Base catalyzed rearrangement of π-conjugated sulfur and selenium bridged propargylic systems

Article abstract of DOI:10.1016/S0040-4020(01)00923-1

A series of novel π-conjugated bis-propargylic sulfides, selenides, sulfoxides and sulfones have been prepared. In the presence of amine bases these compounds underwent facile isomerization to the corresponding allenes, followed by a tandem cyclization an

Full text of DOI:10.1016/S0040-4020(01)00923-1

TETRAHEDRON
Pergamon
Tetrahedron 57 62001) 9177±9185
Base catalyzed rearrangement of p-conjugated sulfur
and selenium bridged propargylic systems
Samuel Braverman,p Yossi Zafrani and Hugo E. Gottlieb
Department of Chemistry, Bar-Ilan University, Ramat Gan 52900, Israel
Received 11 June 2001;revised 13 August 2001;accepted 6 September 2001
AbstractÐA series of novel p-conjugated bis-propargylic sul®des, selenides, sulfoxides and sulfones have been prepared. In the presence of
amine bases these compounds underwent facile isomerization to the corresponding allenes, followed by a tandem cyclization and aromati-
zation of the latter via a diradical intermediate. While the reactions of sulfones and sulfoxides were almost spontaneous and proceeded in
practically quantitative yield, the sul®des and selenides exhibited modest reactivity and required more polar solvents to afford the corre-
sponding thiophenes and selenophenes. Some mechanistic studies and DNA cleaving properties are also presented. q 2001 Elsevier Science
Ltd. All rights reserved.
1. Introduction
synthetic interest. In view of Nicolaou's conclusion
mentioned above, we decided to investigate the base
catalyzed rearrangement of some novel p-conjugated bis-
propargylic sulfones.10 In addition, we decided to compare
the reactivity of such dipropargylic sulfones with the corre-
sponding sul®des, selenides and sulfoxides. Apparently, the
last two have never been investigated before.
The renewal of interest in cycloaromatization reactions over
the last decade has clearly intensi®ed due to the elegant
mode of action of the enediyne natural products.1 The key
to the biological activity of the latter postulated a diradical
cycloaromatization which subsequently leads to DNA-
cleavage. Due to the complexity and scarcity of the
enediyne natural products, synthesis of a variety of enediyne
models posed a great challenge for organic chemists.2 As
one such model the cyclization of bis-g,g-dimethylallenyl
sulfone 61)3 has been used by Nicolaou for the design of a
new class of DNA-cleaving molecules.4 This was based on
our previous discovery that sulfone 1 underwent a quanti-
tative cyclization on heating via a 2,20-bis-allyl diradical
intermediate to the thiophene-1,1-dioxide derivative
shown in Scheme 1. However, subsequent mechanistic
studies by Nicolaou5 and others6 have lead to the conclusion
that an alternative mechanism, the Maxam±Gilbert mecha-
nism,7 involving nucleophilic addition of DNA to the dial-
lenic sulfone was responsible for their biological activity. In
fact, this conclusion is hardly surprising in view of the rela-
tively high temperature required for the cyclization of 1.
2. Results and discussion
The required sulfones 2c, 2g and 2j were readily prepared
by oxidation of the corresponding sul®des 2a, 2e and 2h
with m-CPBA or oxone 6Scheme 2). Our investigation of
base catalyzed tandem isomerization, cyclization and
aromatization of p-conjugated bis-propargylic sulfones
was initiated with an examination of the behavior of bis-
g-phenylpropargyl sulfone 62c). Surprisingly, we have
found that reaction of this sulfone with triethylamine in
CHCl3 at room temperature results in practically spon-
taneous and quantitative tandem rearrangement, cyclization
and aromatization affording the naphthalene derivative 5c.
In order to test the generality of this reaction, we have
examined the reactivity of the other dipropargylic
Based on our previous experience with the cyclization3,8 and
cycloaromatization9 of p and heteroatom bridged diallenic
systems, we became interested in studying the effect of
tandem cyclization and aromatization of some novel
diallenic systems which, beside their potential biological
activity, would also be of considerable mechanistic and
Keywords: sulfur and selenium compounds;allenes;acetylenes;cycli-
zations;radicals;rearrangements.
p
Corresponding author. Tel. 1972-3-531-8322;fax: 1972-3-535-1250;
e-mail: bravers@mail.biu.ac.il
Scheme 1. Cyclization of bis-g,g-dimethylallenyl sulfone.
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020601)00923-1

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S. Braverman et al. / Tetrahedron 57 &2001) 9177±9185
Scheme 2. Preparation of sulfoxides 2b, f, i and sulfones 2c, g, j.
Table 1. Tandem isomerization, cyclization and aromatization of bridged bis-propargylic systems
Entry
2
n
0
1
2
X
Solvent
Time
24 h
Products 6yield)
1
2
3
4
5
6
7
8
2a: R1, R2ˆ6CHvCH)2
2a
S
CH3CN
CHCl3
4a 625)
72 h
5 mina
1 h
No reaction
5b6100)a
5b 6100)
5c 6100)
5c 6100)a
4d 621)
No reaction
5f 678)
5g 695)
2b: R1, R2ˆ6CHvCH)2
S
S
DMSO-d6
CHCl3
CHCl3
2b
2c: R1, R2ˆ6CHvCH)2
2c
1.5 hb
15 min
16 h
c
CDCl3
2d: R1, R2ˆ6CHvCH)2
2e: R1, R2ˆ6CH2CH2)2
2f: R1, R2ˆ6CH2CH2)2
2g: R1, R2ˆ6CH2CH2)2
2h: R1ˆCH3, R2ˆH
2i: R1ˆCH3, R2ˆH
2j: R1ˆCH3, R2ˆH
2k: R1ˆCH3, R2ˆH
0
0
1
2
0
1
2
0
Se
S
S
S
S
S
S
Se
DMSO
DMSO
CH3CN
CHCl3
CH3CN
DMSO
CHCl3
DMSO
7 d
4 h
5 min
18 h
10 min
5 min
62 h
9
10
11
12
13
14
3h 673)
5i 6100)
5j 690)
3k 665)
At room temperature using DBU as base.
a
b
c
1
Determined by H NMR.
Reaction with DBU at 08C.
Using triethylamine as base.
compounds mentioned in Table 1. Examination of the data
presented in Table 1 indicates that the formation of products
3, 4 or 5 as well as the reactivities of 2a±k, are highly
dependent on the oxidation number of the sulfur atom and
on the nature of both the solvent and the base.
slower. Interestingly, while the reaction of sulfoxide 2b was
completed within 1 h in CHCl3 affording 5b quantitatively,
the use of DMSO as solvent reduced the reaction time to
5 min. In sharp contrast, the sul®de analogs 2a and 2h have
been found to be stable to the conditions mentioned above.
