Nucleophilic attack of 2-sulfinyl acrylates: A mild and general approach to sulfenic acid anions

Article abstract of DOI:10.1039/b917217c

An increasing number of reactions of sulfenic acid anions are being demonstrated in the literature. As such, mild, general and reliable means for the generation of sulfenates are due. In the current paper, an addition/elimination of 2-sulfinyl acrylates using various nucleophiles is demonstrated and evaluated as a protocol for alkane- and arenesulfenate generation. Cyclohexanethiolate, methoxide and n-butyllithum each exhibit some merit for the reaction, and the thiolate is established as a mild, selective and effective reagent to release sulfenates from 2-sulfinyl acrylates. The stereospecificity of the addition/elimination of each nucleophile is recognized, and an explanation for the specificity is offered for thiolate and methoxide.

Full text of DOI:10.1039/b917217c

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Nucleophilic attack of 2-sulfinyl acrylates: A mild and general approach to
sulfenic acid anions†
Suneel P. Singh, Jennifer S. O’Donnell and Adrian L. Schwan*
Received 20th August 2009, Accepted 9th January 2010
First published as an Advance Article on the web 10th February 2010
DOI: 10.1039/b917217c
An increasing number of reactions of sulfenic acid anions are being demonstrated in the literature. As
such, mild, general and reliable means for the generation of sulfenates are due. In the current paper, an
addition/elimination of 2-sulfinyl acrylates using various nucleophiles is demonstrated and evaluated as
a protocol for alkane- and arenesulfenate generation. Cyclohexanethiolate, methoxide and
n-butyllithum each exhibit some merit for the reaction, and the thiolate is established as a mild,
selective and effective reagent to release sulfenates from 2-sulfinyl acrylates. The stereospecificity of the
addition/elimination of each nucleophile is recognized, and an explanation for the specificity is offered
for thiolate and methoxide.
Introduction
Sulfenic acid anions (1)1 represent important sulfur nucleophiles
that have served as valuable precursors to a variety of sulfoxides.
Although sulfenate anions may exhibit sulfur or oxygen reactivity,
they can be selectively alkylated at sulfur to produce vinylic,2–5
alkynyl,6 aromatic7–10 and alkyl sulfoxides,7,8 in addition to spe-
cialty targets such as a paracyclophane,11 cyclopropanes12 and
cysteine derivatives.13 Though complementary to sulfide oxidation
protocols,14 sulfenate functionalization chemistry is expected to
respond to an alternative set of experimental variables, and as
such, represents a conceptually different approach to sulfoxides.
Sulfenates (1) are generally not isolable species and are created
in situ for further functionalization. Notwithstanding this con-
cern, increased exploration and recent advances with sulfenates
have facilitated access to increasingly challenging targets.11,13,15
Modern developments in the generation of sulfenates involve a
sulfur oxidation protocol,5,6,16 a retro-Michael reaction,7 fluoride-
induced desilylative fragmentation chemistry10 and an addition
elimination reaction of b-sulfinyl acrylates.8 In that latter work,
we introduced the first general protocol for the release of aryl- and
alkyl-substituted sulfenates. In this paper, we outline our full study,
offering additional examples, some mechanistic implications and
the introduction of n-BuLi as a sulfenate-releasing reagent.
Scheme 1
N-oxides.9 In keeping with our ongoing studies of unsaturated
sulfinyl derivatives,17,19 we decided to probe the general usefulness
of the acrylate as a sulfenate-releasing group, believing that it may
prove more reactive than the aromatic substrates of Furukawa,
and may also permit access to a greater breadth of sulfenates. At
the time this work was commenced, there were no general means
to produce alkanesulfenates.
