Polyfunctional compounds containing the 4,6-dialkoxy-7-arylthioheptene moiety as synthetically useful intermediates. The course of Lewis acid-induced transformations

Article abstract of DOI:10.1021/jo0261202

Data on the selectivity of the Lewis acids induced transformations of the title compounds are presented, and the routes leading to formation of products containing either cyclohexane or 1,3-diene units are described.

Full text of DOI:10.1021/jo0261202

P olyfu n ction a l Com p ou n d s Con ta in in g th e
4,6-Dia lk oxy-7-a r ylth ioh ep ten e Moiety a s Syn th etica lly Usefu l
In ter m ed ia tes. Th e Cou r se of Lew is Acid -In d u ced Tr a n sfor m a tion s
Dmitriy S. Chekmarev,*,†,‡ Margarita I. Lazareva,†,§ Georgy V. Zatonsky,†
Andrei V. Maskaev,| Ron Caple,§ and William Smit*,†
N. D. Zelinsky Institute of Organic Chemistry, Leninsky pr., 47, 119991, Moscow, Russia,
Department of Chemistry, University of Minnesota-Duluth, Duluth, Minnesota 55812, and Higher
College of Chemistry, Russian Academy of Sciences, Leninsky pr., 47, 119991, Moscow, Russia
dchekmarev@mail.ru
Received J une 29, 2002
Data on the selectivity of the Lewis acids induced transformations of the title compounds are
presented, and the routes leading to formation of products containing either cyclohexane or 1,3-
diene units are described.
In tr od u ction
δ-alkoxy group present in the structure of the adducts
(Scheme 2).
Recently, we have described a novel methodology for
the one-pot synthesis of polyfunctional compounds based
upon the controlled sequence of three intermolecular
arylthio-mediated AdE reactions.1 In particular, this
methodology was found to be useful for the ready
preparation of a set of structurally diverse adducts,
bearing the 4,6-dialkoxy-7-arylthioheptene fragment as
a common moiety, from three variable alkene precursors
as is shown in Scheme 1.2a-d
The presence of the aforementioned functionality pat-
tern might have suggested quite a number of options for
the utilization of these compounds as substrates for
further transformations. However, it was also obvious
that the practical usefulness of the various options
depends primarily on the opportunity to exert efficient
control over the selectivity of the reagent interaction with
the polyfunctional substrates of the type shown. Below
are presented the results of our investigation of the
course of the Lewis acid-induced reactions of the title
adducts.
In both cases the subsequent elimination of the respec-
tive alkoxy group should be facilitated due to the nucleo-
philic assistance of the properly positioned arylthio
substituent, and hence the formation of either the episul-
fonium ion (ESI) or thiophanium ion (TPI) intermediate
is to be expected as an immediate result of the â- or
δ-attack, respectively.
As was amply demonstrated earlier,1,2a-d the ESI salts,
once formed as transient intermediates, exhibit a rather
high reactivity as electrophiles, and in the structurally
related systems these species are prone to react readily
with the nucleophilic double bond present in the sub-
strate to give cyclized products.3a-d Hence, the â-attack
should lead eventually to the formation of the substituted
cyclohexane derivatives as is shown in Scheme 2. At the
same time, according to the literature data,4 the TPI salts
belong to the category of stable and comparatively un-
reactive compounds, and therefore the final outcome of
δ-attack could not have been predicted with any cer-
tainty. It is also noteworthy that there were no literature
data enabling one to predict whether the selectivity of
the Lewis acid interaction with the polyfunctional ad-
ducts containing the aforementioned set of nucleophilic
centers might be considered as an achievable goal.
It was reasonable to assume that an initial attack of
Lewis acid could be primarily directed at either the â- or
* To whom correspondence should be addressed. E-mail address of
William Smit: smt@ioc.ac.ru.
† N. D. Zelinsky Institute of Organic Chemistry.
‡ Current address: Chembridge Research Laboratories, 16981 Via
Tazon, Suite G, San Diego, CA 92127.
Here we report that the title adducts can selectively
undergo either type of these transformations, their course
being dependent on the substrate structure and/or reac-
tion conditions.5
§ University of Minnesota-Duluth.
| Higher College of Chemistry.
(1) For a discussion of the principles of the suggested approach, see
a review: Smit, W. A.; Lazareva, M. I.; Smolyakova, I. P.; Caple, R.
Russ. Chem. Bull. 2001, 50, 1949.
(2) (a) Lazareva, M. I.; Kryschenko, Yu. K.; Hayford, A.; Lovdahl,
M.; Caple, R.; Smit, W. A. Tetrahedron Lett. 1998, 39, 1083. (b)
Lazareva, M. I.; Kryschenko, Yu. K.; Dilman, A. D.; Hayford, A.; Caple,
R.; Smit, W. A. Russ. Chem. Bull. 1998, 47, 895. (c) Lazareva, M. I.;
Kryschenko, Yu. K.; Caple, R.; Wakefield, D.; Hayford, A.; Smit, W.
A.; Shashkov, A. S. Tetrahedron Lett. 1998, 39, 8787. (d) Lazareva,
M. I.; Kryschenko, Yu. K.; Caple, R.; Smit, W. A.; Lyssenko, K. A.;
Shashkov, A S. Russ. Chem. Bull. 2000, 49, 85.
(3) (a) Liu, C.; Kuda, K.; Hashimoto, Y.; Saigo, K. J . Org. Chem.
1996, 61, 494. (b) Harring, S, R.; Livinghouse, T. Tetrahedron Lett.
1989, 30, 1499. (c) Kamimura, A.; Sasatani, H.; Hashimoto, T.; Ono,
N. J . Org. Chem. 1989, 54, 4998. (d) van Oeveren, A.; Feringa, B. L.
J . Org. Chem. 1996, 61, 2920.
(4) See for a review, see: Knipe, A. C. Reactivity of Sulphonium
Salts. In The Chemistry of Sulfonium Group; Stirling, C. J . M., Patai,
S., Eds.; Wiley: New York, 1981; Chapter 14, pp 313-376.
10.1021/jo0261202 CCC: $22.00 © 2002 American Chemical Society
Published on Web 10/17/2002
J . Org. Chem. 2002, 67, 7957-7967
7957

Chekmarev et al.
SCHEME 1 a
a
L.a. ) Lewis acid.
SCHEME 2
Resu lts a n d Discu ssion
opening transformed the latter into a mixture of 1,3-
dienes 12a ,b (Scheme 3). It is assumed that the predomi-
nant formation of the isomer 12a could be explained as
a result of the isomerization of the initially formed and
thermodynamically less stable isomer 12b.
The starting compounds used in the present study were
prepared from three variable alkene precursors in ac-
cordance with the formal equation: ArSCl + vinyl ether-I
+ vinyl ether-II + allylsilane (or stannane) f adduct,
following the unified protocol described earlier2a,b and
outlined in Scheme 1. In all cases, p-TolSCl was used as
the starting electrophile and the overall coupling was
carried out as a one-pot procedure that involved a
sequential addition of the reactants and Lewis acid. A
list of the alkene precursors, reaction conditions, and
prepared adducts 1-10 is given in Table 1.
On the other hand, treatment of adduct 1a with the
mixture Et2AlCl (2 equiv)-TMSOTf (2 equiv)8 followed
by quenching with the DBU produced an entirely differ-
ent product, namely, cis-5-methoxy-1-methyl-3-(p-tolylth-
iomethyl)cyclohexene 14a in 59% yield.6 Here again the
TLC monitoring of the reaction revealed an initial
formation of a highly polar material (Rf < 0.05, hexanes-
ethyl acetate, 5:1). To isolate the latter, the reaction
mixture formed upon the complete conversion of 1a was
poured into CCl4 cooled to -25 °C. An oily precipitate
was separated from the supernatant liquid, carefully
washed with CCl4, and dissolved in CD2Cl2. Due to the
presence of the impurities, we were not able to carry out
Initial experiments were carried out with 4,6-dimethoxy-
2-methyl-7-(p-tolylthio)hept-1-ene 1 taken as a model
compound. It was found that the final outcome of the in-
teraction of this adduct with Lewis acid depends crucially
on the nature of the employed reagent. Thus, the treat-
ment of either individual diastereomers (1a or 1b) or
their mixture (1a ,b) with 2 equiv of trimethylsilyl triflate
(TMSOTf) in CH2Cl2 at ambient temperature followed by
the quenching of the reaction with 1,8-diazobicyclo[5.4.0]-
undec-7-ene (DBU) resulted in the formation of mixture
of the conjugated dienes (E)-6-methoxy-2-methyl-7-(p-
tolylthio)hepta-2,4-diene 12a and (E)-6-methoxy-2-meth-
yl-7-(p-tolylthio)hepta-1,3-diene 12b in 50% total yield6
1
complete assignments of the proton signals in H NMR
spectrum of this sample, but its general pattern cor-
responded to that expected for the structure of the bicyclic
TPI salt 13a 9 as is presented in Scheme 3. This compound
was shown to be a true intermediate in the described
(7) 1H NMR-monitored experiment (CD2Cl2, 20 °C) revealed
a
gradual disappearance of one MeO signal. The formation of sulfonium
salt-like intermediate tentatively identified as TPI 11 is substantiated
by the observed downfield shifts of the newly emerged 1H signals of
MeC6H4 fragment (ca. 0.5 ppm, as compared to those of 1a ,b), which
is typical for various arylsulfonium salt (e.g., data in ref. 2c,d; see also
ref 9).
(8) Adducts 1a and 1b turned out to be rather inert toward the
action of Et2AlCl (20 °C, several hours) alone. For the literature data
attesting to the increased strength of the mixed Et2AlCl-TMSOTf
system as a Lewis acid, see: Oishi, M.; Aratake, S.; Yamamoto, H. J .
Am. Chem. Soc. 1998, 120, 8271.
