An Efficient Coupling of p-Quinone Mono-Imine Ketals and Aryl/Alkyl Thiols: Rapid Synthesis of Biaryl/Aryl–Alkyl Sulfides

Article abstract of DOI:10.1002/ejoc.201700017

We report a fast, efficient, and metal-free protocol for the synthesis of unsymmetrical biaryl sulfides and aryl–alkyl sulfides (4-methoxy-2-sulfanyl-phenylcarbamates) under catalytic influence of 2,4-dinitrobenzoic acid. The reaction proceeded in a regioselective anti-Michael addition fashion and all the products were obtained within a very short period of time and in good to excellent yields.

Full text of DOI:10.1002/ejoc.201700017

DOI: 10.1002/ejoc.201700017
Full Paper
C–S Bond Coupling
An Efficient Coupling of p-Quinone Mono-Imine Ketals and
Aryl/Alkyl Thiols: Rapid Synthesis of Biaryl/Aryl–Alkyl Sulfides
[
a]
[a]
Arun Sharma and Rama Krishna Peddinti*
Abstract: We report a fast, efficient, and metal-free protocol ceeded in a regioselective anti-Michael addition fashion and all
for the synthesis of unsymmetrical biaryl sulfides and aryl–alkyl the products were obtained within a very short period of time
sulfides (4-methoxy-2-sulfanyl-phenylcarbamates) under cata- and in good to excellent yields.
lytic influence of 2,4-dinitrobenzoic acid. The reaction pro-
Introduction
Among the carbon-heteroatom bond-forming reactions, C–S
bond coupling reaction is one of the most indispensable ap-
[
1]
proaches in the synthetic organic chemistry. Organic scaffolds
that contain carbon–sulfur bonds, especially aryl sulfide deriva-
tives, are found in many essential molecules that possess bio-
logical activity, drugs in therapeutic areas, such as HIV, inflam-
[
2]
mation, cancer, and Alzheimer's disease (Figure 1). In the area
of modern synthetic organic chemistry, transformations that
involve C–S bond formations have been an alluring branch for
the biological values of organo–sulfur compounds. In recent
years, C–S bond coupling has become a broad area of research
and a plethora of methodologies have been developed in this
area. There are different strategies for the construction of C–S
bonds, which include addition, substitution, sulfenylation, cross
coupling, and oxidative cross coupling. Earlier reported meth-
ods for the synthesis of biaryl sulfide involve mainly the cou-
pling between aryl halides, aryl boronic acids, arylmagnesium
halides with aryl or alkylsulfur partners in the presence of tran-
Figure 1. Some bioactive molecules that contain a disulfide scaffold.
many bioactive molecules, highly functionalized aromatic sys-
[13]
tems and also in various asymmetric transformations.
In the
[
3]
[4]
[5]
[6]
sition metals such as rhodium, copper, palladium, iron,
presence of Brønsted acid organocatalysts and Lewis acid cata-
lysts, QIKs are recognized as highly activated electrophiles to-
wards different nucleophiles, in particular for arylation/alkyl-
[
7]
[8]
[9]
indium, cobalt, and nickel. There are some metal-free/
organocatalytic approaches reported in literature for the syn-
[
10]
[11]
thesis of aryl sulfides. Hua et al. reported an elegant cata-
lyst-free approach for arylthiolation of arylamine with (arylthio)-
pyrrolidine-2,5-diones.
[13]
ation reactions with different substrates.
Recently, our group published two different approaches for
the synthesis of biaryl/aryl–alkyl sulfides (i) with thiols and
masked ortho-benzoquinones and (ii) with molecular iodine
Recently, in our laboratory, oxidative dearomatization by us-
ing diacetoxyiodobenzene as an oxidant has been achieved for
the chemical generation of ortho-benzoquinone mono imines
and dimethyl sulfoxide as oxidant for the oxidative coupling
[14]
between thiols and electron-rich arenes.
In continuation of
[
12a]
from o-aminophenols,
from N-protected p-anisidine derivatives.
proved to be very attractive precursors for the synthesis of
and p-quinone imine ketals (QIKs)
our efforts and with an objective to develop a viable procedure
for the synthesis of biaryl and aryl–alkyl sulfides, we focused on
finding a low cost and efficient catalyst that would give high
yields with an easy handling procedure under aerobic condi-
tions at room temperature.
Tuning the chemo- and regio-selectivity of QIKs is a formida-
ble challenge as these reactive species possess three different
electrophilic sites at C-1, C-2 and C-3 (Scheme 1). Hence, there
are three different possible ways for the attack of the nucleo-
phile on QIKs that lead to formation of a mixture of regioiso-
[
12b]
These entities
[
a] Department of Chemistry, Indian Institute of Technology Roorkee,
Roorkee 247667, Uttarakhand, India
E-mail: rkpedfcy@iitr.ac.in
ramakpeddinti@gmail.com
www.iitr.ac.in/~CY/rkpedfcy
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under http://dx.doi.org/10.1002/ejoc.201700017.
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meric products as shown in Scheme 1. Swenton and co-workers
Table 1. Optimization study.[a]
[
15]
reported regioisomers of 2- and 3-substituted benzamide de-
rivatives, and this study was limited to ethane thiol only. There
is a need for the development of advantageous methods to
synthesize biaryl sulfides regioselectively. The reaction of com-
pound 1 proceeds through activation of the imine moiety with
Brønsted acid to furnish the regioisomer selectively by nucleo-
[
15]
philic attack on QIK. Initially, we envisaged that the acid cata-
lyst may promote reaction through attack of thiophenol at the
C-3 position of QIK to afford product B through Michael addi-
tion reaction followed by aromatization. However, the forma-
tion of desired disulfide was not observed; instead biaryl sulfide
A was formed through attack of thiol at the C-2 position in an
anti-Michael fashion.
Entry
Catalyst
Solvent
Time [min.]
Yield[b] [%]
1
2
3
4
5
6
7
8
9
–
PhCH
PhCH
PhCH
PhCH
PhCH
PhCH
PhCH
PhCH
PhCH
PhCH
PhCH
3
3
3
3
3
3
3
3
3
3
3
240
2
10
10
10
2
30
5
–
73
98
77
80
92
99
33
81
nr
BDHP[
BzOH
4-Br-BzOH
c]
3
3,5-CF -BzOH
2,4-DNBA
–
CSA
[d]
pTSA·H
BF ·OEt
2
O
10
11
12
13
14
15
3
2
–
nr
p-NO
2
-phenol
30
30
5
5
5
60
87
98
98
97
[e]
–
2
H O
CH Cl
2 2
DCE
ACN
2,4-DNBA
2,4-DNBA
2,4-DNBA
Scheme 1. Possible regioisomers from the nucleophilic substitution/addition
reaction of QIKs.
[a] All reactions were carried out with QIK 1a (0.2 mmol) and thiolphenol
(
[
0.25 mmol) with catalyst (5 mol-%) in solvent (1 mL). [b] Isolated yield.
c] BDHP = 1,1′-Binaphthyl-2,2′-diylhydrogenphosphate. [c] 2,4-DNBA = 2,4-
Results and Discussion
Dinitrobenzoic acid. [e] Reaction was performed at 60 °C.