However, using a more polar solvent such as CH3CN led to
formation of the expected products 4a 625%) and 3h 673%)
within 24 and 18 h, respectively. Moreover, the cyclization
of 2e could not be achieved under various conditions, even
in re¯uxing chloroform solution. In view of these results we
decided to investigate the reactivity of selenides 2d and 2k,
which have never been examined before. The required
selenides 2d and 2k were easily prepared by reaction of
the appropriate g-substituted propargyl bromide with
sodium hydrogen selenide11 in aqueous methanol solution,
in excellent yield 6Scheme 3). We have thus found that the
cyclization of selenides 2d and 2k was considerably slower
than the corresponding sulfur analogs, and required a more
polar solvent such as DMSO to obtain the corresponding
products 4d 621%) and 3k 665%). These results are com-
patible with the fact that the deprotonation of a carbon
Similarly to the reaction of 2c, sulfones 2g and 2j readily
react with DBU in CHCl3 to afford the appropriate naph-
thalene derivatives 5g 695%) and 5j 690%). Of particular
interest, sulfoxide analogs 2b, 2f and 2i have been found
to undergo cyclization in the same manner but somewhat
Scheme 3. Preparation of selenides 2d, k.

S. Braverman et al. / Tetrahedron 57 &2001) 9177±9185
9179
Scheme 4. Tandem isomerization, cyclization and aromatization of bridged propargylic compounds 2a±c.
linked to a sulfur atom is easier than that of a carbon linked
to selenium.12
conditions, using t-BuOK in re¯uxing t-BuOH, which
afforded 5a. However, this mechanism has been rejected
by Garratt, who succeeded in isolating intermediate 4a. In
view of these results and in order to ascertain that the
unusually facile tandem isomerization, cyclization and
aromatization of sulfone 2c and sulfoxide 2b, proceed via
a bridged diallenyl sulfone 7c and sulfoxide 7b, respec-
tively, a brief kinetic study has been performed on sulfoxide
2b.
The generally accepted mechanism for the reaction of di-
propargylic sul®des such as 2a was proposed by Garratt13
6Scheme 4). The key intermediate, diradical 8a, is stabilized
both because of the formation of an aromatic thiophene ring
as well as by the fact that both radical centers are benzylic.
Therefore, one might expect that 8b and 8c, in which the
®ve-membered ring is nonaromatic, would be less favored
and that contrary to our observations the reactions of 2b and
2c should actually be slower. In addition, only intermediate
6b 6and not, e.g. 7b) could be detected. These observations
raised the question of whether or not the cyclization of
6b occurs via the original Garratt mechanism or via an
alternative mechanism involving an intramolecular Diels±
Alder reaction 6IMDA) of the acetylenic triple bond to the
conjugated ene±allene, followed by fast aromatization to
yield 5b directly. Such a mechanism was initially suggested
by Iwai14 for the cyclization of 2a under more drastic
The rate of reaction of 2b could be conveniently monitored
by integrating the appropriate H NMR signals for 2b, 6b
1
and 5b and by measuring their concentrations as function of
time.15 Intermediate 6b, which appears at maximum
concentration near the beginning of the reaction time, and
then gradually decreases, exists as a 6:4 mixture of dia-
stereoisomers due to the chirality of the sulfur atom in sulf-
oxides as well as the structure chirality of allenes 6Table 2).
According to the mechanism involving diallene 7b 6Scheme
Table 2. NMR Data for starting material 2b and for intermediate 6b
Sulfoxide
H1a
H2a
H3
H4
C-prop.
C1
C3
2b
6b major
6b minor
4.13 6d, Jˆ15 Hz)
4.06 6d, Jˆ15.5 Hz)
4.02 6d, Jˆ16 Hz)
3.96 6d, Jˆ15 Hz)
3.99 6d, Jˆ15.5 Hz)
3.99 6d, Jˆ16 Hz)
±
±
41.9
46.2
46.2
±
±
6.75 6d, Jˆ6 Hz)
6.64 6d, Jˆ6 Hz)
102.7
102.8
101.5
102.2
6.71 6d, Jˆ6 Hz)
6.66 6d, Jˆ6 Hz)
a
ABq system.

9180
S. Braverman et al. / Tetrahedron 57 &2001) 9177±9185
Table 3. Rate constants for the rearrangement of bis-g-phenylpropargyl sulfoxide
[Sulfoxide 2b]a 6M)
[DBU]a 6M)
103k1 6s21
)
103k2 6s21
)
[Sulfoxide 6b]b
max
0.20
0.20
0.20
0.06
0.20
0.60
0.65
1.70
3.50
2.0
5.0
10.0
0.21
0.24
0.21
a
In the communication which preceded this paper10 these concentrations were reported incorrectly.
Molar fraction.
b
4), we would expect that both prototropic steps de®ned by
gradually decreases over the reaction time 6Table 3). More-
over, the rate constants k1 and k2, which were obtained by
®tting the experimental points to calculated curves 6one
example is illustrated in Fig. 1), show the same dependence
on base concentration. The data presented in Table 3 indi-
cate that the isomerization of bis-propargyl sulfoxide 2b to
propargyl allene 6b is the rate determining step and it is
about three times slower than the second isomerization
from 6b to diallene 7b. This conclusion may explain the
unexpected difference in the rate of reaction of dipropargyl
sul®de 2a, relative to the corresponding sulfoxide and
sulfone, since the ®rst step is dependent on the relative
acidity of the a-hydrogens of these three systems and is
slowest in the case of sul®de 2a. The effects of solvent
polarity on the reaction rates are also consistent with this
mechanism. Thus, the rate of conversion for 2b in CDCl3 is
slower than the rate in DMSO-d6, where the reaction is
complete within 5 min, using 1 equiv. of DBU at room
temperature. With all three systems investigated the cycli-
zation step is proceeding at high rate, regardless of the
nature of the bridging functionality, or of the nature of the
diradical intermediate 8a±c. Therefore, only intermediate
6b can be detected. One should add, that in view of the
relative instability of thiophene monoxides in general,16
the facile and quantitative tandem cyclization and aromati-
zation of 2b is rather remarkable.
k1=k21 and k2=k22 would be sensitive to the base concen-
tration. In contrast, according to the alternative mechanism,
involving IMDA of 6b, only the ®rst step ꢀk1=k21† would be
affected since k02 is not dependent on base concentration.