1
(12a :12b ) 7:1, H NMR data). TLC monitoring of this
reaction revealed a gradual disappearance of the spot
corresponding to the presence of the starting material
1a ,b (Rf ) 0.5, 5:1 hexanes-ethyl acetate) substituted
by the spot of a highly polar compound (Rf < 0.05) (total
conversion time ca. 2 h), which was converted into the
final product 12a ,b (Rf ) 0.6) upon treatment with DBU.
These observations suggested that under these condi-
tions, the reaction of 1a ,b occurred as an initial attack
of TMSOTf at the δ-methoxy group to give an intermedi-
ate that was presumably identified as the TPI salt 11.7
Base-induced proton elimination and thiophanium ring
(9) 1H NMR spectrum revealed a nearly complete absence of the
proton signals of the dCH2 fragment present in the starting material
1a and appearance of a new signal of Me protons as a singlet shifted
upfield to 1.3 ppm instead of the Me singlet at 1.79 ppm of 1a . The
observed downfield shift of the signals of aromatic protons (2d at 7.5
and 7.7 ppm as compared to values of 7.1 and 7.3 ppm for the respective
signals of the Haryl fragment in the covalent precursors or products,
e.g., 1a and 14a ) corresponds to that expected for the S-arylthiopha-
nium salts (e.g., data in ref 3a,c). Unfortunately, attempts to purify
the intermediate 13a by dissolving the latter in CH2Cl2 and precipitat-
ing with either precooled ether or hexane failed, obviously due to the
extreme lability of this salt.
(5) For
a preliminary communication, see: Chekmarev, D. S.;
Lazareva, M. I.; Zatonsky, G. V.; Caple, R.; Smit, W. A. Tetrahedron
Lett. 2001, 42, 4289.
(6) Yields (nonoptimized) refer to the isolated products.
7958 J . Org. Chem., Vol. 67, No. 23, 2002

4,6-Dialkoxy-7-arylthioheptene Moiety
TABLE 1. P r ep a r a tion of Ad d u cts Con ta in in g th e 4,6-Dia lk oxy-7-a r ylth ioh ep t-1-en e Moiety
transformation of 1a since the treatment of the isolated
salt 13a with DBU furnished the same product 14a .
These data taken together implied that the cyclohexane
derivative 14a was formed as a result of the multistep
sequence starting with an initial attack of Lewis acid (Et2-
AlCl-TMSOTf) at the â-methoxy group followed by a
nearly-concerted intramolecular cyclization of the tran-
sient ESI-like intermediate to give the stabilized bicyclic
TPI salt 13a (cf. data in ref 3a,d,e), which is further
converted into the final adduct via the ring opening and
proton elimination triggered by the action of the strong
base as is shown in Scheme 3.
Interaction of the diastereomer 1b with TMSOTf-Et2-
AlCl followed the pattern established for 1a (TLC moni-
toring data) except that, in this case, the respective TPI
intermediate 13b turned out to be noticeably less stable
and more reactive than 13a . Conversion of this interme-
diate into a mixture of the cyclized products 14b,c (yield
65%)10 did not require the presence of DBU and pro-
ceeded easily upon the treatment of the reaction mixture
with aqueous NaHCO3. Adduct 14b was shown to differ
from product 14a only by the configuration of the
methoxy substituent that was justified with the help of
two-dimensional gradient-enhanced NMR experiments.
Hence, one may conclude that conversions 1a to 14a and
1b to 14b proceed as highly diastereoselective reactions.
Finally, it was also observed that both the preparation
of adducts 1a ,b (via a four component coupling, cf.
Scheme 1) and their cyclization to give products 14a -c
(82%, a :b:c ) 1.4:1.0:0.3) can be carried out as a one-pot
sequence of three intermolecular and one intramolecular
AdE reactions as is represented in Scheme 3. The net
(10) No attempts were made to isolate the individual adducts 14b
and 14c, and the presence of up to 20% exo-methylene isomer 14c was
ascertained from the analysis of 1H NMR data for the mixture 14b,c.
J . Org. Chem, Vol. 67, No. 23, 2002 7959

Chekmarev et al.
SCHEME 3
outcome of this unprecedented sequence11 is the ready
assembly of the cyclohexane framework from simple
precursors with the formation of three novel C-C bonds.
Most likely the described transformation also involves
the intermediate formation of the stabilized bicyclic
cationoid intermediate TPI 15. To check this suggestion,
the reaction of 2a with TMSOTf was carried out in an
A noticeably different reactivity pattern was observed
for the closely related compound 2. In fact, the â-attack
route was shown to be a highly preferred pathway for
this substrate regardless of the nature of Lewis acid
employed. Thus treatment of the individual diastereo-
mers 2a or 2b (or a mixture of diastereomers 2a ,b) in
CH2Cl2 with 2-3 equiv of TMSOTf at ambient temper-
ature for 5 h followed by the quenching of the reaction
by DBU (20 °C, 2 h) and usual workup furnished products
16a ,b in 65% yield6 as an inseparable mixture of two
diastereomers in a ratio of 1.8:1 (Scheme 4). Formation
of the same mixture of diastereomers 16a ,b suggests that
in a contrast to the related transformation of 1a or 1b,
the cyclization of 2a or 2b is accompanied by an equili-
bration at the CHOMe center. The same results were
obtained for the reactions of 2a or 2b with the mixed
Lewis acid Et2AlCl-TMSOTf.
1
NMR tube (CD2Cl2, 20 °C). Comparison of the H NMR
spectral pattern taken immediately upon mixing and
after 10, 70, and 150 min of reaction time clearly
indicated that to the end of this period almost half of the
starting material underwent a conversion into a novel
compound. Unfortunately, the complexity of the observed
1H NMR spectra did not allow the unambiguous assign-
ment of all signals. Nevertheless, the appearance of
downfield-shifted signals of aromatic protons (ca. 0.4
ppm) and Mearom (ca. 0.2 ppm) at the expense of the
reduced intensity of the respective signals of the starting
material coupled together with the reduction of the
intensity of MeO and CHdCH2 proton signals could be
taken as strong evidence supporting the validity of the
above suggestion about the structure of the cationoid
intermediate represented by formula 15 (cf. the above
discussion of the structure of 13a ). Further treatment of
this sample with DBU resulted in the formation of the
expected cyclized product 16a ,b. Similar changes of the
proton signals pattern have been observed for the 1H
NMR-monitored reaction of 2b with TMSOTf.
(11) Numerous examples of cationic reactions employed as basic
steps in sequential transformations are described in the literature (for
pertinent data, see the reviews: Tietze, L. F. Chem. Rev. 1996, 96,
115. Hudlicky, T. Chem. Rev. 1996, 96, 3). However, practically all of
them belong to the type of intramolecular electrophilic cyclizations.
7960 J . Org. Chem., Vol. 67, No. 23, 2002

4,6-Dialkoxy-7-arylthioheptene Moiety
SCHEME 4
Cyclization of either diastereomer 2a or 2b could be
also triggered by a TiCl4/HCl system to give the chloro-
adduct 17a ,b in 45-50% yield,6 presumably due to the
reaction of the intermediate 15 with Cl- present in the
reaction media. It is noteworthy that this transformation
exhibited a noticeable diastereoselectivity. In fact, the
reaction of 2a furnished the product with a 3:1 ratio of
diastereomers 17a :17b, while the conversion of 2b gave
a 1:2 ratio of the same isomers. We have also found that
preparation of the substrate 2a ,b and its cyclization to
give 17a ,b can be carried out via a nonstop protocol
involving a tandem sequence of three intermolecular and
one intramolecular AdE reactions as is shown in Scheme
4.
upon the treatment with an additional amount of the
Lewis acid (Scheme 4).
The presence of the Me-group at C-4 in adduct 4a ,b
facilitated the preferential removal of the MeO-group
from this center, and under all conditions checked, the
interaction of this compound with Lewis acid was shown
to proceed nonselectively producing both 1,3-dienes and
the cyclized product. Thus, reaction of adduct 4a ,b with
TMSOTf led to the formation of a mixture of the cyclized
derivatives 20a ,b and conjugated diene 21, formed as a
result â- or δ-attack, respectively (Scheme 5).
At the same time, δ-attack turned out to be a highly
preferable pathway for the reactions of the adducts
bearing a gem-dimethyl group at C-5. Thus, interaction
of the substrates 5a ,b or 6a ,b with Lewis acid followed
by the quenching of the reaction with DBU yielded the
respective 1,3-dienes 236 or 246 as the sole products
regardless of the conditions used (TMSOTf or Et2AlCl-
TMSOTf for 5a ,b; Et2AlCl-TMSOTf for 6a ,b, Scheme 6).
The initial formation of TPI-like intermediates (e.g., 22)
in these transformations was ascertained by the data of
TLC monitoring, which indicated the conversion of the
starting material into a highly polar compound (Rf < 0.05,
10:1 ether-hexane, the conversion was complete within
Reaction of adduct 3a ,b with TMSOTf also followed
the â-attack route and produced the inseparable 1:1:1:1
mixture of the isomers 19a -d .6 One may speculate that
the observed formation of a mixture of the positional
isomers 19a ,b and 19c,d is due to the presence of the
angular Me-group in the intermediate TPI 18, which
hinders the otherwise preferable proton removal from
C-6. The same mixture of products was also prepared
with the help of a one-pot assembly of 3a ,b from the
starting alkene components followed by its cyclization
J . Org. Chem, Vol. 67, No. 23, 2002 7961

Chekmarev et al.
SCHEME 5
SCHEME 6
SCHEME 7
5 h at 20 °C). The treatment of the latter with DBU
produced 1,3-diene 23. Product 23 was also assembled
from three alkene precursors via a one-pot sequence as
is shown in Scheme 6.