A number of the requisite starting compounds (2) were obtained
through simple conjugate additions of thiol to methyl propiolate,
followed by MCPBA oxidation (yields over two steps: 21, 38,
45–87%).20 There was no effort made to secure a preferred double
bond isomer and both were obtained in many instances. During the
course of these preparations, it was realized that a shorter exposure
time between thiol and alkyne was preferred, and recent yields
for the two step preparation are superior for that reason, with
thiol conjugate addition reaction yields reaching 98%. Z,E- and
Z,Z-bis[2-carbomethoxyethenyl] sulfoxides (2j) and homocysteine
derivative 2l were prepared using the newly introduced caesium
2-Z-carbomethoxyethenethiolate methodology.21 Other methods
may be suitable for the preparation of the requisite sulfoxides 2,
such as the sulfenic addition protocol of Aversa et al.,22 which
would yield selectively the E-isomer, but this was not exploited for
the current work.
Results and discussion
As part of our studies regarding the sulfur substitution chemistry
of a,b-unsaturated sulfenate esters, we encountered a situation
where an alkoxide displaced a sulfenate anion under ostensibly
an addition/elimination mechanism (Scheme 1).17 The reaction
resembles an intermolecular version of a Smiles rearrangement18
on a sulfoxide, but also was similar to chemistry offered from
the Furukawa group for the release of sulfenate anions from the 2-
position of benzothiazoles, or from 2-sulfinyl substituted pyridine-
Although a number of conditions and nucleophiles were eval-
uated for their sulfenate-releasing reactivity with sulfoxides 2, the
study herein focuses on n-butyllithium/hexane in THF, lithium
cyclohexanethiolate in THF, and NaOMe/MeOH solution in-
troduced into THF. The assessment of the chemistry occurred
through quenching the mixtures with a reactive electrophile, so
Department of Chemistry, University of Guelph, Guelph, Ontario, Canada
N1G 2W1. E-mail: schwan@uoguelph.ca
† Electronic supplementary information (ESI) available: Further experi-
mental and characterization details. See DOI: 10.1039/b917217c
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that the sulfenates could be efficiently captured through sulfoxide
formation by way of S-alkylation. It is well established that
the structure and intermediacy of the sulfenate can be inferred
through characterization of the stable sulfoxide.1 In this work,
the electrophile, most commonly benzyl bromide or methyl
iodide, was added as a THF solution 1–15 min after nucleophile
addition. After warming and stirring for 12 h, the mixtures were
concentrated and subjected to flash chromatography.
Fig. 1 By-products of the addition/elimination reactions.
Table 1 shows the yields of isolated and purified sulfoxides.
Overall, the chemistry is amenable to a wide variety of sulfenates,
including both arene- and alkanesulfenates, making it only one
of two methods possessing such general applicability.7 There are
nevertheless some important observations to glean from Table 1,
which relate primarily to the selection of the nucleophile.
Sodium methoxide proved useful to release aromatic sulfenates,
but yields were sometimes low and irreproducible for alkanesulfe-
nates, most notably in the instances of methyl (2b) and benzyl (2d),
where the carbon a to the sulfoxide may exhibit increased acidity
toward the unhindered methoxide base. The effectiveness of n-
BuLi was surprising in light of the electrophilic functional groups
in each substrate. Nevertheless, n-BuLi is effective for aromatic
substrates and some alkyl systems, such as benzyl.
Lithium cyclohexanethiolate appears to be the most mild, and
presumably selective, reagent. In particular, it created sulfenate 1i
from sulfoxide 2i. The latter would be expected to react differently
under conditions of base treatment7 and create sulfenate 1j,
assuming that conjugate addition did not occur. Clearly, the use
of thiolate for the addition/elimination chemistry is preferred
for base-sensitive substrates. This is underscored when viewing
recently published chemistry, where a cysteinesulfenate (1m) can
be prepared from a base-sensitive precursor.13
A direct comparison of electrophilicity is evident in the reaction
of sulfoxide 2h with thiolate: the acrylate was more receptive
to nucleophilic addition than the benzothiazole. This provides
a direct indication that the acrylate displacement chemistry
presented herein is milder and more chemoselective than the
benzothiazole-based method of Furukawa,9 at least when thiolate
is adopted as the nucleophilic reagent.
