Lewis acid mediated reactions of n-arylsulfonimidoyl chlorides with alkenes. some steric effects of alkene substitution

Article abstract of DOI:10.1021/jo980503b

The Lewis acid-mediated reaction of AT-phenyl-S-(4-methylphenyl)sulfonimidoyl chloride with alkenes was explored in order to determine the effect of alkene substitution on the stereochemical outcome of the reaction. With monosubstituted alkenes, benzothia

Full text of DOI:10.1021/jo980503b

J . Org. Chem. 1998, 63, 6845-6851
6845
Lew is Acid Med ia ted Rea ction s of N-Ar ylsu lfon im id oyl Ch lor id es
w ith Alk en es. Som e Ster ic Effects of Alk en e Su bstitu tion
Michael Harmata* and Mehmet Kahraman
Department of Chemistry, University of MissourisColumbia, Columbia, Missouri 65211
Received March 17, 1998
The Lewis acid-mediated reaction of N-phenyl-S-(4-methylphenyl)sulfonimidoyl chloride with
alkenes was explored in order to determine the effect of alkene substitution on the stereochemical
outcome of the reaction. With monosubstituted alkenes, benzothiazines are produced with relatively
low diastereoselection, with one unique exception, trimethylsilylethene. 1,1-Disubstituted alkenes
give products with even lower stereoselectivity. With trisubstituted alkenes, steric effects begin
to change the course the reaction from one which can be rationalized as a cycloaddition to one
which seems to definitely produce a carbocationic intermediate. Interestingly, the stereoselection
observed in the reaction of (E)- and (Z)-2-butenes shows large deviations from the norm with (E)-
2-butene giving rise to two diastereomeric benzothiazines in a ratio of 45:1.
Sch em e 1
In tr od u ction
The Lewis acid-mediated reaction of N-arylsulfonimi-
doyl chlorides with alkynes and alkenes is a powerful
synthetic approach to the synthesis of benzothiazines
such as 2 and 3 (Scheme 1).1 The reaction is further
characterized by a reasonable range of generality and
compares very favorably with related methodology in-
volving the direct cycloaddition of sulfinylanilines with
alkenes, the latter reaction being possible only with
strained alkenes.2 Further, the product benzothiazines
have tremendous potential as intermediates in organic
synthesis, and their facile conversion to alkylanilines,
alkenylanilines, and allylanilines has been demon-
strated.3 In an earlier study, we obtained some interest-
ing results regarding the preparation of benzothiazines
2 from alkenes with respect to diastereoselectivity.1b We
decided to investigate the matter more deeply and
examine a series of alkenes with the aim of establishing
a relationship between the number and size of substit-
uents on the alkene and the diastereoselectivity of the
reaction. This report details the results of that investi-
gation.
imidoyl chloride 4 was treated with monosubstituted
alkenes in the presence of AlCl3 at -78 °C in CH2Cl2 to
produce benzothiazines in good to excellent yields. These
results obtained are shown in Table 1.
All crude reaction products were subjected to capillary
GC analysis in order to determine the isomer ratios
shown in Table 1. The extent of diastereoselectivity was
small, ranging from 1.4:1 to 4.1:1, even for R1 ) tert-butyl.
Interestingly, with (trimethylsilyl)ethene a reasonable
diastereoselectivity was obtained (Table 1, entry 6). The
size of the trimethylsilyl group is greater than that of
the tert-butyl group.4 Further, because of the greater
carbon-silicon bond length vis-a`-vis the carbon-carbon
bond, that steric bulk is projected further away from the
reactive alkene centers. Which factor is responsible for
the observed diastereoselectivity is not known. It should
be stated that we have shown in several cases that
benzothiazine stereochemistry remains intact under the
reaction conditions.1b The low yield associated with the
formation of 10 can be attributed to the formation of a
desilylated side product.5
Resu lts a n d Discu ssion
Mon osu bstitu ted Alk en es. In this series, a small
number of monosubstituted alkenes were chosen to
examine the effect of steric interactions on the diaste-
reoselectivity of the reaction with respect to carbon 4 of
the benzothiazines formed in this reaction. The sulfon-
(1) (a) Harmata, M.; Schlemper, E. O. Tetrahedron Lett. 1987, 28,
5997. (b) Harmata, M.; Claassen, R. J ., II. J . Org. Chem. 1991, 56,
5059.
(2) (a) Hanson, P.; Wren, S. A. C. J . Chem. Soc., Perkin Trans. 2
1987, 197. (b) Borthakur, D. R.; Projapati, D.; Sandhu, J . S. Hetero-
cycles 1986, 24, 2739. (c) Zoller, U.; Roan, P. Tetrahedron Lett. 1985,
27, 2813. (d) Hanson, P.; Stone, T. W. J . Chem. Soc., Perkin Trans. 1
1984, 2429. (e) Hanson, P.; Lewis, R. J .; Stone, T. W. J . Chem. Soc.,
Perkin Trans. 2 1983, 1719. (f) Hogeveen, H.; Kingma, R. F.; Kok, D.
M. J . Org. Chem. 1982, 47, 1909. (g) Maculso, A.; Hamer, J . J . Org.
Chem. 1967, 32, 506. (h) Collins, G. R. J . Org. Chem. 1964, 29, 1688.
(3) (a) Harmata, M.; J ones, D. E. Tetrahedron Lett. 1995, 36, 4769.
(b) Harmata, M.; Kahraman, M. Synthesis 1995, 713. (c) Harmata, M.;
Kahraman, M. Synthesis 1994, 142. (d) Harmata, M.; Herron, B. F.
Tetrahedron 1991, 47, 8855.
The relative stereochemistry of the benzothiazines was
assigned on the basis of NMR shift reagent studies.
Lanthanide shift reagents are commonly used on organic
(4) Bock, H.; Ruppert, K.; Na¨ther, C.; Haulas, Z.; Herrmann, H.-F.;
Arad, C.; Go¨bel, I.; J ohn, A.; Meuret, J .; Nick, S.; Rauschenbach, A.;
Seitz, W.; Vaupel, T.; Solovki, B. Angew Chem., Int. Ed. Engl. 1992,
31, 550.
(5) Harmata, M.; Kahraman, M.; J ones, D. E.; Pavri, N.; Weather-
wax, S. E. Tetrahedron 1998, 54, in press.
S0022-3263(98)00503-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 09/12/1998

6846 J . Org. Chem., Vol. 63, No. 20, 1998
Harmata and Kahraman
Ta ble 1. Rea ction s of 4 w ith Mon osu bstitu ted Alk en es
Ta ble 3. Rea ction s of 4 w ith Disu bstitu ted Alk en es
entry
R1
Et
i-Pr
t-Bu
product
a:ba
yieldb (%)
entry
R1
Et
n-Pr
i-Pr
Ph
product
a:ba
yieldb (%)
1
2
3
11
12
13
1.2:1
2.4:1
1.2:1
46
33
57
1
2
3
4
5
6
5
6
7
8
9
1.5:1
1.6:1
2.4:1
1.4:1
4.1:1
10:1
90
66
78
62
65
35
a
Determined by capillary GC analysis of crude reaction mix-
b
t-Bu
TMS
tures. After chromatographic purification.
10
Ta ble 4. Sh ift Rea gen t Stu d y for 11-13a
a
Determined by capillary GC analysis of crude reaction mix-
b
∆δ isomer a b
∆δ isomer bb
tures. After chromatographic purification.
entry
benzothiazine
1
2
3
11
12
13
0.23
0.14
0.137
0.26
0.21
0.139
Ta ble 2. Sh ift Rea gen t Stu d ya
entry
benzothiazine
∆δ isomer a b
∆δ isomer bb
a
1
2
3
4
5
6
5
6
7
8
9
0.84
0.43
0.32
0.80
0.30
0.10
1.19
0.83
0.54
1.08
0.46
0.36
Chemical shift change of the C-4 methyl group after addition
b
of 20 mol % Eu(fod)3. Downfield, in ppm.
groups which are cis to S-2 oxygen at the C-4 position
would block the polar group and reduce the polarity of
the isomer.
