Economical and environmentally friendly syntheses of 2-(phenylsulfonyl)-1,3-cyclohexadiene and 2-(phenylsulfonyl)-1,3-cycloheptadiene

Article abstract of DOI:10.1021/jo0107047

A large-scale and inexpensive synthesis of dienes 1 and 2 has been developed via a four-step procedure starting with benzenethiol and the corresponding cyclic ketone. No chromatography is required.

Full text of DOI:10.1021/jo0107047

200
J . Org. Chem. 2002, 67, 200-204
Econ om ica l a n d En vir on m en ta lly F r ien d ly Syn th eses of
2-(P h en ylsu lfon yl)-1,3-cycloh exa d ien e a n d
2-(P h en ylsu lfon yl)-1,3-cycloh ep ta d ien e1
David J . Meyers and Philip L. Fuchs*
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907
pfuchs@purdue.edu
Received J uly 13, 2001
A large-scale and inexpensive synthesis of dienes 1 and 2 has been developed via a four-step
procedure starting with benzenethiol and the corresponding cyclic ketone. No chromatography is
required.
Sch em e 1. Ca ta lytic J a cobsen Asym m etr ic
Ep oxid a tion of Dien e 1 a n d 2a
In tr od u ction
An area of current research has focused on the chem-
istry of 6- and 7-ring vinyl sulfone epoxides,2 3 and 4,
obtained from J acobsen catalytic asymmetric epoxida-
tion3 of 2-(phenylsulfonyl)-1,3-cyclohexadiene 1 and 2-
(phenylsulfonyl)-1,3-cycloheptadiene 2, respectively
(Scheme 1). When this research was in its infancy, two
simple and efficient methods by Ba¨ckvall provided ample
amounts of material for initial experiments. Ba¨ckvall’s
synthesis of 2-(phenylsulfonyl)-1,3-cyclohexadiene 1 in-
volves a phenylsulfonylmercuration of 1,3-cyclohexadi-
ene4 followed by the â-elimination of mercury(0) to form
the 2-phenylsulfonyl-substituted diene.5 The synthesis of
2-(phenylsulfonyl)-1,3-cycloheptadiene 2 is accomplished
by a tandem selenosulfonation-oxidation6 of 1,3-cyclo-
heptadiene7 with phenyl benzeneselenosulfonate. Now
that both enantiomers of epoxides 3 and 4 are the
mainstay of many research projects, the demand for
2-arylsulfonyl-1,3-cyclodienes8 has increased manyfold in
this research group and others.9 Three main drawbacks
to the above procedures exist: expense of the starting
materials10 and reagents,11 toxicity of the reagents, and
a
P3NO ) 4-(3-phenylpropyl)pyridine N-oxide. ((R,R)-Mn) )
(R,R)-(-)-N,N′-Bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane-
diaminomagnesium(III) chloride.
stoichiometric production of heavy metal waste. An
alternative synthesis of dienes 1 and 2 is reported herein.
Resu lts a n d Discu ssion
The original synthetic plan involved conversion of the
cyclic ketone to the enol thioether, followed by regio-
selective bromination. Oxidation of the corresponding
phenyl sulfide to sulfone would then activate a base-
catalyzed 1,4-elimination to yield the 2-substituted 1,3-
diene. Numerous methods for the transformation of
ketones to vinyl sulfides exist, but they involve multiple
steps, corrosive Lewis acids, or moisture-sensitive anhy-
drides as reagents. Labiad found that enol thioethers
could be efficiently synthesized from their respective
cyclic ketones using acidic clay catalysis.12 A slight
modification of this procedure (longer reaction time and
less catalyst) has produced phenyl vinyl sulfides 5 and
14 in 88% and 86% yield after distillation, respectively.
With the vinyl sulfides in hand, optimization of the
regioselective bromination of 5 and 14 was undertaken.
Trost and Lavoie have extensively studied the bromina-
tion of various vinyl sulfides13 including 5; however, their
(1) Synthesis via vinyl sulfones. 85. Chiral Carbon Collection. 9.
(2) (a) Hentemann, M. F.; Fuchs, P. L. Tetrahedron Lett. 1997, 38,
5615-5618. (b) Hentemann, M.; Fuchs, P. L. Org. Lett. 1999, 1, 355-
357. (c) J iang, W.; Lantrip, D. A.; Fuchs, P. L. Org. Lett. 2000, 2, 2181-
2184.
(3) (a) Lee, N. H.; J acobsen, E. N. Tetrahedron Lett. 1991, 32, 6533-
6536. (b) Chang, S.; Heid, R. M.; J acobsen, E. N. Tetrahedron Lett.
1994, 35, 669-672.
(4) 1,3-Cyclohexadiene was prepared in two steps from cyclohexene.