Increasing the base concentration should then increase the
maximal concentration of 6b, while in the case of the
diallene mechanism the maximal concentration of 6b
would not change. Therefore, we decided to determine the
maximal concentration of 6b in order to distinguish
between the two mechanistic alternatives by reacting
0.1 mmol of 2b with 5, 15 and 45 mL of DBU in 0.5 mL
of CDCl3. We thus found that the maximal concentrations of
6b in these three experiments were roughly similar;the
concentration of the two diastereoisomeric intermediates
Interestingly, while in all cases studied, compounds 2b±k
have led to a single product, 3,4 or 5, the reaction of sul®de
2a afforded a mixture of 4a 625%) and 9 619%) as shown in
Scheme 5. The latter product was not reported by Garratt13
and Ollis,17 who used t-BuOK as base in the cyclization of
the bis-propargylic sul®des. The formation of hydroxy-
ketone 9 could arise from the reaction of molecular oxygen
Figure 1. Fitting results for the reaction of 2b 60.02 mmol) with 5 mL of
DBU 60.006 mmol).
Scheme 5. Suggested mechanism for the formation of 9 from the reaction of sul®de 2a with DBU.

S. Braverman et al. / Tetrahedron 57 &2001) 9177±9185
9181
Scheme 6. The formation and cyclization of a-phenylpropargyl-g-phenylallene sul®nate 610).
with diradical intermediate 8a, followed by a disproportion-
ation process 6Scheme 5). Sondheimer18 and Garratt19 have
shown that such diradical intermediates formed by cycli-
zation of bridged diallenes could be trapped by molecular
oxygen to afford the appropriate peroxides. In order to
con®rm this mechanism, we have performed the reaction
of 2a with DBU in dry CH3CN under an oxygen atmos-
phere. Under these conditions, the 4a:9 ratio 6determined
by 1H NMR) changes from 58:42 to 38:62. One may wonder
why the other sul®des, sulfoxides and sulfones do not give
the appropriate hydroxy ketone product, especially since
reaction of the selenide analog 2d under the same conditions
yielded only the cyclization product 4d 621%). We assume
that the reduced stability of thiophene monoxide 6and
dioxide) diradical may explain their preference of the cycli-
zation pathway rather than reaction with oxygen. The
relative stability of 8a may be explained by the
`dibenzylic-like' radical system and comparison between
thiophene diradical 8a with the selenophene diradical
analog is consistent with the reduced aromaticity of seleno-
phene vs. thiophene20 as well as the lack of a-radical
stabilization by the selenium atom.21
proceeds by the mechanism presented above, a brief kinetic
study has been performed on this reactive compound. In
view of the high reactivity of sulfone 2c, we had to select
a weak enough base for the reaction to be slowed down to a
measurable rate. Thus, with 0.5 equiv. of triethylamine
in CDCl3, only intermediate 6c could be detected by
NMR and the reaction rates are k1ˆ7.0£1024 s21 and k2ˆ
2.3£1023 s21. This behavior is therefore similar to that of
sulfoxide 2b.
3. DNA-Cleaving activity
The DNA cleaving properties of bis-propargylic sul®de 2a,
sulfoxides 2b,i and sulfones 2c,j were assayed using double-
stranded supercoiled FX174 form I DNA in 10% DMSO±
tris-HCl at pH 8.5. Despite our expectation for DNA
cleavage by both pairs of sulfones 2c,j and sulfoxides 2b,i
due to their facile base catalyzed diradical cyclization, we
were surprised to ®nd that only sulfone 2c exhibited such
biological activity. Thus, incubation of bis-g-phenylpro-
pargyl sulfone 62c) with FX174 form I DNA aerobically
at 378C led to cleaved DNA as shown by gel electrophoresis
analysis 6Fig. 2). The lack of activity of bis-propargylic
sulfoxides 2b,i may be partly explained by the relatively
slow acetylene±allene isomerization comparable to the
corresponding sulfones. A different another interpretation
is required to explain the unexpected lack activity of sulfone
2j. Due to the short life of the diradical intermediate formed
by the tandem isomerization and cyclization of 2j, one may
expect this intermediate will undergo faster coupling than
that of the more stable diradical 8c.
Further mechanistic evidence of bis-allene formation in the
cyclization of bis-g-phenylpropargyl sulfone 62c) is pro-
vided by the double [2,3]-sigmatropic rearrangement of
bis-a-phenylpropargyl sulfoxylate to bis-g-phenylallenyl
sulfone 67c). Bis-a-phenylpropargyl sulfoxylate was pre-
pared by the reaction of a-phenylpropargyl alcohol with
SCl2, and subsequently underwent spontaneous [2,3]-sigma-
tropic rearrangement to a-phenylpropargyl g-phenylallene-
sul®nate 610) 6Scheme 6). Surprisingly, we have found that
during attempted isolation and puri®cation of the latter by
column chromatography, a spontaneous tandem rearrange-
ment, cyclization and aromatization was observed, affording
naphthalene derivative 5c. The product was identical to the
one described above in all respects. Moreover, in order to
ascertain that the unusually facile cyclization of sulfone 2c
4. Conclusion
The whole body of evidence in this paper establishes
unambiguously that the pathway for cyclization of
Figure 2. DNA Cleavage by sulfone 2c. FX 174 form I DNA 650 mM per base pair) was incubated for 24 h at 378C with compounds 2a±c,i,j in 10% DMSO in
tris-HCl buffer 6pH 8.5, 50 mM) and analyzed by electrophoresis 61% agarose gel, ethidium bromide stain). 6a) lanes 1±5 correspond to DNA and sul®de 2a,
sulfoxide 2b, sulfone 2c, sulfoxide 2i and sulfone 2j at 1000 mM respectively, and lane 6 to DNA alone;6b) lanes 1±3 correspond to DNA and sulfone 2c at
1000, 500 and 100 mM respectively, lane 4 to DNA and naphtalenic product 5c at 1000 mM and lane 5 to DNA alone. Forms I, II and III correspond to
supercoiled, relaxed and linear DNA, respectively.

9182
S. Braverman et al. / Tetrahedron 57 &2001) 9177±9185
bis-propargylic systems goes through base-catalyzed
isomerizations to bis-allenic species, which then cyclize
through a diradical intermediate. The latter can be stabilized
by adjacent p systems, in which case the cyclization is quite
fast;the diallene can never be detected by NMR. Diradical
8c, which is formed the fastest and is ef®ciently stabilized, is
also the one with best DNA-cleaving properties.
