Novel synthesis of oxathiocine derivatives by Wittig olefination and intramolecular Heck reaction via an 8-endo-trig cyclization

Article abstract of DOI:10.1055/s-0028-1083228

Syntheses of hitherto unreported heterocycles, such as oxathiocine derivatives, in excellent yields, and a doubly cyclized oxathiocine derivative, through a Wittig olefination and intramolecular Heck reaction sequence via an unusual 8-endo-trig cyclization, are reported. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1083228

PAPER
3857
Novel Synthesis of Oxathiocine Derivatives by Wittig Olefination and
Intramolecular Heck Reaction via an 8-endo-trig Cyclization
N
ovel Synthesis of
r
O
xathio
i
cine
D
s
erivativeshna C. Majumdar,* Buddhadeb Chattopadhyay, Biswajit Sinha
Department of Chemistry, University of Kalyani, Kalyani 741 235, India
E-mail: kcm_ku@yahoo.co.in
Received 30 July 2008; revised 13 August 2008
ular Heck reaction.7 Denieul and Skrydstrup recently
showed that during the intramolecular Heck cyclization,
the 7-exo-trig mode of cyclization of a compound having
a vinyl group attached to an aromatic ring was favored
over the 8-endo-trig mode.8 Subsequently, Guy et al. sup-
ported this statement by synthesizing the 8-endo Heck
products through a Heck reaction with the activated vinyl-
ic systems.9 The same authors also synthesized eight-
membered sulfur heterocycles via the 8-endo-trig mode of
cyclization by the same protocol, starting from the highly
activated vinylic double bond. These results prompted us
to undertake a study on the intramolecular Heck reaction
of different Heck precursors with a view to synthesizing
eight-membered oxathio-heterocycles fused with diaryl
moieties; synthetically, this is a challenge due to the pres-
ence of strain within such compounds. Additionally, we
were interested in studying the Heck cyclization under
ligand-free10 conditions using aryl bromides in view of a
recent finding that ligand-free approaches do not work for
the usually preferred aryl bromides.10 To our knowledge,
the synthesis of oxathiocine heterocycles has not yet been
reported.
Abstract: Syntheses of hitherto unreported heterocycles, such as
oxathiocine derivatives, in excellent yields, and a doubly cyclized
oxathiocine derivative, through a Wittig olefination and intramolec-
ular Heck reaction sequence via an unusual 8-endo-trig cyclization,
are reported.
Key words: Wittig olefination, intramolecular Heck reaction, pal-
ladium catalyst, oxathiocine, 8-endo-trig
The importance of medium-sized rings in synthetic organ-
ic chemistry is exemplified by their presence as the struc-
tural core moiety in a large number of biologically
important natural products.1 Moreover, these units serve
as target molecules in numerous synthetic studies.2 Sever-
al excellent articles and monographs have documented
such medium-ring syntheses well.3 Though synthetic pro-
tocols for five- and six-membered ring systems are com-
mon, seven- and eight-membered ring formations are not
abundant. The cyclization strategies for medium-sized
rings are often restricted due to entropy factors and trans-
annular interactions.4 In general, the number of methods
available for the synthesis of medium-sized heterocycles
are relatively small. Among the various protocols, the pal-
ladium-catalyzed intramolecular Heck reaction has be-
come a useful synthetic method due to its excellent
functional group tolerance and high stereoselectivity. Re-
cently, we have reported the synthesis of some interesting
medium-ring heterocycles by the application of radical
cyclization,5 ring-closing metathesis6 and the intramolec-
The intramolecular Heck reaction, as stated earlier, can
undergo ring-closure by two possible modes, namely exo-
and endo-cyclization. Between these two possible modes,
small to medium size (5–8) ring-formation is usually fa-
vored by an exo-mode,11 since the endo-mode is sterically
very demanding; the endo-mode requires that the olefinic
system moves into the loop of the substrate, generating an
Br
Br
SO2Cl
CHO
CHO
OH
Br
O
O
S
(i)
S
(ii)
+
O
O
O
O
1a
2
3a
CHO
4a
Br
O
SO2Cl
Br
CHO
Br
OH
(i)
O
S
(ii)
S
+
O
O
O
O
R
R
R
2
1b–e
3b–e
4b–e
R = H, Me, OMe, Cl
Scheme 1 Reagents and conditions: (i) anhyd CH2Cl2, Et3N, DMAP, 0 °C→r.t., 2–3 h, stirring; (ii) PPh3MeI, n-BuLi, THF, 0 °C→r.t., 1.5 h,
stirring.