Schaefer, J . P.; Endres, L. Organic Syntheses; Wiley: New York, 1973;
Collect. Vol. V, pp 285-288.
(5) (a) Ba¨ckvall, J . E.; J untunen, S. K.; Andell, O. S. Org. Synth.
1989, 68, 148-154. (b) Andell, O. S.; Ba¨ckvall, J . E. Tetrahedron Lett.
1985, 26, 4555-4558.
(6) (a) Ba¨ckvall, J . E.; Najera, C.; Yus, M. Tetrahedron Lett. 1988,
29, 1445-1448. (b) Back, T. G.; Collins, S. J . Org. Chem. 1981, 46,
3249-3256.
(7) 1,3-Cycloheptadiene was prepared from the dissolving metal
reduction of cycloheptatriene. Dirkzwager, H.; Nieuwstad, T. J .; Van
Wijk, A. M.; Van Bekkum, H. Recl. Trav. Chim. Pays-Bas 1973, 92,
35-43.
(8) For a synthesis of 2-phenylsulfonyl-1,3-cyclooctadiene, see: Har-
dinger, S. A.; Fuchs, P. L. J . Org. Chem. 1987, 52, 2739-2749.
(9) For the most recent reviews of sulfone and sulfoxide chemistry
and recent applications of 2-arylsulfonyl-1,3-dienes, see: J onsson, S.
Y.; Lo¨fstro¨m, C. M. G.; Ba¨ckvall, J . E. J . Org. Chem. 2000, 65, 8454-
8457.
(11) For the synthesis of phenyl benzeneselenosulfonate, see: (a)
Back, T. G.; Collins, S. Tetrahedron Lett. 1980, 21, 2213-2214. (b) Lin,
H.-S.; Coghlan, M. J .; Paquette, L. A. Org. Synth. 1988, 67, 157-162.
(12) Labiad, B.; Villemin, D. Synthesis 1989, 143-144.
(13) Trost, B. M.; Lavoie, A. C. J . Am. Chem. Soc. 1983, 105, 5075-
5090.
(10) Aldrich Chemical Co. (2000-2001): 1,3-cyclohexadiene, 100 mL,
$244; 1,3-cycloheptadiene, 5 g, $146.
10.1021/jo0107047 CCC: $22.00 © 2002 American Chemical Society
Published on Web 12/11/2001

Synthesis of 2-(Phenylsulfonyl)-1,3-cyclohexadiene
J . Org. Chem., Vol. 67, No. 1, 2002 201
Sch em e 2. Syn th esis of 1
Sch em e 3. Syn th esis of 2
alcohol, which upon heating and water removal yielded
1 in near-quantitative yield. For most of our purposes,
crude 1 could be directly used in the next reaction
(Scheme 1), but recrystallized 1 could be obtained in 89%
yield from diethyl ether.
reported procedure led to an inseparable mixture of 6 and
7 in a ∼3:2 ratio (Scheme 2). In our hands, bromination
of 5 with a variety of bromine sources and conditions also
resulted in the initial formation of approximately 1:1
mixtures of desired allylic bromide 6 and the vinyl
bromide 7 along with trace amounts of the dibromide 8.
However, it was observed that a neat mixture of 6 and 7
equilibrates to an approximately 9:1 thermodynamic
mixture with 6 as the major product. The equilibrated
oil was diluted with hexanes and chilled in a freezer (-30
°C) to crystallize 6 selectively. The mother liquor was
concentrated and reequilibrated, and the process was
repeated three times to give 6 in 86% yield. Oxone
oxidation of 6 in methanol and water resulted in conver-
sion of the sulfide to the sulfone, but as the reaction
progressed, byproduct allylic methyl ether 10 was formed
in increasing amounts. Substitution of 2-propanol for
methanol eliminated this problem. Bromide 9 was then
submitted to basic conditions (tertiary amines, alkoxides)
to facilitate elimination to produce diene 1. These condi-
tions readily generated diene 1, but it was found that 1
subsequently reacted with base to form the very interest-
ing isomerized 1,4-diene 11. Attempts to minimize the
formation of 11 or crystallize diene 1 selectively were
unsuccessful.14 To avoid formation of 11, an acid-
catalyzed elimination proved highly effective. Thus,
bromide 9 was hydrolyzed to allylic alcohol 12 in water
at reflux. After cooling, alcohol 12 crystallized from the
reaction mixture, and the highly acidic water (pH ) 1)
was decanted. 1,2-Dichloroethane15 and a catalytic amount
of concentrated sulfuric acid were added to the resultant
Bromination of the analogous 7-ring vinyl sulfide 14
(Scheme 3) was unknown; thus, conditions for the forma-
tion of allylic bromide 17 were sought. After extensive
optimization with numerous solvents, bases, and bromi-
nating agents, allylic bromide 17 was obtained as the
major product along with 3-5% of vinyl bromide 15 and
1-2% of dibromide 16 as impurities. Oxidation16 of the
mixture led to the respective sulfones, which underwent
selective crystallization of 18 in 68% over two steps.