TPI salt 25 fully correlated with the results of the
1
detailed analysis of its H and 13C NMR spectral param-
eters (see Experimental Section). The appearance of
downfield-shifted proton signals at 4.06 (1H, dd) and 4.23
(1H, m) identified as protons at C-1 and C-8, respectively,
taken together with the observation of the substantial
downfield shift of the signals of MeC6H4 group (2.51, s,
3H; 7.55 and 7.71, 2d, 4H; cf. data for the respective
proton signals for adduct 7 and see also data in ref 2c,d)
could be taken as diagnostic features substantiating the
suggested structure.
Rather surprisingly, an interaction of the five-mem-
bered analogues 8a ,b with the same reagent under
closely similar conditions proceeded with attack at the
tertiary methoxy group resulting in the elimination of
an MeOH fragment and formation of 1,6-diene 27. This
conversion did not involve the intermediate formation of
the stabilized cationoid complexes, and hence no quench-
ing of the reaction with a strong base was required. At
the same time, an exclusive attack at the secondary
methoxy group resulting in the formation of stabilized
intermediate, presumably TPI 28, occurred upon the
Adduct 7 prepared from 1-methoxycyclohexene con-
tains the axial MeO-group at the tertiary center, and one
might have thought that this group would be the pref-
erential target for the attack of electrophile. However, it
turned out that this group is rather inert toward the
action of Lewis acid and an exclusive elimination of MeO
group from the secondary position takes place upon the
interaction of 7 with TMSOTf. A subsequent treatment
of the reaction mixture with DBU gave the respective
1,3-diene 26 as the only isolable product (Scheme 7). For
this conversion the intermediacy of the bicyclic thiopha-
nium salt 25 was firmly established from the results of
the NMR monitored experiment. In fact, the 1H NMR
spectrum of the sample prepared by the mixing of 7 with
TMSOTf in CD2Cl2 at 0 °C revealed that after 1 h, the
reaction mixture does not contain signals of the starting
material. Instead, the signals of a nearly individual
compound were observed. The structure of the latter as
7962 J . Org. Chem., Vol. 67, No. 23, 2002

4,6-Dialkoxy-7-arylthioheptene Moiety
and 2.33 (m, 2H, AB-part ABX system, J AB ) 14.5, J AX ) J BX
) 7.3, CH2Cd), 2.32 (s, 3H, MePh), 3.06 (m, 2H, AB-part ABX
system, J AB ) 13.5, J AX ) J BX ) 5.5, CH2S), 3.31 (s, 3H, MeO),
3.33 (s, 3H, MeO), 3.46 (m, 2H, 2CHOMe), 4.78 and 4.83 (2 s,
broadened, CH2d), 7.10 and 7.29 (dd, 4Harom). 13C NMR
(CDCl3) δ: 21.9 (MePh), 23.8 (Me), 38.2 (CHCH2CH), 39.6
(CH2S), 43.2 (CH2Cd), 57.2 and 57.8 (2 MeO), 77.3 and 78.2
(2CHOMe), 113.8 (CH2d), 130.6 and 131.1 (CHarom), 134.1 and
137.2 (Carom).
1b. 0.160 g, Rf ) 0.51 (hexanes-ethyl acetate, 5:1). 1H NMR
(CDCl3) δ: 1.68 (m, 2H, CHCH2CH), 1.76 (s, 3H, Me), 2.05
and 2.37 (m, 2H, AB-part ABX system, J AB ) 16.5, J AX ) J BX
) 7.5, CH2Cd), 2.32 (s, 3H, MePh), 2.97 and 3.1 (m, 2H, AB-
part ABX system, J AB ) 15, J AX ) J BX ) 8.0, CH2S), 3.35 (s,
3H, MeO), 3.39 (s, 3H, MeO), 3.58 (m, 2H, 2CHOMe), 4.72 and
4.78 (2 s, broadened, CH2d), 7.10 and 7.29 (dd, 4Harom). 13C
NMR (CDCl3) δ: 21.9 (MePh), 23.8 (Me), 39.8 (CH2S), 40.3
(CHCH2CH), 43.2 (CH2Cd), 57.4 and 58.3 (2 MeO), 77.0 and
78.0 (2CHOMe), 113.9 (CH2d), 130.6 and 131.1 (CHarom), 134.1
and 137.2 (Carom). Anal. Calcd for C17H2602S: C, 69.34; H, 8.75;
S, 10.64. Found: C, 69.37; H, 8.90; S, 10.89.
4,6-Dim eth oxy-7-(p-tolylth io)h ep t-1-en e (2a ,b) was pre-
pared using the same procedure described for 1a ,b, the only
difference being that the final step (the reaction with less
active NuC, trimethylallylsilane) was carried out at 20 °C for
10 h. Adduct 2a ,b was prepared in 82% yield (ratio a :b ) 1.4:
1). Individual diastereomers were isolated with the help of
flash chromatography on SiO2. The identity of 2a and 2b was
established by comparison (1H NMR) with the samples pre-
pared earlier.1b
treatment of 8a ,b with the mixed Lewis acid, Et2AlCl-
TMSOTf. Quenching of this intermediate with DBU led
to the formation of 1,3-diene 29 in a nearly quantitative
yield (Scheme 7).
For adducts 9a ,b and 10a ,b prepared with the use of
dihydropyran as the first alkene component, â-attack
seems to be an unlikely option due to the well-known
stability of this ring system toward the action of Lewis
acid. Therefore, it was not surprising to find that interac-
tion of these substrates with TMSOTf or TMSOTf-Et2-
AlCl led to the formation of the respective dienes 30 and
31 as the only isolable products. In both cases, the
formation of 3-4 unidentified minor products was also
observed.
Con clu sion
Results presented in this paper clearly demonstrate
the possibility of controlling the selectivity of the Lewis
acid-induced transformations of multifunctional adducts
that could be easily assembled with the help of consecu-
tive intermolecular AdE reactions.1a-d Even more impor-
tant is the finding that both the preparation of adducts
and their subsequent conversion into the cyclohexane
derivatives or the products bearing 1,3-diene moiety can
be achieved as a result of a one-pot sequence of four
cationic reactions (three intermolecular plus one in-
tramolecular). Our current studies are aimed at the
evaluation of the potential of the newly elaborated mode
of consecutive transformations as a promising protocol
for the synthesis of polycyclic compounds.
4,6-Dim eth oxy-6-m eth yl-7-(p-tolylth io)h ept-1-en e (3a,b).
To a stirred solution of p-TolSCl (0.159 g, 1 mmol) in CH2Cl2
(10 mL) at -70 °C were added sequentially a solution of
2-methoxypropene (0.072 g, 1 mmol), TiCl4 (0.228 g, 1.2 mmol),
and methyl vinyl ether (0.116 g, 2 mmol). The mixture was
kept for 1 h at this temperature; then, tributylallyl stannane
(0.99 g, 3 mmol) was added, and the temperature was raised
to 0 °C. After the reaction was complete (6 h, TLC control),
the reaction was quenched with NaHCO3-ether followed by
the usual workup. The residue after solvent removal was
additionally washed with aqueous NaOH (20%) to remove tin-
containing impurities. Product 3a ,b was isolated after column
chromatography on SiO2 as a colorless oil (Rf ) 0.66, 30:1
hexanes-ethyl acetate, 290 mg, 98% yield) as a mixture of
Exp er im en ta l Section
Gen er a l. All reactions were carried out under argon in
oven-dried glassware. 1H (500 MHz) and 13C NMR (125 MHz)
spectra were recorded in CDCl3 solution unless stated other-
wise. Chemical shifts (δ) are reported in parts per million with
tetramethylsilane as an internal standard. J values are given
in hertz. Signal assignments were ascertained using standard
protocols with the help of two-dimensional gradient-enhanced
experiments geCOSY, geHNQC, and geHMBC. Results of
geNOESY and geROESY experiments were employed to
establish the stereochemistry of the products. Organic solvents
used were dried by standard methods. Flash chromatography
was performed on silica gel (230-400 mesh) and TLC on silica
gel.
1
two diastereomers in ratio of 1.6:1.0. H NMR (for the major
isomer 3a ) (CDCl3) δ: 1.31 (s, 3H, Me), 1.75-1.81 (m, 2H,
CH2), 2.27-2.31 (m, 2H, CH2,all), 2.31 (s, 3H, MeAr), 3.12 (m,
2H, CH2S), 3.18 and 3.32 (2s, 3H, MeO), 3.44 (m, 1H, CHOMe),
5.09 (m, 2H, CH2d), 5.80 (m, 1H, CHd), 7.09 and 7.28 (dd,
4Harom). 13C NMR (CDCl3) δ: 20.9 (MePh), 22.6 (Me), 38.3 (CH2-
CHd), 41.6 (CCH2CH), 43.9 (CH2S), 49.3 (MeOC), 55.9
(MeOCH), 77.0 (CHOMe), 117.4 (CH2d), 129.5 (2CH-arom),
139.8 (2CH-arom), 133.8 and 135.7 (2C-arom), 134.3 (CHd).
4,6-Dim eth oxy-2-m eth yl-7-(p-tolylth io)h ept-1-en e (1a,b).
To a stirred solution of p-TolSCl (0.159 g, 1 mmol) in MeNO2
(20 mL) at -25 °C was added a solution of methyl vinyl ether
(0.116 g, 2 mmol) in CH2Cl2 followed by a solution of anhydrous
LiClO4 (0.426 g, 4 mmol) in MeNO2 (4 mL). Almost im-
mediately, the formation of white precipitate (LiCl) was
observed. TLC monitoring revealed the gradual disappearance
of the spot with Rf ) 0.35 (5:1 hexanes-ethyl acetate)
corresponding to the initial adduct p-TolSCH2CH(Cl)OMe
substituted by a more polar compound with Rf ) 0.25. After
completion of this conversion (30 min), trimethylmethallyl
silane (0.257 g, 2 mmol) was added, and the mixture was kept
at -25 °C for 3 h and the reaction quenched with an NaHCO3-
ether mixture. Extraction with ether, washing with water,
drying over MgSO4, and solvent removal furnished 1a ,b (0.290
g, yield 98%) as a mixture of diastereomers in ratio of a :b )
1:1.5 (1H NMR data) uncontaminated by other products.