10
a
Chemical shift change of the C-4 proton after addition of 20
mol % Eu(fod)3. Downfield, in ppm.
1,1-Disu bstitu ted Alk en es. 1,1-Disubstituted alk-
enes were also studied to examine the effect of steric
interactions on the diastereoselectivity of the reaction and
to broaden the scope of the reaction. When the sulfon-
imidoyl chloride 4 was reacted with 1,1-disubstituted
alkenes in the presence of AlCl3 at -78 °C in CH2Cl2,
the reaction yielded benzothiazines 11-13 (Table 3). To
determine the isomer ratio (a /b) for benzothiazines 11-
13, all crude reaction mixtures were subjected to capillary
GC analysis. Not surprisingly, the diastereoselection for
these reactions was not very high. Yields for these
reactions varied in a range of 33% to 57% due to the
formation of side products.
All benzothiazines were separated and subjected to
NMR shift reagent study as mentioned above. It was
anticipated that those methyl groups cis to the oxygen
of sulfoximine functionality would experience a greater
downfield shifts than those situated trans. These methyl
shifts for benzothiazines 11-13 are listed in Table 4.
Benzothiazine 11a exhibited a C-4 methyl resonance
at 1.41 ppm. Isomer 11b had the same methyl peak at
1.56 ppm. After the addition of 20 mol % Eu(Fod)3, the
methyl peaks shifted downfield by 0.23 and 0.26 ppm,
respectively. The stereochemical assignments were made
accordingly. Thus, the C-4 methyl group for 11a was
assigned as trans to the oxygen at S-2 position because
it shifts less downfield than C-4 methyl group of 11b.
Because the change in chemical shifts in both isomers is
comparable, the stereochemical assignments should be
considered tentative. Nevertheless, the data are self-
consistent. In all cases, it appears that the major isomers
maintained the same relative stereochemistry in which
there was a cis relationship between alkyl groups at C-4
position of benzothiazines and the oxygen of sulfoximine
functionality.
b
compounds to assign stereochemistry.6 In our studies,
Eu(Fod)3 was chosen for the stereochemical assignments.
In most cases, separated diastereomers were subjected
to this study with the same stock solution of Eu(Fod)3.
However, in a few cases, the mixture of isomers was used.
While one isomer showed relatively large downfield
shifts, the other showed smaller downfield shifts. The
stereochemical assignments are based on the comparison
of these shifts for each isomer. The results for this shift
reagent study are shown in Table 2, which presents the
changes in chemical shifts for the C-4 hydrogen of the
benzothiazines after the addition of 20 mol % of Eu(Fod)3.
It was anticipated that the hydrogen cis to the oxygen
at S-2 would experience a greater downfield shift than
the one situated trans since coordination of the shift
reagent at the sulfoximine oxygen should perturb the C-4
cis hydrogen to a greater extent than one oriented trans.
For example, the C-4 hydrogen of benzothiazine 9a has
a chemical shift of 3.05 ppm. However, after the addition
of 20 mol % of Eu(Fod)3, the same proton had moved to
3.35 ppm, a downfield shift of 0.30 ppm. On the other
hand, the C-4 hydrogen of the minor isomer 9b had a
chemical shift of 3.04 ppm. After the addition of 20 mol
% of shift reagent, this proton shifted to 3.50 ppm, a
downfield shift of 0.46 ppm. The stereochemical assign-
ments for 5 through 8 were made accordingly. These
assignments were supported by X-ray structural deter-
mination of 9a and 10b.
To predict the relative stereochemistry, it is appropri-
ate to mention the polarity of isomers. HPLC analysis
of the crude reaction mixtures showed that the major
isomers for 5-9 had shorter retention times relative to
minor isomers. This result is also consistent with the
data from the shift reagent study because alkyl or aryl
According to these assignments, it is logical to expect
that the major isomer would be less polar than the minor
isomer. HPLC analysis of the crude reaction mixtures
showed that the major isomers of 11-13 all had shorter
retention times relative to their diastereomers.
(6) Lanthanide Shift Reagents in Stereochemical Analysis; Morrill,
T. C., Ed.; VCH: Deerfield Beach, 1986.

Steric Effects of Alkene Substitution
J . Org. Chem., Vol. 63, No. 20, 1998 6847
Ta ble 5. Rea ction s of 4 w ith Tr isu bstitu ted Alk en es
Interestingly, as steric bulk on the alkene increased
the course of the reaction changed. Reaction of 4 with
2,4-dimethyl-2-pentene gave a 34% yield of chlorosulfox-
imine 20 as a 2.4:1 mixture of isomers. Gas chromato-
graphic analysis suggested only very small amounts of
benzothiazine 18 may have been formed. The reaction
with 2,4,4-trimethyl-2 pentene gave only chlorosulfox-
imine 21 as a single, but unassigned, stereoisomer in 48%
yield.
entry
R1
product
a:ba
yieldb (%)
1
2
3
4
Me
Et
i-Pr
t-Bu
16
17
18
19
1.2:1
1.6:1
53
53
c
c
a
Determined by capillary GC analysis of crude reaction mix-
tures. After chromatographic purification. c Benzothiazine not
b
formed.
(Z)- a n d (E)-2-Bu ten e. We had earlier reported some
intriguing stereoselectivities in the reaction of 4 with (Z)-
and (E)-3-hexene.1b To test the lower limit of this
stereoselectivity, we examined the corresponding 2-
butenes. Interestingly, when (E)-2-butene was reacted
with sulfonimidoyl chloride 4 under the standard reaction
conditions, benzothiazine 22 was obtained in 62% yield
as a 45:1 mixture of isomers (eq 1). The relative
Ta ble 6. Sh ift Rea gen t for 16 a n d 17a
entry
benzothiazine
∆δ isomer a b
∆δ isomer bb
1
2
16
17
1.30
1.27
0.39
0.35
a
Chemical shift change of the C-3 proton after addition of 20
b
mol % Eu(fod)3. Downfield, in ppm.
In addition to the benzothiazines mentioned, side
products were observed in some cases. Chlorosulfoximine
14 was isolated in 11% yield as a 1.2:1 mixture of isomers
in the formation of benzothiazine 12. Similarly, 15 was
obtained during the synthesis of 13 in 6% yield. Its
structure was confirmed by X-ray analysis.
stereochemistry of cycloadduct 22a was determined by
X-ray crystallography. The minor isomer 22b could not
be isolated for further study, but it was assumed that it
had the stereochemistry shown in analogy to our earlier
work.1b
In the case of (Z)-2-butene, reaction with 4 gave the
benzothiazine 23 in 78% yield with a diastereomer ratio
of 2.3:1 (eq 2). The relative stereochemical assignment
Tr isu bstitu ted Alk en es. These alkenes were studied
to examine the effect of steric interactions on the dias-
tereoselectivity in benzothiazine formation with respect
to the C-3 position of benzothiazines. The results are
summarized in Table 5. When 2-methyl-2-butene was
treated with 4, benzothiazine 16 was obtained in 53%
yield as a 1.2:1 mixture of diastereomers. With 2-methyl-
2-pentene, 17 was formed in 53% yield as a 1.6:1 mixture
of diastereomers.