610 mL), was added to a well stirred selenium suspension
60.42 g, 5.4 mmol) in water 610 mL). After 10 min the clear
colorless solution of NaHSe was cooled to 08C, and a solu-
tion of 1-bromo-3-phenyl-2-propyne, 61.50 g, 7.7 mmol) in
methanol 615 mL) was added. The yellow solution was
stirred for 1.5 h and then left at room temperature for
another 14 h. The product was extracted with dichloro-
methane, washed with water and dried over anhydrous
MgSO4. Removal of the solvent under reduced pressure
gave the pure selenide as a yellow oil 61.19 g, 100%
5. Experimental
5.1. General
1
yield); H NMR 6300 MHz, CDCl3): d 7.44±7.40 64H, m,
2
Ph), 7.3±7.27 66H, m, Ph), 3.69 64H, s, SeCH2; JSe±H
ˆ
14 Hz); 13C NMR 675.5 MHz, CDCl3): d 131.7, 128.2,
128.1 6Ph), 123.1 6C), 85.7 6C), 83.6 6C), 9.4 6CH2);IR
6neat): 1489, 1441, 1175, 755, 690 cm21;MS 6CI): m/e
307, 308, 309, 311, 313 6MH1, 1:1:3:7:1, 24%), 243
6100%), 232 613.7%);HRMS 6Elemental composition)
calc. 6C18H1580Se) 311.0338, obs. 311.0363.
Melting points were obtained on a Thomas Hoover melting
point apparatus and are uncorrected. IR spectra were
1
recorded on a Nicolet 60 SXB FTIR. H- and 13C NMR
were recorded on Bruker AC-200, DPX-300 or DMX-600
spectrometers in either CDCl3 or other deuterated solvents,
using TMS as internal standard. Chemical shifts are
reported in d units, and coupling constants in Hertz. High-
resolution mass spectra were obtained on a VG-Fison
Autospec instrument. Other mass spectra were obtained on
a Finningan GC/Ms 4021, with either electronic 6EI) or
chemical ionization 6CI). Column chromatography was
performed with Merck silica gel 60 6230±400 mesh), and
TLC was run on precoated Merck silica gel plates 60 F254
62.00 mm). Tetrahydrofuran was distilled from Na, diethyl
ether was dried over Na wires. Other commercially
available chemicals were used without further puri®cation.
5.1.4. Bis-3-isopropenyl-2-propynyl selenide 12k). The
title compound was prepared according to the procedure
described for the preparation of 2d as a yellow oil;yield
1
95%; H NMR 6300 MHz, CDCl3): d 5.27±5.26 62H, m,
CvCH2), 5.20 62H, quintet, Jˆ1.5 Hz, CvCH2), 3.53
2
64H, s, SeCH2; JSe±Hˆ14 Hz), 1.88 66H, dd, Jˆ1.5, 1 Hz,
vCCH3); 13C NMR 675.5 MHz, CDCl3): d 126.5 6C), 121.7
6CH2), 84.67 6C), 84.66 6C), 23.4 6CH3), 9.2 6CH2);IR
6neat): 2221, 1660, 1611, 1451, 1294, 897, 733 cm21;MS
6CI): m/e 234, 235, 236, 238, 240 6M1, 1:1:3:7:1, 46.3%),
158 661%), 131 6100%);HRMS 6Elemental composition)
calc. 6C12H1480Se) 238.0260, obs. 238.0245.
5.1.1. Bis-3-1cyclohex-1-enyl)-2-propynyl sul®de 12e). A
solution of Na2S´9H2O 61.60 g, 6.6 mmol) in water 630 mL)
was slowly added to a magnetically stirred solution of
1-bromo-3-6cyclohex-1-enyl)-2-propyne22,23 61.56 g, 7.84
mmol) in methanol 640 mL) at 08C. After 2 h the turbid
solution was warmed to room temperature and stirred for
further 2 h before 50 mL of ether was added. The organic
layer was separated, washed with water, and dried over
anhydrous MgSO4. The solvent was removed under reduced
pressure to give 1.10 g 64.0 mmol) of pure yellow oil;yield
100%; 1H NMR 6300 MHz, CDCl3): d 6.07 62H, bs,
CvCH), 3.53 64H, s, SCH2), 2.10±2.07 68H, m,
CH2CHvCCH2), 1.63±1.55 68H, m, CH2CH2); 13C NMR
675.5 MHz, CDCl3): d 134.7 6CH), 120.2 6C), 84.9 6C), 81.6
6C), 29.5 6CH2), 25.4 6CH2), 22.1 6CH2), 21.3 6CH2), 19.9
6CH2);IR 6neat): 1434, 1229, 917 cm 21;MS6CI): m/e
271 6MH1, 100%), 237 648.5%), 151611.5%), 119673%);
HRMS 6Elemental composition) calc. 6C18H23S) 271.1520,
obs. 271.1526.
5.1.5. Bis-3-phenyl-2-propynyl sulfoxide 12b). To a
magnetically stirred solution of NaIO4 65.1 g, 23.7 mmol)
in water 640 mL) was added a solution of bis-3-phenyl-2-
propynyl sul®de14 65 g, 19 mmol) in methanol 630 mL) at
08C. The mixture was warmed to room temperature and
stirred for two weeks. It was then diluted with chloroform,
washed with water, satd. NaCl and then dried over
anhydrous MgSO4. Removal of the solvent under reduced
pressure gave a mixture of more than two products which
were separated by column chromatography 6silica gel).
Elution with ethyl acetate±hexane 1:1 gave 2.36 g
68.5 mmol) of a white solid 644%) which was recrystallized
1
from dichloromethane±hexane. Mp 99±1008C; H NMR
6300 MHz, CDCl3): d 7.49±7.46 64H, m, Ph), 7.35±7.32
66H, m, Ph), 4.15 and 3.96 6ABq system, each: 2H, d,
Jˆ15 Hz, S6O)CH2); 13C NMR 650.3 MHz, CDCl3): d
131.5, 128.7, 128.4, 121.5 6Ph), 87.7 6C), 77.2 6C), 41.9
6CH2);IR 6neat): 1066, 1442, 1490 cm 21;MS 6CI):
m/e 279 6MH1, 43%), 147 671%), 115 6100%);HRMS
6Elemental composition), calc. 6C18H15OS) 279.0843, obs.
279.0840.