Individual diastereomers were isolated by flash chromatog-
raphy over SiO2 (17:1 hexanes-ethyl acetate).
1
Nonoverlapping signals of the isomer 3b. H NMR (CDCl3) δ:
1.27 (s, 3H, Me), 3.16 and 3.34 (2s, 3H, MeO)-group. 13C NMR
(CDCl3) δ: 20.9 (MePh), 23.1 (Me), 38.3 (CH2CHd), 40.9
(CCH2CH), 43.6 (CH2S), 49.3 (MeOC), 55.9 (MeOCH), 77.0
(CHOMe), 117.4 (CH2d), 129.5 (2CH-arom), 139.8 (2CH-arom),
133.8 and 135.7 (2C-arom), 134.3 (CHd). Anal. Calcd for
C
17H26O2S: C, 69.34; H, 8.90; S, 10.89. Found (for the mixture
3a ,b): C, 69.37; H, 9.02; S, 11.16.
4,6-Dim eth oxy-4-m eth yl-7-(p-tolylth io)h ept-1-en e (4a,b)-
. To a stirred solution of p-TolSCl (0.159 g, 1 mmol) in CH2Cl2
(20 mL) at -70 °C were added sequentially a solution of methyl
vinyl ether (0.058 g, 1 mmol), SnCl4 (0.52 g, 2 mmol), and
2-methoxypropene (0.144 g, 2 mmol). After 30 min, trimethyl-
allyl silane (0.23 g, 2 mmol) was added, and the temperature
was raised to -50 °C; the mixture was kept at this tempera-
ture for 4 h. After the usual quenching and standard workup,
product 4a ,b was isolated after column chromatography on
SiO2 as a colorless oil (Rf ) 0.6, 30:1 hexanes-ethyl acetate,
140 mg, 49% yield) as a mixture of two diastereomers in a 1:1
1a . 0.110 g, Rf ) 0.46 (5:1 hexanes-ethyl acetate). 1H NMR
(CDCl3) δ: 1.76 (s, 3H, Me), 1.82 (m, 2H, CHCH2CH), 2.13
J . Org. Chem, Vol. 67, No. 23, 2002 7963

Chekmarev et al.
ratio (GC-MS). 1H NMR (for the mixture 4a ,b) (CDCl3) δ: 1.13
and 1.16 (2s, 3H), 1.68-1.93 (m, 2H), 2.26 (m, 2H), 2.32 (s,
3H), 2.9-3.14 (m, 2H), 3.20 and 3.31 (2s, 6H), 3.51 (m, 2H),
5.04 (m, 2H), 5.82 (m, 1H), 7.08 and 7.26 (dd, 4Harom). 13C NMR
(CDCl3) δ: 21.0, 22.9, 23.2, 38.7, 38.8, 40.9, 41.6, 42.9, 49.0,
56.5, 56.6, 75.6, 75.7, 76.5, 76.6, 117.5, 117.6, 129.6, 129.9,
132.7, 136.0, 134.0, 134.5. Anal. Calcd for C17H26O2S: C, 69.34;
H, 8.90; S, 10.89. Found (for the mixture 4a ,b): C, 69.44; H,
8.83; S, 10.89.
132.9 and 136.3 (2Carom), 134.5 (CHd). Anal. Calcd for
C
20H30O2S: C, 71.81; H, 9.04; S, 9.59. Found: C, 71.60; H, 9.28;
S, 9.65.
cis-1-Meth oxy-1-(2′-m eth oxyp en t-2′-en yl)-2-(p-tolylth -
io)cyclop en ta n e (8a ,b) was prepared following the procedure
described for adduct 7, the only difference being the milder
reaction conditions (1 h at -10 °C). Product 8 was obtained in
61% yield as a mixture of diastereomers 8a and 8b (a :b ) 1.4:
1, GC-MS). 1H NMR (for 8a ,b) (CDCl3) δ: 1.55-2.1 (m, 8H,
3CH2,ring and CH2,chain), 2.10 and 2.20 (2m, 2H, CH2,all), 2.30
(s, 3H, MeAr), 3.22, 3.29. 3.30 and 3.35 (4s, 3H, MeO), 3.49
and 3.55 (2m, 1H, CHOMe), 3.41 and 3.59 (2m, 1H, CHS), 5.10
(m, 2H, CH2d), 5.82 (m, 1H, CHd), 7.05 and 7.35 (2d, 4Harom).
13C NMR (CDCl3) δ: 20.4 (CH2-ring), 20.9 (MePh), 32.2 and
32.7 (CH2-ring), 32.9 and 33.0 (CH2-ring), 37.7 and 38.2 (CCH2-
CH), 38.2 and 38.6 (CH2CHd), 49.9, 50.8, 55.9 and 56.0 (MeO),
55.3 and 57.5 (CHS), 76.8 and 77.2 (CHOMe), 86.2 (COMe),
117.6 and 117.7 (CH2d), 129.6 (2CH-arom), 130.9 and 131.04
(2CH-arom), 133.6, 133.6, 136.0 and 136.1 (2C-arom), 134.5
(CHd). Anal. Calcd for C19H28O2S: C, 71.20; H, 8.81; S, 10.01.
Found (for the mixture 8a ,b): C, 71.06; H, 8.67; S, 10.10.
4,6-Dim eth oxy-5,5-d im eth yl-7-(p-tolylth io)h ep t-1-en e
(5a ,b). To a stirred solution of TolSCl (0.159 g, 1 mmol) in CH2-
Cl2 (20 mL) at -25°C were added sequentially a solution of
methyl vinyl ether (0.058 g, 1 mmol), a solution of LiClO4
(0.426 g, 4 mmol) in MeNO2 (4 mL), and after 10 min of
stirring, 1-methoxy-2-methylpropene (0.172 g, 2 mmol). The
mixture was kept at this temperature for 3 h. Then trimethyl-
allyl silane (0.229 g, 2 mmol) was added, the temperature was
raised to 20 °C and the reaction mixture left overnight.
Standard quenching and workup, followed by the column
chromatography at SiO2, furnished product 5a ,b as a mixture
of diastereomers 5a and 5b (0.303 g, yield 94%, 5a :5b ) 1.2:
1
tr a n s-2-(3′-Meth oxy-2′-m eth ylh ex-5′-en -2′-yl)-3-(p-tolylth -
io)tetr a h yd r op yr a n (9a ,b) was prepared as described in ref
2d: yield 90%, 9a :9b ) 4:1.
1.0, GC-MS, Rf ) 0.48, 5:1 hexanes-ethyl acetate). H NMR
(for the mixture 5a ,b) (CDCl3) δ: 0.86 and 0.97 (2s, 6H), 2.05-
2.25 (m, 2H), 2.33 (s, 3H), 2.95 and 3.20 (2m, 2H), 3.20-3.45
(m, 2H), 3.43, 3.45, 3.51, and 3.53 (4s, 3H), 5.0-5.15 (m, 2H),
5.83-6.05 (m, 1H), 7.10 and 7.32 (2d, 4H). 13C NMR (CDCl3)
δ: 18.7, 18.8, 19.7, 19.9, 20.9, 21.0, 35.1, 35.4, 36.9, 37.3, 43.8,
44.2, 59.4, 59.8, 60.4, 61.2, 84.3, 84.9, 85.5, 85.8, 116.0, 116.0,
129.68, 129.8, 130.0, 130.2, 133.5, 133.5, 137.1, 137.3, 136.0,
136.1. Anal. Calcd for C18H28O2S: C, 70.08; H, 9.15; S, 10.39.
Found (for the mixture 5a ,b): C, 70.30; H, 9.28; S, 10.05.
tr a n s-2-(3′-Meth oxy-2′,5′-d im eth ylh ex-5′-en -2′-yl)-3-(p-
tolylth io)tetr a h yd r op yr a n (10a ,b) was prepared under the
conditions described in ref 2d for the preparation of 9a ,b with
the use of trimethylmethallyl silane as a final NuC: yield 78%,
10a :10b ) 1.4: 1 (GC-MS). 1H NMR (CDCl3) δ: 0.93, 1.09,
1.11 and 1.15 (4s, 3H, Me), 1.54-1.66 and 1.90-1.98 (m, 4H,
2CH2,ring), 1.83 and 1.85 (2s, 3H, Me), 2.12-2.20 (m, 2H, CH2all),
2.35 (s, 3H, MeAr), 3.12 (d, 1H, CHOring), 3.19-3.29 (m, 1H,
CHS), 3.33 and 3.45 (2m, 2H, CH2Oring), 3.40 and 3.41 (2s, 3H,
MeO), 3.94 (m, 1H, CHOMe), 4.84 (m, 2H, CdCH2), 7.12 and
7.33 (2d, 4Harom). 13C NMR (CDCl3) δ: 19.9 and 19.9 (2Me),
20.0 (MePh), 22.8 and 22.9 (CH3-allyl), 25.2 and 31.0 (2CH2-
ring), 39.5 and 39.6 (CH2-allyl), 46.8 and 47.0 (CHS), 60.8 and
61.1 (MeO), 67.3 and 68.3 (CH2O), 82.2 and 82.3 (CHOMe),
85.6 (CHO-ring), 112.9 and 113.0 (CH2d), 129.9 (2CH-arom),
131.7 and 131.8 (C-arom), 133.6 and 133.7 (2CH-arom), 137.3
(C-arom), 138.6 (Cd). Anal. Calcd for C21H32O2S: C, 72.37; H,
9.29; S, 8.70. Found (for the mixture 10a ,b): C, 72.35; H, 9.25;
S, 9.20.
4,6-Dim et h oxy-2,5,5-t r im et h yl-7-(p -t olylt h io)h ep t -1-
en e (6a ,b) was prepared by the coupling of methyl vinyl ether,
1-methoxy-2-methylpropene, and trimethylmethallyl silane
following the procedure described for the preparation of 5a ,b.