We started our investigation by choosing thiophenol and N-
tert-butoxycarbonyl (Boc)-protected QIK 1a as a model system aqueous acidic solution with acid, QIKs hydrolyze to the corre-
to optimize the reaction conditions. At the outset, reaction be- sponding p-quinone ketals.[12a] It is remarkable to note that
tween QIK 1a and thiophenol was carried out in toluene in the when the addition of thiophenol was performed in water at
absence of catalyst at room temperature and corresponding 60 °C, biaryl sulfide 2a was obtained in 87 % yield in 30 min
biaryl sulfide 2a was obtained in 73 % yield in 4 h (Table 1, (Table 1, Entry 12). After having the optimized conditions in
Entry 1).
hand, we moved our attention to evaluate the substrate scope.
Encouraged by the formation of a single regioisomer and to For this purpose, we performed the reaction of N-Boc protected
improve the yield of the reaction, the reaction was performed QIK 1a with various aryl and alkyl thiol derivatives. In all instan-
in the presence of binaphthol-derived phosphoric acid BDHP ces corresponding biaryl/alkyl–aryl sulfides 2b–2j were ob-
(
5 mol-%) as catalyst. We were pleased to find that correspond- tained in good to excellent yields (Table 2). When the reaction
ing biaryl sulfide product 2a was formed within 2 min in near was performed with aromatic thiols no significant influence of
quantitative yield (Table 1, Entry 2). When the catalyst was the electronic nature of the substituents on the thiophenol was
changed to benzoic acid the reaction was complete in 10 min observed on the rate of the reaction and on the yield. All biaryl
to afford product 2a in 77 % yield (Table 1, Entry 3). The deple- sulfide derivatives 2b–2e were obtained in good to excellent
tion in yield may be attributed to the lower acidity of benzoic yield in just 2 min. The reaction of 1a with 4-methyl- and 4-
acid relative to BDHP. The reaction worked well under the influ- methoxy-thiophenols gave biaryl sulfides 2b and 2c in 87 and
ence of 4-bromobenzoic acid and 3,5-bis(trifluoromethyl)- 86 % yield, respectively. Similarly, reaction of 4-chloro- and 4-
benzoic acid to furnish biaryl sulfide 2a in 10 min with 80 and bromo-thiophenols with QIK 1a afforded corresponding biaryl
9
2 % yields, respectively (Table 1, Entries 4 and 5). Surprisingly, sulfides 2d and 2e, respectively, in high yield. However, the
when the reaction was performed in the presence of 2,4- reaction of QIK 1a with 2-naphthalenethiol afforded corre-
dinitrobenzoic acid, the reaction was complete almost immedi- sponding product 2f in 65 % yield. No improvement in the yield
ately after adding the catalyst to produce sulfide 2a in 99 % was observed even when the reaction was allowed to react for
yield (Table 1, Entry 6). Further, we screened various acids, such 1 h. The reaction of 1a with aliphatic thiols furnished the aryl–
as trifluoroborate diethyl etherate (BF ·OEt ), camphor-10- alkyl sulfides 2g–2j in very high to excellent yield within a short
3
2
sulfonic acid (CSA), p-toluenesulfonic acid (pTSA) and p-nitro- period of time.
phenol. The reaction of QIK in the presence of pTSA and
Next we performed the reaction of 3-chloro-substituted QIK
BF ·OEt turned dark black and gave a sticky complex insepara- 1b with different thiols to afford biaryl and aryl–alkyl sulfides
3
2
ble mixture. Among the catalysts screened, 2,4-dintrobenzoic 3a–3j in good to excellent yield. Parallel to the reaction of 1a,
acid was found to be the optimum catalyst at room tempera- the reaction of QIK derivative 1b with aromatic thiols bearing 4-
ture. Next we screened different solvents, such as dichloro- Me, 4-OMe, 4-Cl, and 4-Br substituents furnished corresponding
methane, 1,2-dichloroethane, and acetonitrile. Generally, in products 3b–3e in 82–91 % yield. The products obtained from
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Table 2. Scope of the substrates for the synthesis of biaryl and aryl–alkyl sulfides.
[
a] Reaction time: 30 min.
the anti-Michael addition of QIKs 1b and thiols 3a–3e are the ture, and parent QIK 1a and chloro derivative 1b remained in-
key intermediate analogues used for the synthesis of inhibitors tact in the reaction mixture even after 1 h. To minimize the
[
16]
of trypanothione reductase.
The reaction of 1b and 2- decomposition of methoxy derivatives 1c and 1d, the reaction
naphathlenethiol furnished corresponding product 3f in 67 % was carried out at 0 °C with 4-bromothiophenol. Under these
yield (Table 2). The reaction of 1b with aliphatic thiols resulted conditions product 4b was formed only in trace amounts. To
in the formation of products 3g–3j in good to excellent yield. improve the yield of methoxy derivatives of biaryl sulfide the
QIK 1b reacted with benzyl mercaptan to afford corresponding temperature was decreased to –10 °C in toluene. However, the
product 3j in 95 % yield. Thus it is observed that 1a and 1b reaction did not proceed as a result of solubility problems of
have similar a reactivity pattern with different thiols to afford thiophenol and acid. We changed the solvent from toluene to
the biaryl and aryl–alkyl sulfides.
acetonitrile and product 4b was isolated in 53 % yield in
To explore the substrate scope further, the reaction of thiols 30 min. A further increase in the reaction time did not show any
were performed with the 2-methoxy and 3-methoxy QIKs 1c effect on the yield of product 4b. The reaction of 1d produced
and 1d and in both the cases, it was found that these deriva- products 5a and 5d in good yields (Table 3). The reaction of
tives were quite sensitive to the acid catalyst and an inseparable thiophenol and other thiol derivatives except 4-Me and 4-Br
complex mixture was obtained. However, the thiols were intact. thiophenol derivatives were not clean.
To check the stability of QIKs 1a–1d in the presence of acid,
The regiochemistry of aryl sulfides was confirmed on the ba-
each of these derivatives was stirred with 5 mol-% acid at room sis of the coupling constants of the protons present on the
1
temperature and the reaction was monitored by TLC. After amine-substituted aromatic ring. Analysis of the H NMR spec-
2
min, it was found that 1a and 1b remained as such in the tra of compounds 2b–2e and 3a–3e, it is found that a singlet
reaction mixture, whereas 3-methoxy and 2-methoxy deriva- appears around δ = 7.00–7.10 ppm of the proton attached to
tives 1c and 1d were turned into a complex inseparable mix- the C-3 of the amine-substituted aromatic ring. In the products
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Table 3. Reaction of QIKs 1c and 1d with different thiophenols.
obtained from QIK 1a, there exists meta coupling of J = 2.5–
3
6
.0 Hz between the protons attached to C-3 and C-5 at δ =
.80–6.90 ppm that reveals the attack of thiols at the C-2 posi-
tion, which was later confirmed by X-ray analysis of compound
[
17]
3
e (Figure 2).
Based on literature precedents,[15] formation of 2-substituted
biaryl/aryl-alkyl sulfide may occur by two possible paths. In
Path a, protonation of the methoxy group with acid catalyst
generates intermediate A and makes the C-2 position more
electrophilic to facilitate thiophenol attack followed by elimina-
tion of the methoxy group at these positions to produce inter-
mediate B. Re-aromatization of B furnishes the corresponding
aryl sulfide. In Path b, there is the possibility of formation of
nitrenium ion intermediate E by protonation of the methoxy
group with acid catalyst followed by removal of methanol. This
nitrenium ion facilitates the C-2 position for thiol attack and
subsequent aromatization affords the aryl sulfide product as
shown in Scheme 2.