When exposed to triethylamine, bromide 18 smoothly
underwent elimination to yield diene 2 in near-quantita-
tive yield. Unlike the treatment of 9 with base, treatment
of bromide 18 showed no evidence for the formation of
1,4-diene 19, which was independently prepared in 10%
yield. Diene 2 is obtained in 56% overall yield from
cycloheptanone.
A brief explanation for the formation of the allylic,
vinyl, and dibromides seen in Schemes 2 and 3 is
presented in Scheme 4. For simplicity, only the 6-ring
series is shown even though the mechanism is also
applicable to the 7-ring series. Trost and Lavoie13 provide
a thorough explanation upon which much of this research
(15) If toluene is as the solvent, diene 1 is obtained in 80-85% yield
with the remaining material as di(6-cyclohex-1-enesulfonyl)benzene
ether 13.
(14) A table of selected conditions has been placed in the Supporting
Information.
(16) Trost, B. M.; Curran, D. P. Tetrahedron Lett. 1981, 22, 1287-
1290.

202 J . Org. Chem., Vol. 67, No. 1, 2002
Fuchs and Meyers
Sch em e 4. Mech a n ism for th e F or m a tion of
Allylic, Vin yl a n d Dibr om id es a n d th e
Equ ilibr a tion betw een Br om id es 6 a n d 7.
distillation or cyrstallization make the new protocol
attractive for large-scale synthesis.
Exp er im en ta l Section
Silica gel (Silicycle, technical grade) used for filtration and
flash chromatography was 230-400 mesh. Hexane was dis-
tilled before use, and acetonitrile and triethylamine were
distilled from calcium hydride before use, but unless otherwise
noted, all other solvents (toluene, dichloromethane, tetra-
hydrofuran, diethyl ether, 2-propanol, methanol) were used
as received. Cyclohexanone (Aldrich), cycloheptanone (Aldrich),
benzenethiol (97%, Aldrich), montmorillonite KSF (Aldrich),
Oxone (Aldrich), and recently purchased N-bromosuccinamide
(Acros) were all used as received. Melting points were obtained
on a capillary melting point apparatus and are uncorrected.
2-(P h en ylsu lfon yl)-1,3-cycloh exa d ien e (1). 1,2-Dichlo-
roethane (157 mL) and concentrated sulfuric acid (0.05 mL)
were added to crude alcohol 12 (156.9 mmol) and heated at
reflux. Concentrated sulfuric acid was added in 0.05 mL
aliquots every 15 min until the alcohol was consumed as
determined by TLC (ca. 4.5 h, 0.9 mL of concentrated H2SO4).
Water formed during the reaction was removed with a modi-
fied Dean-Stark trap. After being cooled to ambient temper-
ature, the solution was filtered through a pad of silica gel (ca.
7.5 g, 4 cm), and the flask and filter cake were washed with
1,2-dicholorethane. The resulting filtrate was concentrated
under reduced pressure to yield a viscous oil. The oil was
diluted with diethyl ether (10 mL) and placed in a -30 °C
freezer. One crystallization of the oil provided 30.71 g (89%)
of 1 as white crystals: mp 58-61 °C (lit.5 60-63 °C); Rf 0.53
(1:1 v/v ethyl acetate/hexane); 1H and 13C NMR agree with
literature; 13C NMR (125 MHz, CDCl3) δ 20.54, 22.06, 118.17,
127.46, 128.96, 129.87, 133.06, 134.64, 138.45, 139.67.
2-(P h en ylsu lfon yl)-1,3-cycloh ep ta d ien e (2). To a mag-
netically stirred solution of bromide 18 (90.82 g, 288 mmol) in
288 mL of acetonitrile was added triethylamine (44.2 mL, 317
mmol) in one portion. After 24 h at ambient temperature, the
reaction was washed with 5% aqueous HCl and the aqueous
layer extracted with ethyl acetate. The organic layers were
combined, washed with brine, and dried (MgSO4), and the
volatiles were removed in vacuo to give 2 as a pale yellow solid
(67.0 g, 99%): mp 57-58 °C (ether); 1H NMR (300 MHz,
CDCl3) δ 1.85 (m, 2H), 2.31 (m, 2H), 2.56 (q, J ) 5.8 Hz, 2H),
6.03 (m, 2H), 7.28 (t, J ) 5.5 Hz, 1H), 7.46-7.64 (m, 3H), 7.84-
7.90 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 24.53, 30.49, 30.97,
118.91, 127.61, 128.94, 132.90, 138.01, 139.15, 140.00, 141.85.
