Stereospecific Grignard reactions of cholesteryl 1-alkenesulfinate esters: Application of the Andersen protocol to the preparation of non-racemic α,β-unsaturated sulfoxides

Article abstract of DOI:10.1139/v03-002

Enantiomerically enriched α,β-unsaturated sulfinate esters of (-)-cholesterol undergo stereospecific substitutions at sulfur when treated in benzene at 6°C with Grignard reagents. Sulfoxides with ees of 85-99.5% are obtained when enantiopure sulfinates are used. The substitution reactions proceed with inversion of sulfur configuration. Enantiomerically pure cholesteryl (E)-2-carbomethoxyethenesulfinate is not a suitable reactant under the Grignard reaction conditions. It is suggested that the ester group induces unwanted reactions significantly lowering both the yield and sulfur stereogenicity.

Full text of DOI:10.1139/v03-002

423
Stereospecific Grignard reactions of cholesteryl
1-alkenesulfinate esters: Application of the
Andersen Protocol to the preparation of non-
racemic ␣,␤-unsaturated sulfoxides
Rick R. Strickler, John M. Motto, Craig C. Humber, and Adrian L. Schwan
Abstract: Enantiomerically enriched α,β-unsaturated sulfinate esters of (–)-cholesterol undergo stereospecific substitu-
tions at sulfur when treated in benzene at 6°C with Grignard reagents. Sulfoxides with ees of 85–99.5% are obtained
when enantiopure sulfinates are used. The substitution reactions proceed with inversion of sulfur configuration. Enan-
tiomerically pure cholesteryl (E)-2-carbomethoxyethenesulfinate is not a suitable reactant under the Grignard reaction
conditions. It is suggested that the ester group induces unwanted reactions significantly lowering both the yield and
sulfur stereogenicity.
Key words: sulfinate, sulfoxide, Grignard reagents, stereospecific, unsaturated.
Résumé : Lorsqu’on les traite avec des réactifs de Grignard, dans le benzène à 6 °C, les sulfinates α,β-insaturés énan-
tiomériquement enrichis du (–)-chlolestérol subissent des réactions de substitution stéréospécifiques au niveau du
soufre. Des sulfoxydes avec des ee de 95 à 99,5 % sont obtenus lorsqu’on utilise des sulfinates énantiomériquement
purs. Les réactions de substitution se produisent avec inversion de configuration au niveau du soufre. Le (E)-2-carbo-
méthoxyéthènesulfinate de cholestéryle énantiomériquement pur n’est pas un réactif approprié dans les conditions utili-
sées avec les réactifs de Grignard. Il est suggéré que le groupe ester induit des réactions indésirables qui abaissent de
façon significative tant le rendement que la stéréogénicité au niveau du soufre.
Mots clés : sulfinate, sulfoxyde, réactifs de Grignard, stéréospécifique, insaturé.
[Traduit par la Rédaction] Strickler et al. 430
Introduction
as diacetone-D-glucose (DAG), (5b, 9) (1R,2S)-(–)-trans-2-
phenyl-cyclohexanol (10), and cholesterol (7, 11). The major-
ity of recent applications of this protocol have tended to em-
ploy either DAG (4, 5) or (–)-menthol (6).
Enantioentriched sulfoxides can induce the introduction of
carbon chirality into organic molecules by a number of means
including carbanionic chemistry, Diels–Alder reactions and
chiral ligand complexation (1–4). In these reactions it is the
chirality at the sulfur center that plays a pivotal role in con-
trolling the stereochemical outcome of the reaction. As such,
a great deal of effort has gone into developing reliable and ef-
ficient methods for the synthesis of enantiopure sulfoxides.
One mode of preparation of chiral sulfoxides that has enjoyed
sustained popularity (4–7) is based on a protocol introduced
by Andersen (8a). The original Andersen procedure involves
treating a sulfinyl chloride with (–)-menthol to generate a
diastereomeric mixture of menthyl sulfinate esters which, fol-
lowing a separation step, undergo organometallic substitution
to afford enantiomerically pure sulfoxides (Scheme 1,
R*OH = menthol). Since the original Andersen method was
first introduced several improvements have been advanced.
These typically involve the use of other chiral alcohols such
To this point, the application of cholesterol to this chemis-
try has been focused on preparing methanesulfinate esters
(11). The propensity of the large cholesteryl auxiliary to crys-
tallize provided the driving force for the sulfinate separation
by recrystallization and the eventual formation of enantiopure
methanesulfinates and methyl sulfoxides (11). Our group has
established a practical method for the synthesis of 1-
alkenesulfinyl chlorides (12, 13) and while investigating their
conversion to enantiopure α,β-unsaturated sulfinate esters, has
found that cholesterol is a preferred chiral alcohol (14). The
aptitude for cholesterol derivatives to crystallize provided a
benefit no other alcohols could equal. In that investigation the
first collection of optically active 1-alkenesulfinate esters was
reported (eq. [1]) (14). As part of our continuing interest in
this area we investigated the nucleophilic conversion of these
α,β-unsaturated sulfinate esters to enantiopure or enriched α,β-
Received 25 October 2002. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on 7 April 2003.
Dedicated to Professor Don Arnold for his contributions to chemistry.
R.R. Strickler, J.M. Motto, C.C. Humber, and A.L. Schwan.1 Guelph-Waterloo Centre for Graduate Work in Chemistry and
Biochemistry, Department of Chemistry and Biochemistry, University of Guelph, Guelph, ON N1G 2W1, Canada.
1Corresponding author (e-mail: schwan@uoguelph.ca).
Can. J. Chem. 81: 423–430 (2003)
doi: 10.1139/V03-002
© 2003 NRC Canada

424
Can. J. Chem. Vol. 81, 2003
agent [R]-(–)-2,2,2-trifluoro-1-(9-anthryl)ethanol (19).3 The
sulfoxides possessing the highest ees arose from stereo-
specific reactions of sulfinates 1, 3, and 4. Simple ethenyl
sulfoxides could not be produced with high ee, since the pre-
cursor (–)-cholesteryl ethenesulfinate (2) could only be
formed with des as high as 47% (14). Nevertheless, Grig-
nard reactions of 2 still proceeded with high stereo-
specificity and yield when aromatic Grignard reagents were
employed. Aliphatic Grignard reagents afforded somewhat
lower yield and brought on losses of stereogenicity. Uti-
lizing the availability of [SS]-1 (14) the corresponding Grig-
nard reactions and the obtention of [RS]-sulfoxides confirms
the stereospecificity of the substitution pathway and elimi-
nates the possibility of stereoconvergent Grignard reactions.
Scheme 1.
unsaturated sulfoxides, compounds that are well-established
as useful sources of a variety of chiral derivatives (1, 15).
Most of the existing chiral vinylic sulfoxide preparations ei-
ther create the double bond after a chiral sulfoxide has been
prepared, or treat a chiral arenesulfinate with a vinylic organ-
ometallic reagent (15c, 15d). No such syntheses have estab-
lished the chirality once the C=C-S unit was already intact
which is the strategy investigated by us. This paper reports
the outcome of our investigation, a portion of which has al-
ready been communicated (7).