Figure 2. ORTEP diagram of single-crystal X-ray structure of compound 3e[17]
(numbering is arbitrary).
To further investigate the effect of base on the reaction, QIK
1b was treated with thiols in the presence of base. In this case,
Scheme 2. Proposed reaction mechanism.
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we observed diaryl sulfide product 6 as a result of Michael addi- These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre.
tion. When 1,4-diazabicyclo[2.2.2]octane was employed as a
base in the reaction of QIK 1b, the reaction was very slow,
General Procedure for the Synthesis of QIKs (1a–1d):[12b] Step I:
whereas in the presence of 10 mol-% 1,8-diazabicyclo[5.4.0]- To a solution of p-anisidine derivative (10 mmol) in MeOH (30 mL),
undec-7-ene (DBU) the reaction reached completion in 30 min were added Boc-anhydride (1.2 equiv.) and molecular iodine
(
10 mol-%) and the resulting solution was stirred at room tempera-
to afford diaryl sulfide 6. This observation supports the activa-
tion of QIKs with acid catalyst specifically at methoxy group to
furnish the anti-Michael products, which is not possible in base-
catalyzed reactions (Table 4). The presence of meta coupling
ture for 2–3 h. The reaction was monitored by TLC. After completion
of the reaction, MeOH was removed under reduced pressure and
diluted with CH Cl and washed with dil. HCl solution to remove
2
2
the unreacted anisidine. The organic layer was washed with Na SO ,
2
4
(
7
J = 2.4–2.8 Hz) for the protons in the region between δ = 6.21–
.15 ppm in the H NMR spectrum of adducts 6a–6c indicates
concentrated and the crude residue was purified by silica gel col-
umn chromatography (2–10 % ethyl acetate in hexanes) to obtain
pure solid product.
1
that the addition of thiols is taking place at C-3, and confirms
that the products are the result of conjugate addition.
Step II: A 100 mL round-bottomed flask was charged with N-Boc-
p-anisidine (10 mmol) and triethylamine (30 mmol) in MeOH
Table 4. Reaction of QIK 1b with thiols that lead to Michael adducts 6a–6c.
(
(
40 mL). Then a methanolic solution of diacetoxyiodobenze
12 mmol, 1.2 equiv.) was added dropwise at 0 °C and stirred at
room temperature for 4 h. The reaction was monitored by TLC. After
completion of the reaction, the solvent was removed under reduced
pressure and crude mixture was subjected to silica gel (neutralized
by NEt ) column chromatography (5–10 % ethyl acetate in hexanes)
3
to obtain QIKs 1a–1d.
N-(tert-Butoxycarbonyl)-p-Benzoquinone Imine Dimethyl Acetal
1
(
1a): Reaction time: 1 h. Yield: 2.35 g (93 %) light brown liquid. H
NMR (CDCl , 500 MHz): δ = 6.53 (br., 2 H), 6.41 (d, J = 10.5 Hz, 2 H),
3
13
3
.25 (s, 6 H), 1.55 (s, 9 H) ppm. C NMR (CDCl , 125 MHz): δ = 160.9,
3
156.1, 137.2, 130.0, 127.2, 113.8, 92.8, 82.5, 49.9, 27.8 ppm.
N-(tert-Butoxycarbonyl)-3-Chloro-p-benzoquinone Imine Di-
methyl Acetal (1b): Reaction time: 2 h. Yield: 2.64 g (92 %) as light
brown liquid. 1H NMR (CDCl , 500 MHz): δ = 6.70–6.69 (m, 1 H),
3
6
.59–6.55 (m, 1 H), 6.44–6.42 (m, 1 H), 3.24 (s, 6 H), 1.55 (s, 9 H) ppm.
1
3
C NMR (CDCl , 125 MHz): δ = 158.7, 148.7, 136.8, 132.0, 131.9,
3
Conclusions
96.0, 94.2, 81.8, 51.1, 27.7 ppm.
In summary, we have established an efficient metal-free ap-
N-(tert-Butoxycarbonyl)-2-Methoxy-p-benzoquinone Imine Di-
proach for the rapid synthesis of functionally rich biaryl or methyl Acetal (1c): Reaction time: 3 h. Yield: 2.49 g (88 %) as light
alkyl–alkyl sulfides (4-methoxy-2-sulfanyl-phenylcarbamates) brown liquid. 1H NMR (CDCl , 500 MHz): δ = 6.48–6.43 (m, 1 H),
3
from QIKs and aryl/alkyl thiols under open-air conditions. The 6.33–6.29 (m, 1 H), 5.48 (s, 1 H), 3.71 (s, 3 H), 3.30 (s, 6 H), 1.52 (s, 9
H) ppm. 13C NMR (CDCl , 125 MHz): δ = 153.1, 139.3, 134.0, 129.5,
simplicity of the experimental procedure, easily accessible start-
ing materials, and readily available and inexpensive catalysts
are the advantages of this protocol.
3
103.9, 99.9, 80.1, 56.1, 50.3, 28.0 ppm.
N-(tert-Butoxycarbonyl)-3-Methoxy-p-benzoquinone Imine Di-
methyl Acetal (1d): Reaction time: 2 h. Yield: 2.60 g (92 %) as light
1
brown liquid. H NMR (CDCl , 500 MHz): δ = 6.39 (br. d, J = 12.0 Hz,
3
1
3
2
H), 5.74 (s, 1 H), 3.80 (s, 3 H), 3.29 (s, 6 H), 1.57 (s, 9 H) ppm.
C
Experimental Section
NMR (CDCl , 125 MHz): δ = 152.8, 150.5, 132.0, 122.0, 120.9, 118.0,
3
General Methods: All solvents and reagents were purchased at the
highest commercial quality and used without further purification.
Reactions were monitored by thin-layer chromatography (TLC) car-
ried out with 0.25 mm E. RANKEM silica gel “G” on glass plates and
by visualizing in an iodine chamber. IR spectra of the compounds
95.0, 83.2, 56.0, 51.1, 27.7 ppm.
General Procedure for the Synthesis of Biaryl/aryl–alkyl Sulf-
ides 2–5: To a solution of QIKs 1 (0.2 mmol) in dry toluene/aceto-
nitrile (0.5 mL) were added sequentially aryl/alkyl thiol (0.2 mmol)
and 2,4-dinitrobenzoic acid (5 mol-%) at room temperature/ –10 °C.
After completion of addition, the reaction was monitored by TLC.
After completion of the reaction, crude mixture was subjected to
silica gel column chromatography (5–20 % ethyl acetate in hexane)
to obtain the pure product.
TM
were recorded with a Thermo Nicolet FT-IR Nexus and are ex-
–
1
pressed as wavenumbers (cm ). NMR spectra were recorded in
CDCl3 with TMS as the internal standard with a Bruker AMX-500
or JEOL ECX-400-II instrument. HRMS were recorded with a Bruker
micrOTOF -Q-II mass spectrometer (ESI). Chemical shifts of 1
H
TM
NMR spectra were given in parts per million with respect to TMS.
tert-Butyl 4-Methoxy-2-(phenylthio)phenylcarbamate (2a): Re-
The signals from CDCl , 7.26 and 77.0 ppm are set as the reference
action time: 2 min. Yield: 64 mg (98 %) as white solid. M.p. 82–83 °C.