5.1.2. Bis-3-isopropenyl-2-propynyl sul®de 12h). The
title compound was prepared according to the above pro-
cedure as a yellow oil;yield 97%; 1H NMR 6300 MHz,
CDCl3): d 5.29±5.28 62H, m, CvCH2), 5.22 62H, quintet,
Jˆ1.5 Hz, CvCH2), 3.55 64H, s, SCH2), 1.88 66H, dd, Jˆ
1.5, 1 Hz, CCH3); 13C NMR 675.5 MHz, CDCl3): d 126.4
6C), 121.9 6CH2), 84.5 6C), 83.5 6C), 23.4 6CH3), 19.9 6CH2);
IR 6neat): 1613, 1456, 897 cm21;MS 6CI): m/e 191 6MH1,
100%), 111 635.4%);HRMS 6Elemental composition) calc.
6C12H15S) 191.0894, obs. 191.0897.
5.1.6. Bis-3-1cyclohex-1-enyl)-2-propynyl sulfoxide 12f).
The title compound was prepared by the procedure
described for the preparation of 2b and obtained in 18%
yield as a viscous oil, after separation by column chroma-
tography 6silica gel, elution with ethyl acetate±hexane 1:1);
1H NMR 6300 MHz, CDCl3): d 6.18±6.15 62H, m, CvCH),
3.94 and 3.76 6ABq system, each: 2H, d, Jˆ16 Hz,
S6O)CH2), 2.13±2.08 68H, m, CH2CHvCCH2), 1.64±1.26
68H, m, CH2CH2); 13C NMR 675.5 MHz, CDCl3): d 136.5
5.1.3. Bis-3-phenyl-2-propynyl selenide 12d). A solution
of sodium borohydride 60.41 g, 10.7 mmol) in water

S. Braverman et al. / Tetrahedron 57 &2001) 9177±9185
9183
6CH), 119.7 6C), 90.0 6C), 74.1 6C), 42.0 6CH2), 28.9 6CH2),
25.5 6CH2), 22.1 6CH2), 21.2 6CH2);IR 6neat): 1066,
1431 cm21;MS 6CI): m/e 287 6MH1,78.8%), 279 6100%),
119 664%);HRMS 6Elemental composition), calc.
6C18H23OS) 287.1469, obs. 287.1464.
5.1.10. Bis-3-isopropenyl-2-propynyl sulfone 12j). The
title compound was obtained by the reaction of 2h with
m-chloroperoxybenzoic acid according to the above pro-
cedure, puri®ed by column chromatography 6silica gel,
ethyl acetate±hexane 1:2) and recrystallized from dichloro-
methane±hexane as colorless crystals in 92% yield. Mp 38±
398C; 1H NMR 6300 MHz, CDCl3): d 5.42 62H, bs,
CvCH2), 5.35 62H, dq, Jˆ1.5, 1 Hz, CvCH2), 4.16 64H,
s, SO2CH2), 1.91 66H, dd, Jˆ1.5, 1 Hz, vCCH3); 13C NMR
675.5 MHz, CDCl3): d 125.4 6C), 124.1 6CH2), 89.0 6C),
74.7 6C), 44.2 6CH2), 22.8 6CH3);IR 6neat): 1614, 1332,
1129 cm21;MS 6EI): m/e 222 6M1, 62.8%), 158 626.4%),
143 6100%);HRMS 6Elemental composition) calc.
6C12H14O2S) 222.0714, obs. 222.0700.
5.1.7. Bis-3-isopropenyl-2-propynyl sulfoxide 12i). The
title compound was prepared by the procedure described
for the preparation of 2b and obtained in 69% yield as a
viscous oil, after separation by column chromatography
1
6silica gel, ethyl acetate±hexane 1:1); H NMR 6300 MHz,
CDCl3): d 5.37 62H, bs, CvCH2), 5.31 62H, dq, Jˆ1.5,
1 Hz, CvCH2), 3.95 and 3.78 6ABq system, each: 2H, d,
Jˆ16 Hz, S6O)CH2), 1.9 66H, dd, Jˆ1.5, 1 Hz, vCCH3);
13C NMR 675.5 MHz, CDCl3): d 125.7 6C), 123.4 6CH2),
89.3 6C), 76.0 6C), 42.0 6CH2), 23.1 6CH3);IR 6neat): 1614,
1456, 1061 cm21;MS 6CI): m/e 207 6MH1, 64%), 159
659%), 147 6100%);HRMS 6Elemental composition),
calc. 6C12H15OS) 207.0843, obs. 207.0855.
5.2. General procedure for tandem isomerization,
cyclization and aromatization
This procedure refers to all of the sulfur/selenium bridged
bis-propargylic systems, while the exact conditions and
reaction times are as shown in Table 1. All thiophene,
selenophene, sulfoxide and sulfone products were puri®ed
by column chromatography.
5.1.8. Bis-3-phenyl-2-propynyl sulfone 12c). To a magne-
tically stirred solution of bis-3-phenyl-2-propynyl sulfoxide
61.00 g, 3.6 mmol), in methanol 620 mL) at 08C was added a
solution of 49.5% KHSO5 in water 620 mL). The resulting
cloudy slurry was stirred for 4 days at room temperature,
diluted with water and extracted with chloroform. The
organic layer was washed with water, satd. NaCl and then
dried over anhydrous MgSO4. Evaporation of the solvent
gave a mixture of sulfoxide and sulfone, which was
separated by column chromatography 6silica gel, ethyl
acetate±hexane 1:1). The sulfone product 60.45 g, 42%
yield) was recrystallized from dichloromethane±hexane as
To a solution of the appropriate bis-propargylic system
61 mmol) in 30 mL of solvent were added 1.5 equiv. of
DBU. After stirring at room temperature for the appropriate
time the reaction was washed three times with water. The
organic layer was dried over anhydrous MgSO4 and the
solvent was removed under reduced pressure. The solid
products were recrystallized from dichloromethane±hexane
to give the pure products. The data for all products are listed
below.
1
colorless crystals. Mp 114±1158C; H NMR 6300 MHz,
CDCl3): d 7.50±7.47 64H, m, Ph), 7.35±7.32 66H, m, Ph),
4.31 64H, s, SO2CH2); 13C NMR 675.5 MHz, CDCl3): d
131.9, 129.2, 128.3, 121.3 6Ph), 87.9 6C), 75.9 6C), 44.5
5.2.1. 3-Hydroxyphenylmethyl-4-benzoylthiophene 19).