1-(P h en ylth io)cycloh exen e (5). To a solution of cyclo-
hexanone (111 g, 1.13 mol) in toluene (260 mL) was added a
slurry of montmorillonite KSF (10 g) in 20 mL of toluene. An
additional 20 mL of toluene was used to wash any remaining
montmorillonite KSF into the reaction flask. Thiophenol (118.6
g, 1.07 mol) was added, and the mixture was heated at reflux
for 7.5 h with magnetic stirring. Water formed during the
reaction was removed with a Dean-Stark trap. After being
cooled to ambient temperature, the mixture was filtered to
remove the montmorillonite KSF and the filter cake washed
with hexanes. The solution was concentrated in vacuo and the
remaining oil distilled (95-105 °C, 0.1 mmHg) through a 20
cm Vigreux column to yield 180.0 g (88%) of 5 as a pale yellow
oil. This reaction was scaled up to 5.309 mol of thiophenol
(603.05 g, Aldrich, 97% pure) and 5.57 mol of cyclohexanone
(547.14 g) in 750 mL of toluene. The ratio of montmorillonite
KSF was maintained at approximately 10 wt % to that of the
ketone. Mechanical stirring is recommended for reactions
greater than 1 mol. Ona large scale, distillation provided 891.3
g in 88% yield: Rf 0.38 (hexanes); 1H NMR (300 MHz, CDCl3)
δ 1.57-1.72 (m, 4H), 2.11-2.20 (m, 4H), 6.07 (m, 1H), 7.16-
7.33 (m, 5H); 13C NMR (125 MHz, CDCl3) δ 21.50, 23.43, 26.56,
29.79, 126.01, 128.60, 129.87, 131.25, 132.41, 135.09.
and mechanism is based. Formation of R-bromothionium
ion 21 can be envisioned to result from initial sulfur-
bromination of 20 followed by SN2′ trapping with the
bromide anion. Alternatively, lone-pair-assisted electro-
philic bromination could occur directly at the R-carbon
center. Loss of either Ha or Hb would result in the
formation of 6 or 7, respectively. The increased acidity
of Hb over Ha and the conformation of 21 contributes to
the initial kinetic product distribution, but it is difficult
to say which factor has the greatest effect. It is hypoth-
esized that formation of dibromide 8 follows a similar
path. The reaction of 6 with N-bromosuccinamide could
also result in the direct formation of intermediate 22.
Unlike intermediate 21, deprotonation of intermediate
22 would result in the exclusive formation of 8.
It is hypothesized that the equilibration between 6 and
7 may be acid catalyzed. Hydrogen bromide could be
formed by decomposition of the neat reaction mixture.
Protonation of olefin 7 could again lead to intermediate
22. Deprotonation by bromide would regenerate the acid
catalyst and facilitate equilibration of the mixture be-
tween allylic bromide 6 and vinyl bromide 7.
Con clu sion s
In conclusion, we have described an efficient route for
the synthesis of 6- and 7-ring 2-substituted cyclic dienyl
sulfones from inexpensive starting materials and re-
agents. We feel the avoidance of heavy metal wastes and
the purification of all intermediates and products by
6-Br om o-1-(p h en ylth io)cycloh exen e (6). To an ice-
water-cooled solution of 1-(phenylthio)cyclohexene 5 (200.2 g,
1.05 mole) in 700 mL of CH2Cl2 was added N-bromosuccinim-
ide (NBS) in portions (ca. 5-10 g) in order to maintain the

Synthesis of 2-(Phenylsulfonyl)-1,3-cyclohexadiene
J . Org. Chem., Vol. 67, No. 1, 2002 203
reaction temperature below 10 °C. NBS (ca. 0.95-1.0 equiv)
was added until the starting material was consumed as
determined by TLC. Excess NBS lowered the yield and
resulted in the formation of dibromide 8. Care was taken to
powder any lumps of NBS with a mortar and pestle before
addition to the reaction mixture. Once complete, the reaction
was washed with water, and the aqueous layer was extracted
with hexanes. The organic layers were combined, and the
volatiles were removed in vacuo. The neat oil was aged at
ambient temperature until 6 and 7 had equilibrated to
approximately a 9:1 ratio. The equilibration usually occurred
during workup or within 1-2 h, but it has been known to
require as much as 24 h of aging. The dark brown oil was
diluted with 200 mL of hexanes and vacuum filtered through
silica gel (10-15 g, 55 mm Bu¨chner funnel, filter paper was
also placed above the pad of silica gel). The pad of silica gel
was washed with 200-300 mL of hexanes, and the total
volume was reduced to 200-300 mL. The solution is placed
in a -30 °C freezer until crystallization ceased (ca. 12 h). After
the crystals were harvested, the volatiles were removed from
the mother liquor, and the oil was reequilibrated. This process
was repeated (a total of four recrystallizations) to provide 6
(244.9 g, 86%) as pale yellow/tan crystals: mp 30.5-31.5 °C;
(m, 3H), 7.87-7.90 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 15.43
(e), 25.66 (e), 25.78 (e), 56.32 (o), 70.47 (o), 127.55 (o), 128.44
(o), 132.61 (o), 140.62 (e), 141.35 (e), 143.20 (o). Anal. Calcd
for C13H16O3S: C, 61.88; H, 6.39. Found: C, 61.50; H, 6.36.