As for the relative stereochemical assignments, ben-
zothiazines 16 and 17 were submitted to a shift reagent
study. In this case, separation was not possible, even
with HPLC, and mixtures had to be used. It was
relatively easy to distinguish the C-3 proton for the major
and the minor isomers by careful measurement of
integration. It was seen that the C-3 hydrogens of
benzothiazines 16a and 16b had chemical shifts of 3.20
and 2.96 ppm, respectively. After the addition of 20 mol
% of Eu(Fod)3, the C-3 protons of 16a and 16b moved to
4.50 and 3.35 ppm, respectively. The chemical shift
changes were 1.30 and 0.39 ppm. The larger shift should
correspond to the cis hydrogen at carbon 3, and the
stereochemical assignments were made accordingly. The
same result was found for benzothiazine 17 as well (Table
6). In both cases, the major isomer had a longer retention
time on the HPLC column. This is also consistent with
the stereochemical assignments.
for benzothiazines 23a /b was made on the basis of NMR
shift reagent study. The major isomer had two sets of
multuplets at 3.94 and 3.17 ppm. Those peaks cor-
responded to C-3 and C-4 hydrogens, respectively. After
20 mol % Eu(Fod)3 was added, those peaks shifted
downfield 4.29 and 3.81 ppm, a difference of 0.35 and
0.64 ppm, respectively. On the other hand, the minor
isomer had a multiplet at 3.23 ppm for the same two
protons. After the NMR shift reagent study, those
protons shifted to 3.40 ppm and 3.32 ppm, a difference

6848 J . Org. Chem., Vol. 63, No. 20, 1998
Harmata and Kahraman
were obtained as a solution in CDCl3 with TMS as the internal
standard unless otherwise stated. 2,4-Dimethyl-2-pentene was
prepared as described in the literature.7 All other chemicals
were obtained from commercial sources.
Sch em e 2
Gen er a l P r oced u r e for th e P r ep a r a tion of N-P h en yl-
S-(4-m eth ylp h en yl)su lfon im id oyl Ch lor id e (4). A flame-
dried 50 mL recovery flask equipped with a magnetic stir bar,
a septum, and a nitrogen balloon was charged with 1.034 g
(4.47 mmol, 1 equiv) of N-phenyl-p-toluenesulfinamide8 and
21.9 mL of dry CH2Cl2 to give a 0.20 M solution. This solution
was cooled to -78 °C in a 2-propanol/dry ice bath. tert-Butyl
hypochlorite (0.545 mL, 4.56 mmol, 1.02 equiv) was added via
a syringe over 5 min. The solution turned yellow after 10 min.
The completion of the reaction was monitored by TLC. The
product 4 can be obtained by evaporating the solvent and
excess t-BuOCl on a rotary evaporator at 0 °C. However, all
reactions were carried out in one pot as discussed below.
Gen er a l P r oced u r e for th e Rea ction of N-P h en yl-S-
(4-m eth ylp h en yl)su lfon im id oyl Ch lor id e (4) w ith Alk -
en es. Meth od A. In the case of gaseous alkenes, a solution
of the sulfonimidoyl chloride (1.18 g, 4.47 mmol, 1 equiv),
prepared as decribed above, was cooled to -78 °C in a
2-propanol/dry ice bath in the same flask equipped with a
septum, magnetic stir bar, and a nitrogen balloon. Gaseous
alkenes were passed through the solution of the sulfonimidoyl
chloride solution for 10-15 min by using a simple gas line
connected to a needle. Powdered AlCl3 (1.789 g, 13 mmol, 3
equiv) was added to the reaction mixture in three portions over
15 min time period. The color of the solution turned brown.
The alkene was continuously bubbled through the solution.
The mixture was allowed to stir at -78 °C for 1 h. The
reaction was monitored by TLC. It was quenched with 20 mL
of 1 N HCl. It was poured into a separatory funnel along with
30 mL of ethyl acetate. The organic layer was washed with
water (3 × 30 mL) and brine solution (1 × 30 mL), dried over
MgSO4, and filtered, and the solvent was removed in vacuo to
give the product as either a brownish viscous oil or light brown
solid which was purified by either flash chromatography or
MPLC.
Meth od B. In the case of liquid alkenes, the sulfonimidoyl
chloride (1.18 g, 4.47 mmol, 1 equiv) prepared as described
above was cooled to -78 °C in a 2-propanol/dry ice bath in
the same flask equipped with a septum, magnetic stir bar, and
nitrogen balloon. The alkene (5.36 mmol, 1.2 equiv) was added
to this solution via a syringe at -78 °C. The solution was
allowed to stir for 5-10 min, followed by the addition of 1.78
g (13 mmol, 3 equiv) of powdered AlCl3 in three portions over
a 15 min time period. The color of the solution turned brown
immediately. The mixture was allowed to stir at -78 °C for
1 h. The reaction was monitored by TLC. The reaction was
quenched and worked up as described for method A.
(()-(2S*,4R*)-3,4-Dih yd r o-4-eth yl-2-(4-m eth ylp h en yl)-
2λ4-2,1-ben zoth ia zin e 2-Oxid e (5a ) a n d (()-(2S*,4S*)-3,4-
Dih yd r o-4-eth yl-2-(4-m eth ylp h en yl)-2λ4-2,1-ben zoth ia z-
in e 2-Oxid e (5b). Meth od A. Chromatography solvent: 6:1
hexane/ethyl acetate. Combined yield: 90%. Recrystallization
from hexane/ethyl acetate gave an analytical sample of 5a :
mp 89-90 °C; 1H (500 MHz, CDCl3) δ 7.85 (d, 2H, J ) 8.2
Hz), 7.30 (d, 2H, J ) 8.2 Hz), 7.17 (dt, 1H, J ) 0.7, 7.9 Hz),
7.07 (d, 1H, J ) 7.8 Hz), 7.04 (d, 1H, J ) 7.7 Hz), 6.86 (t, 1H,
J ) 7.4 Hz), 3.44 (dd, 1H, J ) 5.2, 13.2 Hz), 3.14 (dd, 1H, J )
5.3, 13.2 Hz), 3.08-3.03 (m, 1H), 2.40 (s, 3H), 2.0-1.93 (m,
2H), 1.00 (t, 3H, J ) 7.33 Hz); 13C NMR (125 MHz, CDCl3) δ
144.4, 144.34, 136.8, 129.6, 128.4, 127.8, 125.0, 123.3, 120.1,
50.8, 38.8, 26.2, 21.3, 11.8. Anal. Calcd for C17H19NSO: C,
71.53; H, 6.71. Found: C, 71.53; H, 6.68.
of 0.17 and 0.11 ppm. On the basis of these data, the
major isomer and minor isomers were assigned as 23a
and 23b, respectively. It was expected that the major
isomer 23a should be more polar than 23b, and this was
observed with HPLC analysis of the product mixture.
Sid e Rea ction s a n d Mech a n istic P ossibilities.
The mechanism of the reaction of 4 with alkenes is still
in question. The stereochemical data we obtained previ-
ously and as well as that in this study suggests a
concerted process or a stepwise one in which collapse of
an intermediate carbocation to a σ complex is faster than
bond rotation. The issue is still unresolved, but it is clear
that carbocation intermediates are accessible in this
reaction, particularly as steric hindrance increases as a
result of alkene substitution.
Most telling in this regard is the formation of the
chlorosulfoximines observed in this work. Their appear-
ance clearly suggests a stepwise process as shown in
Scheme 2 for the formation of 15 and is suggestive of the
formation of carbocationic intermediates in general.
Remaining to be answered are such questions as the
mechanistic basis behind the high diastereoselectivity
found with (E)-1,2-dialkylalkenes and the nature of the
stereochemistry (retention/inversion) at sulfur in ben-
zothiazine formation.
Su m m a r y
In summary, we have examined the effect of alkene
substitution on the course and stereochemical outcome
of the reaction of 4 with alkenes in the presence of a
Lewis acid, aluminum chloride. This study helped to
expand the scope of the reaction. The effects of substitu-
tion of diastereoselectivity seem to be minimal, except
for (E)-1,2-disubstituted alkenes. The reasons for this
are still not clear. Steric bulk on the alkene progressively
steers the course of the reaction away from cycloaddition
and benzothiazine formation in favor of electrophilic
addition. Many mechanistic questions remain unan-
swered, and given the simplicity of this reaction and the
synthetic utility of benzothiazines, further studies are
warranted. Progress will be reported in due course.