A final comment is due on the chemistry of sulfoxides E,Z-2j
and Z,Z-2j and the sulfenate that results from them (1j). These
compounds were prepared to explore the E vs. Z selectivity of
the nucleophiles, and either of these compounds could represent
commercial sources of a masked [SO]-2 equivalent based on a
double sulfenate release protocol. Using thiolate, the mildest
reagent, neither sulfenate S-alkylation product (E/Z-2d) nor
double S-alkylation product (3d) could be detected. The presence
of Z-methyl 3-cyclohexylthiopropenoate (vide infra) indicated
sulfenate was being released, but alkylation was apparently too
slow.23 Similar results were obtained with n-BuLi where Z-6/Z-7
(Fig. 1) could be detected, but S-alkylation products (E/Z-2d/3d)
were not observed. Sodium methoxide proved superior for this
substrate, but the reason may not have its origins in sulfenate
generation, but more likely in sulfenate reactivity. It was previously
established that potassium and sodium sulfenate exhibit greater
reactivity than lithium sulfenates.24 The isolation of sulfoxide E-
2d in 42% yield (alongside the formation of Z-5), and the lack
of alkylation product using lithium thiolate, suggests that Na-
1j is more reactive than Li-1j. It should also be mentioned that
the high yield of sulfenate capture product with a non-activated
electrophilic iodide affording 3aa may be brought about because
sodium is the counterion.
In order to better understand the mechanism of sulfenate
release, additional experiments regarding stereochemistry and
by-products were performed. In the case of methoxide and
thiolate reagents, methyl 3-methoxypropenoate and methyl 3-
cyclohexylsulfanylpropenoate were observed, respectively, point-
ing to an addition/elimination mechanism. In those instances
(2a, 2h) where a single double bond isomer was reacted, the
by-product maintained the geometry of the starting material,
indicating a stereospecific addition/elimination sequence. An
elimination/addition pathway would be expected to afford a mix-
ture of by-products, by way of non-selective conjugate addition to
propiolate. In addition, many of the starting sulfoxides display 13
C
NMR resonances for the electrophilic carbons of 147–150 ppm.
De Lucchi and coworkers have suggested that electron-deficient
compounds with alkene chemical shifts in the order of 138–
140 ppm favour addition/elimination over elimination/addition.25
The mechanism for the reactions with n-BuLi is less certain.
Unsaturated ester 6 and lesser amounts of 7 were consistently
observed as part of the reaction profiles of the reaction with
n-BuLi. Hexenoate 6 is consistent with an addition/elimination
mechanism, but 7 is probably formed by a different mechanism,
one that may begin with Bu- attack at the sulfinyl sulfur or oxygen.
However, no other products diagnostic of additional reaction
mechanism steps were observed.
Also of interest is the rate at which E- vs. Z-sulfinyl acrylates
react with nucleophiles. In separate experiments, a 50 : 50 mixture
of methyl E- and Z-p-toluenesulfinylacrylates (E-2a, Z-2a) were
treated with 0.25 molar equivalents of nucleophile. As shown
in Table 2, in each example, the Z-isomer reacted preferentially,
releasing sulfenate and affording the Z-acrylate as a by-product.
The sulfenate was then captured with benzyl bromide.