3
13
1
–1
peaks in H NMR and C NMR spectra, respectively. The following IR (KBr): ν˜
= 3373, 2974, 1723, 1521, 1254, 1157, 730, 582 cm .
max
1
abbreviations were used to explain the multiplicities: s = singlet,
d = doublet, dd = double doublet, dt = doublet of triplet, t = triplet,
q = quartet, m = multiplet, br. = broad. CCDC 1495949 (for 3e)
contains the supplementary crystallographic data for this paper.
H NMR (CDCl , 500 MHz): δ = 8.03 (d, J = 8.5 Hz, 1 H), 7.25–7.22
3
(m, 3 H), 7.19–7.14 (m, 1 H), 7.13–7.09 (m, 2 H), 7.05 (d, J = 3.0 Hz,
1 H), 6.96 (dd, J = 3.0, 9.0 Hz, 1 H), 3.75 (s, 3 H), 1.43 (s, 9 H) ppm.
13
C NMR (CDCl , 100 MHz): δ = 155.1, 152.8, 135.7, 133.6, 129.2,
3
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1
29.1, 127.5, 126.1, 121.1, 120.4, 116.2, 80.3, 55.5, 28.1 ppm. HRMS IR (KBr): ν˜
= 3375, 2985, 1713, 1553, 1230, 1026, 1160,
max
+
+
–1 1
(ESI) : m/z calcd. for [C H NO S + Na] 354.1134; found 354.1123.
743 cm . H NMR (CDCl , 500 MHz): δ = 7.89 (d, J = 8.0 Hz, 1 H),
1
8
21
3
3
7
.39 (s, 1 H), 7.03 (d, J = 2.5 Hz, 1 H), 6.87–6.82 (m, 1 H), 3.76 (s, 3
H), 3.67 (dt, J = 1.0, 5.5 Hz, 2 H), 2.93 (dt, J = 1.0, 6.0 Hz, 2 H), 2.15
(br., 1 H), 1.51 (s, 9 H) ppm. 13C NMR (CDCl
, 100 MHz): δ = 155.1,
153.2, 133.1, 121.4, 119.7, 114.8, 80.5, 60.2, 55.5, 38.4, 28.3 ppm.
tert-Butyl 4-Methoxy-2-(p-tolylthio)phenylcarbamate (2b): Reac-
tion time: 2 min. Yield: 62 mg (87 %) as a white solid. M.p. 64–65 °C.
–
1
3
IR (KBr): ν˜
= 3401, 2926, 1714, 1514, 1396, 1159, 805, 502 cm .
max
1
H NMR (CDCl , 500 MHz): δ = 8.0 (d, J = 8.0 Hz, 1 H), 7.21 (br. s, 1
3
+
+
HRMS (ESI) : m/z calcd. for [C H NO S + Na] 322.1083; found
14
21
4
H) 7.10–7.02 (m, 3 H), 7.00 (d, J = 3.2 Hz, 1 H), 6.91 (dd, J = 3.2,
9
.2 Hz, 1 H), 3.74 (s, 3 H), 2.29 (s, 3 H), 1.44 (s, 9 H) ppm. 13C NMR
322.1080.
(
1
CDCl , 100 MHz): δ = 155.2, 152.9, 136.4, 133.2, 131.8, 129.9, 128.5,
Methyl
3-[2-(tert-Butoxycarbonyl)-5-methoxyphenylthio]-
3
+
21.2, 119.9, 115.7, 80.3, 55.5, 28.2, 20.9 ppm. HRMS (ESI) : m/z
propanoate (2i): Reaction time: 2 min. Yield: 63 mg (92 %) as color-
less viscous oil. IR (KBr): ν = 3373, 2975, 1710, 1555, 1232, 1028,
+
calcd. for [C H NO S + Na] 368.1219; found 368.1276.
19
23
3
˜
max
–
1 1
1165, 814 cm . H NMR (CDCl , 500 MHz): δ = 8.0 (d, J = 5.5 Hz, 1
3
tert-Butyl
amate (2c): Reaction time: 2 min. Yield: 62 mg (86 %) as a white
= 3394, 2928, 1710, 1518, 1245,
4-Methoxy-2-(4-methoxyphenylthio)phenylcarb-
H), 7.42 (s, 1 H), 7.01 (dd, J = 1.0, 4.0 Hz, 1 H), 6.86 (dd, J = 1.0,
.0 Hz, 1 H), 3.77 (s, 3 H), 3.67 (s, 3 H), 2.99 (dt, J = 1.0, 9.0 Hz, 2 H),
5
solid. M.p. 114–115 °C. IR (KBr): ν˜
max
13
–1
1
2.54 (dd, J = 1.0, 9.0 Hz, 2 H), 1.51 (s, 9 H) ppm. C NMR (CDCl ,
3
1
8
1
161, 1031, 814 cm . H NMR (CDCl , 400 MHz): δ = 7.91 (d, J =
3
1
5
00 MHz): δ = 171.9, 154.8, 152.9, 133.5, 120.1, 115.3, 80.4, 55.5,
.8 Hz, 2 H), 7.19 (d, J = 8.8 Hz, 1 H), 7.13 (s, 1 H), 6.91 (d, J = 2.8 Hz,
+
1.8, 34.0, 30.7, 28.3 ppm. HRMS (ESI) : m/z calcd. for [C H NO S
16
23
5
H), 6.88–6.80 (m, 3 H), 3.76 (s, 3 H), 3.72 (s, 3 H), 1.47 (s, 9 H) ppm.
+
1
3
+ Na] 364.1189; found 364.1191.
C NMR (CDCl , 100 MHz): δ = 159.0, 155.3, 153.0, 132.2, 131.6,
3
1
25.2, 118.8, 114.9, 114.8, 80.2, 85.5, 55.5, 55.2, 28.2 ppm. HRMS
tert-Butyl 2-(Benzylthio)-4-methoxyphenylcarbamate (2j): Reac-
+
+
(ESI) : m/z calcd. for [C H NO S + Na] 384.1240; found 384.1240.
tion time: 2 min. Yield: 62 mg (90 %) as a white solid. M.p. 74–75 °C.
1
9
23
4
–
1 1
IR (KBr): ν˜
= 3375, 2970, 1714, 1525, 1235, 1162, 718 cm . H
tert-Butyl 2-(4-Chlorophenylthio)-4-methoxyphenylcarbamate
2d): Reaction time: 2 min. Yield: 61 mg (84 %) a white solid. M.p.
max
NMR (CDCl , 400 MHz): δ = 7.88 (d, J = 7.7 Hz, 1 H), 7.23 (s, 1 H),
(
8
8
7
3
7
.20–7.09 (m, 3 H), 7.08–6.96 (m, 2 H), 6.81–6.72 (m, 2 H), 3.80 (s, 2
0–81 °C. IR (KBr): ν
15 cm . H NMR (CDCl , 500 MHz): δ = 8.01 (d, J = 8.5 Hz, 1 H),
= 3384, 2926, 1732, 1524, 1469, 1164,
˜
max
13
–1
1
H), 3.58 (s, 3 H), 1.42 (s, 9 H) ppm. C NMR (CDCl , 100 MHz): δ =
3
3
1
54.2, 152.7, 128.7, 128.4, 127.2, 120.0, 115.6, 80.1, 55.4, 40.7,
.21 (d, J = 7.5 Hz, 2 H), 7.13 (br., 1 H), 7.03 (dd, J = 2.5, 6.0 Hz, 3
+
+
13
28.2 ppm. HRMS (ESI) : m/z calcd. for [C H NO S + Na] 368.1291;
H), 6.96 (dd, J = 3.0, 9.0 Hz, 1 H), 3.76 (s, 3 H), 1.44 (s, 9 H) ppm.