This produced an inseparable mixture of diastereomers 6a and
6b (yield 93%, 6a :6b ) 1.1:1.0, Rf ) 0.55, 5:1 hexanes-ethyl
1
acetate). H NMR (for the mixture 6a ,b) (CDCl3) δ: 0.86 and
0.97 (2s, 6H, Me2), 1.82 (s, 3H, MeCd), 2.05-2.25 (m, 2H,
CH2Cd), 2.33 (s, 3H, MeAr), 2.95 and 3.20 (2m, 2H, CH2S),
3.20-3.45 (2m, 2H, CHOMe), 3.32, 3.36, 3.51 and 3.52 (4s, 3H,
MeO), 4.75-4.85 (m, 2H, CH2d), 7.1 and 7.42 (2d, 4H, Har).
13C NMR (CDCl3) δ: 18.5, 18.7, 19.7 and 19.8 (4Me), 21.0
(MePh), 22.8 (CH3-allyl), 37.0 and 37.3 (2CH2S), 39.2 and 39.4
(2CH2-allyl), 43.8 and 44.2 (2C), 59.6, 60.0, 60.3, and 61.1
(4MeO), 83.1, 84.2, 84.3, and 85.4 (4CHOMe), 112.5 and 112.6
(2CH2d), 129.6 (2CH-arom), 130.1 (2CH-arom), 133.4 and
136.1 (2C-arom), 144.0 and 144.2 (2Cd). Anal. Calcd for
(E )-6-Me t h oxy-2-m e t h yl-7-(p -t olylt h io)h e p t a -2,4-d i-
en e (12a ) a n d (E)-6-Meth oxy-2-m eth yl-7-(p-tolylth io)-
h ep ta -1,3-d ien e (12b). TMSOTf (0.556 g, 2.5 mmol) was
added at 20 °C to the stirred solution of 1a ,b (0.263 g, 1 mmol)
in CH2Cl2. After 2 h, TLC data revealed a complete disap-
pearance of the spot corresponding to the starting material
substituted by the spot of the highly polar compound (Rf <
0.05). The reaction mixture was treated with DBU (0.60 g, 4
mmol) and left overnight. Subsequent treatment with NaHCO3/
KH2PO4 and ether followed by the standard workup and
column chromatography furnished a mixture of isomers 12a
C
19H30O2S: C, 70.76; H, 9.38; S, 9.94. Found (for the mixture
6a ,b): C, 70.57; H, 9.35; S, 9.65.
cis-1-Meth oxy-1-(2′-m eth oxyp en t-4′-en yl)-2-(p-tolylth -
io)cycloh exa n e (7). To a stirred solution of p-TolSCl (0.238
g, 1.5 mmol) in CH2Cl2 (20 mL) at -70 °C were added
sequentially 1-methoxycyclohexene (0.168 g, 1.5 mmol), TiCl4
(0.342 g, 1.8 mmol), and the solution of methyl vinyl ether
(0.116 g, 2 mmol). After 30 min, tributylallyl stannane (0.99
g, 3 mmol) was added, and the temperature was raised to -0
°C and the mixture kept at this temperature overnight. After
quenching of the reaction with NaOH (20%, 40 mL) and ether
(30 mL), followed by the standard workup, product 7 was
obtained as an individual isomer after column chromatography
on SiO2 (colorless oil, Rf ) 0.54, 20:1 hexanes-ethyl acetate,
1
and 12b (0.120 g, 50%, ratio of a :b ) 7:1, GC-MS). H NMR
(for the mixture 12a ,b) (CDCl3) δ: for 12a , 1.78 (s, 3H, Me),
1.80 (s, 3H, Me), 2.33 (s, 3H, MePh), 2.98 and 3.10 (pair of dd,
AB part ABX system, 2H, CH2S, J AB ) 13.0, J AX ) 5.4, J BX
6.9), 3.29 (s, 3H, MeO), 3.77 (m, 1H, CHOMe), 5.40 (dd, J 1
)
)
7.9, J 2 ) 15.2, 1H, at C-5), 5.84 (d, J ) 11.1, 1H, at C-3), 6.43
(dd, J 1 ) 11.1, J 2 ) 15.2, 1H, at C-4), 7.10 and 7.28 (2d, 4Harom).
1H NMR for 12b (only nonoverlapping signals are given) δ:
1.83 (s, 3H, Me), 3.37 (s, 3H, MeO), 3.41 (m, 1H, CHOMe),
4.88, 5.6 and 6.2 (d, dd and dd, ratio 2:1:1, conjugated diene
system). 13C NMR for 12a (CDCl3) δ: 18.5 (Me), 21.1 (MePh),
26.1 (Me), 40.1 (CH2S), 56.5 (MeO), 81.2 (CHOMe), 124.2 (C-
3), 128.9 (C-5), 129.7, 130.2, 132.9 and 136.1 (Carom), 130.5 (C-
4), 136.9 (C-2). Anal. Calcd for C16H22OS: C, 73.23; H, 8.45;
S, 12.22. Found (for the mixture 12a ,b): C, 73.13; H, 8.45; S,
11.82.
1
325 mg, 65% yield). H NMR (CDCl3) δ: 1.3-2.0 (m, 8H), 1.8
and 2.2 (dd, J 1 ) 15.1, J 2 ) 9.0) (AB-part of ABX system, 2H
at C-5′), 2.33 (s, 3H, MeAr), 2.36 (m, 2H, CH2Cd), 3.24 and
3.34 (2s, 3H, MeO-groups), 3.35 (dd, 1H, CHS, J 1 ) 9.3, J 2
)
3.5), 3.47 (m, 1H, CHOMe), 5.12 (m, 2H, CH2d), 5.85 (m, 1H,
CHd), 7.05 and 7.35 (2d, 4Harom). 13C NMR (CDCl3) δ: 20.8
(MeAr), 21.7, 24.4, 29.4 and 31.5 (4 CH2,ring), 37.6 and 38.2
(2CH2,chain), 48.5 (CHS), 55.8 and 56.1 (2MeO), 76.7 (COMe),
77.1 (CHOMe), 117.4 (CH2d), 129.4 (2CH arom), 132.1 (2CHarom),
cis-5-Meth oxy-1-m eth yl-3-(p-tolylth iom eth yl)cycloh ex-
en e (14a ). To a stirred solution of 1a (0.140 g, 0.45 mmol) in
7964 J . Org. Chem., Vol. 67, No. 23, 2002

4,6-Dialkoxy-7-arylthioheptene Moiety
CH2Cl2 (9 mL) at 20 °C were added sequentially solutions of
EtAlCl2 (0.121 g, 1 mmol) in toluene (0.56 mL) and TMSOTf
(0.220 g, 0.18 mL). After 5 h, TLC revealed a complete
conversion of the starting compound into a highly polar
material (Rf < 0.05, 5:1 hexanes-ethyl acetate). DBU (0.38 g,
2.5 mmol) was added to the reaction mixture, and the reaction
was left overnight and then quenched with NaHCO3/KH2PO4
(20 mL) and ether (10 mL). After extraction with ether, drying
with MgSO4, solvent removal, and flash chromatography (SiO2,
15:1 hexanes-ethyl acetate) adduct 14a was obtained as a
colorless oil (Rf ) 0.44, 5:1 hexanes-ethyl acetate, 0.078 mg,
and the mixture was kept for 4 h at this temperature. After
the quenching with NaHCO3-ether and the usual workup, the
mixture of 17a and 17b was obtained (0. 018 g, yield 45%,
17a :17b ) 3:1). These diastereomers were separated by flash
chromatography on SiO2. 17a , 1,5-cis, 1,3-trans: Rf ) 0.5 (15:1
1
hexanes-ethyl acetate). H NMR (CDCl3) δ: 1.06 (m, 1H, Ha
at C-4, 1.34 (q, 1Ha at C-6, J ) 13.0), 1.59 (m, 1Ha at C-2),
2.00 (m, 1Ha, at C-5), 2.15 (m, 1He at C-4), 2.32 (s, 3H, MeAr),
2.36 (m, 1H, He at C-6), 2.41 (m, 1He at C-2), 2.81 (dd, 2H,
CH2S, J 1 ) 6.8, J 2 ) 1.2), 3.25 (s, 3H, MeO), 3.62 (quint,
CHOMe, J ) 2.8), 4.12 (tt, 1H, CHCl, J 1 ) 1.5, J 2 ) 3.8), 7.09
and 7.25 (2d, 4Harom). 13C NMR (CDCl3) δ: 21.0 (MeAr), 32.1
(C-5), 34.0 (C-4), 40.3 (C-2), 41.2 (CH2S), 42.7 (C-6), 55.1
(CHCl), 55.9 (MeO), 75.8 (CHOMe), 129.7 and 130.0 (CHarom),
132.9 and 136.2 (Carom). MS: m/z 284 and 282 (M+). 17b, 1,3,5-
cis: (Rf ) 0.43, 15:1 hexanes-ethyl acetate). 1H NMR (CDCl3)
δ: 0.93 (q, 1H, Ha at C-4, J ) 12.5), 1.30 (q, 1Ha at C-6, J )
12.5.), 1.47 (q, 1Ha at C-2, J ) 12.5), 1.60 (m, 1Ha, at C-5),
2.32 (s, 3H, MeAr), 2.41 (m, 1He at C-4), 2.52-2.62 (m, 2H, He
at C-2 and C-6), 2.84 (d, 2H, CH2S, J ) 7.5), 3.12 (tt, CHOMe,
J 1 ) 3.8, J 2 ) 12.5), 3.35 (s, 3H, MeO), 3.75 (tt, 1H, CHCl, J 1
) 12.5, J 2 ) 3.8), 7.09 and 7.25 (2d, 4Harom). MS: m/z 284 and
282 (M+).