The title compound was obtained as a mixture with 4a12a
and separated by column chromatography 6silica gel, ethyl
6CH2);IR 6neat): 1326, 1135 cm 21;MS 6CI):
m/e
295 6MH1, 22.7%), 230 654.3%), 115 6100%);HRMS
6Elemental composition), calc. 6C18H15O2S) 295.0793,
obs. 295.0780.
1
acetate±hexane 2:8), as viscous oil in 19% yield; H NMR
6300 MHz, CDCl3): d 7.79 61H, d, Jˆ3.2 Hz, SCH), 7.78±
7.76 62H, m, Ph), 7.62±7.57 61H, m, Ph), 7.50±7.42 6m,
4H), 7.36±7.30 62H, m, Ph), 7.27±7.24 61H, m, Ph), 6.99
61H, dd, Jˆ3.2, 0.6 Hz, SCH), 6.02 61H, s, CHOH); 13C
NMR 675.5 MHz, CDCl3): d 193.0 6C), 147.0 6C), 142.1
6C), 139.0 6C), 138.6 6C), 138.4 6CH), 132.9 6CH), 129.8
6CH), 128.4 6CH), 128.2 6CH), 127.3 6CH), 126.5 6CH),
125.9 6CH), 70.7 6CH);IR 6neat): 1633, 1451, 1254,
1179, 1024 cm21;MS 6EI): m/e 294 6M1, 46.4%), 277
5.1.9. Bis-3-1cyclohex-1-enyl)-2-propynyl sulfone 12g). A
solution of 70% m-chloroperoxybenzoic acid 61.18 g,
4.8 mmol) in dichloromethane 620 mL) was added to a
solution of 2e 60.53 g, 1.96 mmol) in dichloromethane
620 mL) at 08C. After the addition, the mixture was warmed
to room temperature and further stirred for 18 h. Then, the
organic layer was washed with 5% aqueous solutions of KI
650 mL), K2S2O3 620 mL), NaHCO3 62£30 mL) and water
63£50 mL). The solution was dried over anhydrous MgSO4
and the solvent was removed under reduced pressure to
afford a white solid, which was puri®ed by column chroma-
tography 6silica gel, ethyl acetate±hexane 1:2) and recrys-
tallized from dichloromethane±hexane as colorless crystals
6100%);HRMS
6C18H14O2S) 294.0714, obs. 294.0700.
6Elemental
composition)
calc.
5.2.2. 4-Isopropenyl-6-methyl-4,5-dihydrobenzo[c]thio-
phene 13h). The title compound was obtained in 73%
yield after separation by column chromatography 6silica
gel, chloroform±hexane 1:8) as a yellowish viscous oil.
1H NMR 6300 MHz, CDCl3): d 6.80±6.75 62H, m, SCH),
6.26 61H, s, CvCH), 4.88 61H, dq, Jˆ1.5, 1 Hz, CvCH2),
4.84 61H, bs, CvCH2), 3.59 61H, dd, Jˆ10.5, 7 Hz,
CH2CH), 2.36 and 2.22 62H, ABX system, JABˆ16.5 Hz,
JAXˆ10.5 Hz, JBXˆ7 Hz, CH2CH;long range couplings
are also visible), 1.88 63H, s, C6CH3), 1.77±1.76 63H, m,
vCCH3); 13C NMR 675.5 MHz, CDCl3): d 146.4 6C), 138.0
6C), 137.7 6C), 136.4 6C), 119.2 6CH), 118.2 6CH), 116.5
6CH), 112.4 6CH2), 44.3 6CH), 34.9 6CH2), 23.4 6CH3), 19.2
1
60.13 g, 22% yield). Mp 94±958C; H NMR 6300 MHz,
CDCl3): d 6.20 62H, quintet, Jˆ2 Hz, CvCH), 4.13 64H,
s, SO2CH2), 2.13±2.10 68H, m, CH2CHvCCH2), 1.63±160
68H, m, CH2CH2); 13C NMR 675.5 MHz, CDCl3): d 137.3
6CH), 119.4 6C), 89.6 6C), 73.1 6C), 44.2 6CH2), 28.7 6CH2),
25.6 6CH2), 22.0 6CH2), 21.2 6CH2);IR 6neat): 1434, 1332,
1127 cm21;MS 6CI): m/e 303 6MH1, 46.9%), 239 615.8%),
119 6100%);HRMS 6Elemental composition) calc.
6C18H23O2S) 303.1419, obs. 303.1415.

9184
S. Braverman et al. / Tetrahedron 57 &2001) 9177±9185
6CH3);IR 6neat): 1645, 1437, 1347, 893, 847, 786 cm 21;MS
6CI): m/e 191 6MH1, 100%), 149 637%);HRMS 6Elemental
composition) calc. 6C12H15S) 191.0894, obs. 191.0897.
20,20-dioxide 15c). The title compound was obtained as a
pure yellowish solid product in 100% yield before it was
recrystallized from dichloromethane±hexane mp 187±
1
1888C; H NMR 6300 MHz, CDCl3): d 7.88±7.83 62H, m,
5.2.3.
4-Isopropenyl-6-methyl-10,30-dihydrobenzo[c]-
C1H, C8H), 7.55±7.45 66H, m), 7.31±7.28 62H, m), 4.59
62H, s, SO2CH2), 4.24 62H, s, SO2CH2); 13C NMR
650.3 MHz, CDCl3): d 138.1 6C), 137.5 6C), 133.2 6C),
132.1 6C), 129.5 6CH), 129.0 6CH), 128.6 6C), 128.3
6CH), 127.9 6CH), 126.9 6CH), 126.8 6CH), 126.3 6CH),
124.9 6CH), 57.2 6CH2), 56.5 6CH2);IR 6neat): 1317,
1133 cm21;MS 6CI): m/e 295 6MH1, 100%), 230 641%);
HRMS 6Elemental composition), calc. 6C18H15O2S)
295.0790, obs. 295.0730.
thiophene-20-oxide 15i). The title compound was obtained
in 100% yield as a viscous yellow oil. 1H NMR 6300 MHz,
CDCl3): d 7.08 61H, s, ArH), 7.03 61H, s, ArH), 5.26 61H,
quintet, Jˆ1.5 Hz, CvCH2), 4.93±4.92 61H, m, CvCH2),
4.27 and 4.26 6ABq system, each: 1H, d, Jˆ16 Hz,
S6O)CH2), 4.14 and 4.11 6ABq system, each: 1H, d, Jˆ
16 Hz, S6O)CH2), 2.35 63H, s, C6CH3), 2.08 63H, dd, Jˆ
1.5, 0.6 Hz, vCCH3); 13C NMR 675.5 MHz, CDCl3): d
143.5 6C), 141.9 6C), 138.4 6C), 135.6 6C), 128.9 6C),
127.9 6CH), 125.7 6CH), 115.8 6CH2), 59.0 6CH2), 58.4
6CH2), 23.6 6CH3), 21.1 6CH3);IR 6neat): 1612, 1443,
5.2.7.