1
It was decided that the H NMR – solvating agent method
(19) of ee determination had a detection limit of 98% for
1
samples that had only one set of peaks evident: the H NMR
of solvated 6f shows the minor isomer and the ee of the sam-
ple of 6f was found to be 98%. A closer inspection of the ro-
tation data for 8b further corroborates the detection limit,
and hence the optical purity of the sulfoxides. The literature
reports a value of [α]D25 +166.0° (CHCl3) for 8b with 100%
optical purity (20) while we obtained [α]2D5 +165.1° (CHCl3)
meaning our isolated sample of 8b possessed an ee of
99.5%.
Successful 2-furyl Grignard reactions were obtained after
several attempts and it was found that 2-furylMgBr gener-
ated in THF by the reaction of 2-furyllithium with MgBr2-
Et2O (6d, 21) reacts with [RS]-1 in THF at –20°C in 78%
yield and with >98% ee. Sulfoxides bearing the furyl group
are important in organic synthesis and have been used in the
synthesis of naturally occurring compounds (22). Also, note-
worthy is that MeMgBr induced a 15% reduction in the
measured ees of the sulfoxides obtained. Several repetitions
and variations were performed but ees could not be im-
proved and yields consistently ranged from 56 to 67%.
Many of the synthetic protocols for racemic and homo-
Results and discussion
A synthetically useful organometallic displacement of the
cholesteryl unit requires both high yield and maintenance of
the stereogenicity at the sulfur. In work outlined in the prelimi-
nary communication (7), it was established using cyclohexyl
analogs of the available enantioenriched sulfinate esters (14)
that Grignard reagents (2 equiv) were readily found to be fa-
vored over organolithiums (16). To find the preferred condi-
tions for maximum enantiomeric excesses, samples of [RS]-(–)-
cholesteryl (E)-3,3-dimethyl-1-butenesulfinate (1) possessing
88–100% optical purity were treated with n-BuMgCl under
various conditions.2 The results directed us to perform all sub-
sequent substitution reactions in benzene (17) at 6°C where
possible, although ethyl ether was the original solvent for such
reactions (8b, 18).
Using the reaction conditions found in those preliminary
experiments, the reactions of enantiopure or enantioenriched
selected [RS]- and [SS]-sulfinates 1–4 with commercial and
prepared Grignard reagents were proved to be efficient and
chemoselective affording a wide variety of substituted α,β-
unsaturated sulfoxides as outlined in Table 1 (eq. [2]). The
enantiomeric excesses and the configurational assignments
of the sulfoxides were determined using the chiral solvating
chiral α,β-unsaturated sulfoxides introduce the double bond
in the last stage of the preparation and sometimes lead to
2 The reader is referred to the table of preliminary data presented in the communication (ref. (7)).
3 In some cases, one can gain confirmation of the assigned sulfur configuration by comparison of the sample’s optical rotation with literature
values.
© 2003 NRC Canada

Strickler et al.
425
Table 1. Grignard reactions of optically enriched α,β-unsaturated sulfinates.
Sulfoxide
Sulfinate and config.
Grignard reagenta
Structure
% Yield
80
[α]2D5b
%eec
1
2
2: 42% [RS]
7g
+153.4° (c 1.09)
41 [RS]
2: 22% [SS]
7g
83
–79.9° (c 1.42)
22 [SS]
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
2: 22% [SS]
2: 42% [RS]
2: 42% [RS]
2: 36% [RS]
1:100% [RS]
1:100% [RS]
1:100% [RS]
1:100% [RS]
1:100% [RS]
1:100% [RS]
1:100% [RS]
1:71% [SS]
c-C6H11MgCl
p-TolylMgBr
2-FurylMgBrf
PhCMe2CH2MgCl
nBuMgCl
7d
7b
7c
7j
6a
6e
6f
6d
6h
6b
6c
6f
42(63)d
77(85)d
59
39
86
56–67
85
86
78
86
78
76
79
70
70
87
62
74
–51.6° (c 0.32)
+136.3° (c, 1.08)e
+72.3° (c, 0.83)
+43.0° (c 1.96)
+130.7° (c 1.57)
+238.2° (c 2.90)
+150.3° (c 1.95)
+61.4° (c 2.38)
+142.0° (c 1.31)
+116.6° (c 1.41)h
+125.8° (c 1.69)
–112.3° (c 1.53)
–41.4° (c 2.30)
–46.6° (c 1.08)
+109.8° (c 0.96)
+116.7° (c 1.69)
+62.3° (c 1.61)
+62.1° (c 0.89)
–53.9° (c 1.04)
+125.3° (c 0.64)
+176.9° (c, 1.03)j
+152.0° (c 1.11)
23 [SS]
42 [RS]
41 [RS]
28 [SS]
>98 [SS]
MeMgBr
i-PrMgCl
85 to 86 [SS]
98 [SS]
>98 [SS]
91 [SS]
94 [RS]
>98 [RS]
72 [RS]
71 [RS]
41.5 [SS]
97 [RS]
91 [SS]
92 [SS]
n/di
c-C6H11MgBr
PhCH2MgBrg
p-TolylMgBr
2-FurylMgBrf
i-PrMgCl
c-C6H11MgBr
tBuMgCl
t-BuMgCl
i-PrMgCl
c-C6H11MgBr
n-BuMgCl
PhCH2MgBrg
PhCMe2CH2MgCl
p-TolylMgBr
1:71% [SS]
3:42%[SS]
6d
8i
8i
3:100% [RS]
3:100% [RS]
3:100% [RS]
3:100% [RS]
3:100% [RS]
3:100% [RS]
3:100% [RS]
3:100% [RS]
8f
8d
8a
8h
8j
8b
8g
56(87)c
81
76
82
91 [SS]
91 [SS]
>98 [RS]
95 [RS]
25
4:86%[SS]
9g
61
–49.5° (c 2.52)
86 [SS]
26
4:85% [SS]
c-C6H11MgBr
9d
73
–28.0° (c 1.17)
79 [RS]
aUsed 2 equiv of Grignard reagent unless otherwise noted. Reactions were performed in benzene at 6°C unless otherwise noted.
bOptical rotations were obtained in acetone, unless otherwise noted.
cEes were determined using [R]-(–)-2,2,2-trifluoro-1-(9-anthryl)ethanol as an NMR solvating agent. See ref. (19).
dYield in brackets is based on recovered starting material.
eLit. (20) value +386° (ethanol, 94% [RS]).
fPrepared from lithiated furanyl anion; see text and Experimental section for details.
gExperiment was done with 1 equiv of Grignard reagent.
hLit. (23d) value +33° (acetone).
iNot determinable.
j
[α]2D5 +165.1° (c, 1.03, CHCl3) (lit. (20) value +166.0°; (CHCl3, 100% [RS])).
mixtures of double bond isomers (6g, 20, 23, 24). At no
point were the sulfoxides obtained herein contaminated with
any cis-isomer. Our protocol establishes the geometry of the
double bond at a very early stage of the chemistry, and the
double bond configuration is never jeopardized thereafter. In
this regard we are demonstrating the stereospecific transfer
of selected chiral alkenesulfinyl units, while maintaining the
double bond geometry. Hence, the sulfinates represent the
first usage of an intact chiral [RCH=CHSO]+ synthon.
compound for 5 to employ in an investigation of the behav-
ior of this unique sulfinate. The reaction of 10 with
MeMgBr (eq. [3]) typifies the results of several trials.
