
1H), 7.48-7.46 (m, 2H), 5.79 and 5.70 (2 × m, each 0.5H), 4.42,
4.41, 4.34, 4.33, 4.32, 4.31, 4.26 and 4.15 (4 × ABq, J ) 16.0
Hz, each 0.5H), 2.31-2.25 (m, 2H), 1.75-1.68 (m, 4H). 13C
NMR (150.9 MHz, CDCl3): δ 59.3, 59.2, 58.3, 57.9, 30.9, 29.9,
25.5, 25.4, 23.0, 22.2 (all CH2 of two diastereorotamers).
4-(Cyclop en t-1-en yl)-1,3,5,6,7,8-h exa h yd r on a p h th o[2,3-
c]t h iop h en e 2-oxid e (19a ) was obtained from 14a by the
general procedure as a mixture with 18a in 30% yield as an
orange viscous oil, after purification by column chromatogra-
phy (silica gel, ethyl acetate-methanol 12:1). 1H NMR (600
MHz, CDCl3): δ 6.98 (s, 1H), 5.57 (m, 1H), 4.21, 4.10, 4.00
and 3.89 (2 × ABq, J ) 16.0 Hz, each 1H), 2.78 (m, 2H), 2.63
(m, 2H), 2.53-2.48 (m, 4H), 2.03 (m, 2H), 1.76-1.70 (m, 4H).
13C NMR (150.9 MHz, CDCl3): δ 142.8 (C), 138.1 (C), 138.0
(C), 135.6 (C), 132.4 (C), 131.4 (C), 130.2 (CH), 125.8 (CH),
59.8 (CH2), 59.0 (CH2), 36.6 (CH2), 33.5 (CH2), 30.4 (CH2), 27.5
(CH2), 24.4 (CH2), 23.7 (CH2), 23.2 (CH2). IR (neat): 1645,
1447, 1039 cm-1. MS (CI): m/z 273 (MH+, 68), 257 (14), 223
(100). HRMS: calcd (C17H21OS) 273.1313, obsd 273.1296.
4-(Cycloh ex-1-en yl)-3,5,6,7-t et r a h yd r o-1H-2-t h ia -s-in -
d a cen e 2-oxid e (18a ). 1H NMR (600 MHz, CDCl3): δ 7.08
(s, 1H), 5.57 (m, 1H), 4.22, 4.14, 4.00 and 3.95 (2 × ABq, J )
16.0 Hz, each 1H), 2.89 (t, J ) 7.0 Hz, 2H), 2.80 (t, J ) 7.0
Hz, 2H), 2.17-2.11 (m, 4H), 2.05 (m, 2H), 1.76-1.70 (m, 4H).
13C NMR (150.9 MHz, CDCl3): δ 145.5 (C), 142.8 (C), 139.7
(C), 136.7 (C), 133.7 (C), 131.3 (C), 127.0 (CH), 120.7 (CH),
59.6 (CH2), 58.3 (CH2), 33.3 (CH2), 31.8 (CH2), 29.1 (CH2), 26.1
(CH2), 25.6 (CH2), 23.3 (CH2), 22.6 (CH2).
6-Meth yl-4-p h en yl-1,3-d ih yd r oben zo[c]th iop h en e 2-ox-
id e (18d ) was obtained from 14d by the general procedure in
74% yield as an orange viscous oil, after separation by column
chromatography (silica gel, ethyl acetate-hexane 4:1). 1H
NMR (300 MHz, CDCl3): δ 7.44-7.33 (m, 5H), 7.17 (s, 1H),
7.15 (s, 1H), 4.32 and 4.17 (ABq, J ) 16.0 Hz, each 1H), 4.27
and 4.11 (ABq, J ) 16.0 Hz, each 1H), 2.40 (s, 3H). 13C NMR
(75.5 MHz, CDCl3): δ 140.6 (C), 140.0 (C), 138.8 (C), 135.8
(C), 130.0 (CH), 129.9 (C), 128.5 (2 × CH), 128.48 (2 × CH),
127.6 (CH), 126.1 (CH), 59.1 (CH2), 58.4 (CH2), 21.2 (CH3). IR
(neat): 1448, 1036 cm-1. MS (CI): m/z 243 (MH+, 32), 193
(100). HRMS: calcd (C15H15OS), 243.0844, obsd 243.0855.
Compound 19d was prepared by the procedure mentioned
above using chloroform as solvent and obtained in 8% yield
Ack n ow led gm en t. The financial support of this
study by the Israel Science Foundation is gratefully
acknowledged.
Su p p or tin g In for m a tion Ava ila ble: 1H (5b,c and 20)
and 13C 1D-NMR spectra; EXSY spectra (5b,c and 19d ,e); 13
C
line shape analysis for 18e; full 1H and 13C assignment for
18a and 19a ; geometrical parameters from molecular mechan-
ics calculations (3, 5a -c). This material is available free of
charge via the Internet at http://pubs.acs.org.
J O010947Z