NMR (CDCl , 100 MHz): δ = 155.2, 152.8, 134.4, 133.5, 132.1, 129.3,
C
19 23 3
found 368.1276.
3
1
29.2, 129.2, 129.2, 128.7, 121.5, 120.4, 116.5, 80.4, 55.5, 28.1 ppm.
tert-Butyl 5-Chloro-4-methoxy-2-(phenylthio)phenylcarbamate
(3a): Reaction time: 2 min. Yield: 70 mg (95 %) as white crystalline
+
+
HRMS (ESI) : m/z calcd. for [C H ClNO S + Na] 388.0742; found
1
8
20
3
3
88.0724.
tert-Butyl 2-(4-Bromophenylthio)-4-methoxyphenylcarbamate
2e): Reaction time: 2 min. Yield: 70 mg (85 %) as a white solid. M.p.
solid. M.p. 83–84 °C. IR (KBr): ν˜
= 3379, 1723, 1503, 1377, 1287,
max
–
1 1
1
7
3
159, 1024, 744 cm . H NMR (CDCl , 500 MHz): δ = 8.29 (s, 1 H),
3
.29 (br., 1 H), 7.27–7.23 (m, 2 H), 7.21–7.16 (m, 1 H), 7.10–7.06 (m,
(
H), 3.82 (s, 3 H), 1.44 (s, 9 H) ppm. 13C NMR (CDCl , 100 MHz): δ =
8
8
7
6
1
1
7–88 °C. IR (KBr): ν˜
= 3383, 2925, 1731, 1523, 1246, 1162,
14 cm . H NMR (CDCl , 400 MHz): δ = 8.01 (d, J = 8.8 Hz, 1 H),
3
max
–1
1
152.4, 150.5, 135.6, 134.5, 129.2, 127.1, 126.2, 125.0, 121.3, 119.0,
3
+
8
0.8, 56.4, 28.1 ppm. HRMS (ESI) : m/z calcd. for [C H ClNO S +
.34 (d, J = 8.4 Hz, 2 H), 7.13 (s, 1 H), 7.03 (d, J = 2.8 Hz, 1 H), 7.00–
18 20 3
+
1
3
Na] 388.074; found 388.073.
tert-Butyl 5-Chloro-4-methoxy-2-(p-tolylthio)phenylcarbamate
3b): Reaction time: 2 min. Yield: 72 mg (95 %) as a white solid.
M.p. 108 °C. IR (KBr): ν = 3352, 2927, 1732, 1509, 1376, 1159,
.90 (m, 3 H), 3.75 (s, 3 H), 1.44 (s, 9 H) ppm. C NMR (CDCl3,
00 MHz): δ = 155.3, 152.8, 135.1, 133.5, 132.1, 128.9, 121.6, 120.5,
+
19.9, 116.6, 80.5, 55.5, 28.1 ppm. HRMS (ESI) : m/z calcd. for
(
+
[C H BrNO S + Na] 432.0329; found 432.0217.
18
20
3
˜
max
–
1 1
tert-Butyl 4-Methoxy-2-(naphthalen-1-ylthio)phenylcarbamate
2f): Reaction time: 30 min. Yield: 49 mg (65 %) as a white solid.
M.p. 81–82 °C. IR (KBr): ν = 3369, 2975, 1718, 1519, 1249, 1154,
1044, 877 cm . H NMR (CDCl
(br., 1 H), 7.10–7.05 (m, 3 H), 7.10–7.05 (d, J = 8.4 Hz, 2 H), 3.81 (s,
3 H), 2.30 (s, 3 H), 1.45 (s, 9 H) ppm. 13C NMR (CDCl
, 100 MHz): δ =
152.5, 150.4, 136.5, 134.1, 131.8, 130.0, 127.8, 124.6, 121.3, 118.6,
3
, 400 MHz): δ = 8.26 (s, 1 H), 7.30
(
˜
max
3
–1 1
8
7
14 cm . H NMR (CDCl , 400 MHz): δ = 7.96 (d, J = 8.8 Hz, 1 H),
3
+
.70–7.55 (m, 3 H), 7.47–7.43 (m, 1 H), 7.40–7.30 (m, 2 H), 7.20–7.10 80.8, 56.4, 28.1, 20.9 ppm. HRMS (ESI) : m/z calcd. for [C19H22ClNO S
3
+
(
(
m, 2 H), 7.01 (d, J = 3.2 Hz, 1 H), 6.89 (dd, J = 2.8, 9.2 Hz, 1 H), 3.66
s, 3 H), 1.27 (s, 9 H) ppm. C NMR (CDCl , 100 MHz): δ = 155.3,
+ Na] 402.0901; found 402.0893.
1
3
3
tert-Butyl 5-Chloro-4-methoxy-2-(4-methoxyphenylthio)phenyl-
carbamate (3c): Reaction time: 2 min. Yield: 71 mg (91 %) as a
1
1
52.9, 133.7, 133.6, 130.0, 131.8, 128.9, 127.6, 127.1, 126.6, 126.0,
+
25.8, 125.8, 121.4, 120.4, 116.3, 80.3, 55.5, 28.1 ppm. HRMS (ESI) :
white solid. M.p. 145–146 °C. IR (KBr): ν˜
= 3392, 2928, 1725, 1507,
max
+
m/z calcd. for [C H NO S + Na] 404.1291; found 404.1287.
–1 1
22
23
3
1
283, 1157, 1031, 817 cm . H NMR (CDCl , 400 MHz): δ = 8.17 (s,
3
tert-Butyl 2-(Cyclohexylthio)-4-methoxyphenylcarbamate (2g):
Reaction time: 2 min. Yield: 56 mg (83 %) as a white solid. M.p.
1 H), 7.24 (s, 1 H), 7.15 (d, J = 8.8 Hz, 2 H), 6.89 (s, 1 H), 6.82 (d, J =
1
3
8.8 Hz, 2 H), 3.79 (s, 3 H), 3.77 (s, 3 H), 1.47 (s, 9 H) ppm. C NMR
= 3369, 2928, 1726, 1517, 1454, 1160, (CDCl , 100 MHz): δ = 159.1, 152.2, 150.6, 133.3, 132.6, 130.9, 125.2,
max
3
4
1
7
3
1
8–49 °C. IR (KBr): ν˜
–1
1
+
058 cm . H NMR (CDCl , 400 MHz): δ = 7.98 (d, J = 8.8 Hz, 1 H),
124.0, 121.7, 117.8, 115.0, 80.7, 56.4, 55.3, 28.2 ppm. HRMS (ESI) :
3
+
.57 (s, 1 H), 7.02 (d, J = 2.8 Hz, 1 H), 6.85 (dd, J = 2.8, 8.8 Hz, 1 H),
.76 (s, 3 H), 2.86 (tt, J = 3.6, 10.8 Hz, 1 H), 1.95–1.85 (m, 2 H), 1.80–
.70 (m, 2 H), 1.60–1.50 (m, 1 H), 1.51 (s, 9 H) 1.40–1.15 (m, 5
m/z calcd. for [C19H22ClNO S + Na] 418.0850; found 418.0859.