Sulfoxide 11 could only be obtained in 0–20% yield and the
reaction mixture always contained vinyl ether 12. Changing
to other organometallic species such as organolithium and
organocerium reagents offered little improvement.
Reactions of cholesteryl (E)-2-carbomethoxyethene-
sulfinate
Grignard reactions of optically pure sulfinate 5 proved
troublesome. Under our established conditions little or no
sulfoxide was observed. Hence, cyclohexyl (E)-2-carbo-
methoxyethenesulfinate (10) (12) was enlisted as a model
© 2003 NRC Canada

426
Can. J. Chem. Vol. 81, 2003
Scheme 2.
A mechanism to account for the observed results is of-
fered in Scheme 2. It was felt that the sulfur substitution is
indeed occurring, but the product is prone to counterattack
by the displaced alkoxide. That attack occurs conjugate to
the ester, the stronger electron-withdrawing group, and to
conclude what appears to be an addition–elimination mecha-
nism, a sulfenic acid anion (13) is released. To test this
mechanism, sulfoxide 11 (R = MeOC6H4CH2), the precursor
of sulfinates 5 (14) and 10 (12), was treated with lithium
cyclohexylate and the mixture was quenched with benzyl
bromide to capture any reactive sulfenate (e.g., 13). The ob-
servation of 12 as a reaction constituent and the isolation of
14 (R = MeOC6H4CH2) in 47% purified yield from that mix-
ture offer strong support for the proposed mechanism
(Scheme 2).
A number of experiments were performed to see if the
sulfoxide could be intercepted before the addition–elimina-
tion reaction took place. To this end, sulfinate 10 was treated
with nucleophiles 15–19. It was hoped that dianions 15 (25),
16, and 17 (26) would effect sulfoxide formation and rapidly
perform an intramolecular Michael addition. As an alterna-
tive strategy, it was suggested that 18 (5d) and 19 could
achieve sulfoxide formation and the presence of a (thio)car-
bonyl group β to the sulfinyl unit would enhance the acidity
of the intervening methylene hydrogens thereby providing
the displaced alkoxide the recourse of deprotonation rather
than Michael attack. None of these efforts provided signifi-
cant sulfoxide and vinyl ether 12 was evident in the reaction
mixtures.
bon-based ligands. Alternatively, attack by previously re-
leased cholesteryloxy anion on 5 would bring about a
similar outcome, as precedented by counterattack and race-
mization by thiolate on chiral thiosulfinates (28). However,
control experiments have shown that racemization of 5 by
cholesteryloxy anion is minimal.
Conclusions
Andersen, Mikolazcyk, and co-workers (11) have previ-
ously obtained optically pure cholesteryl [RS]- and [SS]-
methanesulfinates in <5% yield. Although the behavior of
cholesteryl ethenesulfinate would appear to be similar to
those methanesulfinates, we were able to secure more substi-
tuted 1-alkenesulfinates in higher yield through recrystal-
lization chemistry (14) and demonstrate in this paper that
they are suitable 1-alkenesulfinyl transfer agents. Based on
this observation, diastereomeric mixtures of cholesteryl
sulfinate esters bearing large aryl and alkyl groups attached
to sulfur may prove readily separable and hence worthy of
investigation.
Those sulfinate esters that we have been able to secure un-
dergo stereospecific substitution with inversion at sulfur
yielding a range of α,β-unsaturated sulfoxides. The presence
of a carbomethoxy group trans to the sulfinate ester creates
significant unwanted reactions under Grignard treatment
conditions. The method outlined herein is not limited to
vinylic sulfoxides bearing only a p-tolyl group, the prepa-
rations of which have been amply demonstrated in the lit-
erature, buts allows for the preparation of a broader array
of alkyl or aryl 1-alkenyl sulfoxides. It would appear that
the collection of sulfoxides accessible by this protocol is
only limited by the number of enantioenriched sulfinates
available; we are currently exploring other means of pre-
Not completely discouraged, we pursued several reactions
of 5 with Grignard reagents. Equation [4] depicts the best re-
sults that could be achieved, and although the low yields of
sulfoxide 11 and of vinyl ether 20 were foreseen, the loss of
sulfur stereochemistry was unexpected. The loss of sulfur
chirality is presumably because of the presence of the conju-
gating carboxylic ester group. It has recently been shown
(27) that the presence of a vinylic ester conjugating to a
sulfinyl lone pair and the consequent mesomeric donation of
that lone pair toward the ester leads to a reduced inversion
barrier for the sulfinyl group. Based on this behavior, it fol-
lows that the sulfinyl group in a compound such as 11 exhib-
its increased electrophilicity at sulfur. Hence, a reasonable
explanation for the loss of sulfur stereochemistry entails at-
tack of 11 by excess Grignard agent, a pseudorotation step
of the intermediate sulfurane at which time loss of stereo-
genicity occurs followed by release of one of the two car-
© 2003 NRC Canada

Strickler et al.
427
[SS]-Ethenyl 1-(2-methyl-2-phenylpropyl) sulfoxide (7j):
paring
a larger selection of enantiopure 1-alkene-
IR (neat) (cm–1): 3089, 3034, 2967, 2932, 1497, 1444,
1370, 1047. 1H NMR (400 MHz) δ: 7.31–7.24 (m, 3H),
7.17–7.14 (m, 2H), 6.25 (dd, J = 16.4, 9.6 Hz, 1H), 5.92 (d,
J = 16.4 Hz, 1H), 5.73 (d, J = 9.6 Hz, 1H), 2.89 (ABq, J =
13.4 Hz, 2H), 1.16 (s, 3H), 0.78 (s, 3H). 13C NMR
(100.6 MHz) δ: 146.7, 141.5, 128.5, 126.6, 125.6, 120.7,
70.0, 37.8, 29.9, 27.2. MS (EI) m/z (%): 209, (82), 133 (91),
91(100), 55(20). Anal. calcd. for C12H16OS: C 69.19, H
7.74; found: C 69.38, H 7.59.
sulfinates.
Experimental
General
Our general experimental methods have been outlined in a
previous publication (12). Unless noted below, all Grignard
reagents were purchased as stock solutions from Aldrich.
Optical rotation measurements were performed on an
Autopol III automatic polarimeter.