3-(P h en ylsu lfon yl)-1,4-cycloh exa d ien e (11): white crys-
tals; mp 80-87 °C dec; Rf 0.53 (1:1 v/v ethyl acetate/hexane);
1H NMR (300 MHz, CDCl3) δ 1.97-2.02, 2.05-2.10 (m, 1H),
2.46-2.52, 2.54-2.59 (m, 1H), 4.43 (m, 1H), 5.87-6.00 (m, 4H),
7.45-7.52 (m, 2H), 7.59-7.64 (m, 1H), 7.79-7.82 (m, 1H); 13
C
NMR (125 MHz, CDCl3) δ 26.42, 63.59, 118.31, 128.25, 130.07,
132.34, 133.45, 135.45. Anal. Calcd for C12H12O2S: C, 65.43;
H, 5.49. Found: C, 65.06; H, 5.44.
2-(P h en ylsu lfon yl)cycloh ex-2-en ol (12). A mixture of
bromide 9 (20.03 g, 66.49 mmol) and deionized water (100 mL)
was heated at reflux (biphasic) for 12 h. Hydrogen bromide
gas generated during the reaction was vented to an alkali trap.
The reaction was allowed to cool to ambient temperature, and
the mixture was aged 12 h. During that time, white crystals
of alcohol 12 formed, and the water was decanted. Deionized
water (100 mL) was added to the crude crystals of alcohol 12
and heated a reflux for an additional 12 h. The reaction was
allowed to cool to ambient temperature, and the mixture was
aged 12 h. The crystals were then washed several times with
deionized water to remove all traces of hydrogen bromide. The
crude product was used in the next reaction without purifica-
tion: white crystals; mp 100-101 °C; Rf 0.32 (1:1 v/v ethyl
1
Rf 0.18 (hexanes); H NMR (300 MHz, CDCl3) δ 1.7-1.8 (m,
1H), 1.92-2.20 (m, 2H), 2.22-2.44 (m, 3H), 4.65 (m, 1H), 6.19
(t, J ) 4.0 Hz, 1H), 7.2-7.44 (m, 5H); 13C NMR (75 MHz,
CDCl3) δ 16.65 (e), 26.69 (e), 33.21 (e), 50.91 (o), 127.10 (o),
129.08 (o), 130.94 (o), 134.03 (e), 134.13 (e), 136.93 (o). Anal.
Calcd for C12H13BrS: C, 53.54; H, 4.87. Found: C, 53.69; H,
4.83. Compounds 7 and 8 were isolated by flash column
chromatography and/or recrystallization from the mother
liquor. Dibromide 8 constitutes approximately <5% of the
1
acetate/hexane); H NMR (300 MHz, CDCl3) δ 1.41-1.55 (m,
1H), 1.57-1.70 (m, 1H), 1.73-1.90 (m, 1H), 1.90-2.00 (m, 1H),
2.11-2.26 (m, 1H), 2.36-2.50 (m, 1H), 2.95 (bs, 1H), 4.33 (m,
1H), 7.20 (dd, J ) 2.8, 4.9 Hz, 1H), 7.55 (m, 2H), 7.64 (m, 1H),
7.88-7.93 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 15.67 (e), 26.06
(e), 29.82 (e), 61.34 (o), 127.84 (o), 129.16 (o), 133.39 (o), 139.40
(e), 141.21 (e), 142.98 (o). Anal. Calcd for C12H14O3S: C, 60.48;
H, 5.92. Found: C, 60.58; H, 6.00.
1
crude reaction mixture as determined by H NMR.
1-Br om o-2-(p h en ylth io)cycloh exen e (7): clear colorless
1
oil; Rf 0.29 (hexanes); H NMR (300 MHz, CDCl3) δ 1.68 (m,
Di(6-cycloh ex-1-en esu lfon yl)ben zen e eth er (13): white
4H), 2.05 (m, 2H), 2.63 (m, 2H), 4.65 (m, 1H), 7.20-7.44 (m,
5H); 13C NMR (125 MHz, CDCl3) δ 23.09, 24.25, 31.86, 37.33,
122.72, 123.89, 127.48, 128.79, 131.54, 132.60.