The data in Table 2 indicate that the Z-isomer reacts prefer-
entially faster than the E-isomer, and the results underscore the
stereospecificity of the reaction. Additional evidence was obtained
from the reaction of the nucleophiles with E-2a, the E-isomer
of byproducts 4–7 was observed in each case. The specificity
has been observed previously in a number of related addi-
tion/elimination reactions, with substrates possessing comparable
structural features.26,27 That mechanism is most likely to occur
when there is some, but not extensive, stabilization of the Michael
adduct and when there is a good leaving group. The sulfenate,
whose conjugate acid has a pKa in the range 6–10,28 would be
considered a mid-strength to weak nucleofuge, and as such would
permit bond rotation in the conjugate addition intermediately
prior to leaving group release. However, the react◦ion that releases
sulfenate is almost instantaneous in THF at -78 C.13 Given this,
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Table 1 Sulfoxide formation through sulfenate intermediacy (Scheme 2)
Starting material
Sulfenate
Reagent (eq.)a
R2X (eq.)b
Sulfoxide/%
E/Z-2a
MeO-Na+
MeO-Na+
n-BuLi
BnBr
C16H33I
BnBr
BnBr
3a/84
3aa/87
3a/78
3a/84
CyS-Li+
Z-2a
n-BuLi
BnBr
BnBr
3a/88
3a/81
MeO-Na+
E-2a
n-BuLi
n-BuLi
BnBr
MeI
3a/81
3ab/85
E/Z-2b
E-2c
MeO-Na+
CyS-Li+
BnBr
BnBr
3b/0–27
3b/62
MeO-Na+
n-BuLi
BnBr
BnBr
BnBr
3c/65
3c/53
3c/55
CyS-Li+
E/Z-2d
MeO-Na+
MeO-Na+
n-BuLi
BnBr
MeI
BnBr
BnBr
3d/13-84
3b/12-48
3d/74
CyS-Li+
3d/75
E-2e
E-2f
Z-2g
MeO-Na+
MeI
3e/63
MeO-Na+
n-BuLi
BnBr
BnBr
3f/77
3f/29
MeO-Na+
n-BuLi
BnBr
BnBr
3g/50
3g/54
E/Z-2h
Z-2h
CyS-Li+
BnBrc
3h/70
MeO-Na+
n-BuLi
BnBrc
BnBrc
BnBrc
3h/33
3h/49
3h/66
CyS-Li+
E-2h
CyS-Li+
CyS-Li+
BnBrc
3h/78
3i/57
E/Z-2i
2-BrC6H4CH2Brc
E,Z-2j
CyS-Li+
MeO-Na+
n-BuLi
BnBrc
BnBrc
BnBrc
E/Z-2d/0
E-2d/42%
E/Z-2d/0
Z,Z-2j
CyS-Li+
n-BuLi
BnBrc
BnBrc
E/Z-2d /0
E/Z-2d/0
c
E,E-/E,Z-2k
CyS-Li+
BnBrd
3k/74 (1.25)e
Z-2l
CyS-Li+
CyS-Li+f
BnBr
3l/45 (1.5)e
E-2m
Various ArCH2Brg
3m/51–76g
a 1.0 molar equivalents of nucleophile were employed, unless otherwise noted. b 1.2 molar equivalents of electrophile were employed, unless otherwise
noted. c 2.0 molar equivalents were employed. d 2.4 molar equivalents were employed. e Ratio of diastereomers. f 0.95 molar equivalents were employed.
g See ref. 13.
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Table 2 Outcome of reactions of methyl E- and Z- p-toluene-
sulfinylacrylates (2) with reduced nucleophile equivalents
Isolated compounds’ yields (%)
Nucleophile
E-2aa
Z-2aa
3aa
cC6H11S-Li+
MeO-Na+
Bu-Li+
50
50
50
27
25
25
23
18
20
Z-4, 95%b
Z-5c
Z-6, 7c
a Isolated yields are based on starting materials (50 : 50 = E/Z-p-
tolylsulfinylacrylate). b Yield based on thiolate. c Yield not obtained.
Scheme 2
we suggest a mechanism as shown in Scheme 3, which can account
for the chemistry involving methoxide and thiolate nucleophiles.