[SS]-(E)-3,3-Dimethyl-1-butenyl 1-butyl sulfoxide (6a):
IR (neat) (cm–1): 2959, 2932, 2906, 2870, 1625, 1465,
1
1364, 1265, 1074, 1039, 971. H NMR (400 MHz) δ: 6.45
Typical procedure for the conversion of optically enriched
sulfinates 1–4 to sulfoxides
(d, J = 15.4 Hz, 1H), 6.09 (d, J = 15.4 Hz, 1H), 2.70 (t, J =
7.7 Hz, 2H), 1.68 (m, 2H), 1.48 (m, 2H), 1.11 (s, 9H), 0.96
(t, J = 7.3 Hz, 3H). 13C NMR (100.6 MHz) δ: 151.1, 128.1,
53.8, 34.2, 28.8, 24.1, 22.0, 13.7. MS (EI) m/z (%): 188 (8),
171 (39), 132 (35), 118 (21), 117 (100), 115 (34), 101 (40),
99 (33), 97 (25), 85 (32), 84 (20), 83 (86), 79 (18), 74 (29),
71 (22), 69 (27), 67 (29), 65 (26), 59 (71), 57 (78), 56 (18),
55 (70), 53 (28), 51 (17). Anal. calcd. forC10H20OS: C
63.78, H 10.70; found: C 63.83, H 10.45.
Diastereomerically pure cholesteryl 1-alkenesulfinate ester
(1–4, 1 equiv) was dissolved in benzene (10 mL) and cooled
to 6°C under N2. After 10 min the Grignard reagent (com-
mercially available stock solution; 1 to 2 equiv) was added
dropwise. The reaction mixture was stirred until complete by
TLC analysis (1 to 2 h) and then quenched with NH4Cl
(10 mL). The solution was diluted with EtOAc and the or-
ganic layer separated, washed with brine, dried with MgSO4,
filtered, and concentrated under reduced pressure. The
enantioenriched sulfoxides were isolated using silica gel
flash chromatography, with EtOAc–hexanes as the eluent.
Chemical yields, enantiomeric purities, and optical rotation
data (in acetone) are presented in Table 1. All sulfoxides ex-
cept 6c, 7c, 11a, and 11b were prepared by this protocol.
Structural characterization of the sulfoxides follows.
[RS]-(E)-3,3-Dimethyl-1-butenyl 4-methylphenyl sulfoxide
(6b) (29):
1H NMR (400 MHz) δ: 7.49 (d, J = 8.0 Hz, 2H), 7.31 (d,
J = 8.0 Hz, 2H), 6.59 (d, J = 15.4 Hz, 1H), 6.11 (d, J =
15.4 Hz, 1H), 2.41 (s, 3H), 1.08 (s, 9H).
[SS]-(E)-3,3-Dimethyl-1-butenyl cyclohexyl sulfoxide (6d):
[RS]-1-Ethenyl 4-methylphenyl sulfoxide (7b) (23c):
1H NMR (400 MHz) δ: 7.52 (d, J = 8.0 Hz, 2H), 7.32 (d,
J = 8.4 Hz, 2H), 6.58 (dd, J = 16.4, 9.6 Hz, 1H), 6.19 (d, J =
16.4 Hz, 1H), 6.18 (d, J = 9.6 Hz, 1H), 2.41 (s, 3H).
IR (CH2Cl2) (cm–1): 3029, 2935, 2855, 1622, 1474, 1463,
1
1451, 1365, 1264, 1055, 971. H NMR (400 MHz) δ: 6.42
(d, J = 15.6 Hz, 1H), 6.04 (d, J = 15.6 Hz, 1H), 2.54 (m,
1H), 2.04 (m, 1H), 1.88 (m, 3H), 1.67 (m, 1H), 1.31 (m,
5H), 1.11 (s, 9H). 13C NMR (100.6 MHz) δ: 152.2, 126.1,
60.5, 34.3, 28.9, 26.0, 25.6, 25.5, 25.3, 24.8. MS (EI) m/z
(%): 214 (M+, 8), 198 (19), 183 (32), 132 (100), 117 (78),
115 (27), 101 (48), 83 (88), 81 (19), 74 (20), 67 (26), 59
(41), 53 (17), 55 (85). Anal. calcd. for C12H22OS: C 67.23,
H 10.34; found: C 67.08, H 9.93.
[SS]-1-Ethenyl cyclohexyl sulfoxide (7d):
Mp: 48–50°C. IR (CH2Cl2) (cm–1): 3043, 2933, 2856,
1
1452, 1055. H NMR (400 MHz) δ: 6.57 (dd, J = 16.5,
10.0 Hz, 1H), 6.07 (d, J = 16.5 Hz, 1H), 6.00 (d, J =
10.0 Hz, 1H), 2.57 (tt, J = 11.6, 3.6 Hz, 1H), 2.02–1.87 (m,
3H), 1.80–1.60 (m, 2H), 1.50–1.15 (m, 5H). 13C NMR
(100.6 MHz) δ: 138.6, 122.9, 60.2, 26.0, 25.5, 25.3, 24.2.
MS (CI, NH3) m/z (%): 159 ([M + 1]+, 21), 108 (24), 91
(100), 90 (35), 74 (28), 73 (14). Anal. calcd. for C8H14OS: C
60.71, H 8.92; found: C 60.92, H 8.70.
[SS]-(E)-3,3-Dimethyl-1-butenyl methyl sulfoxide (6e) (23d):
1H NMR (400 MHz) δ : 6.47 (d, J = 15.4 Hz, 1H), 6.17
(d, J = 15.4 Hz, 1H), 2.61 (s, 3H), 1.11 (s, 9H). MS (EI) m/z
(%): 146 (M+, 20), 131 (28), 130 (32), 117 (12), 115 (100),
83 (47), 81 (21), 71 (20), 58 (21), 57 (62), 53 (29), 51 (22).
Anal. calcd. for: C7H14OS: C 57.49, H 9.65; found: C 57.45,
H 9.52.
[RS]-4-Fluoro-3-methylphenyl ethenyl sulfoxide (7g):
IR (neat) (cm–1): 3064, 3032, 2928, 1597, 1577, 1485,
1449, 1395, 1384, 1368, 1240, 1183, 1120, 1085, 1055,
1
[SS]-(E)-3,3-Dimethyl-1-butenyl 2-propyl sulfoxide (6f):
1015, 986. H NMR (400 MHz) δ: 7.48 (dd, J = 6.8, 1.6 Hz,
1H), 7.42 (m, 1H), 7.14 (t, J = 8.8 Hz, 1H), 6.57 (dd, J =
16.4, 9.6 Hz, 1H), 6.20 (d, J = 16.4 Hz, 1H), 6.91 (d, J =
9.6 Hz, 1H), 2.33 (s, 3H). 13C NMR (100.6 MHz) δ: 162.9
(d, J = 250.6 Hz), 142.8, 138.1, 128.0 (d, J = 6.0 Hz), 126.9
(d, J = 18.5 Hz), 124.3 (d, J = 8.9 Hz), 120.6, 116.1 (d, J =
23.7 Hz), 14.5 (d, J = 3.2 Hz). MS (EI) m/z (%): 184 (M+,
11), 157 (21), 141 (18), 137 (11), 136 (100), 135 (21), 110
(18), 109 (33), 108 (10), 107 (12), 97 (11), 83 (20), 59 (10),
57 (13), 45 (19). Anal. calcd. for C9H9FOS: C 58.68, H
4.92; found: C 58.77, H 5.02.