1
crystals; Rf 0.30 (1:99 v/v MeOH/CHCl3); mp 202-204 °C; H
NMR (300 MHz, CDCl3) δ 1.20-1.34 (m, 2H), 1.46-1.64 (m,
4H), 2.06-2.34 (m, 6H), 4.42 (m, 2H), 7.13 (dd, J ) 3.1, 4.5
Hz, 2H), 7.41 (m, 6H), 7.53 (m, 4H), 7.74-7.77 (m, 6H); 13C
NMR (75 MHz, CDCl3) δ 15.21 (e), 25.84 (e), 26.17 (e), 65.48
(o), 127.19 (o), 128.65 (o), 132.60 (o), 139.66 (e), 141.35 (e),
146.06 (o). Anal. Calcd for C24H26O5S2: C, 62.86; H, 5.71.
Found: C, 62.50; H, 5.71.
1,3-Dibr om o-2-(p h en ylth io)cycloh exen e (8): pale yellow
crystals; mp 38-39 °C; Rf 0.18 (hexanes); 1H NMR (300 MHz,
CDCl3) δ 1.74-1.88 (m, 1H), 1.88-2.06 (m, 1H), 2.16-2.38 (m,
2H), 2.76-2.94 (m, 2H), 5.14 (m, 1H), 4.57 (s, 1H), 7.50-7.56
(m, 2H), 7.24-7.38 (m, 3H), 7.38-7.46 (m, 2H); 13C NMR (125
MHz, CDCl3) δ 19.55, 32.66, 37.42, 50.98, 127.79, 129.15,
131.97, 132.10, 132.25, 133.70. Anal. Calcd for C12H12Br2S: C,
41.40; H, 3.47. Found: C, 41.43; H, 3.09.
1-(P h en ylt h io)cycloh ep t en e (14). Preparation of 14
followed the procedure described above for the synthesis of 5
using cycloheptanone (540 g, 4.81 mol), montmorillonite KSF
(50 g), and thiophenol (557 g, 5.05 mol) in toluene (200 mL).
The mixture was vigorously heated at reflux for 48 h with
mechanical stirring. The crude oil was distilled (120-125 °C,
0.1 mmHg) through a 20 cm Vigreux column to obtain 14
(845.9 g, 86% yield) as a pale yellow oil: Rf 0.31 (hexanes); 1H
NMR (500 MHz, CDCl3) δ 1.52-1.57 (m, 4H), 1.72-1.77 (m,
2H), 2.18-2.20 (m, 2H), 2.34-2.36 (m, 2H), 6.16 (t, J ) 6.4
Hz, 1H), 7.18-7.22 (m, 1H), 7.27-7.33 (m, 4H), 7.88-7.94 (m,
2H); 13C NMR (125 MHz, CDCl3) δ 26.70, 27.02, 29.28, 31.86,
35.21, 126.25, 128.72, 130.23, 135.48, 135.60, 137.18.
1,3-Dibr om o-2-(p h en ylth io)cycloh ep ten e (16). Under an
inert atmosphere of argon was added dropwise bromine (5.3
mL, 102.7 mmol) to a stirred solution of 7 (10.0 g, 481.9 mmol)
and pyridine (11.9 mL, 146.8 mmol, distilled from CaH2) in
dry CH2Cl2 (100 mL) at -78 °C. The reaction and cooling bath
were allowed to slowly warm to room temperature over ∼10
h. The reaction was washed with 10% aqueous Na2SO3 and
5% aqueous HCl and dried (anhyd MgSO4). The volatiles
removed in vacuo to afford 16 (17.4 g, 98%) as a yellow solid.
An analytical sample is prepared by recrystallization from
hexanes: pale yellow crystals; mp 86-88 °C (hexanes); 1H
NMR (300 MHz, CDCl3) δ 1.56-1.68 (m, 2H), 1.72-1.86 (m,
2H), 1.90-2.14 (m, 4H), 2.98 (dd, J ) 6.4, 15.6 Hz, 1 H), 3.18
(ddd, J ) 1.5, 11.6, 16.2 Hz, 1H), 4.81 (dd, J ) 2.2, 6.1 Hz,
1H), 7.28-7.38 (m, 3H), 7.40-7.45 (m, 2H); 13C NMR (75 MHz,
CDCl3) δ 25.52, 25.70, 35.15, 41.74, 54.47, 127.89, 129.28,
131.73, 133.22, 135.13, 135.98. Anal. Calcd for C13H14Br2S: C,
43.12; H, 3.90. Found: C, 43.13; H, 3.77.