In the scheme, the nucleophile could add from either face
and presumably has a preference based on the configuration of
the sulfinyl group.29 Since the substrates are racemic, the face
selectivity was not brought into consideration. For both E and Z-
substrates, Michael addition would deliver the Nu a to the sulfinyl
group and the counterion (M+) to the carbonyl oxygen. From that
point, a 60◦ rotation is required to align the S–C bond with the
p-orbitals of the enolate p systems, a configuration optimum for
elimination. Many substrates have exhibited a preference for the
small 60◦ rotation vs. a less desirable 120◦ option.26 Elimination
of the sulfenate follows.
Scheme 3
rate of the reaction. Lithium cyclohexanethiolate is the preferred
mild choice, and should be utilized for base-sensitive substrates.13
The chemistry presented herein is suitable for a wide variety of
sulfenates and can be achieved at low temperature with some
functional group selectivity.
Experimental
General experimental aspects are summarized in the ESI†.
Procedures for, and characterization of, the starting 2-
carbomethoxyethenyl sulfoxides (2), data for known sulfoxides 3,
and by-products 4–7 are found in the ESI†. Data for new sulfoxides
3 are shown below.
An additional benefit of the 60◦ rotation is the creation of
a stabilizing interaction between the ester enolate counterion
and the Lewis acidic sulfinyl oxygen which, in turn, accelerates
sulfenate loss, as shown by the mechanism arrows in Scheme 3.
This interaction is readily available in the Z-isomer prior to the 60◦
rotation and, indeed, a preliminary interaction between the metal
ion and the sulfinyl oxygen may assist in the conjugate addition,
which could be the reason for the observed higher reactivity of the
Z-isomer.
General procedure for the liberation of sulfenates and synthesis of
Ar(alk)yl sulfoxides 3
Method A. A solution of cyclohexyl thiol (1 eq.) was prepared
in dry THF and cooled to -78 ◦C under N2. While stirring, n-BuLi
(1.0 eq. as a 2.5 M or 1.6 M solution in hexanes) was added via
Conclusions
◦
syringe. The mixture was stirred for 30 min at -78 C, taken up
It is increasingly apparent that creating an (conjugated) anion
b to a sulfinyl group is a preferred method for the generation
of a sulfenate anion.2,7,9,10,30,31 Those protocols that can achieve
this under mild and selective conditions should be useful for
preparing sulfenates. The current work outlines details of an
inviting approach which can be performed with various common
nucleophilic agents. Sulfinyl acrylates are readily available and the
double bond configuration does not affect the chemical yield of
eventual sulfoxide generation, but does exert an influence on the
into a syringe, and transferred to a solution of a,b-unsaturated
sulfoxide (2) (1 eq.) in dry THF (1 mL/10 mg; 1–2 mL for thiolate
and 8–9 mL for sulfoxide flasks) at -78 ◦C. The reaction was stirred
◦
for 1–15 min, and a -78 C solution of RX (1.2 eq.) in THF (1-
2 mL) was then added. The reaction mixture was stirred overnight
while slowly warming to RT, concentrated under reduced pressure,
and purified by flash chromatography using EtOAc–hexanes as
the eluent. Sulfoxide yields are obtained from the starting a,b-
unsaturated sulfoxide.
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Method B. To a solution of 2 (1 eq.) in dry THF (1 mL/10 mg)
of benzyl bromide (217 mL, 1.83 mmol) in THF (1 mL) was added.
The reaction mixture was stirred overnight while slowly warming
to RT and then concentrated under reduced pressure. When E,Z-
2j was used as the starting material, E-2d (65 mg, 42%) was isolated
after flash chromatography (30% EtOAc–hexanes to 40% EtOAc–
hexanes). Z-5 was observed in the reaction mixture as a major
product. The reaction of Z,Z-2j resulted in a complicated mixture.
◦
at -78 C was added MeO-Na+ or n-BuLi (1.0 eq., 25% sodium
methoxide solution in MeOH; 1.6 M or 2.5 M n-BuLi in hexanes)
and the solution was stirred for 1–15 min. A -78 ◦C solution of RX
(1.2 eq.) in THF (1–2 mL) was then added. Procedure followed as
per Method A.