SYNTHESIS 2008, No. 23, pp 3857–3863
x
x.
x
x
.
2
0
0
8
Advanced online publication: 14.11.2008
DOI: 10.1055/s-0028-1083228; Art ID: Z18408SS
© Georg Thieme Verlag Stuttgart · New York

3858
K. C. Majumdar et al.
PAPER
Br
O
S
O
O
S
O
O
O
O
S
O
O
6
5a
unexpected but found
4a
expected but not found
Scheme 2
energetically favorable substituted alkene product. Con-
Table 1 Optimization of the Palladium-Catalyzed Intramolecular
versely, large ring (~20) formation with a flexible tether Heck Reactiona
usually favors endo-cyclization.12 To the best of our
knowledge, only a limited number of examples of endo-
cyclization for the formation of medium-sized rings have
been reported.9,13
Br
O
S
O
S
O
O
The required Heck precursors 4a–e were synthesized in
88–95% yields by a Wittig olefination reaction of sub-
strates 3a–e. The Wittig reagent was prepared from
Ph3PMeI in anhydrous tetrahydrofuran in the presence of
butyllithium, between 0 °C and room temperature, for 30
minutes. The substrates 3a–e were synthesized in 74–90%
yield by the reaction of hydroxyaldehydes 1a–e with 2-
bromobenzenesulfonyl chloride (2) in anhydrous dichlo-
romethane in the presence of triethylamine and a catalytic
amount of 4-(N,N-dimethylamino)pyridine (DMAP) at
between 0 °C and room temperature for 2–3 hours
(Scheme 1). Compounds 1a–e were prepared in turn by
the Reimer–Tiemann reaction of the corresponding phe-
nolic compounds.
O
O
4a
5a
Entry
Catalystb
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Basec
Solvent
DMF
DMF
Yield (%)d
90
1
2
KOAc
K2CO3
Et3N
81
3
DMF
<5
4
Ag2CO3
Cs2CO3
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
DMF
NR
NR
21
5
DMF
6
Pd(PPh3)2Cl2
PdCl2
DMF
7
DMF
NR
NR
NR
NR
<5
When the intramolecular Heck reaction was carried out
with the substrate 4a using the concept of Jeffery’s two-
phase protocol14 in the presence of Pd(OAc)2 as catalyst
(which is mostly used in this type of intramolecular Heck
reaction) in anhydrous N,N-dimethylformamide as sol-
vent, potassium acetate as base and tetrabutylammonium
bromide (TBAB) as additive for one hour under a nitrogen
atmosphere, compound 5a, the eight-membered endo-
Heck product, was obtained in 90% yield (Scheme 2)
without any contamination of the expected 7-exo-Heck
product 6. The endo-Heck product 5a was easily charac-
8
Pd(PPh3)4
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
DMF
9
MeCN
dioxane
toluene
10
11
a Reactions were carried out at 80 °C, TBAB used as additive.
b Catalyst used 5 mol%.
c 2.75 equivalents of base used.
d Isolated yield. NR indicates no reaction.
1
terized from its H NMR spectrum, which indicated the
presence of two olefinic protons belonging to the oxathio-
cine ring at d = 7.20 (d, J = 12.2 Hz, 1 H) and 7.27 (d,
J = 12.2 Hz, 1 H) ppm, with additional support from its
13C NMR spectrum and other analytical data.
important role in the Heck cyclization because, in the ab-
sence of TBAB, the reaction did not proceed at all. Guy et
al.9 synthesized the endo-Heck product with a sophisticat-
ed catalytic combination system [Pd(OAc)2, DMA,
Et4NCl, Cy2NMe, 12 h, 100 °C], but our optimized condi-
tion are relatively simple [Pd(OAc)2, DMF, KOAc,
TBAB, 80 °C] and it takes only 45–70 min for complete
conversion while their reaction required 12 hours. To test
the generality of the reaction, substrates 4b–e were also
treated under the optimized conditions to afford the novel
oxathiocine derivatives 5b–e in 79–91% yield. The results
are summarized in Table 2.
Optimum conditions for the cyclization were established
through a series of experiments whereby various changes
were made to the catalyst, base, additive and solvent
(Table 1).