IR (neat) (cm–1): 2961, 2932, 2905, 2868, 1628, 1475,
1
1463, 1365, 1266, 1062, 1024, 973. H NMR (400 MHz) δ :
6.43 (d, J = 15.6 Hz, 1H), 6.01 (d, J = 15.6 Hz, 1H), 2.78
(m, J = 6.8 Hz, 1H), 1.24 (d, J = 6.8 Hz, 3H), 1.22 (d, J =
6.8 Hz, 3H), 1.10 (s, 9H). 13C NMR (100 MHz) δ: 152.3,
125.4, 51.7, 34.3, 28.9, 15.2, 14.6. MS (EI) m/z (%): 174
(M+, 15), 158 (20), 143 (38), 132 (90), 117 (100), 115 (42),
101 (59), 99 (39), 83 (81), 74 (30), 67 (35), 65 (31), 59 (85),
57 (27). Anal. calcd. for C9H18OS: C 62.02, H 10.41; found:
C 61.82, H 10.25.
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Can. J. Chem. Vol. 81, 2003
[SS]-(E)-3,3-Dimethyl-1-butenyl benzyl sulfoxide (6h) (30):
1H NMR (400 MHz) δ: 7.25–7.23 (m, 3H), 7.16–7.13 (m,
2H), 6.12 (d, J = 15.5 Hz, 1H), 5.89 (d, J = 15.4 Hz, 1H),
3.89 (ABq, J = 12.6 Hz, 2H), 0.90 (s, 9H).
[RS]-(E)-2-Phenylethenyl benzyl sulfoxide (8h) (31):
IR (CDCl3) (cm–1): 3032, 2359, 1576, 1497, 1455, 1052,
1
965. H NMR (400 MHz) δ: 7.34 (m, 10H), 7.11 (d, J =
15.5 Hz, 1H), 6.76 (d, J = 15.5 Hz, 1H), 4.09 (ABq, J =
12.5 Hz, 2H). 13C NMR (100.6 MHz) δ: 137.2, 133.8, 130.3,
129.8, 129.7, 129.4, 128.9, 128.8, 128.4, 127.6, 61.2.
[RS]-(E)-2-Phenylethenyl 1-butyl sulfoxide (8a):
IR (CDCl3) (cm–1): 3084, 3030, 2961, 2933, 2875, 1615,
[RS]-(E)-2-Phenylethenyl 1-(2-methyl-2-phenylpropyl) sulfoxide
(8j):
1
1494, 1467, 1070, 1039, 965. H NMR (400 MHz) δ: 7.45
(m, 2H), 7.35 (m, 3H), 7.21 (d, J = 15.5 Hz, 1H), 6.82 (d,
J = 15.5 Hz, 1H), 2.78 (m, 2H), 1.75 (m, 2H), 1.48 (m, 2H),
0.94 (t, J = 8 Hz, 3H). 13C NMR (100.6 MHz) δ: 136.8,
133.8, 130.5, 129.6, 128.9, 127.6, 53.9, 24.0, 22.0, 13.7. MS
(EI) m/z (%): 208 (4, M+), 192 (53), 152 (31) 136 (17), 135
(72), 94 (100). Anal. calcd. for C12H16OS: C 69.19, H 7.74;
found: C 68.98, H 7.61.
1H NMR (400 MHz) δ: 7.31 (m, 10H), 7.10 (d, J =
15.4 Hz, 1H), 6.48 (d, J = 15.4 Hz, 1H), 3.14 (ABq, J =
13.4 Hz, 2H), 1.71 (s, 3H), 1.56 (s, 3H). 13C NMR
(100.6 MHz) δ: 146.6, 135.5, 133.8, 131.3, 129.4, 128.8,
128.6, 127.5, 126.7, 125.7, 70.7, 37.8, 30.2, 27.2. IR
(CDCl3) (cm–1): 3085, 3027, 2967, 2933, 2879, 1615, 1602,
1497, 1044, 1031, 965. Anal. calcd. for C18H20OS: C 76.01,
H 7.09; found: C 76.22, H 7.10.
[RS]-(E)-2-Phenylethenyl 4-methylphenyl sulfoxide (8b) (23c):
1H NMR (400 MHz) δ: 7.58 (d, J = 6.8 Hz, 2H), 7.47–
7.44 (m, 2H), 7.39–7.32 (m, 6H), 6.82 (d, J = 15.6 Hz, 1H),
2.41 (s, 3H).
[RS]-(E)-2-Phenylethenyl 2,2-dimethylethyl sulfoxide (8i) (29):
1H NMR (400 MHz) δ: 7.46 (m, 2H), 7.35 (m, 3H), 7.21
(d, J = 15.5 Hz, 1H), 6.78 (d, J = 15.5 Hz, 1H), 1.28 (s, 9H).
[RS]-(Z)-2-Chloro-2-phenylethenyl cyclohexyl sulfoxide (9d):
IR (neat) (cm–1): 3058, 2933, 2855, 1625, 1594, 1489,
1454, 1296, 1066, 1063, 1030, 992. 1H NMR (400 MHz) δ:
7.49–7.41 m, 3H), 7.39–7.36 (m, 2H), 6.73 (s, 1H), 2.18 (tt,
J = 12.0, 3.6 Hz, 1H), 1.90–1.32 (m, 7H), 1.28–1.11 (m,
3H). 13C NMR (100.6 MHz) δ: 142.4, 130.0, 129.5, 129.0,
128.4, 122.8, 56.7, 27.3, 25.7, 25.2 (2 C’s), 21.5. MS (EI)
m/z (%): 270 (50), 269 (M+, 100), 188 (14), 186 (36), 185
(21), 83 (18), 55 (89), 54 (20). Anal. calcd. for C14H17ClOS:
C 62.55, H 6.38; found: C 63.01, H 6.33.
[SS]-(E)-2-Phenylethenyl cyclohexyl sulfoxide (8d):
Mp: 90 to 91°C. IR (CDCl3) (cm–1): 3088, 3055, 2936,
2857, 1449, 1263, 1253, 1234, 1167, 1159, 1032, 1015, 967.
1H NMR (400 MHz) δ: 7.50–7.47 (m, 2H), 7.41–7.33 (m,
3H), 7.22 (d, J = 15.4 Hz, 1H), 6.81 (d, J = 15.4 Hz, 1H),
2.68 (tt, J = 11.8, 3.5 Hz, 1H), 2.09–1.96 (m, 2H), 1.91–1.87
(m, 2H), 1.73–1.70 (m, 1H), 1.55–1.40 (m, 2H), 1.40–1.15
(m, 3H). 13C NMR (100.6 MHz) δ: 137.7, 134.0, 129.6,
128.9, 128.6, 127.5, 61.1, 26.1, 25.5 (2 C’s), 25.3, 24.6. MS
(EI) m/z (%): 234 (M+, 2), 152 (100), 135 (25), 104 (22), 91
(12), 83 (13), 77 (12), 73 (22), 55 (50), 45 (20), 41 (28).
Anal. calcd. for C14H18OS: C 71.75, H 7.74; found: C 71.73,
H 7.32.