4-1Cyclohex-1-enyl)-10,30,5,6,7,8,-hexahydro-
naphtho[2,3-c]thiophene-20,20-dioxide 15g). The title
compound was obtained in 95% yield and recrystallized
from dichloromethane±hexane as colorless prisms. Mp
1039 cm21;MS 6CI):
m/e 207 6MH1, 100%), 191
637.5%), 157 647%);HRMS 6Elemental composition)
calc. 6C12H15OS) 207.0843, obs. 207.0827.
1
208±2098C; H NMR 6300 MHz, CDCl3): d 6.90 61H, s,
C1H), 5.52±5.50 61H, m, CvCH), 4.32 62H, s, SO2CH2),
4.28 and 4.13 6ABq system, each: 1H, d, Jˆ16 Hz,
S6O)CH2), 2.78±2.76 6m, 2H, CvCCH2), 2.74 and 2.52
6ABq system, each: 1H, dm, Jˆ16 Hz, CvCCH2), 2.15±
1.89 64H, m, CH2CHvCCH2), 1.78±1.67 68H, m,
CH2CH2); 13C NMR 675.5 MHz, CDCl3): d 141.8 6C),
138.2 6C), 136.2 6C), 135.5 6C), 127.7 6C), 126.8 6CH),
126.7 6C), 124.6 6CH), 57.4 6CH2), 56.2 6CH2), 29.9
6CH2), 28.6 6CH2), 26.6 6CH2), 25.2 6CH2), 23.0 6CH2),
22.8 6CH2), 22.6 6CH2), 22.0 6CH2);IR 6neat): 1445,
1316, 1133, 1096 cm21;MS 6CI): m/e 303 6MH1, 57.5%),
237 6100%);HRMS 6Elemental composition), calc.
6C18H23O2S) 303.1419, obs. 303.1415.
5.2.4.
naphtho[2,3-c]thiophene-20-oxide
4-1Cyclohex-1-enyl)-10,30,5,6,7,8-hexahydro-
15f). The title
compound was obtained in 78% yield after separation by
column chromatography 6silica gel, ®rst with chloroform
then ethyl acetate±methanol 12:1) as an orange viscous
oil. These data refer to two stable rotamers which are easily
distinguishable by the appearance of two ole®nic triplets of
triplets, resulting from the orientation of the cyclohexenyl
1
double bond with respect to the sul®nyl oxygen. H NMR
6300 MHz, CDCl3): d 6.96 61H, s, C1H), 5.56 and 5.47 6each
0.5H, 2 tt, Jˆ7, 1.5 Hz, CvCH), 4.26, 4.10;4.26, 4.09, 4.20
and 3.93;63 ABq systems, each: 0.5H, d, Jˆ16 Hz,
S6O)CH2), 4.11 62£0.5H, s, S6O)CH2), 2.77±2.50 64H, m,
CH2CvCCH2), 2.18±1.80 64H, m, CH2CHvCCH2), 1.77±
1.25 68H, m, CH2CH2); 13C NMR 675.5 MHz, CDCl3): d
142.4 6C), 142.3 6C), 137.8 6C), 136.8 6C), 136.0 6C), 134.9
6C), 131.34 6C), 131.29 6C), 130.4 6C), 130.1 6C), 126.5
6CH), 126.2 6CH), 125.1 6CH), 59.2 6CH2), 59.1 6CH2),
58.3 6CH2), 57.9 6CH2), 29.9 6CH2), 29.0 6CH2), 28.8
6CH2), 26.7 6CH2), 26.6 6CH2), 25.2 6CH2), 25.1 6CH2),
23.2 6CH2), 22.9 6CH2), 22.8 6CH2), 22.1 6CH2);IR 6neat):
1637, 1448, 1044 cm21;MS 6CI): m/e 287 6MH1, 20%),
271 6100%), 237 654.8%);HRMS 6Elemental composition)
calc. 6C18H23OS) 287.1470, obs. 287.1492.
5.2.8.
4-Isopropenyl-6-methyl-10,30-dihydrobenzo[c]-
thiophene-20,20-dioxide 15j). The title compound was
obtained in 90% yield and recrystallized from dichloro-
1
methane±hexane as colorless prisms. Mp 139±1408C; H
NMR 6300 MHz, CDCl3): d 7.06 61H, s, ArH), 7.03 61H,
s, ArH), 5.26 61H, quintet, Jˆ1.5 Hz, CvCH2), 4.90 61H,
bs, CvCH2), 4.34 62H, s, SO2CH2), 4.33 62H, s, SO2CH2),
2.36 63H, s, C6CH3), 2.05 63H, dd, Jˆ1.5, 1 Hz, vCCH3);
13C NMR 650.3 MHz, CDCl3): d 143.3 6C), 141.7 6C), 138.7
6C), 131.6 6C), 128.4 6CH), 125.6 6C), 125.2 6CH), 116.2
6CH2), 57.1 6CH2), 56.4 6CH2), 23.5 6CH3), 21.3 6CH3);IR
6neat): 1637, 1603, 1448, 1377, 1302, 1087 cm21;MS 6EI):
m/e 222 6M1, 29%), 158 693.5%), 143 6100%);HRMS
6Elemental composition), calc. 6C12H14O2S) 222.0714,
obs. 222.0716.
5.2.5. 4-Phenyl-10,30-dihydronaphtho[2,3-c]thiophene-
20-oxide 15b). The title compound was obtained in 100%
yield as an orange viscous oil, which was recrystallized
from dichloromethane±hexane as yellowish crystals: mp
1
1618C. H NMR 6300 MHz, CDCl3): d 7.87±7.85 62H, m,
5.2.9.
4-Isopropenyl-6-methyl-4,5-dihydrobenzo[c]-
C1H, C8H), 7.6±7.26 6m, 8H, Ph, C5H, C6H, C7H), 4.45 and
4.36 6ABq system, each: 1H, d, Jˆ15 Hz, S6O)CH2), 4.17
and 4.02 6ABq system, each: 1H, d, Jˆ16 Hz, S6O)CH2);
13C NMR 675.5 MHz, CDCl3): d 138.2 6C), 137.7 6C), 133.5
6C), 132.8 6C), 132.1 6C), 131.9 6C), 129.8 6CH), 129.4
6CH), 128.6 6CH), 128.5 6CH), 127.7 6CH), 126.3 6CH),
126.1 6CH), 126.0 6CH), 125.2 6CH), 58.9 6CH2), 58.4
6CH2);IR 6neat): 1492, 1444, 1041 cm 21;MS 6CI): m/e
230 665%), 279 6MH1, 100%), 230 664.7%), 202 65.5%),
169 66%);HRMS 6Elemental composition), calc.