During the course of optimization of the reaction, we
found that the catalyst, base, additive and solvent all have
profound effects on the reaction yield (Table 1). It is im-
portant to note that aryl bromides are reported to usually
undergo Heck cyclization in the presence of a ligand.
However, in the present instance the reaction was
achieved under ligand-free conditions.10 TBAB plays an
After achieving the synthesis of the endo-Heck products,
we extended the reaction to the readily available, inexpen-
sive starting material 2,7-dihydroxynaphthalene. 2,7-Di-
Synthesis 2008, No. 23, 3857–3863 © Thieme Stuttgart · New York

PAPER
Novel Synthesis of Oxathiocine Derivatives
3859
Yield (%)b
90
Table 2 Summarized Results of the Heck Reactiona
Entry
1
Substrate
Time (min) Product
Br
4a
60
55
5a
5b
O
O
S
S
O
O
O
O
Br
2
3
4
5
4b
4c
4d
4e
88
91
84
79
O
O
S
S
O
O
O
O
Br
45
60
70
5c
5d
5e
O
O
S
S
O
O O
O
Me
MeO
Cl
Me
MeO
Cl
Br
O
O
S
S
O
O O
O
Br
O
O
S
S
O
O
O
O
a All the reactions were performed under optimized reaction conditions [Pd(OAc)2, DMF, KOAc, TBAB, 45–70 min, 80 °C].
b Isolated yield.
hydroxynaphthalene-1,8-dicarboxaldehyde (1f) was The substrate 4f was reacted under the optimized reaction
readily prepared from 2,7-dihydroxynaphthalene by a conditions (Table 1, entry 1) for 30 minutes at 120 °C to
Reimer–Tiemann reaction. The hydroxyaldehyde 1f, on furnish the 8-endo double Heck product 5f in only 26%
reaction with 2-bromobenzenesulfonyl chloride (2), gave yield along with unidentified products. Increasing the re-
compound 3f which, on treatment with Ph3PMeI in the action time caused considerable decomposition of the
presence of n-BuLi in THF, afforded the corresponding doubly cyclized oxathiocine product. When the condi-
di-Heck precursor 4f (Scheme 3).
tions described in Table 1 (except entry 1) were applied to
CHO CHO
Br
S
Br
HO
OH
OH
HO
CHO CHO
(i)
(ii)
O
O
77%
45%
S
O
3f
O
O
O
1f
Br
Br
S
(iii)
61%
O
O
S
O
4f
O
O
O
Scheme 3 Reagents and conditions: (i) CHCl3, aq NaOH, 70 °C, srirring, 4 h, H2SO4; (ii) 2, anhyd CH2Cl2, Et3N, DMAP, 0 °C→r.t., 1 h; (iii)
anhyd THF, PPh3MeI, n-BuLi, stirring, 2 h.
Synthesis 2008, No. 23, 3857–3863 © Thieme Stuttgart · New York

3860
K. C. Majumdar et al.
PAPER
Br
Br
O
O
O
O
S
S
S
S
26%
O
O
O
O O
O
O
O
5f
4f
Scheme 4
Preparation of 1a–f by Reimer–Tiemann Reaction; Typical
Procedure
this reaction, no satisfactory results were obtained
(Scheme 4).
2-Naphthol (14 g, 0.1 mol) was added to a round-bottomed flask
and a hot solution of NaOH (32 g, 0.8 mol) in H2O (40 mL) was add-
ed. The reaction was heated to ~70 °C in an oil bath and CHCl3 (16
mL) was added dropwise to it. The reaction mixture was stirred for
1 h at the same temperature and then allowed to cool to r.t. The re-
action mixture was transferred to a 500 mL beaker with hot H2O and
subsequently acidified with H2SO4 (10N) and extracted with
CH2Cl2 (3 × 75 mL), washed with H2O (2 × 50 mL) and dried
(Na2SO4). The organic layer was collected and the solvent was dis-
tilled off. The crude material was purified by column chromatogra-
phy over silica gel (PE) to afford the product 1a. Compounds 1b–f
were prepared in a similar manner.
The cyclization of substrates 4 with the sulfonate ester
tether may occur via two alternative pathways – either an
8-endo-trig or a 7-exo-trig cyclization. It is interesting to
note that we have observed only 8-endo-trig cyclization to
afford, exclusively, the eight-membered oxathiocine de-
rivatives.