1
59%). H NMR (CDCl3) δ: 1.19 (q, 1Ha at C-4, J ) 12.0), 1.70
(s, 3H, Me), 1.94 and 2.22 (2 m, 2H at C-6), 2.33 (s, 3H, MePh),
2.38 (m, 1H at C-3), 2.88 (m, AB part ABX system, 2H, CH2S),
3.37 (s, 3H, MeO), 3.42 (m, 1H, CHOMe), 5.38 (s, 1H, CHd),
7.10 and 7.28 (dd, 4Harom). 13C NMR (CDCl3) δ: 21.1 (MePh),
23.6 (Me at C-1), 34.3 (CH2, C-4), 35.7 (CHall), 36.8 (CH2,all),
41.1 (CH2S), 55.9 (MeO), 76.7 (CHOMe), 124.0 (CHd), 129.8
and 130.2 (4CHarom), 132.0 and 136.1 (2Carom), 133.1 (Cd). Anal.
Calcd for C16H22OS: C, 73.23; H, 8.45; S, 12.22. Found: C,
73.44; H, 8.58; S, 11.97.
tr a n s-5-Meth oxy-1-m eth yl-3-(p-tolylth iom eth yl)cyclo-
h exen e (14b) was prepared under similar conditions by the
interaction of 1b with EtAlCl2 and TMSOTf. 14b: yield 65%,
a colorless oil, Rf 0.40, 5:1 hexanes-ethyl acetate. 1H NMR
(CDCl3) δ: 1.30 (m, 2H, CH2), 1.68 (s, 3H, Me), 1.98 and 2.08
(2m, 2H at C-6), 2.33 (s, 3H, MePh), 2.48 (m, 1H at C-3), 2.86
(m, AB part ABX system, 2H, CH2S), 3.34 (s, 3H, MeO), 3.61
(m, 1H, CHOMe), 5.42 (s, 1H, CHd), 7.10 and 7.28 (dd, 4Harom).
The presence of the exo-methylene isomer 14c (ca. 25%, GC-
MS) was ascertained from the appearance of the following
nonoverlapping signals: 3.3 (s, 3H, MeO), 3.55 (m, 1H,
CHOMe), and 4.78 (CdCH2).
On e-P ot Syn th esis of 14a -c via P r ep a r a tion of 1a ,b
in Situ . To a stirred solution of 4-TolSCl (0.159 g, 1 mmol) in
CH2Cl2 (20 mL) at -78°C were added sequentially a solution
of methyl vinyl ether (0.174 g, 3 mmol) in CH2Cl2 (2 mL) and
Et2AlCl (0.363 g, 3 mmol) in toluene (1.08 mL). After additional
stirring for 15 min at this temperature, methallyltrimethyl-
silane (0.257 g, 2 mmol) was added and the mixture was kept
for 3 h at -78 °C until TLC data revealed complete conversion
of the intermediate compound into adduct 1a ,b. Then, the
temperature was raised to 20 °C and TMSOTf (0.66 g, 3 mmol)
was added. The mixture was kept at this temperature for 10
h. Toward the end of this period, TLC data indicated a nearly
complete transformation of 1a ,b into a highly polar material
(Rf < 0.05). The reaction was next quenched with DBU as
described above. Usual workup and chromatography separa-
tion furnished product 14a -c (0.215 g, yield 82%). 1H NMR
spectrum of this product revealed the presence of all three
isomers, their ratio (a :b:c ) 1.4:1.0:0.3) having been evaluated
by the integration of the nonoverlapping signals.
Under essentially the same conditions, the diastereomer 2b
was converted into a mixture of the same products 17a ,b in
50% yield (17a :17b ) 1:2).
On e-P ot Syn th esis of 17a ,b via P r ep a r a tion of 2a ,b in
Situ . To a stirred solution of 4-TolSCl (0.159 g, 1 mmol) in
CH2Cl2 (20 mL) at -78°C was added a solution of methyl vinyl
ether (0.058 g, 1 mmol) in CH2Cl2 (1 mL) followed by TiCl4
(0.190 g, 1 mmol) and an additional 1 equiv of methyl vinyl
ether. The mixture was kept for 2 h at -20 °C; then, the
temperature was raised to 0 °C, and trimethylallylsilane (0.229
g, 3 mmol) was added, and mixture was kept at this temper-
ature for 3 h. Toward the end of this period, the TLC control
indicated the complete formation of 2a ,b. After that, the
temperature was raised to 20 °C and the mixture saturated
with dry HCl (ca. 3 equiv); an additional amount of TiCl4 (2
equiv) was added, and stirring was continued for 3 h. Quench-
ing of the reaction with NaHCO3-ether, followed by the
standard workup and chromatography on SiO2, gave 17a ,b:
0.12 g, yield 37%, 17a :17b ) 3:1 (1H NMR).
5-Met h oxy-3-m et h yl-3-(p -t olylt h iom et h yl)cycloh ex-
en e (19a ,b) a n d 3-Meth oxy-5-m eth yl-5-(p-tolylth iom eth -
yl)cycloh exen e (19c,d ) were prepared as an inseparable
mixture of diastereomers from the mixture of diastereomers
3a ,b using TMSOTf as a Lewis acid under the conditions
described above for the synthesis of 14a ,b (yield 49%, 19a :
1
19b:19c:19d ) 1:1:1:1). H NMR (CDCl3) δ: 1.08, 1.14, 1.17
and 1.19 (4s, 3H), 1.35, 1.5, 1.6 and 1.7 (4dd, 2H), 1.9-2.35
(m, 2H), 2.32 (s, 3H), 2.9-3.1 (4dd, 2H), 3.26, 3.35, 3.39 and
3.40 (4s, 3H), 3.45-3.6 (2m, 1H), 3.78 and 3.88 (2m, 1H), 5.5,
5.6, 5.75 and 5.80 (4m, 1H), 7.09 and 7.28 (dd, 4Harom). The
ratio of isomers was estimated by the integration of nonover-
lapping signals. Similarly, four sets of closely related signals
were observed in 13C NMR. 13C NMR (CDCl3) δ: 21.2, 24.5,
27.7, 28.0, 28.3, 32.0, 37.0, 38.0, 38.9, 39.1, 39.5, 40.1, 45.7,
74.80, 49.1, 49.2, 56.0, 56.1, 74.6, 74.1, 123.7, 123.9, 127.3,
127.5, 128.1, 128.1, 129.7, 129.9, 130.5, 130.6, 134.8 and 135.3.
Anal. Calcd for C16H22OS: C, 73.23; H, 8.45; S, 12.22. Found
(for the mixture 19a -d ): C, 73.48; H, 8.52; S, 11.66.
5-Met h oxy-3-(p -t olylt h iom et h yl)cycloh exen e (16a ,b )
was prepared as an inseparable mixture of diastereomers from
either of the individual diastereomers 2a or 2b with the use
of TMSOTf as a Lewis acid under the conditions described
above for the synthesis of 14a ,b (yield 65%, 16a :16b ) 1.8:1).
1H NMR (for the mixture 16a ,b) (CDCl3) δ: 1.24, 1.70, 1.94
and 2.07 (4m, 2H), 2.21-2.56 (m, 3H, allyl), 2.31 (s, 3H, MePh),
2.89 (m, 2H, CH2S), 3.32 and 3.36 (2s, 3H, MeO), 3.41 and
3.56 (2m, 1H, CHOMe), 5.65 (m, 2H, CHdCH), 7.09 and 7.26
(2d, 4H). 13C NMR (CDCl3) δ: 21.0 (MePh), 31.0, 31.4, 31.7,
34.4, 40.4 and 40.6 (6 CH2), 32.4 and 35.9 (2CH), 55.7 and 55.8
(2 MeO), 73.2 and 76.1 (2 CHOMe), 124.9 and 125.1 (2 CHd
CH), 129.6 and 130.1 (CHarom), 132.7, 13.8 and 136.1 (Carom).
On e-P ot Syn th esis of 19a -c via P r ep a r a tion of 3a ,b
in Situ . To a stirred solution of 4-TolSCl (0.159 g, 1 mmol) in
CH2Cl2 (10 mL) at -78 °C were added sequentially a solution
of 2-methoxypropene (0.072 g, 1 mmol) in CH2Cl2 (2 mL), TiCl4
(0.230 g, 1.2 mmol), and methyl vinyl ether (0.094 g, 1.8 mmol).
After additional stirring for 1 h at -20 °C, allyltributyl
stannane (0.663 g, 2 mmol) was added, the temperature raised
to 0 °C, and the mixture kept at this temperature for 3 h until
TLC data revealed complete conversion of the intermediate
compound into adduct 3a ,b. At this moment, the temperature
was raised to 20 °C and TMSOTf (0.44 g, 2 mmol) was added.
GC-MS: M+ 248 for both 16a and 16b. Anal. Calcd for C15H20
-
OS: C, 72.53; H, 8.12; S, 12.91. Found (for the mixture
16a ,b): C, 72.40; H, 8.25; S, 12.70.
1-Ch lor o-3-m e t h oxy-5-(p -t olylt h iom e t h yl)cycloh e x-
a n e (17a ,b). To a solution of 2a (0.04 g, 0.014 mmol) in CH2-
Cl2 (5 mL) at 20 °C was introduced a flow of dry HCl for 15
min (ca. 3 equiv); then, TiCl4 (0.040 g, 0.020 mmol) was added,
J . Org. Chem, Vol. 67, No. 23, 2002 7965

Chekmarev et al.
The mixture was kept at this temperature for 1 h. Toward the
end of this period, TLC data indicated a nearly complete
transformation of 3a ,b into a highly polar material (Rf < 0.05).