Recrystallization from hexane/ethyl acetate gave an analyti-
1
cal sample of 5b: mp 93-94 °C; H (500 MHz, CDCl3) δ 7.93
(dd, 2H, J ) 1.8, 8.3 Hz), 7.36 (d, 2H, J ) 8.1 Hz), 7.23-7.19
(m, 2H), 7.11 (dd, 1h, J ) 1.3, 7.9 Hz), 6.92 (dt, 1H, J ) 1.37,
7.5 Hz), 3.45-3.37 (m, 2H), 2.87 (dd, 1H, J ) 1.8, 11.8 Hz),
Exp er im en ta l Section
Gen er a l Meth od s. See ref 1b. 1H and 13C spectra were
obtained at 500 and 125.8 MHz, respectively. All NMR spectra
(7) Shapiro, R. H.; Kolonko, K. J . J . Org. Chem. 1978, 43, 1404.
(8) Prepared by the reaction of aniline with p-toluenesulfinyl
chloride in the presence of triethylamine.

Steric Effects of Alkene Substitution
J . Org. Chem., Vol. 63, No. 20, 1998 6849
2.44 (s, 3H), 2.17-2.11 (m, 1H) 1.86-1.77 (m, 1H), 0.96 (t, 3H,
J ) 7.4 Hz); 13C NMR (125 MHz, CDCl3) δ 145.3, 144.7, 135.9,
129.9, 128.9, 128.0, 125.6, 125.3, 123.7, 120.4, 51.4, 34.6, 24.2,
21.5, 10.5. Anal. Calcd for C17H19NSO: C, 71.53; H, 6.61.
Found: C, 71.31; H, 6.69.
) 1.4, 7.5 Hz), 6.59 (d, 1H, J ) 7.7 Hz), 4.27 (dd, 1H, J ) 8.2,
8.3 Hz), 3.67-3.65 (m, 2H), 2.46 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 145.7,144.9, 139.1, 136.9, 130.0, 128.9, 128.9, 128.7,
128.6, 127.7, 127.6,126.6, 123.8, 120.8, 54.5, 42.5, 21.6. Anal.
Calcd for C21H19NOS: C, 75.68; H, 5.75. Found: C, 75.88; H,
5.82.
(()-(2S*,4R*)-3,4-Dih yd r o-4-(1,1-d im et h ylet h yl)-2-(4-
m eth ylp h en yl)-2λ4-2,1-ben zoth ia zin e 2-Oxid e (9a ) a n d
(()-(2S*,4S*)-3,4-Dih yd r o-4-(1,1-d im eth yleth yl)-2-(4-m e-
th ylp h en yl)-2λ4-2,1-ben zoth ia zin e 2-Oxid e (9b). Meth od
B. Chromatography solvent: 4:1 hexane/ethyl acetate.
Yield: 65%. Recrystallization from hexane/ethyl acetate gave
an analytical sample of 9a : mp 173-174 °C; 1H NMR (500
MHz, CDCl3) δ 7.76 (d, 2H, J ) 8.2 Hz), 7.29-7.22 (m, 3H),
7.12 (d, 1H, J ) 8.0 Hz), 7.05 (d, 1H, J ) 7.1 Hz), 6.89 (dt, 1H,
J ) 0.8, 7.5 Hz), 3.90 (dd, 1H, J ) 1.5, 13.9 Hz), 3.10-3.03
(m, 2H), 2.41 (s, 3H), 1.15 (s, 9H); 13C NMR (125 MHz, CDCl3)
δ 146.4, 143.9, 139.6, 130.4, 129.7, 128.3, 127.8, 123.5, 122.7,
(()-(2S*,4R*)-3,4-Dih ydr o-2-(4-m eth ylph en yl)-4-pr opyl-
2λ4-2,1-ben zoth ia zin e 2-Oxid e (6a ) a n d (()-(2S*,4S*)-3,4-
Dih yd r o-2-(4-m et h ylp h en yl)-4-p r op yl-2λ4-2,1-b en zot h i-
a zin e 2-Oxid e (6b). Meth od B. Chromatography solvent:
3:1 hexane/ethyl acetate. Combined yield: 66%. Recrystal-
lization from hexane/ethyl acetate gave an analytical sample
of 6a : mp 115-116 °C; 1H NMR (500 MHz, CDCl3) δ 7.88 (d,
2H, J ) 8.2 Hz), 7.33 (d, 2H, J ) 8.1 Hz), 7.21 (t, 1H, J ) 0.8
Hz), 7.10 (d, 1H, J ) 7.9 Hz), 7.05 (d, 1H, J ) 7.2 Hz), 6.89 (t,
1H, J ) 7.2 Hz), 3.46-3.42 (m, 2H), 2.91-2.86 (m, 1H) 2.43
(s, 3H), 1.98-1.90 (m, 2H), 1.55-1.47 (m, 1H), 1.42-1.32 (m,
1H), 0.94 (t, 3H, 7.4 Hz); 13C NMR (125 MHz, CDCl3) δ 144.6,
144.6, 137.1, 129.9, 128.7, 128.1, 127.9, 125.5, 123.6, 120.4,
51.6, 37.1, 35.4, 21.5, 20.6, 13.8. Anal. Calcd for C18H21NOS:
C, 72.20; H, 7.06. Found: C, 72.09; H, 7.05.
119.7, 51.0, 49.2, 34.7, 28.5, 21.4. Anal. Calcd for C19H23
NOS: C, 72.88; H, 7.39. Found: C, 73.06; H, 7.33.
-
Flash chromatographic purification gave the analytical
sample of 6b as a yellow oil: 1H (500 MHz, CDCl3) δ 7.93 (d,
2H, J ) 8.2 Hz), 7.35 (d, 2H, J ) 8.1 Hz), 7.25-7.19 (m, 2H),
7.11 (d, 1H, J ) 7.7 Hz), 6.91 (t, 1H, J ) 7.0 Hz), 3.46-3.40
(m, 2H), 2.91-2.86 (m, 1H), 2.44 (s, 3H), 2.08-2.01 (m, 1H),
1.74-1.67 (m, 1H), 1.45-1.36 (m, 1H), 1.35-1.26 (m, 1H), 0.95
(t, 3H, J ) 7.4 Hz); 13C NMR (125 MHz, CDCl3) δ 145.3, 144.7,
136.1, 129.9, 128.9, 128.0, 125.8, 125.6, 123.7, 120.4, 51.8, 33.6,
33.4, 21.5, 19.4, 14.0. Anal. Calcd for C18H21NOS: C, 72.20;
H, 7.06. Found: C, 72.11; H, 6.95.
Recrystallization from hexane/ethyl acetate gave an analyti-
cal sample of 9b: mp 115-116 °C; 1H NMR 500 MHz, CDCl3)
δ 7.97 (d, 2H, J ) 8.2 Hz), 7.36 (d, 2H, J ) 8.1 Hz), 7.25-7.20
(m, 2H), 7.14 (d, 1H, J ) 7.6 Hz), 6.92 (t, 1H, J ) 7.2 Hz),
3.70 (dd, 1H, J ) 6.6, 14.2 Hz), 3.57 (dd, 1H, J ) 6.2, 14.2
Hz), 3.03 (dd, 1H, J ) 6.4 Hz), 2.45 (s, 3H), 1.00 (s, 9H); 13C
NMR (125 MHz, CDCl3) δ 145.6, 144.3, 136.9, 129.8, 129.7,
128.4, 128.1, 125.0, 120.4, 53.6, 46.5, 34.3, 28.5, 21.5. Anal.
Calcd for C19H23NOS: C, 72.88; H, 7.39. Found: C, 72.63; H,
7.24.