Denieul and Skrydstrup have reported8a that the palladi-
um-catalyzed cyclization of a similar substrate with an es-
ter tether to give a mixture of three products: the 7-exo-
trig cyclization product (i.e. seven-membered lactone,
major product), the 8-endo-trig cyclization product (eight-
membered lactone, minor product) and the biaryl coupling
product (trace). The authors optimized the 7-exo-trig
product with unactivated olefinic systems.8a
Preparation of Compounds 3a–f; Typical Procedure
DMAP (10 mg) and Et3N (2 mL) were added to a solution of 1a
(200 mg, 1.17 mmol) in anhydrous CH2Cl2 (20 mL) at 0 °C. 2-Bro-
mobenzenesulfonyl chloride (2; 300 mg, 1.17 mmol) in anhydrous
CH2Cl2 (10 mL) was added dropwise and reaction mixture and
stirred for 2 h. The reaction mixture was washed with H2O (3 × 10
mL) and brine (10 mL) and dried (Na2SO4). Evaporation of the
CH2Cl2 gave a crude mass, which was purified by silica gel chroma-
tography (EtOAc–PE, 10%) to afford product 3a. Compounds
3b–f were obtained in a similar manner.
The exclusive formation of benzoxathiocine derivatives
5a–e and 5f via the 8-endo-mode of cyclization is quite
unusual. Beletskaya and Cheprakov reported15 that the
endo-Heck cyclization can occur when the Heck precur-
sor possesses a Michael-type olefinic fragment,13 such as
a highly activated double bond, otherwise exclusive exo-
cyclization occurs. Subsequently, Guy et al. found that for
8-endo-Heck cyclization to occur, the substrate required
an activated vinylic double bond. However, in our present
work, the eight-membered oxathiocine derivatives were
found to form exclusively via the unusual 8-endo-trig
mode of cyclization without such requirements.
3a
Yield: 83%; solid; mp 115–116 °C.
IR (KBr): 1697, 1371, 1197 cm–1.
1H NMR (CDCl3, 400 MHz): d = 7.34 (d, J = 9.2 Hz, 1 H, ArH),
7.45 (t, J = 6.8 Hz, 1 H, ArH), 7.56–7.58 (m, 2 H, ArH), 7.69 (t,
J = 7.2 Hz, 1 H, ArH), 7.85–7.89 (m, 2 H, ArH), 8.00–8.05 (m, 2 H,
ArH), 9.20 (d, J = 8.8 Hz, 1 H, ArH), 10.66 (s, 1 H, CHO).
In conclusion, we have developed an efficacious, regiose-
lective method for the construction of eight-membered
oxathiocine derivatives (and a doubly Heck cyclized
endo-Heck product) via an unusual 8-endo-trig cycliza-
tion using a Wittig reaction followed by intramolecular
Heck cyclization as the key steps. The method represents
a simple synthetic protocol for the formation of fused ox-
athiocine (and doubly cyclized oxathiocine) derivatives.
MS: m/z = 390 [M+], 392 [M+ + 2].
Anal. Calcd for C17H11BrO4S: C, 52.19; H, 2.83. Found: C, 52.03;
H, 2.97.
3b
Yield: 81%; solid; mp 97–98 °C.
IR (KBr): 1693, 1378, 1160 cm–1.
1H NMR (CDCl3, 400 MHz): d = 7.15 (dd, J = 8.4, 1.2 Hz, 1 H,
ArH), 7.37 (t, J = 7.6 Hz, 1 H, ArH), 7.43 (dt, J = 7.6, 1.2 Hz, 1 H,
ArH), 7.50–7.54 (m, 2 H, ArH), 7.84 (dd, J = 7.6, 1.2 Hz, 1 H,
ArH), 7.91 (dd, J = 8.0, 1.6 Hz, 1 H, ArH), 7.98 (dd, J = 8.0, 2.0 Hz,
1 H, ArH), 10.27 (s, 1 H, CHO).
Melting points were determined in open capillaries and are uncor-
rected. IR spectra were recorded in KBr discs. NMR spectra were
determined as solutions in CDCl3 with TMS as internal standard.
Silica gel (60–120 mesh) was used for chromatographic separation.
Silica gel-G [Spectrochem (India)] was used for TLC. Petroleum
ether (PE) refers to the fraction boiling between 60–80 °C. IR spec-
tra were recorded on a Perkin-Elmer L 120-000A spectrophotome-
MS: m/z = 340 [M+], 342 [M+ + 2].
