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N. Surineni et al. / Tetrahedron Letters 56 (2015) 6965–6969
Cl
RSH
OAc
SR
Br
O
O
Br
NCS, Dry CH2Cl2
4a
, 78%)
3a
Where R = 4-BrC6H4
Scheme 1. Chlorothiolation of internal alkyne.
But in our case we obtained 4a as a sole product. To confirm the
exact structure as well as configuration of vinyl sulfide, we trans-
formed 4g into sulfoxide 5g using PIDA as mild oxidant. Further
chlorovinyl sulfoxide 5g was treated with 4-methylbenzenethiol
in the presence of excess triethylamine resulting the substituted
product 6 (Scheme 2).
Similarly, most of synthetic methods selected for oxidation of
sulfides to sulfoxides are an intermediate step in the synthesis of
sulfones.12 Hence investigations toward finding mild oxidants
which convert sulfides to only sulfoxides is a very interesting area
of synthetic organic chemistry as well.
Figure 1. ORTEP diagram of compound 6.
Table 1
Optimization of chlorothiolation reaction
Entry
Solventa
Time (h)
Yieldb (%)
1
2
3
4
5
EtOAc
DCE
Toluene
CH3CN
DCM
5
6
7
8
3
65
70
68
63
78
The product 6 was purified by using the column chromato-
graphic technique and the ORTEP diagram of 6 confirms the
original structure of product 4g (Fig. 1).
a
Anhydrous solvents used.
Isolated yields.
b
After confirming the exact structure of 6, we next studied the
solvent effects on this reaction. Initially, the effectiveness of differ-
ent solvents such as EtOAc, DCE, toluene and CH3CN were tested
and we found that there was no dramatic change in the product
in all these solvent systems. N-bromosuccinimide also reacted with
thiol to produce sulfenyl bromide that underwent addition with
alkyne 3a to produce bromovinyl sulfide with mild regioselectivity.
In the absence of a halogen source (NBS, NCS) no reaction took
place. Thus, we have found the halogen source (NCS, NBS) is essen-
tial for the in situ generation of sulfenyl halide to undergo addition
with internal alkyne (3) to afford anti product as shown in Table 1.
With these successful regio/stereoselective chlorothiolation condi-
tions in hand, we next proceeded to examine the generality of
these reactions as illustrated in Table 2. Various substituted thiols
were treated with internal alkyne 3 as shown in Table 2 (4b–4p) in
good to excellent yields. Under these conditions electron rich thiols
underwent chlorothiolation faster as compared to electron defi-
cient thiols like –F, but the thiols containing the NO2 group do
not undergo reaction with the substrate 3a. Even the alkylated thi-
ols , like cyclohexane thiol underwent chlorothiolation to yield the
corresponding chloroalkenyl sulfide (4h). Finally, chlorothiolation
strategy was also utilized by changing the alkyne containing –Me
and –OMe substituent in the place of –Br to produce vinyl sulfides
4o (60%) and 4p (77%). However in the case of a substrate bearing
an –OMe group, afforded a vinyl sulfide mixture (see Scheme 3).
In recent years, hypervalent iodine reagents are broadly applied
as powerful electrophiles and highly selective oxidants due to their
low toxicity, mild reactivity, high stability, and easy handling in
organic synthesis.13 Firstly Togo et al. converted diaryl sulfides into
corresponding sulfoxides and sulfones by using phenyl iodine di
acetate (PIDA) as oxidant.14 Recently Yu et al. synthesized
sulfoxides and sulfones from sulfides by using in situ generated
Koser’s reagent in aqueous media.13g In addition to this, PIDA is
used as
a mild oxidant and found in several sulfoxides
synthesised from sulfides.15 Recently Sokolenko et al. explored
the utility of perfluroalkyl vinyl sulfoxides by alkylation via Heck
reaction.16 These results prompted us to work on vinyl sulfides
followed by sulfoxide synthesis and here we wish to report
regio/stereoselective chlorothiolation of alkynoates and PIDA
mediated oxidation to sulfoxides.
As organo sulfoxides are important intermediates in the synthe-
sis of various biologically important natural products as well as vinyl
sulfoxides used as starting materials in Heck coupling reaction also,
we decided to convert our synthesized b-chloro alkenyl sulfides to
b-chloroalkenyl sulfoxides. In general, oxidation of sulfides involved
different hypervalent iodine reagents which are required prior to
the preparation of catalyst or synthesis of Koser’s reagent as oxidant
in the presence of stoichiometric amounts of additives. To the best of
our knowledge there is no report on metal free chlorothiolation
reaction of internal alkynoates and their subsequent PIDA mediated
selective oxidations to corresponding sulfoxides.
Finally, we carried out the oxidation of sulfur by using PIDA as
oxidant to convert b-chloroalkenyl sulfides into sulfoxides. We
began our investigation on a model substrate 4a. PIDA mediated
oxidation proceeded at room temperature in a solvent system con-
sisting of DCE/AcOH (2:1) and we observed the formation of a trace
amount of sulfoxide. To complete the conversion of 4a, we heated
the reaction mixture at 80 °C to afford sulfoxide 5a with high selec-
tivity. The formation of sulfoxide was confirmed by 1H NMR, 13C
AcO
AcO
AcO
HS
Cl
S
Cl
PIDA
S
S
S
excess Et3N,
THF:H2O (2:1)
R.T., 2hr
DCE: AcOH (2:1),
80oC
O
O
MeO
MeO
MeO
Br
Br
Br
4g
5g
6
Scheme 2. Synthesis of (E)-3-(4-bromophenyl)-2-((2-methoxyphenyl)sulfinyl)-3-(p-tolylthio)allyl acetate 6.
Surineni, Naresh