(()-(2S*,4R*)-3,4-Dih yd r o-4-(1-m eth yleth yl)-2-(4-m eth -
ylp h en yl)-2λ4-2,1-ben zoth ia zin e 2-Oxid e (7a ) a n d (()-
(2S*,4S*)-3,4-Dih yd r o-4-(1-m eth yleth yl)-2-(4-m eth ylp h e-
n yl)-2λ4-2,1-ben zoth ia zin e 2-Oxid e (7b). Meth od B. Chro-
matography solvent: 6:1 hexane/ethyl acetate. Combined
yield: 78%. Recrystallization from hexane/ethyl acetate gave
an analytical sample of 7a : mp 136-137 oC; 1H NMR (500
MHz, CDCl3) δ 7.82 (d, 2H, J ) 8.0 Hz), 7.30 (d, 2H, J ) 8.1
Hz), 7.19 (t, 1H, J ) 7.8 Hz), 7.10 (d, 1H, J ) 7.9 Hz), 7.02 (d,
1H, J ) 7.5 Hz), 6.86 (t, 1H, J ) 7.4 Hz), 3.67 (dd, 1H, J ) 5.1
Hz, J ) 13.6 Hz), 3.06 (dd, 1H, J ) 4.8, 13.6 Hz), 2.81-2.78
(m, 1H), 2.51-2.44 (m, 1H), 2.40 (s, 3H), 1.33 (d, 3H, J ) 6.6
Hz), 0.91 (d, 3H, J ) 6.6 Hz); 13C NMR (125 MHz, CDCl3) δ
145.1, 144.3, 137.7, 129.7, 129.0, 128.3, 128.0, 124.6, 123.3,
119.7, 49.8, 44.8, 28.0, 21.8, 21.4, 20.1. Anal. Calcd for C18
H21NOS: C, 72.20; H, 7.06. Found: C, 72.33; H, 7.15.
Flash chromatographic purification gave the analytical
sample of 7b as a yellow oil: 1H (500 MHz, CDCl3) δ 7.96 (d,
2H, J ) 8.3 Hz), 7.36 (d, 2H, J ) 8.1 Hz), 7.21-7.17 (m, 2H),
7.11 (dd, 1H, J ) 1.4, 8.8 Hz), 6.92 (dt, 1H, J ) 1.4, 7.6 Hz),
3.37 (dd, 1H, J ) 4.1, 12.5 Hz), 3.27-3.23 (m, 1H), 2.94 (dd,
1H, J ) 12.09, 12.11 Hz), 2.71-2.65 (m, 1H), 2.44 (s, 3H), 1.05
(d, 3H, J ) 6.8 Hz), 0.77 (d, 3H, J ) 6.8 Hz); 13C NMR (125
MHz, CDCl3) δ 145.5, 144.7, 135.9, 129.9, 128.9, 127.9, 126.1,
124.9, 124.0, 120.4, 48.0, 40.0, 26.7, 21.5, 21.1, 16.8. Anal.
Calcd for C18H21NOS: C, 72.20; H, 7.06. Found: C, 71.88;
H,7.15.
(()-(2S*,4R*)-3,4-Dih yd r o-2-(4-m eth ylp h en yl)-4-(tr im -
eth ylsilyl)-2λ4-2,1-ben zoth ia zin e 2-Oxid e (10a ) a n d (()-
(2S*,4S*)-3,4-Dih yd r o-2-(4-m eth ylp h en yl)-4-(tr im eth yls-
ilyl)-2λ4-2,1-b en zot h ia zin e 2-Oxid e (10b ). Met h od B.
Chromatography solvent: 9:1 hexene/ethyl acetate. Yield:
35%. Recrystallization from hexane/ethyl acetate gave an
analytical sample of 10a : mp 132-133 °C. 1H NMR (250
MHz, CDCl3) δ 7.86 (d, 2H, J ) 8.2 Hz), 7.33 (d, 2H, J ) 8.2
Hz), 7.17-7.06 (m, 2H), 6.97 (d, 1H, J ) 6.7 Hz), 6.86 (dt, 1H,
J ) 1.2, 7.2 Hz), 3.56 (dd, 1H, J ) 3.1, 12.6 Hz), 3.14 (dd, 1H,
J ) 6.6, 12.6 Hz), 2.78 (dd, 1H, J ) 3.1, 6.5 Hz), 2.44 (s, 3H),
0.17 (s, 9H); 13C NMR (CDCl3, 125 MHz) δ 144.8, 144.8, 136.7,
129.8, 128.7, 127.6, 126.8, 123.7, 123.3, 120.1, 49.3, 28.4, 21.5,
-1.8. Anal. Calcd for
Found: C, 65.43; H, 6.94.
C18H23NOSSi: C, 65.61; H, 7.04.
Flash chromatographic purification gave 10b as a solid.
Recrystallization from hexane/ethyl acetate gave an analytical
1
sample: mp 129-130 °C; H NMR (250 MHz, CDCl3) δ 7.96
(d, 2H, J ) 8.2 Hz), 7.38 (d, 2H, J ) 8.2 Hz), 7.27-7.17 (m,
2H), 7.08 (dd, 1H, J ) 1.4, 8.0 Hz), 6.86 (dt, 1H, J ) 1.4, 7.5
Hz), 3.35 (dd, 1H, J ) 4.0, 12.1 Hz), 3.06 (dd, 1H, J ) 3.9,
15.0 Hz), 2.73 (dd, 1H, J ) 12.1, 15.0 Hz), 2.46 (s, 3H), 0.24
(s, 9H); 13C NMR (CDCl3, 125 MHz) δ 145.9, 144.8, 135.2,
129.9, 129.1, 128.2, 127.4, 124.4, 123.3, 120.0, 49.0, 22.3, 21.6,
-1.2. Anal. Calcd for C18H23NOSSi: C, 65.61; H, 7.04.
Found: C, 65.87; H, 6.80.
(()-(2S*,4R*)-3,4-Dih yd r o-4-eth yl-4-m eth yl-2-(4-m eth -
ylp h en yl)-2λ4-2,1-b en zot h ia zin e 2-Oxid e (11a ) a n d (()-
(2S*,4S*)-3,4-Dih ydr o-4-eth yl-4-m eth yl-2-(4-m eth ylph en yl)-
2λ4-2,1-ben zoth iazin e 2-Oxide (11b). Meth od B. Chromato-
graphy solvent: 9:1 hexene/ethyl acetate. Yield: 46%. Re-
crystallization from hexane/ethyl acetate gave an analytical
(()-(2S*,4R*)-3,4-Dih yd r o-2-(4-m eth ylp h en yl)-4-p h en -
yl-2λ4-2,1-ben zoth ia zin e 2-Oxid e (8a ) a n d (()-(2S*,4S*)-
3,4-Dih ydr o-2-(4-m eth ylph en yl)-4-ph en yl-2λ4-2,1-ben zoth i-
a zin e 2-Oxid e (8b). Meth od B. Chromatography solvent
(MPLC): 9:1 hexane/ethyl acetate. Combined yield: 62%.
Recrystallization from hexane/ethyl acetate gave an analytical
1
sample of 11a : mp 91-92 °C; H NMR (500 MHz, CDCl3) δ
1
sample of 8a : mp 145-146 °C; H NMR (500 MHz, CDCl3) δ
7.86 (d, 2H, J ) 8.2 Hz), 7.32 (d, 2H, J ) 8.1 Hz), 7.25 (dd,
1H, J ) 1.0, 8.6 Hz), 7.18 (dt, 1H, J ) 1.0, 8.0 Hz), 7.11 (dd,
1H, J ) 0.9, 8.1 Hz), 6.92 (dt, 1H, J ) 1.0, 7.7 Hz), 3.50 (d,
1H, J ) 13.4 Hz), 2.88 (d, 1H, J ) 13.4 Hz), 2.42 (s, 3H), 2.08-
2.03 (m, 1H), 1.93-1.83 (m, 1H), 1.40 (s, 3H), 0.96 (t, 3H, J )
7.4 Hz); 13C NMR (125 MHz, CDCl3) δ 144.4, 144.1, 137.6,
129.8, 129.6, 128.5, 128.0, 125.2, 123.8, 120.4, 56.2, 38.9, 32.6,
25.2, 21.5, 8.9. Anal. Calcd for C18H21NOS: C, 72.20; H, 7.07.
Found: C, 72.25; H, 6.69.