Anal. Calcd for C13H9BrO4S: C, 45.76; H, 2.66. Found: C, 45.79; H,
2.54.
ter. NMR spectra were recorded on
a Bruker DPX-400
3c
spectrometer. Mass spectra were recorded on Jeol JMS600 and
QTOF Micro YA 263 instruments. Elemental analyses were carried
out on a Perkin-Elmer 2400 series II CHN analyzer.
Yield: 90%; solid; mp 90–91 °C.
IR (KBr): 1694, 1372, 1195 cm–1.
Synthesis 2008, No. 23, 3857–3863 © Thieme Stuttgart · New York

PAPER
Novel Synthesis of Oxathiocine Derivatives
3861
1H NMR (CDCl3, 400 MHz): d = 2.37 (s, 3 H, CH3), 7.03 (d, J = 8.4
Hz, 1 H, ArH), 7.32 (d, J = 8.4 Hz, 1 H, ArH), 7.45 (t, J = 7.6 Hz,
1 H, ArH), 7.54 (t, J = 7.6 Hz, 1 H, ArH), 7.71 (s, 1 H, ArH), 7.87
(d, J = 8.0 Hz, 1 H, ArH), 7.97 (dd, J = 7.6, 1.2 Hz, 1 H, ArH),
10.26 (s, 1 H, CHO).
Hz, 1 H, ArH), 7.48–7.53 (m, 3 H, ArH), 7.69 (d, J = 9.2 Hz, 1 H,
ArH), 7.81–7.82 (m, 1 H, ArH), 7.48 (dd, J = 6.8, 1.2 Hz, 1 H,
ArH), 7.93 (dd, J = 7.6, 1.6 Hz, 1 H, ArH), 8.11–8.13 (m, 1 H,
ArH).
13C NMR (CDCl3, 125 MHz): d = 121.4, 122.0, 123.7, 126.1, 126.7,
127.3, 128.0, 128.7, 129.2, 129.5, 132.5, 132.6, 132.7, 132.8, 135.3,
136.3, 137.2, 144.7.
MS: m/z = 354 [M+], 356 [M+ + 2].
Anal. Calcd for C14H11BrO4S: C, 47.34; H, 3.12. Found: C, 47.63;
H, 2.99.
HRMS: m/z calcd for C18H13BrO3S: 410.9666 [M + Na], 412.9666
[M + 2 + Na]; found: 410.9666 [M + Na], 412.9647 [M + 2 + Na].
3d
Anal. Calcd for C18H13BrO3S: C, 55.54; H, 3.37. Found: C, 55.61;
H, 3.31.
Yield: 77%; solid; mp 78–79 °C.
IR (KBr): 1691, 1375, 1199 cm–1.
4b
1H NMR (CDCl3, 400 MHz): d = 3.83 (s, 3 H, OCH3), 7.04 (d,
J = 2.0 Hz, 1 H, ArH), 7.37–7.38 (m, 2 H, ArH), 7.45 (dt, J = 7.6,
1.6 Hz, 1 H, ArH), 7.55 (dt, J = 7.6, 1.6 Hz, 1 H, ArH), 7.88 (dd,
J = 8.0, 1.2 Hz, 1 H, ArH), 7.98 (dd, J = 7.6, 1.6 Hz, 1 H, ArH),
10.25 (s, 1 H, CHO).
Yield: 89%; solid; mp 69–70 °C.
IR (KBr): 1379, 1193 cm–1.
1H NMR (CDCl3, 400 MHz): d = 5.24 (dd, J = 11.2, 1.6 Hz, 1 H,
=CHaHb), 5.67 (dd, J = 17.6, 1.6 Hz, 1 H, =CHaHb), 6.79–6.81 (m,
1 H, CH2=CH), 6.92–6.97 (m, 2 H, ArH), 7.13–7.17 (m, 2 H, ArH),
7.40–7.52 (m, 2 H, ArH), 7.85 (dd, J = 6.8, 1.2 Hz, 1 H, ArH), 7.96
(dd, J = 6.4, 1.6 Hz, 1 H, ArH).
MS: m/z = 370 [M+], 372 [M+ + 2].
Anal. Calcd for C14H11BrO5S: C, 45.30; H, 2.99. Found: C, 45.53;
H, 3.13.
MS: m/z = 338 [M+], 340 [M+ + 2].
3e
Anal. Calcd for C14H11BrO3S: C, 49.57; H, 3.27. Found: C, 49.37;
H, 3.07.