1-(P h en ylsu lfon yl)-6-br om ocycloh exen e (9). To a solu-
tion of bromide 6 (50.06 g, 186 mmol) in THF (100 mL) was
added 2-propanol (750 mL). The solution was then cooled with
an ice-water bath, and a solution of aqueous Oxone (171.5 g,
279 mmol, in 750 mL of deionized water) was added in portions
under mechanical stirring. The reaction temperature was
maintained below 30 °C during the addition of the Oxone
solution. After approximately half of the oxone solution had
been added, the ice-water bath was removed and the remain-
ing Oxone solution added in one portion. The slurry was stirred
for 14 h at ambient temperature. Upon completion, the slurry
was filtered and the 2-propanol removed from the water in
vacuo. The filter cake was washed with 2-propanol and added
to the above filtrate. The aqueous layer was extracted with
ethyl acetate and dried (anhydrous MgSO4), and the volatiles
were removed to afford 9 (49.85 g, 89%) as white crystals: mp
73-74 °C; Rf 0.53 (1:1 v/v ethyl acetate/hexane); 1H NMR (300
MHz, CDCl3) δ 1.74-1.85 (m, 1H), 1.90-2.10 (m, 2H), 2.18-
2.32 (m, 1H), 2.37-2.52 (m, 1H), 2.52-2.66 (m, 1H), 5.14 (m,
1H), 7.29 (dd, J ) 3.1, 4.3 Hz, 1H), 7.50-7.56 (m, 2H), 7.59-
7.64 (m, 1H), 7.91-7.96 (m, 2H); 13C NMR (75 MHz, CDCl3) δ
15.87, 25.74, 32.46, 40.79, 128.45, 128.85, 133.41, 140.19,
141.69, 143.59. Anal. Calcd for C12H13BrO2S: C, 47.85; H, 4.35.
Found: C, 48.04; H, 4.34.
1-(P h en ylsu lfon yl)-6-m eth oxycycloh exen e (10): color-
1
less oil; Rf 0.46 (1:1 v/v ethyl acetate/hexane); H NMR (300
MHz, CDCl3) δ 1.38-1.52 (m, 1H), 1.54-1.72 (m, 2H), 1.98-
2.10 (m, 1H), 2.12-2.28 (m, 1H), 2.32-2.45 (m, 1H), 3.16 (s,
3H), 4.20 (m, 1H), 7.23 (dd, J ) 2.9, 4.9 Hz, 1H), 7.47-7.60

204 J . Org. Chem., Vol. 67, No. 1, 2002
Fuchs and Meyers
7-Br om o-1-(p h en ylth io)cycloh ep ten e (17). Preparation
of 17 followed the procedure described above for the synthesis
of 6 using 14 (87.25 g, 0.427 mol) in 425 mL of CH2Cl2. The
dark brown oil was diluted with 100 mL of hexanes and
vacuum filtered through silica gel (10-15 g, 55 mm Bu¨chner
funnel, filter paper was also placed above the pad of silica gel).
The pad of silica gel was washed with 100-200 mL of hexanes,
and the volatiles were removed in vacuo to give a pale yellow
oil which was used in the next step without purification. A
crystalline analytical sample was prepared by adding an equal
volume of hexanes to the crude oil and chilling the solution in
1-(P h en ylsu lfon yl)-2-br om ocycloh ep ten e: colorless oil;
1H NMR (300 MHz, CDCl3) δ 1.48-1.66 (m, 4H), 1.72-1.84
(m, 2H), 2.85 (m, 2H), 2.92 (m, 2H), 7.48-7.58 (m, 2H), 7.58-
7.64 (m, 1H), 7.90-7.96 (m, 2H); 13C NMR (75 MHz, CDCl3) δ
23.70, 25.07, 30.17, 30.72, 44.66, 127.56, 128.70, 133.14,
136.26, 140.42, 143.31. Anal. Calcd for C13H15BrO2S: C, 49.53;
H, 4.80. Found: C, 49.81; H, 4.81.
2-(P h en ylsu lfon yl)-1,3-d ibr om ocycloh ep ten e: light tan
needles; mp 118-122 °C; 1H NMR (300 MHz, CDCl3) δ 1.52-
1.70 (m, 1H), 1.82-2.06 (m, 3H), 2.08-2.36 (m, 2H), 2.91 (m,
J ) 1.5, 6.8, 15.6 Hz, 1H), 3.42 (ddd, J ) 1.7, 11.9, 15.6 Hz,
1H), 6.18 (dd, J ) 2.3, 6.0 Hz, 1H), 7.50-7.58 (m, 2H), 7.60-
7.66 (m, 1H), 8.03-8.08 (m, 2H); 13C NMR (75 MHz, CDCl3) δ
24.19, 25.75, 34.74, 44.32, 47.78, 128.17, 128.59, 133.41,
139.93, 144.02, 144.83. Anal. Calcd for C13H14Br2O2S: C, 39.62;
H, 3.58. Found: C, 39.79; H, 3.53.