[SS]-(Z)-2-Chloro-2-phenylethenyl 4-fluoro-3-methylphenyl
sulfoxide (9g):
IR (neat) (cm–1): 3060, 2927, 1580, 1488, 1444, 1239,
1
1184, 1081, 1060. H NMR (400 MHz) δ: 7.35–7.28 (m,
[SS]-(E)-2-Phenylethenyl 2-propyl sulfoxide (8f):
3H), 7.20 (dd, J = 6.8, 1.6 Hz, 1H), 7.11 (s, 1H), 7.10–7.01
(m, 3H), 6.94 (t, J = 8.8 Hz, 1H). 13C NMR (100.6 MHz) δ:
162.9 (d, J = 250.0 Hz), 147.4, 136.7, 129.4, 129.1, 129.0,
128.5, 128.1 (d, J = 6.1 Hz), 126.5 (d, J = 18.5 Hz) 124.6 (d,
J = 9.0 Hz), 122.4, 115.7 (d, J = 23.8 Hz), 14.5 (d, J =
3.1 Hz). Anal. calcd. for C15H12ClFOS: C 61.12, H 4.10;
found: C 61.32, H 4.24.
1
Mp: 50–52°C. H NMR (400 MHz) δ: 7.49–7.47 (m, 2H),
7.41–7.34 (m, 3H), 7.23 (d, J = 15.6 Hz, 1H), 6.78 (d, J =
15.6 Hz, 1H), 2.92 (septet, J = 6.8 Hz, 1H), 1.33 (d, J =
6.8 Hz, 3H), 1.30 (d, J = 6.8 Hz, 1H). 13C NMR
(100.6 MHz) δ: 137.9, 134.0, 129.6, 128.9, 127.9, 127.5,
52.3, 15.4, 14.5. IR (CDCl3) (cm–1): 3056, 2973, 2932,
1625, 1449, 1262, 1255, 1167, 1159, 1148, 1121, 1032,
1014, 967. MS (EI) m/z (%): 194 (M+, 6), 152 (100), 135
(55), 134 (16), 104 (55), 91 (34), 77 (27), 73 (39), 51 (15),
45 (34), 43 (45), 41 (21). Anal. calcd. for C11H14OS: C
68.00, H 7.26; found: C 67.77, H 6.75.
Synthesis of [RS]-2-furyl ethenyl sulfoxide (7c):
n-BuLi (360 µL, 0.73 mmol) was added to a solution of
furan (50 µL, 0.65 mmol) in dry ether (5 mL) at –20°C un-
der N2. After stirring for 20 min, MgBr2 (180 mg,
0.98 mmol) dissolved in dry ether (5 mL) was added slowly
with vigorous stirring over 20 min and then sulfinate [RS]-2
(301 mg, 0.65 mmol) in dry ether (5 mL) was added. After
1 h the reaction was quenched with NH4Cl. The organic
layer was separated, and the aqueous layer was extracted
with EtOAc. The combined organic layers were washed with
brine, dried over MgSO4, and concentrated. Following flash
chromatography (20% EtOAc – hexanes to elute cholesterol,
80% to elute sulfoxide) enantioenriched sulfoxide 7c was
isolated as an oil (42 mg, 59%). IR (neat) (cm–1): 3117,
3039, 3010, 2952, 1600, 1550, 1456, 1453, 1370, 1220,
[RS]-(E)-2-Phenylethenyl 4-fluoro-3-methylphenyl sulfoxide
(8g):
Mp: 58 to 59°C. IR (CDCl3) (cm–1): 3063, 3023, 3011,
2925, 1488, 1447, 1239, 1079, 1051, 1034. 1H NMR
(400 MHz) δ: 7.55–7.45 (m, 1H), 7.49–7.45 (m, 3H), 7.40–
7.37 (m, 4H), 7.37 (d, J = 15.6 Hz, 1H), 7.14 (t, J = 8.8 Hz,
1H), 6.80 (d, J = 15.6 Hz, 1H), 2.33 (s, 3H). 13C NMR
(100.6 MHz) δ: 162.9 (d, J = 250 Hz), 138.8 (broad), 136.2,
133.6, 132.7, 129.8, 128.9, 128.0 (d, J = 5.9 Hz), 127.3,
126.9 (d, J = 18.4 Hz), 124.3 (d, J = 9.0 Hz), 116.1 (d, J =
23.6 Hz), 14.6. MS (CI, NH3) m/z (%): 261 ([M + H]+, 100),
212 (23), 91 (6). Anal. calcd. for C15H13SOF: C 69.21, H
5.03; found: C 69.40, H 5.07.
1
1165, 1066, 1051. H NMR (400 MHz) δ: 7.64 (m, 1H),
6.95 (dd, J = 3.8, 0.4 Hz, 1H), 6.76 (dd, J = 16.4, 9.6 Hz,
1H), 6.53 (dd, J = 3.8, 2.0 Hz, 1H), 6.34 (d, J = 16.4 Hz,
© 2003 NRC Canada

Strickler et al.
429
1H), 6.11 (d, J = 9.6 Hz, 1H). 13C NMR (100.6 MHz) δ:
137.4, 130.5, 130.2, 122.3, 116.4, 111.3. MS (EI) m/z (%):
142 (9), 126 (25), 115 (48), 99 (20), 97 (15), 94 (100),
83(15). Anal. calcd. for C6H6O2S: C 50.69, H 4.25; found: C
50.77, H 4.42.
Characterization data for (–)-cholesteryl (E)-2-carbometh-
oxyethenyl ether (20):
IR (CH2Cl2) (cm–1): 2946, 2906, 2868, 2851, 1715, 1643,
1133, 959. 1H NMR (400 MHz) δ: 7.55 (d, J = 12.4 Hz, 1H),
5.40–5.39 (m, 1H), 5.26 (d, J = 12.4 Hz, 1H), 3.84–3.76 (m,
1H), 3.69 (s, 3H), 2.38–2.35 (m, 2H), 1.01 (s, 3H), 0.91 (d,
J = 6.5, 3H), 0.86 (d, J = 6.6 Hz, 3H), 0.68 (s, 3H), 2.09–
0.80 (remaining peaks for cholesteryl skeleton, 26H). 13C
NMR (100.6 MHz) δ: 168.6, 161.7, 139.3, 123.1, 97.0, 82.3,
56.7, 56.1, 51.0, 50.0, 42.3, 39.7, 39.5, 38.5, 36.8, 36.6,
36.2, 35.8, 31.9, 31.8, 28.2, 28.1, 28.0, 24.3, 23.8, 22.8,
22.6, 21.0, 19.3, 18.7, 11.8. MS (CI, NH3) m/z (%):
471([M + H]+, 37), 370 (29), 369 (100), 61 (13). Anal.
calcd. for C31H50O3: C 79.10, H 10.71; found: C 79.21, H
10.60.