Synthesis of 2-carboethoxyethyl o-bromobenzyl sulfoxide (3i)
(Method A)
Method B (with n-BuLi). E,Z or Z,Z-2j (200 mg, 0.917 mmol)
in THF (15 mL) was treated with n-BuLi (1.6 M, 510 mL,
0.825 mmol) at -78 ◦C. After 1–2 min, a solution of benzyl bromide
(217 mL, 1.83 mmol) in THF (1 mL) was added. The reaction
mixture was stirred overnight while slowly warming to RT, and
then concentrated under reduced pressure. E/Z-2d or 3d was not
observed, while Z-6/Z-7 were detected in the reaction mixture as
major products.
Sulfoxide (E/Z-2i) (500 mg, 2.13 mmol) in anhydrous THF
(20 mL) was treated with a CySH (0.26 mL, 2.13 mmol)/n-BuLi
(1.33 mL, 1.6 M in hexane, 2.13 mmol) solution in anhydrous
THF (5 mL), followed by the addition of 2-bromo benzyl bromide
(1.07 g, 4.27 mmol). Sulfoxide 3i (395 mg, 57%) was recovered
as a liquid after flash chromatography (EtOAc–hexanes 30 : 70)
which solidifies as yellowish solid on prolonged standing under
vacuum. Recrystallization with ethyl acetate–hexane gave a white
Competitive reactions of 2-carbomethoxyethenyl p-tolyl sulfoxides
E/Z-2a
◦
1
solid. Mp: 40–42 C; H NMR (400 MHz, CDCl3), d: 7.59 (m,
1H), 7.37 (m, 1H), 7.30 (m, 1H), 7.18 (m, 1H), 4.24-4.10 (m, 4H),
Method A (with CySLi). 2-Carbomethoxyethenyl p-tolyl sul-
foxide (1 : 1 mixture of E/Z-2a) (200 mg, 0.892 mmol) in THF
(15 mL) was treated with CySH/n-BuLi (27.0 mL, 0.223 mmol;
1.6 M, 139 mL, 0.223 mmol) at -78 ◦C. After 1–2 min, a solution
of benzyl bromide (212 mL, 1.78 mmol) in THF (1 mL) was
added. The reaction mixture was stirred overnight while slowly
warming to RT, and then concentrated under reduced pressure.
E-2a (100 mg, 50%), Z-2a (54 mg, 27%), 3a (47 mg, 23%) and
Z-4 (42 mg, 95%) were isolated after flash chromatography (2%
EtOAc–hexanes to 40% EtOAc–hexanes).
3.08-3.01 (m, 1H), 2.90-2.78 (m, 3H), 1.23 (t, J = 7.1 Hz, 3H); 13
C
NMR (75.5 MHz, CDCl3), d: 170.9, 132.9, 132.2, 129.8, 127.7,
124.8, 60.9, 58.4, 45.7, 26.7, 13.9; IR (CDCl3), cm-1: 2980, 2929,
1732, 1237, 1182, 1043. Analysis calc’d for C12H15O3SBr: C, 45.15;
H, 4.74; found: C, 44.13; H, 4.61.
Synthesis of Cbz-homoCys((O)-Bn)-OMe (3l) (Method A)
Z-Cbz-homoCys((O)-2-carbomethoxyethenyl)-OEt (2l) (120 mg,
0.313 mmol) in THF (10 mL) was treated with a solution of
CySH/n-BuLi (38.3 mL, 0.313 mmol; 1.6 M, 199 mL, 0.319 mmol)
followed by the addition of benzyl bromide (44.7 mL, 0.376 mmol).