4
tert-Butyl 5-Chloro-2-(4-chlorophenylthio)-4-methoxyphenyl-
carbamate (3d): Reaction time: 2 min. Yield: 69 mg (85 %) as white
13
H) ppm. C NMR (CDCl , 100 MHz): δ = 154.4, 152.9, 134.1, 122.2,
1
m/z calcd. for [C H NO S + Na] 360.1604; found 360.1588.
3
solid. M.p. 140–141 °C IR (KBr): ν˜
= 3383, 2925, 1719, 1507, 1377,
max
+
19.8, 115.0, 80.1, 55.5, 48.5, 33.3, 28.3, 26.0, 25.5 ppm. HRMS (ESI) :
–1 1
1
7
288, 1155, 817 cm . H NMR (CDCl , 500 MHz): δ = 8.28 (br., 1 H),
3
+
18
27
3
.22 (d, J = 8.5 Hz, 2 H), 7.20 (br., 1 H), 7.05 (s, 1 H), 7.10 (d, J = 8.0 Hz,
2 H), 3.83 (s, 3 H), 1.45 (s, 9 H) ppm. C NMR (CDCl , 100 MHz): δ =
13
tert-Butyl 2-(2-Hydroxyethylthio)-4-methoxyphenylcarbamate
2h): Reaction time: 2 min. Yield: 47 mg (79 %) colorless viscous oil.
3
(
152.4, 150.6, 134.4, 134.1, 132.2, 129.3, 128.3, 125.4, 121.7, 118.9,
6 © 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org

Full Paper
+
8
1.0, 56.4, 28.1 ppm. HRMS (ESI) : m/z calcd. for [C H Cl NO S + (s, 3 H), 3.79 (s, 3 H), 2.26 (s, 3 H), 1.48 (s, 9 H) ppm. 13C NMR (CDCl3,
18 19 2 3
+
Na] 422.0355; found 422.0389.
100 MHz): δ = 152.7, 150.9, 144.4, 135.6, 135.5, 133.5, 129.8, 126.6,
+
1
18.7, 102.9, 80.5, 56.1, 56.0, 28.2, 20.8 ppm. HRMS (ESI) : m/z calcd.
tert-Butyl 2-(4-Bromophenylthio)-5-chloro-4-methoxyphenyl-
carbamate (3e): Reaction time: 2 min. Yield: 76 mg (86 %) as white
+
for [C H NO S + Na] 398.1397; found 398.1390.
20
25
4
crystalline solid. M.p. 142–143 °C. IR (KBr): ν˜
= 3384, 2924, 1717,
tert-Butyl
amate (4b): Reaction time: 30 min. Yield: 46 mg (53 %) M.p. 106–
107 °C. IR (KBr): ν = 3403, 2977, 1719, 1515, 1383, 1156,
2-(4-Bromophenylthio)-4,6-dimethoxyphenylcarb-
max
–
1 1
1
8
6
503, 1374, 1285, 1154, 816 cm . H NMR (CDCl , 500 MHz): δ =
3
.28 (s, 1 H), 7.36 (d, J = 8.5, Hz, 2 H), 7.20 (br., 1 H), 7.06 (s, 1 H),
˜
max
.93 (d, J = 9.0 Hz, 2 H), 3.83 (s, 3 H), 1.45 (s, 9 H) ppm. 13C NMR
–1
1
811 cm . H NMR (CDCl , 500 MHz): δ = 8.23 (s, 1 H), 7.30 (d, J =
3
(
CDCl , 100 MHz): δ = 152.3, 150.6, 134.9, 134.4, 132.2, 128.4, 125.4,
8.5 Hz, 2 H), 6.97 (d, J = 8.5 Hz, 2 H), 6.83 (s, 1 H), 6.54 (s, 1 H), 3.93
3
(s, 3 H), 3.80 (s, 3 H), 1.51 (s, 9 H) ppm. 13C NMR (CDCl , 100 MHz):
1
21.6, 120.0, 118.9, 81.0, 56.4, 28.1 ppm.
3
δ = 155.8, 152.7, 150.0, 136.9, 130.7, 128.6, 128.3, 126.5, 121.9, 110.6,
tert-Butyl 5-Chloro-4-methoxy-2-(naphthalen-1-ylthio)phenyl-
carbamate (3f): Reaction time: 30 min. Yield: 55 mg (67 %) as white
+
8
+
0.3, 56.5, 55.8, 28.3 ppm. HRMS (ESI) : m/z calcd. for [C H BrNO S
Na] 462.0345; found 462.0335.
19 22
4
+
solid. M.p. 86–87 °C. IR (KBr): ν˜
= 3403, 2924, 1722, 1506, 1286,
max
–1 1
1
7
1
156, 1053, 812 cm . H NMR (CDCl , 500 MHz): δ = 8.32 (s, 1 H),
3
tert-Butyl 3,4-Dimethoxy-5-(p-tolylthio)phenylcarbamate (5a):
Reaction time: 30 min. Yield: 42 mg (56 %) as a brown solid. M.p.
.78 (d, J = 8.0 Hz, 1 H), 7.74 (d, J = 8.5 Hz, 1 H), 7.68 (d, J = 8.0 Hz,
H), 7.56–7.42 (m, 3 H), 7.32 (br., 1 H), 7.20 (dd, J = 1.5, 8.5 Hz, 1
H), 7.12 (s, 1 H), 3.83 (s, 3 H), 1.38 (s, 9 H) ppm. C NMR (CDCl3,
1
15–116 °C. IR (KBr): ν˜
= 3397, 1726, 1519, 1323, 1157, 1076,
max
1
3
–1 1
816 cm . H NMR (CDCl , 500 MHz): δ = 7.92 (s, 1 H), 7.50 (s, 1 H),
3
1
00 MHz): δ = 152.5, 150.6, 134.5, 133.7, 132.9, 131.8, 129.0, 127.7,
7
.04, (d, J = 8.0 Hz, 2 H), 7.01 (s, 1 H), 6.95 (d, J = 8.0 Hz, 2 H), 3.95
1
27.1, 126.8, 126.0, 125.3, 125.1, 121.6, 119.0, 80.8, 56.5, 28.1 ppm.
13
(
s, 3 H), 3.81 (s, 3 H), 2.28 (s, 3 H), 1.46 (s, 9 H) ppm. C NMR (CDCl3,
100 MHz): δ = 155.4, 152.6, 149.5, 129.4, 126.0, 121.6, 95.9, 80.1,
+
+
HRMS (ESI) : m/z calcd. for [C H ClNO S + Na] 438.0901; found
2
2
22
3
4
38.0890.