Quenching of the reaction mixture with DBU, followed by the
standard workup, furnished product 19 as a mixture 19a -d
(0.06 g, yield 42%), its 1H NMR spectrum being identical to
that described in the previous experiment.
conversion of the starting material (Rf ) 0.45, 5:1 hexanes-
ethyl acetate) into a highly polar compound (Rf < 0.05, the
same system). Treatment of the mixture with DBU (0.60 g, 4
mmol) overnight followed by quenching with aqueous NaHCO3/
KH2PO4 (20 mL)-ether (20 mL) and standard workup yielded
after purification on SiO2 adduct 24 (Rf ) 0.45, 17:1 hexane-
1
ethyl acetate, 0.194 g, yield 67%) as a colorless oil. H NMR
(CDCl3) δ: 1.09 (s, 6H, 2Me), 1.86 (s, 3H, Me), 2.33 (s, 3H,
MeAr), 2.82 (dd, 1H, CHAS, J 1 ) 8.8, J 2 ) 13.2), 3.04 (dd, 1H,
CHOMe, J 1 ) 2.2, J 2 ) 8.8), 3.11 (dd, 1H, CHBS, J 1 ) 2.2, J 2
) 13.2), 3.53 (s, 3H, MeO), 4.94 (s, broad, 2H, CH2d), 5.17 (d,
1H, C-CHd, J ) 16.2), 6.12 (d, 1H, C-CHdCH, J 1 ) 16.2),
7.11 and 7.27 (dd, 4Harom). 13C NMR (CDCl3) δ: 18.7 (Meall),
20.9 (MeAr), 22.4 and 24.8 (2Me), 37.2 (CH2S), 45.3 (C), 61.8
(MeO), 88.0 (CHOMe), 115.3 (CH2d), 129.6 (2CHarom), 129.7
(2CHarom), 130.5 (CH2d), 133.2 and 135.9 (2Carom). Anal. Calcd
for C18H26OS: C, 74.43; H, 9.02; S, 11.04. Found: C, 74.22; H,
8.81; S, 11.40.
cis-1-Meth oxy-1-((E)-p en ta -2′,4′-d ien yl)-2-(p-tolylth io)-
cycloh exa n e (26). To a stirred solution of 7 (0.1 g, 0.3 mmol)
in CH2Cl2 (15 mL) at 0 °C was added TMSOTf (0.133 g, 0.6
mmol). After 1 h, TLC data indicated the complete conversion
of the starting material into a highly polar compound 25 (see
below). The reaction mixture was then treated with DBU
followed by the quenching with NaHCO3/KH2PO4-ether and
standard workup. Column chromatography on SiO2 gave
adduct 26 as a colorless liquid (0.060 g, 73%, Rf ) 0.71, 5:1
hexanes-ether). 1H NMR (CDCl3) δ: 1.1-2.0 (m, 8H, 4CH2ring),
2.3 (s, 3H, MeAr), 2.43 and 2.82 (2H, CH2,all, AB-part of ABX
5-Met h oxy-5-m et h yl-3-(p -t olylt h iom et h yl)cycloh ex-
en e (20a ,b) a n d (E)-6-m eth oxy-4-m eth yl-7-(p-tolylth io)-
h ep ta -1,3-d ien e (21). A mixture of these products was
prepared by the initial treatment of 4a ,b with TMSOTf
following the procedure described above for the preparation
of 14a ,b. Products 20a ,b and 21 were isolated by flash
chromatography on SiO2. 20a ,b: yield 13%, Rf ) 0.6, 15:1
hexanes-ether, 20a :20b ) 1.5:1, GC-MS. 1H NMR (CDCl3) δ:
1.15 and 1.20 (2s, 3H), 1.25 (m, 2H), 1.90-2.25 (m, 2H), 2.31
(s, 3H), 2.90 (m, 2H), 3.15 and 3.25 (2s, 3H), 5.60-5.60 (CHd
CH), 7.09 and 7.27 (dd, 4Harom). Anal. Calcd for C16H22OS: C,
73.23; H, 8.45; S, 12.22. Found (for the mixture of 20a ,b): C,
73.35; H, 8.62; S, 11.58. 21: yield 25%, Rf ) 0.7, 15:1 hexanes-
1
ether. H NMR (CDCl3) δ: 1.77 (s, 3H), 2.33 (s, 3H), 2.36 (m,
2H), 3.00 (m, 2H), 3.35 (s, 3H), 3.48 (m, 1H), 5.06 (m, 2H),
5.88 (dd, 1H, J ) 10.5), 6.55 (m, 1H), 7.10 and 7.27 (dd, 4Harom).
Anal. Calcd for C16H22OS: C, 73.23; H, 8.45; S, 12.22. Found:
C, 73.45; H, 8.38; S, 12.40.
(E)-6-Meth oxy-5,5-d im eth yl-7-(p-tolylth io)h ep ta -1,3-d i-
en e (23). To a stirred solution of adduct 5a ,b (0.140 g, 0.45
mmol) in CH2Cl2 (15 mL) at 20 °C were added sequentially
Et2AlCl (0.121 g, 1 mmol in toluene solution, 0.56 mL) and
TMSOTf (0.022 g, 1 mmol). After 5 h, TLC data indicated a
complete conversion of the starting material (Rf ) 0.48, 5:1
hexanes-ethyl acetate) into a highly polar compound, presum-
ably TPI salt 22 (Rf < 0.05, the same system). Treatment of
the mixture with DBU (0.45 g, 3 mmol) overnight followed by
the quenching with aqueous NaHCO3/KH2PO4 (20 mL)-ether
(20 mL) and standard workup yielded after purification on
SiO2 adduct 23 (Rf ) 0.45, 17:1 hexane-ethyl acetate, 0.110
g, yield 91%) as a colorless oil. 1H NMR (CDCl3) δ: 1.07 (s,
6H, 2Me), 2.33 (s, 3H, MeAr), 2.83 (dd, 1H, CHAS, J 1 ) 9.0, J 2
) 13.5), 3.04 (dd, 1H, CHOMe, J 1 ) 2.2, J 2 ) 9.0), 3.11 (dd,
1H, CHBS, J 1 ) 2.2, J 2 ) 13.5), 3.53 (s, 3H, MeO), 5.04 and
5.16 (2d, 2H, CH2d, J 1 ) 10.2, J 2 ) 17.0), 5.72 (d, 1H, C-CHd
, J ) 15.7), 6.04 (dd, 1H, C-CHdCH, J 1 ) 10.2, J 2 ) 15.7),
6.33 (dt, CHdCH2, J 1 ) 10.2, J 2 ) 17.0), 7.11 and 7.27 (dd,
4Harom). 13C NMR (CDCl3) δ: 21.0 (MeAr), 2.6 and 24.5 (2Me),
37.2 (CH2S), 45.0 (C), 61.7 (MeO), 87.9 (CHOMe), 115.7 (CH2d
), 128.8 (CHdCHCHd), 129.6 (2CHarom), 129.8 (2CHarom), 133.5
and 137.1 (2Carom), 137.4 (CHdCH2), 141.1 (CCHd). Anal.
Calcd for C17H24OS: C, 73.86; H, 8.75; S, 11.60. Found: C,
74.05, H, 8.98, S, 11.20.
On e-P ot Syn th esis of 23 via th e P r ep a r a tion of 5a ,b
in Situ . To a stirred solution of 4-TolSCl (0.159 g, 1 mmol) in
CH2Cl2 (20 mL) at -78 °C were added sequentially a solution
of methyl vinyl ether (0.058 g, 1 mmol) in CH2Cl2 (1 mL),
TMSOTf (0.022 g, 1.0 mmol), and 1-methoxy-2-methylpropene
(0.172 g, 2.0 mmol). After additional stirring overnight, allyl-
trimethylsilane (0.229 g, 2 mmol) was added, the temperature
raised to 20 °C, and the mixture kept for 3 h at this
temperature until TLC data revealed complete conversion of
the intermediate compound into adduct 5a ,b. At this moment,
the temperature was raised to 20 °C, and TMSOTf (0.088 g, 4
mmol) was added. The mixture was kept at this temperature
for 100 h. Toward the end of this period, TLC data indicated
a complete transformation of 5a ,b into a highly polar material
(Rf < 0.05). Quenching of the reaction mixture with DBU
followed by the standard workup furnished product 23 (0.180
g, yield 65%), its 1H NMR spectrum being identical to that
described in the previous experiment.
system, J 1 ) 13.3, J 2 ) 8.2, J 3 ) 7.3), 3.0 (dd, 1H, CHS, J 1
)
11.2, J 2 ) 4.1), 3.27 (s, 3H, MeO), 5.02 and 5.1 (2d, 2H, CH2d,
J 1 ) 16.9, J 2 ) 10.1), 5.7 (m, 1H, CH2CHd), 6.2 (dd, 1H, CH2-
CHdCH, J 1 ) 15.0, J 2 ) 10.1), 6.34 (dt, 1H, CHdCH2, J 1
)
16.9, J 2 ) 10.1), 7.1 and 7.32 (2d, 4Harom). 13C NMR (CDCl3) δ:
21.0 (MeAr), 21.1, 25.6, 29.7 and 31.0 (CH2, ring), 38.7 (CH2,all),
48.5 (MeO), 55.3 (CHS), 78.0 (COMe), 115.6 (CH2d), 129.5
(2CHarom), 129.6 (C-CHdCH), 132.2 (2CHarom), 132.5 and 136.5
(2Carom), 134.7 (CdCHCHd), 137.0 (CHdCH2). Anal. Calcd for
C
19H20OS: C, 75.45; H, 8.66; S, 10.60. Found: C, 75.60; H,
8.91; S, 9.87.
Id en t ifica t ion of t h e St r u ct u r e of In t er m ed ia t e 25.