Yield: 74%; solid; mp 108–109 °C.
IR (KBr): 1694, 1378, 1169 cm–1.
4c
1H NMR (CDCl3, 400 MHz): d = 7.15 (d, J = 8.8 Hz, 1 H, ArH),
7.50–7.55 (m, 2 H, ArH), 7.58 (dt, J = 7.6, 1.6 Hz, 1 H, ArH), 7.88–
7.89 (m, 2 H, ArH), 8.02 (dt, J = 8.0, 1.6 Hz, 1 H, ArH), 10.23 (s,
1 H, CHO).
Yield: 92%; solid; mp 77–78 °C.
IR (KBr): 1362, 1170 cm–1.
1H NMR (CDCl3, 400 MHz): d = 2.40 (s, 3 H, CH3), 5.20 (dd,
J = 11.2, 1.6 Hz, 1 H, =CHaHb), 5.63 (dd, J = 17.6, 1.6 Hz, 1 H,
=CHaHb), 6.73–6.78 (m, 1 H, CH2=CH), 6.90 (s, 1 H, ArH), 6.93 (d,
J = 7.2 Hz, 1 H, ArH), 7.06 (d, J = 3.0 Hz, 1 H, ArH), 7.51 (dt,
J = 7.8, 1.7 Hz, 1 H, ArH), 7.58 (dt, J = 7.6, 1.7 Hz, 1 H, ArH), 7.89
(dd, J = 7.7, 1.2 Hz, 1 H, ArH), 7.99 (dd, J = 8.2, 1.2 Hz, 1 H, ArH).
MS: m/z = 374 [M+], 376 [M+ + 2].
Anal. Calcd for C13H8BrClO4S: C, 41.57; H, 2.15. Found: C, 41.73;
H, 1.96.
3f
Yield: 77%; solid; mp 134–135 °C.
MS: m/z = 352 [M+], 354 [M+ + 2].
IR (KBr): 1395, 1371, 1195 cm–1.
1H NMR (DMSO-d6, 400 MHz): d = 7.39 (d, J = 8.5 Hz, 2 H, ArH),
7.51–7.89 (m, 8 H, ArH), 8.13 (m, 2 H, ArH), 10.53 (s, 2 H, CHO).
Anal. Calcd for C15H13BrO3S: C, 51.00; H, 3.71. Found: C, 50.87;
H, 3.89.
4d
MS: m/z = 652, 654, 656.
Yield: 95%; solid; mp 81–82 °C.
IR (KBr): 1363, 1169 cm–1.
Anal. Calcd for C24H14Br2O8S2: C, 44.06; H, 2.16. Found: C, 43.91;
H, 1.99.
1H NMR (CDCl3, 400 MHz): d = 3.78 (s, 3 H, OCH3), 5.23 (dd,
J = 11.2, 1.6 Hz, 1 H, =CHaHb), 5.61 (dd, J = 17.6, 1.6 Hz, 1 H,
=CHaHb), 6.67–6.70 (m, 1 H, CH2=CH), 6.85 (s, 1 H, ArH), 6.90 (d,
J = 6.8 Hz, 1 H, ArH), 7.02 (d, J = 3.2 Hz, 1 H, ArH), 7.42 (dt,
J = 8.0, 1.2 Hz, 1 H, ArH), 7.51 (dt, J = 7.6, 1.6 Hz, 1 H, ArH), 7.83
(dd, J = 7.6, 1.2 Hz, 1 H, ArH), 7.94 (dd, J = 8.0, 1.6 Hz, 1 H, ArH).
Synthesis of Heck Precursors 4a–f by Wittig Olefination; Typi-
cal Procedure
Wittig salt PPh3MeI (403 mg, 0.99 mmol) in anhydrous THF (25
mL) was added to a 25 mL round-bottomed flask. n-BuLi (1.6 M in
hexane, 1.2 mL) was added at 0 °C under a nitrogen atmosphere.
Compound 3a (300 mg, 0.76 mmol) in anhydrous THF (5 mL) was
added to the reaction mixture at 0 °C and stirring was continued at
r.t. for 1.5 h. THF was removed under reduced pressure and aq
NH4Cl (10 mL) was added, and the mixture was extracted with
CH2Cl2 (3 × 30 mL), washed with H2O (2 × 20 mL) and dried
(Na2SO4). CH2Cl2 was evaporated and the crude product was puri-
fied by column chromatography over silica gel (EtOAc–PE, 5%) to
give 4a. Compounds 4b–f were prepared in a similar manner.