Synthesis of [SS]-(E)-3,3-dimethyl-1-butenyl 2-furyl sulfoxide
(6c):
As described for 7c, n-BuLi (341 µL, 0.68 mmol), furan
(40 µL, 0.57 mmol) in dry ether (5 mL), MgBr2 (125.8 mg,
0.68 mmol) in dry ether (5 mL) were all brought together
and enantiopure sulfinate [RS]-1 (295 mg, 0.57 mmol, 100%
[RS]) in dry ether (5 mL) was added. Work-up as for 7c and
flash chromatography (20% EtOAc – hexanes to elute cho-
lesterol, 80% to elute sulfoxide) afforded enantioenriched
sulfoxide 6c as an oil (114.2 mg, 78%). Data for 6c: IR
(neat) (cm–1): 3114, 2961, 2905, 2868, 1625, 1475, 1366,
Acknowledgements
1
1266, 1218, 1128, 1066, 1008, 970. H (400 MHz) δ: 7.63
The authors thank the Petroleum Research Fund, adminis-
tered by the American Chemical Society and the Natural
Sciences and Engineering Research Council of Canada
(NSERC) for generously funding this research. RRS also
thanks NSERC and the Ontario government for graduate
scholarships.
(m, 1H), 6.88 (d, J = 3.6 Hz, 1H), 6.66 (d, J = 15.4 Hz, 1H),
6.51 (dd, J = 3.6, 1.6 Hz, 1H), 6.35 (d, J = 15.4 Hz, 1H),
1.13 (s, 9H). 13C NMR (100.6 MHz) δ: 152.7, 151.7, 146.8,
125.9, 115.2, 111.3, 34.3, 28.7. MS (EI) m/z (%): 199 ([M +
1]+, 6), 150 (51), 135 (69), 107 (11), 99 (15), 91 (10), 83
(17), 81 (16), 79 (15), 71 (14), 67 (11), 59 (22), 57 (57), 55
(82), 53 (17), 45 (32), 43 (37), 41 (100). Anal. calcd. for
C10H14O2S: C 60.57, H 7.12; found: C 60.69, H 7.06.
References
Synthesis of (E)-[SS]-2-carbomethoxyethenyl 1-butyl sulfoxide
(11a):
1. M.C. Carreño. Chem. Rev. 95, 1717 (1995).
2. A.J. Walker. Tetrahedron: Asymmetry, 3, 961 (1992).
3. (a) N. Khiar, I. Fernandez, A. Alcudia, and F. Alcudia. In Ad-
vances in sulfur chemistry. Vol. 2. Edited by C.M. Rayner. JAI
Press, Stamford. 2000. pp. 57–115; (b) S.M. Allin and P.C.
Bulman Page. In Advances in sulfur chemistry. Vol. 2. Edited
by C.M. Rayner. JAI Press, Stamford. 2000. pp. 117–153.
4. N. Khiar, C.S. Araújo, F. Alcudia, and I. Fernández. J. Org.
Chem. 67, 345 (2002).
5. (a) Y. Arroyo-Gómez, J.A. López-Sastre, J.F. Rodríguez-Amo,
M. Santos-Garcia, and M.A. Sanz-Tejedor. J. Chem. Soc.,
Perkin Trans. 1, 2177 (1994); (b) N. Khiar, I. Fernandez, and
F. Alcudia. Tetrahedron Lett. 35, 5719 (1994); (c) V. Guerrero-
de la Rosa, M. Ordoñez, J.M. Llera, and F. Alcudia. Synthesis,
761 (1995); (d) C. Alayrac, S. Nowaczyk, M. Lemarié, and P.
Metzner. Synthesis, 669 (1999); (e) N. Khiar, F. Alcudia, J.-L.
Espartero, L. Rodriguez, and I. Fernandez. J. Am. Chem. Soc.
122, 7598 (2000); (f) S. Nakamura, M. Kuroyanagi, Y.
Watanabe, and T. Toru. J. Chem. Soc., Perkin Trans. 1, 3143
(2000); (g) S. Nakamura, M. Oda, H. Yasuda, and T. Toru. Tet-
rahedron, 57, 8469 (2001).
The reaction of sulfinate 5 (336 mg, 0.65 mmol, 100%
[RS]) with n-BuMgCl (388 µL, 0.78 mmol, as a 2 M solution
in Et2O) in anhydrous ether at –78°C generated vinyl ether
by-product 20 (117 mg, 38%) as a solid after chromatogra-
phy (20% EtOAc – hexanes). Enantioenriched sulfoxide 11a
was isolated as a solid (37 mg, 30%, 51% [SS]) after addi-
tional chromatography (80% EtOAc – hexanes); mp: 53 to
54°C. [α]2D5 +120.6° (c 0.73, acetone). IR (cm–1): 3030, 2959,
2932, 1719, 1621, 1292, 1223, 1146, 1041. 1H NMR
(400 MHz) δ: 7.58 (d, J = 15.0 Hz, 1H), 6.66 (d, J =
15.0 Hz, 1H), 3.81 (s, 3H), 2.87 (ddd, J = 13.2, 10.0, 5.8 Hz,
1H), 2.74 (ddd, J = 13.2, 10.0, 5.8 Hz, 1H), 1.81 (m, 1H),
1.69 (m, 1H), 1.48 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H). 13C
NMR (100.6 MHz) δ: 164.3, 149.7, 126.0, 52.6, 52.3, 24.0,
21.9, 6.6. MS (CI, NH3) m/z (%): 191 ([M + 1]+, 100), 175
(5.6), 151 (12), 141 (9), 135 (8), 121 (16), 107 (18), 57 (33).
Anal. calcd. for C7H14O2S: C 50.66, H 7.42; found: C 50.50,
H 7.42.
6. (a) K.H. Bell and L.F. McCaffery. Aust. J. Chem. 47, 1925,
(1994); (b) A.B. Bueno, M.C. Carreño, J.L. Garcia Ruano, and
J. Fischer. Tetrahedron Lett. 36, 3737 (1995); (c) G. Solladié,
C. Bauder, and L. Rossi. J. Org. Chem. 60, 7774 (1995);
(d) L.D. Girodier, C.S. Maignan, and F.P. Rouessac. Tetrahe-
dron: Asymmetry, 6, 2045 (1995); (e) G. Solladié and N.
Huser. Tetrahedron: Asymmetry, 6, 2679 (1995); (f) G.
Solladié, L. Gressot, and F. Colobert. Eur. J. Org. Chem. 357
(2000); (g) W.E. Noland and B.L. Kedrowski. Org. Lett. 2,
2109 (2000); (h) N. Maezaki, M. Izumi, S. Yuyama, H.
Sawamoto, C. Iwata, and T. Tanaka, Tetrahedron, 56, 7927
(2000); (i) C. Rolland, G. Hanquet, J.B. Ducep, and G.
Solladié. Tetrahedron Lett. 42, 9077 (2001); (j) S. Nakamura,
H. Yasuda, Y. Watanabe, and T. Toru. J. Org. Chem. 65, 8640
(2000); (k) S.G. Davies, T. Loveridge, M.F.C.C. Teixeira, and
Synthesis of (E)-[RS]-2-carbomethoxyethenyl 4-methylphenyl
sulfoxide (11b) (23f):
The reaction of sulfinate 5 (471.5 mg, 0.91 mmol, 100%
[RS] with p-tolMgBr (1.09 mL, 1.09 mmol, as a 1 M solution
in Et2O) in anhydrous ether warming from –78 to –40°C gen-
erated vinyl ether by-product 20 (76 mg, 18%) as a solid after
chromatography (20% EtOAc – hexanes). Enantioenriched
sulfoxide 11b was isolated as a solid (50.5 mg, 25%, 21%
[RS]) after additional chromatography (80% EtOAc – hex-
anes). [α]2D5 +62.4° (c 0.22, acetone) (lit. (23f) value +421°)
1
(acetone, >98% [RS]). H NMR (400 MHz) δ: 7.52 (d, J =
8.0 Hz, 2H), 7.48 (d, J = 15.0 Hz, 1H), 7.33 (d, J = 8.0 Hz,
2H), 6.73 (d, J = 15.0 Hz, 1H), 3.77 (s, 3H), 2.47 (s, 3H).