Interaction of adduct 7 dissolved in CD2Cl2 with TMSOTf (0
°C, 30 min, cf. previous experiment) produced a solution of
the salt 25, which was transferred into a NMR tube, and its
1H and 13C NMR spectra were immediately recorded at this
temperature. 1H NMR did not reveal the presence of 7 in a
noticeable amount. 1H NMR (CD2Cl2) δ: 1.41 (m, 1H, Ha at
C-3), 1.51 (m, 1H, Ha at C-4), 1.63 (m, 1H, Ha at C-5), 1.69 (m,
1H, He at C-4), 1.91 (m, 1H, He at C-2), 1.98 (m, 1H, He at
C-3), 2.11 (dd, 1HA at C-7, J 1 ) 12.3, J 2 ) 14.0), 2.19 (m, 1H,
Ha at C-2), 2.25 and 2.43 (2 m, 2H at C-9); 2.40 (m, 1H, He at
C-5), 2.51(s, 3H, MeAr), 2.92 (dd, 1HB at C-7, J 1 ) 6.0, J 2
14.0); 3.29 (3H, s, MeO); 4.06 (dd, 1H at C-1, J 1 ) 4.2, J 2
)
)
12.3); 4.23 (m, 1H at C-8); 4.82 (d, 1H at C-11, J ) 17.2); 5.24
(d, 1H at C-11, J ) 10.3); 5.52 (m, 1H at C-10); 7.55 and 7.71
(2d, 4H, Ar). 13C -NMR (CD2Cl2) δ: 19.0 (C-4), 21.3 (MeAr),
23.0 (C-2), 24.8 (C-3), 28.3 (C-5), 33.5 (C-9), 40.5 (C-7), 49.0
(MeO), 58.0 (C-8), 70.9 (C-1), 82.0 (C-6), 119.2 (C-11), 131.5
(C-10), 131.8, 133.0, 132.2, 147.4 (C-Ar). Assignment of all
1H and 13C signals was made with the help DEPT, HETCOR,
COSY, and NOESY protocols. The attempt to isolate the salt
in the free state by precipitation with the cooled hexane or
carbon tetrachloride led to the formation of the oily residue,
which decomposed almost instantaneously at room tempera-
ture.
1-(2′-Me t h oxyp e n t -4′-e n yl)-2-(p -t olylt h io)cyclop e n -
ten e (27). To a stirred solution of 8a ,b (0.10 g, 0.33 mmol) in
CH2Cl2 (5 mL) at 20 °C was added TMSOTf (0.1 g, 0.45 mmol).
After 1 h, TLC data indicated the complete conversion of the
starting material into a product 27. The reaction mixture was
then treated with NaHCO3/ether. Standard workup and
column chromatography on SiO2 gave adduct 27 as a colorless
(E)-6-Meth oxy-2,5,5-tr im eth yl-7-(p-tolylth io)h ep ta -1,3-
d ien e (24). To a stirred solution of adduct 6a ,b (0.140 g, 0.42
mmol) in CH2Cl2 (15 mL) at 20 °C was added TMSOTf (0.033
g, 1.5 mmol). After 7 h, TLC data indicated a complete
7966 J . Org. Chem., Vol. 67, No. 23, 2002

4,6-Dialkoxy-7-arylthioheptene Moiety
1
liquid (0.045 g, 46%, Rf ) 0.75, 5:1 hexanes-ether). H NMR
(CDCl3) δ: 1.88 (m, 2H, CH2,ring), 2.32 (m, 2Hall,yl chain), 2.42
and 2.58 (m, 4H, CH2, allyl, ring), 2.61(m, 2H, CH2,allyl, chain), 3.41
(s, 3H, MeO), 3.48 (m, 1H, CHOMe), 5.10 (m, 2H, CH2d), 5.90
(m, 1H, CHd), 7.05 and 7.31 (2d, 4Harom). 13C NMR (CDCl3) δ:
20.7 (MeAr), 22.0, 33.7, 36.5, 36.9, 38.3 (5CH2), 56.5 (MeO),
79.7 (CHOMe), 116.9 (CH2d), 118.3 (SCdC), 129.5 and 129.8
(4CHarom), 133.9 and 135.9 (2Carom), 134.9 (CHd), 144.5 (SCd
C). Anal. Calcd for C18H24OS: C, 74.95; H, 8.39; S, 11.11.
Found: C, 74.78; H, 8.19; S, 11.06.
Me2), 1.61 (m, 1H, CHaCHS), 1.67 (m, 2H, CH2CH2O), 1.94
(m, 1H, CHbCHS), 2.38 (s, 3H, Mearom), 3.12 (m, 2H, CHS,
CHO), 3.46 and 4.01 (2m, 2H, CH2O), 5.05 and 5.18 (2d, 2H,
J 1 ) 10.1, J 2 ) 16.9, CdCH2), 5.97 (d, 1H, C-CHdCH, J )
15.6), 6.12 (dd, 1H, C-CHdCH, J 1 ) 15.6, J 2 ) 10.2), 6.39
(dt,1H, CHdCH2, J 1 ) 15.6, J 2 ) 10.1), 7.1 and 7.32 (2d,
4Harom). 13C NMR (CDCl3) δ: 21.1 (MeAr), 23.1 and 26.0 (2Me),
24.4 (CH2CH2O), 29.9 (CH2CHS), 41.2 (Cquat), 46.8 (CHS), 67.2
(CH2O), 87.2 (CHO), 115.1 (CH2d), 128.0 (C-CHdCH), 129.6
and 133.2 (4CHarom), 131.0 and 137.2 (2Carom), 137.8 (CHdCH2),
142.6 (C-CHdCH). Anal. Calcd for C19H26OS: C, 75.45; H,
8.66; S, 10.60. Found: C, 75.19; H, 8.84; S, 9.82.
tr a n s-2-((E)-2′,5′-Dim et h ylh exa -3′,5′-d ien -2′-yl)-3-(p -
tolylth io)tetr a h yd r op yr a n (31) was prepared upon the
treatment of 10a ,b with TMSOTf under conditions described
in the previous experiment. 31: colorless oil, yield 29%, Rf )
0.90 (30:1 hexanes-ethyl acetate). 1H NMR (CDCl3) δ: 1.19
(s, 6H), 1.61 and 1.89 (2m, 4H), 1.89 (s, 3H), 2.34 (s, 3H), 3.09
(m, 2H), 3.42 and 3.98 (2m, 2H), 4.92 (s, 2H), 5.93 (d, 1H, J )
17.0), 6.17 (d, 1H, J ) 17.0), 7.1 and 7.32 (2d, 4Harom). 13C NMR
(CDCl3) δ: 18.8, 21.0, 22.7, 26.4, 24.4, 29.8, 41.0, 46.8, 67.2,
87.4, 114.5, 129.6, 131.0, 137.1, 138.1, 142.5. Anal. Calcd for
cis-1-Meth oxy-1-((E)-p en ta -2′,4′-d ien yl)-2-(p-tolylth io)-
cyclop en ta n e (29). To a stirred solution of 8a ,b (0.32 g, 1.0
mmol) in CH2Cl2 (5 mL) at 20 °C were added sequentially Et2-
AlCl (0.445 g, 2 mmol, toluene solution) and TMSOTf (0.55 g,
2.0 mmol). After 8 h, TLC data indicated the complete
conversion of the starting material into a highly polar com-
pound (Rf < 0.05, 10:1 hexanes-ethyl acetate). The reaction
mixture was then treated with DBU followed by the quenching
with NaHCO3/KH2PO4-ether and standard workup. Column
chromatography on SiO2 afforded adduct 29 as a colorless
liquid (0.27 g, 94%, Rf ) 0.7, 5:1 hexanes-ether). 1H NMR
(CDCl3) δ: 1.75-2.2 (m, 6H, 3CH2ring), 2.33 (s, 3H, MeAr), 2.56
(d, 2H, CH2,all, J ) 7.6), 3.26 (d, 1H, CHS, J ) 5.6), 3.30 (s,
3H, MeO), 5.01 and 5.07 (dd, 2H, CH2d, J 1 ) 16.9, J 2 ) 10.0),
5.68 (dt, 1H, CH2CHd, J 1 ) 14.9, J 2 ) 7.6), 6.07 (dd, 1H, CH2-
C
20H28OS: C, 75.90; H, 8.92; S, 10.13. Found: C, 75.68; H,
8.74; S, 9.70.
CHdCH, J 1 ) 14.9, J 2 ) 10.4), 6.30 (dt, 1H, CHdCH2, J 1
)
Ack n ow led gm en t. This research was supported by
the RFBR (Grant 00-03-3790), the US CRDF agency
(Award RC2-2207), and the donors of the Petroleum
Research Fund, administered by the American Chemi-
cal Society (Grant ACP-PRF # 35453-B1).
16.9, J 2 ) 10.3), 7.08 and 7.33 (2d, 4Harom). 13C NMR (CDCl3)
δ: 21.0 (MeAr), 20.7, 30.8, and 32.6 (CH2, ring), 36.4 (CH2,all),
50.3 (CHS), 56.0 (MeO), 86.9 (COMe), 115.8 (CH2d), 129.6
(2CHarom), 129.7 (C-CHdCH), 131.7 (2CHarom), 133.2 and 136.3
(2Carom), 134.5 (CdCHCHd), 136.9 (CHdCH2). Due to instabil-
ity, it was not possible to obtain reproducible elemental
analysis data for 29. The homogeneity of the compound was
substantiated by GC-MS data: M+ 288.
Su p p or tin g In for m a tion Ava ila ble: Assignment of sig-
nals for compounds 4a ,b, 5a ,b, 19a -d , 20a ,b, 21, and 31; 1H
1
NMR spectra for compounds 17a ,b and 29; and copies of H
tr a n s-2-((E)-2′-Meth ylh exa -3′,5′-d ien -2′-yl)-3-(p-tolylth -
io)tetr a h yd r op yr a n (30) was prepared upon the treatment
of 9a ,b with TMSOTf under conditions described in the
previous experiment. 30: colorless oil, yield 41%, Rf ) 0.93
(30:1 hexanes-ethyl acetate). 1H NMR (CDCl3) δ: 1.23 (s, 6H,
and 13C NMR, DEPT, HETCOR, COSY, and NOESY spectra
for 25. This material is available free of charge via the Internet
at http://pubs.acs.org.
J O0261202
J . Org. Chem, Vol. 67, No. 23, 2002 7967