MS: m/z = 368 [M+], 370 [M+ + 2].
Anal. Calcd for C15H13BrO4S: C, 48.79; H, 3.55. Found: C, 48.61;
H, 3.74.
4e
Yield: 91%; solid; mp 76–77 °C.
IR (KBr): 1365, 1169 cm–1.
1H NMR (CDCl3, 400 MHz): d = 5.25 (dd, J = 11.2, 1.6 Hz, 1 H,
=CHaHb), 5.69 (dd, J = 17.6, 1.6 Hz, 1 H, =CHaHb), 6.76–6.83 (m,
1 H, CH2=CH), 6.92 (s, 1 H, ArH), 6.96 (d, J = 7.4 Hz, 1 H, ArH),
7.11 (d, J = 2.3 Hz, 1 H, ArH), 7.39–7.56 (m, 2 H, ArH), 7.91 (dd,
J = 8.1, 1.0 Hz, 1 H, ArH), 8.01 (dd, J = 7.9, 1.0 Hz, 1 H, ArH).
4a
Yield: 88%; solid; mp 122–123 °C.
IR (KBr): 1372, 1165 cm–1.
1H NMR (CDCl3, 400 MHz): d = 5.53 (dd, J = 11.2, 1.6 Hz, 1 H,
=CHaHb), 5.62 (dd, J = 17.6, 1.6 Hz, 1 H, =CHaHb), 6.82–6.89 (m,
1 H, CH2=CH), 7.16 (d, J = 8.8 Hz, 1 H, ArH), 7.42 (dt, J = 6.4, 1.2
MS: m/z = 372 [M+], 374 [M+ + 2].
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K. C. Majumdar et al.
PAPER
Anal. Calcd for C14H10BrClO3S: C, 45.00; H, 2.70. Found: C, 45.23;
H, 2.66.
Hz, 1 H, ArH), 7.49 (dt, J = 6.4, 1.2 Hz, 1 H, ArH), 8.02 (dd,
J = 8.1, 1.0 Hz, 1 H, ArH).
MS: m/z = 272 [M+].
4f
Anal. Calcd for C15H12O3S: C, 66.16; H, 4.44. Found: C, 66.30; H,
4.29.
Yield: 61%; solid; mp 143–144 °C.
IR (KBr): 1373, 1171 cm–1.
1H NMR (DMSO-d6, 400 MHz): d = 5.59 (dd, J = 11.2, 1.6 Hz, 2 H,
=CHaHb), 5.69 (dd, J = 17.6, 1.6 Hz, 2 H, =CHaHb), 6.99–7.11 (m,
2 H, CH2=CH), 7.19 (d, J = 7.9 Hz, 2 H, ArH), 7.45–7.59 (m, 8 H,
ArH), 8.19 (dd, J = 7.2, 1.6 Hz, 2 H, ArH).
5d
Yield: 84%; solid; mp 142–143 °C.
IR (KBr): 1355, 1162 cm–1.
1H NMR (CDCl3, 400 MHz): d = 3.71 (s, 3 H, OCH3), 6.61 (d,
J = 3.0 Hz, 1 H, ArH), 6.78 (dd, J = 7.6, 1.6 Hz, 1 H, ArH), 6.82 (d,
J = 12.2 Hz, 1 H, =CHa), 7.02 (d, J = 12.2 Hz, 1 H, =CHb), 7.30 (s,
1 H, ArH), 7.33 (t, J = 7.3 Hz, 1 H, ArH), 7.40 (d, J = 9.0 Hz, 1 H,
ArH), 7.50 (dt, J = 7.5, 1.0 Hz, 1 H, ArH), 8.02 (dd, J = 7.9, 1.2 Hz,
1 H, ArH).
MS: m/z = 648, 650, 652.
Anal. Calcd for C26H18Br2O6S2: C, 48.02; H, 2.79. Found: C, 48.19;
H, 2.91.
Synthesis of Compounds 5a–f by the Heck Reaction; Typical
Procedure
MS: m/z = 288 [M+].