3-(P h en ylsu lfon yl)-1,4-cycloh ep ta d ien e (19). Under an
inert atmosphere of argon was added dropwise LiHMDS (16.1
mL, 16.1 mmol, 1 M THF) to a stirred solution of 2 (3.14 g,
13.4 mmol) in dry THF (54 mL) at -78 °C. After being stirred
at -78 °C for 10 min, the reaction was warmed to 0 °C for 15
min. The reaction was quenched with 5% aqueous HCl, the
aqueous layer was extracted with ethyl acetate, the combined
organic layers were dried (anhydrous MgSO4), and the volatiles
were removed to afford a viscous oil. Flash chromatography
provided 2.286 g of a yellow semicrystalline solid. Recrystal-
lization provided 19 (331 mg, 10% yield) as white crystals: mp
91-93 °C (Et2O/Hexanes); 1H NMR (300 MHz, CDCl3) δ 1.52-
1.57 (m, 4H), 4.49 (m, J ) 6.1 Hz, 1H), 5.71 (m, J ) 6.1, 11.4
Hz, 2H), 6.10 (m, J ) 11.3 Hz, 2H), 7.50 (m, 2H), 7.62 (m,
1H), 7.82-7.86 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 26.15
(e), 68.87 (o), 120.48 (o), 128.39 (o), 129.78 (o), 133.55 (o), 136.43
(e), 138.27 (o). Anal. Calcd for C13H14O2S: C, 66.64; H, 6.02.
Found: C, 66.66; H, 5.92.
1
a -30 °C freezer overnight: mp <25 °C; H NMR (300 MHz,
CDCl3) δ 1.40-1.56 (m, 1H), 1.76-2.04 (m, 3H), 2.04-2.24 (m,
2H), 2.24-2.46 (m, 2H), 4.75 (d, J ) 5,6 Hz, 1H), 6.42 (ddd, J
) 1.1, 5.3, 7.7 Hz, 1H), 7.18-7.40 (m, 5H); 13C NMR (75 MHz,
CDCl3) δ 26.21, 26.41, 29.00, 35.64, 56.68, 126.73, 128.92,
129.98, 134.91, 136.68, 142.59.
1-(P h en ylsu lfon yl)-7-br om ocycloh epten e (18). The crude
mixture of bromides 15-17 (combined ∼0.427 mol) was
dissolved in 1.7 L of methanol and cooled using an ice-water
bath. A solution of aqueous Oxone (393.7 g, 640.5 mmol, in
1.7 L deionized water) was added in portions under mechanical
stirring. The reaction temperature was maintained below 30
°C during the addition of the Oxone solution. After ap-
proximately half of the oxone solution had been added, the
ice-water bath was removed and the remaining oxone solution
was added in one portion. The slurry was stirred for 14 h at
25 °C. Upon completion, the slurry was filtered and the
methanol removed from the water in vacuo. The filter cake
was washed with methanol and added to the above filtrate.
The aqueous layer was extracted with ethyl acetate and dried
(anhydrous MgSO4), and the volatiles were removed to afford
a viscous oil. The oil was dissolved in diethyl ether and placed
in a -30 °C freezer. Three crops produced 91.4 g of 18 as a
1
white solid in 68% yield: mp 68-70 °C; H NMR (300 MHz,
Ack n ow led gm en t. We thank Carl Wood and Arlene
Rothwell for mass spectral data, Daniel Lee for elemen-
tal analysis, and Tony Thompson for 125 MHz 13C data.
CDCl3) δ 1.30-1.48 (m, 1H), 1.67-1.81 (m, 1H), 1.84-2.04 (m,
2H), 2.04-2.26 (m, 2H), 2.36.2.50 (m, 1H), 2.50-2.64 (m, 1H),
5.15 (d, J ) 5.3 Hz, 1H), 7.49 (ddd, J ) 1.4, 4.5, 9.0, 1H), 7.51-
7.59 (m, 2H), 7.60-7.67 (m, 1H), 7.87-7.93 (m, 2H); 13C NMR
(75 MHz, CDCl3) δ 25.17, 26.35, 28.05, 34.84, 46.18, 128.12,
1
Su p p or tin g In for m a tion Ava ila ble: 13C and H spectra
for compounds 1, 2, 5-14, and 16-19 and the corresponding
sulfones of 15 and 16. A table of selected conditions for the
transformation of 6 into dienes 1 and 11. This material is
available free of charge via the Internet at http://pubs.acs.org.
128.98, 133.35, 139.13, 144.41, 147.96. Anal. Calcd for C13H15
-
BrO2S: C, 49.53; H, 4.80. Found: C, 49.79; H, 4.89. 1-Phen-
ylsulfonyl-2-bromocycloheptene and 2-phenylsulfonyl-1,3-di-
bromocycloheptene were isolated by flash column chroma-
tography and/or recrystallization from the mother liquor.
J O0107047