6C18H15OS) 279.0843, obs., 279.0840.
selenophene 13k). The title compound was obtained in
65% yield after separation by column chromatography
6silica gel, ethyl acetate±hexane 5:95) as a yellowish
viscous oil. 1H NMR 6300 MHz, CDCl3): d 7.44±7.41
62H, m, SeCH), 6.23 61H, s, CvCH), 4.90 61H, dq, Jˆ
1.5, 1 Hz, CvCH2), 4.84±4.83 61H, m, CvCH2), 3.52
61H, dd, Jˆ10.5, 7 Hz, CH2CH), 2.35 and 2.31 62H, ABX
system, JABˆ16.5 Hz, JAXˆ10.5 Hz, JBXˆ7 Hz, CH2CH;
long range couplings are also visible), 1.88 63H, s,
C6CH3), 1.77 63H, dd, Jˆ1.5, 1 Hz, vCCH3); 13C NMR
675.5 MHz, CDCl3): d 146.3 6C), 140.4 6C), 140.2 6C),
136.4 6C), 123.3 6CH), 120.9 6CH), 120.0 6CH), 112.6
6CH2), 46.3 6CH), 34.9 6CH2), 23.3 6CH3), 19.3 6CH3);IR
5.2.6. 4-Phenyl-10,30-dihydronaphtho[2,3-c]thiophene-

S. Braverman et al. / Tetrahedron 57 &2001) 9177±9185
9185
6neat): 1644, 1434, 893, 847, 776 cm21;MS 6EI): m/e 234,
235,236, 238, 240 6M1, 1:1:3:7:1, 100%), 193, 194, 195,
197, 199 61:1:3:7:1, 47%);HRMS 6Elemental composition)
calc. 6C12H1480Se) 238.0260, obs. 238.0256.
6. 6a) Kerwin, S. M. Tetrahedron Lett. 1994, 35, 1023.
6b) McPhee, M. M.;Kerwin, S. M. J. Org. Chem. 1996, 61,
9385. 6c) Sakai, Y.;Bando, Y.;Shishido, K.;Shibuya, M.
Tetrahedron Lett. 1992, 33, 957. 6d) Toshima, K.;Ohta, K.;
Ohtsuka, A.;Matsumura, S.;Nakata, M. J. Chem. Soc., Chem.
Commun. 1993, 1406. 6e) Xie, G.;Morgan, A. R.;Lown, J. W.
Biorg. Med. Chem. Lett. 1993, 3, 1565.
5.2.10. 4-Phenyl-1,4-dihydronaphtho[2,3-c]selenophene
14d). The title compound was obtained in 21% yield
after separation by column chromatography 6silica gel,
7. Maxam, A. M.;Gilbert, W. MethodEnzymol. 1980, 65, 499.
8. 6a) Braverman, S.;Reisman, D. J. Am. Chem. Soc. 1977, 99,
605. 6b) Braverman, S.;Duar, Y. J. Am. Chem. Soc. 1983, 105,
1061. 6c) Braverman, S.;Cohen, D.;Reisman, D.;Basch, H.
J. Am. Chem. Soc. 1980, 102, 6556. 6d) Braverman, S.;
Freund, M. Tetrahedron 1990, 46, 5759.
1
ethyl acetate±hexane 5:95) as a yellow viscous oil. H
NMR 6300 MHz, CDCl3): d 7.68 61H, dtd, Jˆ2.5, 1.5,
1 Hz, SeCH), 7.58 61H, ddt, Jˆ2.5, 1, 0.5 Hz, SeCH),
7.30±7.12 69H, m, Ph, C5H, C6H, C7H, C8H), 5.21 61H, s,
Ph±CH), 3.90 62H, s, vCCH2); 13C NMR 675.5 MHz,
CDCl3): d 144.1 6C), 142.8 6C), 140.2 6C), 139.7 6C),
136.7 6C), 128.5 6CH), 128.4 6CH), 128.1 6CH), 126.6
6CH), 126.5 6CH), 126.4 6CH), 124.7 6CH), 122.8 6CH),
50.1 6CH), 34.0 6CH2);MS 6CI): m/e 307, 308, 309, 311,
313 6MH1, 1:1:3:7:1 100%), 229, 230, 231, 233, 235
61:1:3:7:1, 72.7%);HRMS 6Elemental composition) calc.
6C18H1580Se) 311.0338, obs. 311.0327.
9. 6a) Braverman, S.;Duar, Y. J. Am. Chem. Soc. 1990, 112,
5830. 6b) Braverman, S.;Duar, Y. Tetrahedron Lett. 1978,
1493. 6c) Braverman, S.;Duar, Y.;Segev, D. Tetrahedron
Lett. 1976, 3181.
10. Braverman, S.;Zafrani, Y.;Gottlieb, H. E. Tetrahedron Lett.
2000, 41, 2675.
11. Klayman, D. L.;Scott, G. T. J. Am. Chem. Soc. 1973, 95, 197.
12. Bordwell, F. G.;Bares, J. E.;Bartmess, J. E.;Drucker, G. E.;
Gerhold, J.;McCollum, G. J.;Van Der Puy, M.;Vanier, N. R.
J. Org. Chem. 1977, 42, 326.
Acknowledgements
13. 6a) Garratt, P. J.;Neoh, S. B. J. Org. Chem. 1979, 44, 2667.
6b) Garratt, P. J.;Neoh, S. B. J. Am. Chem. Soc. 1975, 97,
3255. 6c) Cheng, Y. S. P.;Garratt, P. J.;Neoh, S. B.;
Rumjamebe, V. M. Isr. J. Chem. 1985, 26, 101.
14. Iwai, I.;Ide, J. J. Chem. Pharm. Bull. Jpn 1964, 12, 1094.
15. Goldschmidt, Z.;Genizi, E.;Gottlieb, H. E. J. Organomet.
Chem. 1999, 81, 587.
The ®nancial support of this study by the Israel Science
Foundation is gratefully acknowledged. We are also very
much indebted to Dr Shai Rahimipour of the Weizmann
Institute of Science for performing the DNA testing.
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