A mixture of 4a (50 mg, 0.13 mmol), TBAB (50 mg, 0.15 mmol)
and anhydrous KOAc (34.6 mg, 0.35 mmol) was taken in anhydrous
DMF (10 mL) under a nitrogen atmosphere. Pd(OAc)2 (5 mol%,
1.43 mg) was added and the reaction mixture was stirred at 80 °C
for 60 min. The reaction mixture was cooled, and H2O (10 mL) was
added, the mixture was extracted with EtOAc (3 × 30 mL) and the
combined organic layer was washed with H2O (2 × 40 mL), fol-
lowed by brine (30 mL). The organic layer was dried (Na2SO4), and
the solvent was distilled off to furnish a viscous mass, which was
purified by column chromatography over silica gel (EtOAc–PE,
4%) to give 5a. Substrates 4b–f were treated similarly to give prod-
ucts 5b–f.
Anal. Calcd for C15H12O4S: C, 62.49; H, 4.20. Found: C, 62.61; H,
4.03.
5e
Yield: 79%; solid; mp 122–123 °C.
IR (KBr): 1334, 1167 cm–1.
1H NMR (CDCl3, 400 MHz): d = 6.64 (d, J = 2.8 Hz, 1 H, ArH),
6.79 (d, J = 6.9 Hz, 1 H, ArH), 6.83 (d, J = 12.2 Hz, 1 H, =CHa),
7.04 (d, J = 12.2 Hz, 1 H, =CHb), 7.31 (s, 1 H, ArH), 7.36 (dd,
J = 7.6, 1.2 Hz, 1 H, ArH), 7.44–7.48 (m, 2 H, ArH), 8.04 (dd,
J = 8.1, 1.7 Hz, 1 H, ArH).
MS: m/z = 292 [M+].
5a
Yield: 90%; solid; mp 200–201 °C.
IR (KBr): 1350, 1180 cm–1.
Anal. Calcd for C14H9ClO3S: C, 57.44; H, 3.10. Found: C, 57.61; H,
2.97.
1H NMR (CDCl3, 400 MHz): d = 7.20 (d, J = 12.2 Hz, 1 H, =CHa),
7.27 (d, J = 12.2 Hz, 1 H, =CHb), 7.28–7.30 (m, 2 H, ArH), 7.41–
7.52 (m, 3 H, ArH), 7.62 (d, J = 9.0 Hz, 1 H, ArH), 7.81 (m, 3 H,
ArH), 8.01 (dd, J = 5.7, 3.0 Hz, 1 H, ArH).
5f
Yield: 26%; solid; mp 211–212 °C.
IR (KBr): 1352, 1183 cm–1.
1H NMR (DMSO-d6, 400 MHz): d = 7.24 (d, J = 12.2 Hz, 2 H,
=CHa), 7.29 (d, J = 12.2 Hz, 2 H, =CHb), 7.31 (d, J = 7.4 Hz, 2 H,
ArH), 7.44–7.56 (m, 6 H, ArH), 7.61 (dd, J = 6.9, 1.0 Hz, 2 H,
ArH), 8.07 (dd, J = 8.2, 1.7 Hz, 2 H, ArH).
13C NMR (CDCl3, 125 MHz): d = 121.0, 125.3, 127.0, 127.2, 127.6,
128.5, 128.8, 129.9, 130.0, 130.6, 131.5, 131.6, 131.7, 132.2, 133.2,
134.6, 135.3, 145.4.
HRMS: m/z calcd for C18H12O3S: 331.0405 [M + Na]; found:
331.0405 [M + Na].
MS: m/z = 488 [M+].
Anal. Calcd for C26H16O6S2: C, 63.92; H, 3.30. Found: C, 63.71; H,
3.13.
Anal. Calcd for C18H12O3S: C, 70.11; H, 3.92. Found: C, 70.09; H,
4.02.
5b
Acknowledgment
Yield: 88%; solid; mp 120–121 °C.
IR (KBr): 1354, 1163 cm–1.
We thank the DST (New Delhi) for financial assistance. B.C. and
B.S. are grateful to the CSIR (New Delhi) for a senior and a junior
research fellowship, respectively.
1H NMR (CDCl3, 400 MHz): d = 6.86 (d, J = 12.2 Hz, 1 H, =CHa),
7.01 (d, J = 12.2 Hz, 1 H, =CHb), 7.13–7.21 (m, 2 H, ArH), 7.27–
7.34 (m, 3 H, ArH), 7.47–7.51 (m, 2 H, ArH), 8.02 (d, J = 8.0 Hz,
1 H, ArH).
References
MS: m/z = 258 [M+].
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5c
Yield: 91%; solid; mp 132–133 °C.
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