© 2003 NRC Canada

430
Can. J. Chem. Vol. 81, 2003
J.M. Clough. J. Chem. Soc., Perkin Trans. 1, 3405 (1999); (l)
H. Yoshizaki, T. Tanaka, E. Yoshii, T. Koizumi, and K.
Takeda. Tetrahedron Lett. 39, 47 (1998).
18. K. Mislow, M.M. Green, P. Laur, T.T. Mellilo, T. Simmons,
and A.L. Ternay, Jr. J. Am. Chem. Soc. 87, 1958 (1965).
19. (a) W.H. Pirkle and D.J. Hoover. Top. Stereochem. 13, 263
(1982); (b) M. Mikolaczyk and J. Drabowicz. Top.
Stereochem. 13, 333 (1982).
7. R.R. Strickler and A.L. Schwan. Tetrahedron: Asymmetry, 10,
4065 (1999).
8. (a) K.K. Andersen. Tetrahedron Lett. 93 (1962); (b) K.K.
Andersen, W. Gaffield, N.E. Papanikolaou, J.W. Foley, and
R.I. Perkins. J. Am. Chem. Soc. 86, 5637 (1964); (c) M.
Mikolajcyk, J. Drabowicz, and P. Kielbasinski. Chiral sulfur
reagents. CRC Press, Boca Raton. 1997. pp. 7–28; (d) S. Allin.
In Organosulfur chemistry. Synthetic and stereochemical as-
pects. Vol. 2. Edited by P. Page. Academic Press, San Diego.
1998. pp. 41–48.
9. (a) J.M. Llera, I. Fernández, and F. Alcudia. Tetrahedron Lett.
32, 7299 (1991); (b) I. Fernández, N. Khiar, A. Roca, A.
Benabra, A. Alcudia, J.L. Espartero, and F. Alcudia. Tetrahe-
dron Lett. 40, 2029 (1999).
10. (a) J.K. Whitesell and M.S. Wong. J. Org. Chem. 56, 4552
(1991); (b) J.K. Whitesell and M.S. Wong. J. Org. Chem. 59,
597 (1994).
11. K.K. Andersen, B. Bujnicki, J. Drabowicz, M. Mikolajczyk,
and J.B. O’Brien. J. Org. Chem. 49, 4070 (1984).
12. A.L. Schwan, R.R. Strickler, Y. Lear, M.L. Kalin, T.E. Rietveld,
T.-J. Xiang, and D. Brillon. J. Org. Chem. 63, 7825 (1998).
13. A.L. Schwan, R.R. Strickler, R. Dunn-Dufault, and D. Brillon.
Eur. J. Org. Chem. 1643 (2001).
20. M. Mikolajczyk, W. Midura, S. Grzejszczak, A. Zatorski, and
J. Chefczynska. J. Org. Chem. 43, 473 (1978).
21. Y. Arroyo, M.C Carreño, J.L. García Ruano, J.F. Rodríguez
Amo, M. Santos, and M. Ascensión Sanz Tejedor. Tetrahe-
dron: Asymmetry, 11, 1183 (2000).
22. Y. Arai, T. Masuda, S. Yoneda, Y. Masaki, and M. Shiro. J.
Org. Chem. 65, 258 (2000).
23. (a) M. Mikolajczyk, W. Perlikowska, J. Omelanczuk, H.-J.
Cristau, and A. Perraud-Darcy. Synlett, 913 (1991); (b) M.
Mikolajczyk, W. Perlikowska, J. Omelanczuk, H.-J. Cristau,
and A. Perraud-Darcy. J. Org. Chem. 63, 9716 (1998); (c) J.H.
van Steenis, J.J.G.S. van Es, and A. van der Gen. Eur. J. Org.
Chem. 2787 (2000); (d) F. Chaigne, J.P. Gotteland, and M.
Malacria. Tetrahedron Lett. 30, 1803 (1989); (e) C.
Cardellicchio, A. Iacuone, and F. Naso. Tetrahedron Lett. 36,
6563 (1995); (f) K. Kokin, S. Tsuboi, J. Motoyoshiya, and S.
Hayashi. Synthesis, 637 (1996).
24. (a) R. Tanikaga, N. Konya, T. Tamura, and A. Kaji. J. Chem.
Soc., Perkin Trans. 1, 825 (1987); (b) R. Tanikaga, N. Konya,
and A. Kaji. Chem. Lett. 1583 (1985).
25. E. Block, V. Eswarakrishnan, M. Gernon, G. Ofori-Okai, C.
Saha, K. Tang, and J. Zubieta. J. Am. Chem. Soc. 111, 658
(1989).
14. R.R. Strickler and A.L. Schwan. Tetrahedron: Asymmetry, 11,
4843 (2000).
15. (a) E. Lacôte, B. Delouvrié, L. Fensterbank, and M. Malacria.
Angew. Chem. Int. Ed. 37, 2116 (1998); (b) J.C. de la Rosa,
N. Díaz, and J.C. Carretero. Tetrahedron Lett. 41, 4107
(2000); (c) A.D. Westwell and C.M. Rayner. In Organosulfur
chemistry. Synthetic and stereochemical aspects. Vol. 2. Edited
by P. Page. Academic Press, San Diego. 1998. Chap. 5; (d) M.
Mikolajcyk, J. Drabowicz, and P. Kielbasinski. Chiral sulfur
reagents. CRC Press, Boca Raton. 1997. pp. 144–191.
16. R.R. Strickler. Ph.D Thesis, University of Guelph, Guelph,
Ontario, 2000.
26. K.H. Geiss, D. Seebach, and B. Seuring. Chem. Ber. 110, 1833
(1977).
27. F. Yuste, B. Ortiz, J.I. Pérez, A. Rodríguez-Hernández, R.
Sánchez-Obregón, F. Walls, and J.L. García Ruano. Tetrahe-
dron, 58, 2613 (2002).
28. D.A. Cogan, G. Liu, K. Kim, B.J. Backes, and J.A. Ellman. J.
Am. Chem. Soc. 120, 8011 (1998).
29. J. Fawcett, S. House, P.R. Jenkins, N.J. Lawrence, and D.R.
Russell. J. Chem. Soc., Perkin Trans. 1, 67 (1993).
30. A.L. Schwan and Y. Lear. Sulfur Lett. 23, 111 (2000).
31. T. Kageyama, Y. Ueno, and M. Okawara. Synthesis, 815 (1983).
17. J. Drabowicz, B. Bujnicki, and M. Mikolajcyk. J. Org. Chem.
47, 3325 (1982).
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