7.94 (d, 2H, J ) 8.3 Hz), 7.59-7.23 (m, 7H), 7.20-7.17 (m,
1H), 7.12 (dd, 1H, J ) 1.2, 7.9 Hz), 6,76 (dt, 1H, J ) 1.3, 7.6
Hz), 6.64 (d, 1H, J ) 7.7 Hz), 4.74 (dd, 1H, J ) 4.2, 14.1 Hz),
3.52 (dd, 1H, J ) 4.3, 12.0 Hz), 3.20 (dd, 1H, J ) 14.04, 12.1
Hz), 2.43 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 145.1, 145.1,
140.2, 134.8, 130.0, 129.2, 129.0, 128.9, 128.4, 128.2, 127.7,
125.2, 123.6, 120.4, 53.1, 40.7, 21.6. Anal. Calcd for C21H19
NOS: C, 75.68; H, 5.75. Found: C, 75.47; H, 5.83.
-
Recrystallization from hexane/ethyl acetate gave an analyti-
cal sample of 8b: mp 175-176 °C. 1H NMR (500 MHz, CDCl3)
δ 7.97 (d, 2H, J ) 8.3 Hz), 7.38-7.16 (m, 9H), 6.79 (dd, 1H, J
Flash chromatographic purification gave an analytical
sample of 11b as a yellow oil: 1H NMR (500 MHz, CDCl3) δ
7.94 (d, 2H, J ) 8.2 Hz), 7.36 (d, 2H, J ) 8.1 Hz), 7.25-7.16

6850 J . Org. Chem., Vol. 63, No. 20, 1998
Harmata and Kahraman
(m, 2H), 7.11 (d, 1H, J ) 7.7 Hz), 6.93 (dt, 1H, J ) 0.9, 7.6
Hz), 3.25 (d, 1H, J ) 13.2 Hz), 3.17 (d, 1H, J ) 13.3 Hz), 2.44
(s, 3H), 1.98-1.89 (m, 1H), 1.79-1.70 (m, 1H), 1.55 (s, 3H),
0.74 (t, 3H, J ) 7.3 Hz); 13C NMR (125 MHz, CDCl3) δ 144.6,
144.2, 137.0, 129.0, 128.7, 128.7, 127.8, 124.9, 124.6, 120.9,
56.5, 38.9, 33.4, 28.2, 21.5, 8.5. Anal. Calcd for C18H21NOS:
C, 72.20; H, 7.07. Found: C, 72.45; H, 7.14.
(()-(2S*,4R*)-3,4-Dih yd r o-4-m eth yl-4-(1-m eth yleth yl)-
2-(4-m eth ylp h en yl)-2λ4-2,1-ben zoth ia zin e 2-Oxid e (12a )
an d (()-(2S*,4S*)-3,4-Dih ydr o-4-m eth yl-4-(1-m eth yleth yl)-
2-(4-m eth ylp h en yl)-2λ4-2,1-ben zoth ia zin e 2-Oxid e (12b).
Meth od B. Chromatography solvent: 6:1 hexane/ethyl ac-
etate. Yield: 33%. Flash chromatographic purification gave
an analytical sample of 12a as a yellow oil: 1H NMR (500
MHz, CDCl3) δ 7.80 (d, 2H, J ) 8.3 Hz), 7.30 (d, 2H, J ) 8.0
Hz), 7.22-7.19 (m, 2H), 7.14 (dd, 1H, J ) 1.2, 8.2 Hz), 6.91
(dt, 1H, J ) 1.3, 7.7 Hz), 3.70 (d, 1H, J ) 13.8 Hz), 2.78 (d,
1H, J ) 13.8 Hz), 2.67-2.61 (m, 1H), 2.41 (s, 3H), 1.30 (s, 3H),
1.12 (d, 3H, J ) 6.7 Hz), 0.79 (d, 3H, J ) 6.8 Hz); 13C NMR
(125 MHz, CDCl3) δ 144.7, 144.2, 138.6, 129.8, 129.5, 128.3,
128.0, 126.5, 123.7, 119.8, 56.2, 42.1, 30.8, 21.5, 19.3, 17.9, 17.5.
Anal. Calcd for C19H23NOS: C, 72.80; H, 7.39: Found: C,
72.57; H, 7.41.
Recrystallization from hexane/ethyl acetate gave an analyti-
cal sample of 12b as white crystals: mp 139-140 °C; 1H NMR
(500 MHz, CDCl3) δ 7.97 (d, 2H, J ) 8.3 Hz), 7.37 (d, 2H, J )
8.1 Hz), 7.22 (dd, 1H, J ) 1.2, 7.8 Hz), 7.15 (dt, 1H, J ) 1.4,
7.9 Hz), 7.1 (dd, 1H, J ) 1.3, 7.9 Hz), 6.92 (dt, 1H, J ) 1.4, 7.8
Hz), 3.26 (d, 1H, J ) 13.5 Hz), 3.23 (d, 1H, J ) 13.5 Hz), 2.45-
2.43 (m, 1H), 2.45 (s, 3H), 1.52 (s, 3H), 0.86 (d, 3H, J ) 6.8
Hz), 0.63 (d, 3H, J ) 6.8 Hz); 13C NMR (125 MHz, CDCl3) δ
144.6, 143.9, 136.7, 129.9, 129.4, 128.8, 127.6, 125.4, 124.9,
120.9, 54.0, 41.8, 34.2, 25.6, 21.5, 17.6, 17.0. Anal. Calcd for
°C; major isomer 16a 1H NMR (500 MHz, CDCl3) δ 7.89 (d,
2H, J ) 8.3 Hz), 7.32 (d, 2H, J ) 8.1 Hz), 7.24 (dd, 1H, J )
1.5, 7.7 Hz), 7.17 (dt, 1H, J ) 1.5, 7.9 Hz), 7.09 (dd, 1H, J )
1.3, 7.9 Hz), 6.91-6.87 (m, 1H), 3.20 (q, 1H, J ) 7.2 Hz), 2.42
(s, 3H), 1.63 (s, 3H), 1.41 (s, 3H), 0.81 (d, 1H, J ) 7.2 Hz);
minor isomer 16b 1H NMR (500 MHz, CDCl3) δ 7.80 (d, 2H, J
) 8.3 Hz), 7.31 (d, 2H, J ) 7.8 Hz), 7.27 (dd, 1H, J ) 1.5, 7.9
Hz), 7.15 (dt, 1H, J ) 1.6, 7.7 Hz), 7.04 (dd, 1H, J ) 1.3, 7.9
Hz), 6.91-6.87 (m, 1H), 2.96 (q, 1H, J ) 6.9 Hz), 2.41 (s, 3H),
1.44 (s, 6H), 1.35 (d, 3H, J ) 6.9 Hz); 13C NMR (125 MHz,
CDCl3) δ 144.5, 145.0, 143.4, 143.2, 135.3, 134.2, 131.2, 130.2,
129.8, 129.6, 129.6, 129.5, 129.5, 127.9, 125.2, 124.9, 123.9,
120.9, 120.6, 61.6, 59.4, 38.7, 38.4, 30.3, 27.2, 26.5, 24.0, 21.5,
12.9, 8.5. Anal. Calcd for C18H21NOS: C, 72.20; H, 7.07.
Found: C, 72.40; H, 6.90.