+
56.5, 55.8, 28.2, 20.8 ppm. HRMS (ESI) : m/z calcd. for [C H NO S
20 25 4
+
tert-Butyl 5-Chloro-2-(cyclohexylthio)-4-methoxyphenylcarb-
amate (3g): Reaction time: 2 min. Yield: 70 mg (94 %) as a white
+ Na] 398.1397; found 398.1407.
tert-Butyl 2-(4-Bromophenylthio)-4,5-dimethoxyphenylcarb-
amate (5b): Reaction time: 30 min. Yield: 49 mg (56 %) as a white
= 3373, 2926, 1693, 1523, 1154,
solid. M.p. 97–98 °C. IR (KBr): ν˜
= 3352, 2927, 1732, 1509, 1376,
max
–1 1
1
7
1
159, 1044, 877 cm . H NMR (CDCl , 500 MHz): δ = 8.22 (s, 1 H),
3
solid. M.p. 135–136 °C. IR (KBr): ν˜
max
.61 (s, 1 H), 7.03 (s, 1 H), 3.85 (s, 3 H), 2.83 (tt, J = 3.5, 7.0 Hz, 1 H),
–1 1
1
2
2
057, 822 cm . H NMR (CDCl , 500 MHz): δ = 7.43 (d, J = 8.5 Hz,
3
.93–1.86 (m, 2 H), 1.79–1.71 (m, 2 H), 1.64–1.57 (m, 1 H), 1.37–1.20
H), 7.32 (s, 1 H), 7.24 (d, J = 8.5 Hz, 2 H), 6.32 (s, 1 H), 6.22 (d, J =
1
3
(
m, 5 H), 1.52 (s, 9 H) ppm. C NMR (CDCl , 100 MHz): δ = 152.6,
13
3
.0 Hz, 1 H), 3.87 (s, 3 H), 3.79 (s, 3 H), 1.47 (s, 9 H) ppm. C NMR
1
2
49.8, 135.0, 124.1, 120.3, 119.8, 119.4, 80.6, 56.5, 48.9, 33.3, 28.3,
(
1
CDCl , 100 MHz): δ = 153.2, 152.5, 142.6, 135.1, 133.6, 133.4, 132.3,
3
+
8.2, 26.0, 25.4 ppm. HRMS (ESI) : m/z calcd. for [C H ClNO S +
+
1
8
26
3
30.2, 121.6, 111.5, 102.8, 80.6, 60.6, 55.9, 28.2 ppm. HRMS (ESI) :
+
Na] 394.1214; found 394.1187.
+
m/z calcd. for [C H BrNO S + Na] 462.0345; found 462.0335.
19
22
4
tert-Butyl 5-Chloro-2-(2-hydroxyethylthio)-4-methoxyphenyl-
carbamate (3h): Reaction time: 2 min. Yield: 58 mg (87 %) as color-
General Procedure for the Synthesis of Biaryl/aryl–alkyl Sulf-
ides 6: To a solution of QIK 1b (0.2 mmol) in dry toluene (0.5 mL)
were added sequentially aryl/alkyl thiol (0.2 mmol) and DBU
less viscous oil. IR (KBr): ν˜
= 3353, 2928, 1739, 1523, 1374, 1115,
max
–1 1
1
1
6
1
3
3
042, 843 cm . H NMR (CDCl , 500 MHz): δ = 8.17 (s, 1 H), 7.56 (s,
3
(0.02 mmol, 10 mol-%) at room temperature and stirred for 30 min.
H), 7.06 (s, 1 H), 3.85 (s, 3 H), 3.68 (t, J = 6.0 Hz, 2 H), 2.91 (t, J =
.0 Hz, 2 H), 1.51 (s, 9 H) ppm. C NMR (CDCl , 100 MHz): δ = 152.7,
50.2, 134.2, 124.1, 121.3, 121.1, 120.3, 118.6, 80.9, 60.2, 56.5, 53.4,
8.8, 28.2 ppm. HRMS (ESI) : m/z calcd. for [C H ClNO S + Na]
After completion of the reaction, as monitored by TLC, the crude
mixture was subjected to silica gel column chromatography (5–
1
3
3
2
0 % ethyl acetate in hexane) to obtain pure product 6.
tert-Butyl 5-Chloro-4-methoxy-3-(p-tolylthio)phenylcarbamate
6a): Reaction time: 30 min. Yield: 51 mg (68 %) as a white solid.
+
+
1
4
20
4
56.0694; found 356.0683.
(
Methyl 3-[2-(tert-Butoxycarbonyl)-4-chloro-5-methoxyphenyl-
thio]propanoate (3i): Reaction time: 2 min. Yield: 69 mg (93 %) as
1
M.p. 125–126 °C. H NMR (CDCl , 400 MHz): δ = 7.60 (br., 1 H), 7.36
3
(
d, J = 8.4 Hz, 2 H), 7.20 (d, J = 8.0 Hz, 2 H), 6.29 (d, J = 2.8 Hz, 1
colorless viscous liquid. IR (KBr): ν˜
= 3350, 2920, 1735, 1526,
max
13
–
1
1
H), 3.88 (s, 3 H), 2.38 (s, 3 H), 1.45 (s, 9 H) ppm. C NMR (CDCl
00 MHz): δ = 152.2, 147.9, 138.9, 135.1, 134.8, 134.2, 130.4, 128.4,
128.1, 117.8, 116.7, 80.9, 60.4, 28.2, 21.2 ppm.
3
,
1
376, 1115, 1062, 853 cm . H NMR (CDCl , 400 MHz): δ = 8.24 (br.
3
1
s, 1 H), 7.52 (s, 1 H), 7.06 (s, 1 H), 3.86 (s, 3 H), 3.68 (s, 3 H), 2.97 (t,
J = 5.2 Hz, 2 H), 2.53 (t, J = 6.8 Hz, 2 H), 1.52 (s, 9 H) ppm. 13C NMR
(
CDCl , 100 MHz): δ = 171.8, 152.5, 150.1, 134.5, 124.5, 120.7, 119.3,
3
tert-Butyl 5-Chloro-4-methoxy-3-(naphthalen-1-ylthio)phenyl-
1
18.9, 80.9, 56.5, 51.8, 33.9, 31.1, 28.2 ppm.
tert-Butyl 2-(Benzylthio)-5-chloro-4-methoxyphenylcarbamate
3j): Reaction time: 2 min. Yield: 72 mg (95 %) as a semi solid. IR
carbamate (6b): Reaction time: 30 min. Yield: 47 mg (57 %) as
1
white solid. M.p. 130–131 °C. H NMR (CDCl , 400 MHz): δ = 7.98 (d,
3
J = 1.6 Hz, 1 H) 7.87–7.77 (m, 3 H), 7.66 (br. s, 1 H), 7.56–7.50 (m, 2
H), 7.46 (dd, J = 1.6, 8.4 Hz, 1 H), 6.40 (dd, J = 2.8 Hz, 1 H), 6.24 (br.,
(
–
1 1
(
KBr): ν˜
= 3376, 2975, 1713, 1535, 1230, 1160, 719 cm . H NMR
max
1
1
H), 3.90 (s, 3 H), 1.41 (s, 9 H) ppm. 13C NMR (CDCl , 100 MHz): δ =
52.2, 148.4, 135.2, 133.7, 133.6, 132.8, 130.2, 129.6, 129.2, 128.5,
(CDCl , 500 MHz): δ = 8.22 (s, 1 H), 7.41 (br., 1 H), 7.28–7.20 (m, 3
3
3
H), 7.10–7.05 (m, 2 H), 6.69 (s, 1 H), 3.84 (s, 2 H), 3.66 (s, 3 H), 1.50
s, 9 H) ppm. 1 C NMR (CDCl , 100 MHz): δ = 152.3, 149.6, 137.3,
3
127.7, 127.6, 126.7, 126.6, 118.3, 117.7, 80.8, 60.5, 28.1 ppm.