Sulfoxide 3l (54.5 mg, 45%) was isolated as an oil after flash
chromatography (eluted with 50% EtOAc–hexanes, then 3%
MeOH–EtOAc) as a mixture of diastereomers (dr 1.5 : 1). 1H
NMR (400 MHz, CDCl3), d: 7.35 (m, 8H), 7.26 (m, 2H), 5.81
(two d, J = 7.7 Hz, J = 7.7 Hz, 1H), 5.10 (s, 2H), 4.43 (m, 1H),
3.96 (ABq, J = 12.9 Hz, 2H), 3.72 (s, 3H), 2.67 (m, 2H), 2.33 (m,
1H), 2.12 (m, 1H); 13C NMR (100.6 MHz, CDCl3), d: 171.7, 155.9,
136.1, 129.9, 129.5, 129.0, 128.9, 128.5, 128.4, 128.1, 67.1, 58.1,
53.0, 52.6, 46.3, 25.6; IR (CHCl3), cm-1: 3424, 2996, 1740, 1721,
1346, 1017; MS (EI), m/z (%): 389 (M+, 2), 345 (4), 238 (3), 182
(2), 181 (12), 140 (3), 108 (2), 107 (3), 92 (8), 91 (100), 83 (2), 79 (2),
65 (4), 55 (3); Calc’d for C20H23NO5S: 389.1298; found: 389.1296.
Method B (with MeONa). 2-Carbomethoxyethenyl p-tolyl
sulfoxide (1 : 1 mixture of E/Z-2a) (200 mg, 0.892 mmol) in THF
(15 mL) was treated with MeONa (25% wt in methanol, 50.8 mL,
0.223 mmol) at -78 ◦C, followed by the immediate addition
of a solution of benzyl bromide (212 mL, 1.78 mmol) in THF
(1 mL). The reaction mixture was stirred overnight while slowly
warming to RT, and then concentrated under reduced pressure.
E-2a (100 mg, 50%), Z-2a (54 mg, 27%), 3a (37 mg, 18%) and Z-5
were isolated after flash chromatography (2% EtOAc–hexanes to
40% EtOAc–hexanes).
Method B (with n-BuLi). 2-Carbomethoxyethenyl p-tolyl sul-
foxide (1 : 1 mixture of E/Z-2a) (200 mg, 0.892 mmol) in THF
(15 mL) was treated with n-BuLi (139 mL, 0.223 mmol) at -78 ◦C,
followed by the immediate addition of a solution of benzyl bromide
(212 mL, 1.78 mmol) in THF (1 mL). The reaction mixture was
stirred overnight slowly warming to RT, and then concentrated
under reduced pressure. E-2a (100 mg, 50%), Z-2a (50 mg,
25%), 3a (41 mg, 20%), Z-6 and Z-7 were isolated after flash
chromatography (2% EtOAc–hexanes to 40% EtOAc–hexanes).
Reactions of bis(carbomethoxyethenyl) sulfoxides E,Z/Z,Z-2j
Method A (with CySLi). E,Z or Z,Z-2j (200 mg, 0.917 mmol)
in THF (15 mL) was treated with CySH/n-BuLi (101 mL,
0.825 mmol; 1.6 M, 510 mL, 0.825 mmol) at -78 ◦C. After 1–
2 min, a solution of benzyl bromide (217 mL, 1.83 mmol) in THF
(1 mL) was added. The reaction mixture was stirred overnight
while slowly warming to RT and then concentrated under reduced
pressure. Formation of E/Z-2d or 3d was not observed, while
Z-4 (165 mg, 95%) was isolated as a major product after flash
chromatography.
Acknowledgements
The authors wish to thank the Natural Sciences and Engineering
Research Council of Canada for partial funding of this research.
Acknowledgement is also made to the Donors of the American
Chemical Society Petroleum Research Fund for partial support of
this research. JSO thanks the Ontario Government for a Science
and Technology Graduate Fellowship.
Method
B (with MeONa). E,Z or Z,Z-2j (200 mg,
0.917 mmol) in THF (15 mL) was treated with MeONa (25% in
MeOH, 157 mL, 0.917 mmol) at -78 ◦C. After 1–2 min, a solution
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