(()-(2S*,3R*)-3,4-Dih yd r o-3-et h yl-4,4-d im et h yl-2-(4-
m eth ylp h en yl)-2λ4-2,1-ben zoth ia zin e 2-Oxid e (17a ) a n d
(()-(2S*,3S*)-3,4-Dih yd r o-3-eth yl-4,4-d im eth yl-2-(4-m eth -
ylp h en yl)-2λ4-2,1-ben zoth ia zin e 2-Oxid e (17b). Meth od
B. Chromatography solvent (MPLC): 10% ethyl acetate in
hexanes. Combined yield: 53%. Recrystallization from hex-
ane/ethyl acetate gave an analytical sample of a mixture of
isomers: mp 34-36 °C; major isomer 17a 1H NMR (500 MHz,
CDCl3) δ 7.90 (dd, 2H, J ) 1.6, 6.8 Hz), 7.28 (d, 1H, J ) 7.9
Hz), 7.18 (dd, 2H, J ) 1.5, 7.7 Hz), 7.13-7.08 (m, 2H), 6.86-
6.84 (m, 1H), 2.91 (dd, 1H, J ) 2.87, 6.57 Hz), 2.38 (s, 3H),
1.58 (s, 3H), 1.41 (s, 3H), 1.14-1.05 (m, 2H), 0.51 (t, 3H, J )
7.52 Hz); minor isomer: 17b 1H NMR (500 MHz, CDCl3) δ
7.77 (d, 2H, J ) 6.8 Hz), 7.27 (d, 2H, J ) 7.5 Hz), 7.22 (dd,
1H, J ) 1.5, 7.9 Hz), 7.08-7.04 (m, 1H), 6.98 (dd, 1H, J ) 1.1,
7.9 Hz), 6.84-6.82 (m, 1H), 2.74 (dd, 1H, J ) 3.2, 5.7 Hz), 2.36
(s, 3H), 2.13-2.07 (m, 1H), 1.86-1.85 (m, 1H), 1.43 (s, 3H),
1.41 (s, 3H), 0.49 (t, 3H, J ) 7.62 Hz); 13C NMR (125 MHz,
CDCl3), δ 144.6, 144.5, 143.7, 143.0, 136.2 134.5, 131.5, 130.4,
130.3, 129.9, 129.6, 129.3, 127.9, 127.8, 125.3, 124.5, 123.8,
123.80, 120.9, 120.6, 69.2, 66.8, 39.6, 39.4, 30.3, 27.3, 25.9, 24.5,
21.6, 20.5, 17.3, 14.7, 13.2. Anal. Calcd for C19H23NOS: C,
72.84; H, 7.34. Found: C, 72.52; H, 7.16.
C
19H23NOS: C, 72.80; H, 7.39. Found: C, 72.54; H, 7.47.
(()-(2S*,4R*)-3,4-Dih yd r o-4-m eth yl-4-(1,1-d im eth yleth -
yl)-2-(4-m eth ylph en yl)-2λ4-2,1-ben zoth iazin e 2-Oxide (13a)
a n d (()-(2S*,4S*)-3,4-Dih yd r o-4-m eth yl-4-(1,1-d im eth yl-
eth yl)-2-(4-m eth ylp h en yl)-2λ4-2,1-ben zoth ia zin e 2-Oxid e
(13b). Meth od B. Chromatography solvent (MPLC): 9:1
hexanes/ethyl acetate. Yield: 57%. Recrystallization from
hexane/ethyl acetate gave an analytical sample of 13a : mp
(()-(2S*,3S*,4R*)-3,4-Dih yd r o-3,4-d im eth yl-2-(4-m eth -
ylp h en yl)-2λ4-2,1-ben zoth ia zin e 2-Oxid e (22a ). Meth od
A. Chromatography solvent: 4:1 hexanes/ethyl acetate. Com-
bined yield: 62%. Recrystallization from hexane/ethyl acetate
1
136-137 °C; H NMR (500 MHz, CDCl3) δ 7.77 (d, 2H, J )
8.3 Hz), 7.29-7.27 (m, 3H), 7.20 (dt, 1H, J ) 1.4, 8.0 Hz), 7.11
(dd, 1H, J ) 1.2, 7.9 Hz), 6.90 (dt, 1H, J ) 1.3, 7.8 Hz), 3.85
(d 1H, J ) 14.8 Hz), 2.82 (d, 1H, J ) 14.8 Hz), 2.39 (s, 3H),
1.39 (s, 3H), 1.11 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 146.3,
143.9, 139.9, 129.7, 128.0, 127.7, 127.2, 123.6, 119.8, 56.6, 46.0,
37.4, 27.0, 26.0, 21.4. Anal. Calcd for C20H25NOS: C, 73.35;
H, 7.69. Found: C, 73.46; H, 7.86.
1
gave an analytical sample of 22a : mp 138-139 °C; H NMR
(500 MHz, CDCl3) δ 7.90 (d, 2H, J ) 8.3 Hz), 7.34 (d, 2H, J )
8.2 Hz), 7.19 (dt, 1H, J ) 1.4, 8.0 Hz), 7.09-7.07 (m, 2H), 6.91
(dt, 1H, J ) 1.2, 7.4 Hz), 3.25-3.19 (m, 1H), 3.09-3.03 (m,
1H), 2.44 (s, 3H), 1.54 (d, 3H, J ) 7.3 Hz), 0.97 (d, 3H, J ) 7.0
Hz); 13C NMR (125 MHz, CDCl3) δ 144.7, 143.4, 133.3, 130.3,
129.6, 128.0, 127.5, 125.8, 123.7, 120.7, 57.2, 38.5, 21.5, 19.4,
15.8. Anal. Calcd for C17H19NOS: C, 71.53; H, 6.71. Found:
C, 71.60; H, 6.80.
Recrystallization from hexane/ethyl acetate gave an analyti-
cal sample of 13b: mp 137-138 °C; 1H NMR (500 MHz, CDCl3)
δ 8.02 (d, 2H, J ) 8.3 Hz), 7.42-7.38 (m, 3H), 7.15 (dt, 1H, J
) 1.4, 8.0 Hz), 7.06 (dd, 1H, J ) 1.4, 7.8 Hz), 6.89 (dt, 1H, J
) 1.4, 8.1 Hz), 3.65 (d, 1H, J ) 13.7 Hz), 3.31 (d, 1H, J ) 13.7
Hz), 2.46 (s, 3H), 1.63 (s, 3H), 0.92 (s, 9H); 13C NMR (125 MHz,
CDCl3) δ 144.7, 144.2, 135.8, 130.0, 128.6, 128.4, 128.2, 127.9,
125.8, 120.4, 59.6, 45.1, 39.3, 26.5, 25.9, 21.6. Anal. Calcd
for C20H25NOS: C, 73.35; H, 7.69. Found: C, 73.39; H, 7.69.
(()-N-P h en yl-S-(3-ch lor o-2,2,3-t r im et h ylb u t yl)-S-(4-
m eth ylp h en yl)su lfoxim in e (15) was formed as a side prod-
uct during the preparation of 13: chromatography solvent 10:1
(()-(2S*,3S*,4S*)-3,4-Dih yd r o-3,4-d im eth yl-2-(4-m eth -
ylp h en yl)-2λ4-2,1-b en zot h ia zin e 2-Oxid e (23a ) a n d (()-
(2S*,3R*,4R*)-3,4-Dih yd r o-3,4-d im eth yl-2-(4-m eth ylp h e-
n yl)-2λ4-2,1-b en zot h ia zin e 2-Oxid e (23b ). Met h od A.
Chromatography solvent: 6:1 hexanes/ethyl acetate. Com-
bined yield: 78%. Recrystallization from hexane/ethyl acetate
1
gave an analytical sample of 23a : mp 162-163 °C; H NMR
(500 MHz, CDCl3) δ 7.95 (dd, 2H, J ) 1.7, 8.3 Hz), 7.36 (d,
2H, J ) 8.0 Hz), 7.06 (dd, 1H, J ) 1.2, 8.2 Hz), 6.91 (dt, 1H,
J ) 1.3, 7.5 Hz), 3.95-3.90 (m, 1H), 3.18-3.13 (m, 1H), 2.45
1
hexane/ethyl acetate; yield: 6%; H NMR (500 MHz, CDCl3)
(s, 3H), 1.51 (d, 3H, J ) 7.1 Hz), 0.66 (d, 3H, J ) 7.0 Hz); 13
C
δ 7.80 (d, 2H, J ) 8.3 Hz), 7.27 (d, 2H, J ) 8.2 Hz), 7.07 (dt,
2H, J ) 1.8, 7.6 Hz), 6.97 (dt, 2H, J ) 1.0, 8.4 Hz), 6.81 (t, 1H,
J ) 7.2 Hz), 3.68 (d, 1H, J ) 14.4 Hz), 3.56 (d, 1H, J ) 14.3
Hz), 2.37 (s, 3H), 1.56 (s, 3H), 1.54 (s, 6H), 1.31 (s 3 H); 13C
NMR (125 MHz, CDCl3) δ 145.2, 143.6, 137.7, 130.0, 128.8,
128.8, 123.3, 121.2, 78.4, 64.0, 43.7, 28.0, 27.8, 22.2, 21.5, 21.2.
(()-(2S*,3R*)-3,4-Dih yd r o-3,4,4-t r im et h yl-2-(4-m et h -
ylp h en yl)-2λ4-2,1-b en zot h ia zin e 2-Oxid e (16a ) a n d (()-
(2S*,3S*)-3,4-d ih yd r o-3,4,4-tr im eth yl-2-(4-m eth ylp h en yl)-
2λ4-2,1-ben zoth iazin e 2-Oxide (16b). Meth od B. Chromato-
graphy solvent (MPLC): 9:1 hexane/ethyl acetate. Combined
yield: 53%. Recrystallization from hexane/ethyl acetate gave
an analytical sample of the mixture of isomers: mp 124-125
NMR (125 MHz, CDCl3) δ 144.9, 144.4, 131.9, 130.4, 129.7,
128.0, 125.9, 124.5, 122.9, 120.5, 54.9, 31.2, 21.6, 15.6, 9.1.
Anal. Calcd for C17H19NOS: C, 71.53; H, 6.71. Found: C,
71.57; H, 6.71.
Further purification of the mixture on a Chromatotron (1
mm plate, 2% ethyl acetate in hexane) gave an oil, 23b: 1H
NMR (500 MHz, CDCl3) δ 7.77 (d, 2H, J ) 8.3 Hz), 7.28 (d,
2H, J ) 8.0 Hz), 7.12 (dt, 1H, J ) 1.5, 7.5 Hz), 7.06 (d, 1H, J
) 8.0 Hz), 6.98-6.96 (m, 1H), 6.84 (dt, 1H, J ) 1.2, 7.4 Hz),
3.22-3.16 (m, 2H), 2.38 (s, 3H), 1.39 (d, 3H, J ) 7.2 Hz), 1.31
(d, 3H, J ) 6.8 Hz); 13C NMR (125 MHz, CDCl3) δ 144.4, 135.7,
130.2, 129.7, 129.7, 129.5, 129.1, 127.9, 127.6, 123.0, 120.3,

Steric Effects of Alkene Substitution
J . Org. Chem., Vol. 63, No. 20, 1998 6851
55.1, 36.8, 21.4, 15.9, 9.6. Anal. Calcd for C17H19NOS: C,
71.53; H, 6.71. Found: C, 71.61; H, 6.83.
N-P h en yl-S-(4-m eth ylp h en yl)-S-(2-ch lor o-2-m eth yl-1,1-
d im eth yleth yl)p r op ylsu lfoxim in e (21). Meth od B. Chro-
matography solvent: 7:1 hexane/ethyl acetate. Yield: 48%.
21: mp 118-120 °C; 1H NMR (500 MHz, CDCl3) δ 7.50 (d,
2H, J ) 8.3 Hz), 7.29-7.24 (m, 2H), 7.20 (d, 2H, J ) 8.0 Hz),
7.16 (dt, 1H, J ) 7.6, 1.4 Hz), 6.93-6.89 (m, 2H), 3.28 (s, 1H),
2.38 (s, 3H), 1.80 (s, 3H), 1.78 (s, 3H), 1.22 (s, 9H); 13C NMR
(125 MHz, CDCl3) δ 144.6, 143.8, 137.0, 129.5, 128.0, 126.1,
122.4, 120.2, 76.1, 41.2, 37.2, 32.0, 28.9, 24.2, 21.4. Anal. Calcd
for C21H28ClNOS: C, 66.73; H, 7.47. Found: C, 67.0; H, 7.70.
(()-N-P h en yl-S-)4-m et h ylp h en yl)-S-(3-ch lor o-2,3-d i-
m eth ylbu tyl)su lfoxim in e (14) was obtained in the prepara-
tion of 12. Chromatography solvent: gradient MPLC using
hexane/ethyl acetate as eluent. Yield: 11% as a mixture in a
ratio of 1.2:1. Major isomer: 1H NMR (500 MHz, CDCl3) δ
7.78 (d, 2H, J ) 8.2 Hz), 7.28 (d, 2H, J ) 8.0 Hz), 7.09-7.06
(m, 2H), 6.98-6.96 (m, 2H), 6.83-6.80 (m, 1H), 3.75 (dd, 1H,
J ) 0.61, 14.2 Hz), 3.04 (dd, 1H, J ) 8.8, 14.3 Hz), 2.57-2.52
(m, 1H), 2.38 (s, 3H), 1.59 (s, 3H), 1.50 (s, 3H), 1.13 (d. 3H, J
) 6.78 Hz); 13C (125 MHz, CDCl3) δ 145.2, 144.0, 135.8, 130.2,
129.2, 128.8, 123.2, 121.2, 73.3, 61.6, 40.7, 31.4, 29.7, 21.5, 16.1.
Minor isomer: 1H NMR (500 MHz, CDCl3) δ 7.80 (d, 2H, J )
8.3 Hz), 7.30 (d, 2H, J ) 8.0 Hz), 7.11-7.08 (m, 2H), 6.99 (dd,
2H, J ) 1.1, 8.5 Hz), 6.85-6.82 (m, 1H), 3.67 (d, 1H, J ) 14.4
Hz), 3.26 (dd, 1H, J ) 8.9, 14.5 Hz), 2.39 (s, 3H), 2.28-2.23
(m, 1H), 1.44 (s, 3H), 1.43 (s, 3H), 1.31 (d, 3H, J ) 6.8 Hz).
Anal. Calcd for C19H24ClNOS: C, 65.25; H, 6.86. Found: C,
65.47; H, 6.84.
Ack n ow led gm en t. We thank the donors of the
Petroleum Research Fund, administered by the Ameri-
can Chemical Society, for support of this work. We
thank the National Science Foundation for partial
support of the NMR (PCM-8115599) facility at the
University of MissourisColumbia and for partial fund-
ing for the purchase of a 500 MHz spectrometer (CHE-
89-08304) and an X-ray diffractometer (CHE-90-11804).
We thank Dr. Darin E. J ones for the preparation of 10
and Dr. Charles L. Barnes for X-ray data.
(()-N-P h en yl-S-(4-m et h ylp h en yl)-S-[1-(m et h ylet h yl)-
2-m eth yl-2-ch lor op r op yl]su lfoxim in e (20). Meth od B.
Chromatography solvent: 8:1 hexane/ethyl acetate. Yield:
34% as a mixture of isomers in a ratio of 2.4:1. Major isomer:
1
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C NMR for
5-17 and 20-23, selected IR and MS data, and X-ray
crystallographic data for 9a , 10b, 15, and 22 (94 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
mp 79-80 °C; H NMR (500 MHz, CDCl3) δ 7.99 (d, 2H, J )
8.4 Hz), 7.36 (d, 2H, J ) 8.1 Hz), 7.25 (dd, 2H, J ) 7.7, 1.5
Hz), 7.18 (dt, 1H, J ) 7.8, 1.5 Hz), 7.09 (dd, 1H, J ) 7.9, 1.4
Hz), 6.9 (dt, 1H, J ) 7.5, 1.4 Hz), 3.26 (d, 1H, J ) 1.7 Hz),
2.46 (s, 3H), 2.04-1.99 (m, 1H), 1.73 (s, 3H), 1.63 (s, 3H), 0.90
(d, 3H, J ) 7.4 Hz), 0.44 (d, 3H, J ) 7.3 Hz); 13C NMR (125
MHz, CDCl3) δ 144.6, 143.7, 130.3, 129.7, 127.6, 123.8, 123.2,
121.0, 72.4, 39.6, 33.6, 29.1, 27.6, 21.6, 18.1. Anal. Calcd for
C
20H26ClNOS: C, 66.00; H, 7.20. Found: C, 66.37; H, 7.31.
J O980503B