(
3
1
4
34.5, 128.9, 128.5, 128.4, 127.4, 124.3, 120.2, 119.4, 80.6, 56.2, 53.3,
0.9, 28.2 ppm.
tert-Butyl 5-Chloro-3-(cyclohexylthio)-4-methoxyphenylcarb-
amate (6c): Reaction time: 30 min. Yield: 57 mg (77 %) as a white
1
tert-Butyl 2,4-Dimethoxy-6-(p-tolylthio)phenylcarbamate (4a):
solid. M.p. 114–115 °C. H NMR (CDCl , 400 MHz): δ = 7.40 (br. s, 1
3
Reaction time: 30 min. Yield: 39 mg (52 %) as a white solid. M.p.
H), 7.11 (d, J = 2.4 Hz, 1 H), 6.39 (s, 1 H), 3.83 (s, 3 H), 3.28–3.16 (m,
9
8
8
8–99 °C. IR (KBr): ν˜
= 3440, 1723, 1513, 1385, 1157, 1025, 1 H), 2.05–1.92 (m, 2 H), 1.82–1.72 (m, 2 H), 1.50 (s, 9 H), 1.45–1.22
max
–1
1
13
09 cm . H NMR (CDCl , 500 MHz): δ = 8.13 (s, 1 H), 7.07 (d, J = (m, 6 H) ppm. C NMR (CDCl , 100 MHz): δ = 152.5, 150.1, 134.9,
3
3
.0 Hz, 2 H), 7.01 (d, J = 8.0 Hz, 2 H), 6.76 (s, 1 H), 6.50 (s, 1 H), 3.89
132.1, 128.5, 119.4, 118.3, 81.0, 60.4, 44.9, 33.2, 28.3, 25.9, 25.8 ppm.
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[
[
5] a) M. A. Fernandez-Rodrıguez, Q. Shen, J. F. Hartwig, J. Am. Chem. Soc.
Acknowledgments
2006, 128, 2180–2181; b) G. Y. Li, Angew. Chem. Int. Ed. 2001, 40, 1513–
A. S. thanks the Council of Scientific and Industrial Research
1516; Angew. Chem. 2001, 113, 1561; c) T. Itoh, T. Mase, Org. Lett. 2004,
6
4
, 4587–4590; d) C. C. Eichman, J. P. Stambuli, J. Org. Chem. 2009, 74,
005–4008; e) P. Anbarasan, H. Neumann, M. Beller, Chem. Commun.
(CSIR) for a research fellowship. We thank the DST for providing
HRMS facilities through the FIST program.
2
011, 47, 3233–3235; f) M. Kuhn, F. C. Falk, J. Paradies, Org. Lett. 2011,
3, 4100–4103; g) X. S. Zhang, G. Li, X. G. Zhang, X. H. Zhang, Tetrahedron
015, 71, 5458–5464.
6] a) A. Correa, M. Carril, C. Bolm, Angew. Chem. Int. Ed. 2008, 47, 2880–
883; Angew. Chem. 2008, 120, 2922; b) J. R. Wu, C. H. Lin, C. F. Lee,
1
2
Keywords: Synthetic methods · Quinones · Regioselectivity ·
Carbamates · Sulfides
2
Chem. Commun. 2009, 4450–4452; c) Y. Y. Lin, Y. J. Wang, C. H. Lin, J. H.
Cheng, C. F. Lee, J. Org. Chem. 2012, 77, 6100–6106.
[7] a) P. Reddy, A. V. Kumar, K. Swapna, K. R. Rao, Org. Lett. 2009, 11, 1697–
1700; b) V. P. Reddy, K. Swapna, A. V. Kumar, K. R. Rao, J. Org. Chem.
2009, 74, 3189–3191.
[8] Y. C. Wong, T. T. Jayanth, C. H. Cheng, Org. Lett. 2006, 8, 5613–5616.
[9] a) O. B. Pantaleón, S. H. Ortega, D. M. Morales, Adv. Synth. Catal. 2006,
348, 236–242; b) N. Taniguchi, J. Org. Chem. 2004, 69, 6904–6906; c) Y.
Zhang, K. C. Ngeow, J. Y. Ying, Org. Lett. 2007, 9, 3495–3498.
[10] a) C. Ravi, D. C. Mohan, S. Adimurthy, Org. Lett. 2014, 16, 2978–2981;
b) R. Samanta, K. Matcha, A. P. Antonchick, Eur. J. Org. Chem. 2013, 5769–
5804.
[
1] For reviews, see: a) T. Kondo, T. Mitsudo, Chem. Rev. 2000, 100, 3205–
220; b) C. S. Yeung, V. M. Dong, Chem. Rev. 2011, 111, 1215–1292;
c) I. P. Beletskaya, V. P. Ananikov, Chem. Rev. 2011, 111, 1596–1636; d) C.
Shen, P. Zhang, Q. Sun, S. Bai, T. S. A. Hor, X. Liu, Chem. Soc. Rev. 2015,
3
4
4, 291–314.
[
2] a) S. W. Kaldor, V. J. Kalish, J. F. Davies, B. V. Shetty, J. E. Fritz, K. Appelt,
J. A. Burgess, K. M. Campanal, N. Y. Chirgadze, D. K. Clawson, B. A. Dress-
man, S. D. Hatch, D. A. Khalil, M. B. Kosa, P. P. Lubbehusen, M. A. Muesing,
A. K. Patick, S. H. Reich, K. S. Su, J. H. Tatlock, J. Med. Chem. 1997, 40,
3979–3985; b) G. D. Martino, M. C. Edler, G. L. Regina, A. Cosuccia, M. C.
Barbera, D. Barrow, R. I. Nicholson, G. Chiosis, A. Brancale, E. Hamel, M.
Artico, R. Silvestri, J. Med. Chem. 2006, 49, 947–954; c) G. Liu, J. R. Huth,
E. T. Olejniczak, F. Mendoza, S. W. Fesik, T. W. VonGeldern, J. Med. Chem.
[11] H. Tian, H. Yang, C. Zhu, H. Fu, Adv. Synth. Catal. 2015, 357, 481–488.
[12] a) N. Bodipati, R. K. Peddinti, Org. Biomol. Chem. 2012, 10, 1958–1961;
b) N. Bodipati, R. K. Peddinti, Org. Biomol. Chem. 2012, 10, 4549–4553.
[13] a) Y. C. Zhang, J. J. Zhao, F. Jiang, S. B. Sun, F. Shi, Angew. Chem. Int. Ed.
2014, 53, 13912–13915; Angew. Chem. 2014, 126, 14132; b) F. Jiang, Y. C.
Zhang, S. B. Sun, L. J. Zhou, F. Shi, Adv. Synth. Catal. 2015, 357, 1283–
1292; c) Y. C. Zhang, F. Jiang, S. L. Wang, F. Shi, S. J. Tu, J. Org. Chem. 2014,
79, 6143–6152; d) T. Hashimoto, H. Nakatsu, Y. Takiguchi, K. Maruoka, J.
Am. Chem. Soc. 2013, 135, 16010–16013; e) L. H. Liao, M. M. Zhanga, Y. J.
Liao, W. C. Yuana, X. M. Zhang, Synlett 2015, 26, 1720–1724.
[14] a) S. K. R. Parumala, R. K. Peddinti, Green Chem. 2015, 17, 4068–4072;
b) S. K. R. Parumala, S. R. Surasani, R. K. Peddinti, New J. Chem. 2014, 38,
5268–5271.
2001, 44, 1202–1210; d) S. F. Nielsen, E. Ø. Nielsen, G. M. Olsen, T. Lilje-
fors, D. Peters, J. Med. Chem. 2000, 43, 2217–2226; e) G. Smith, G. Mikkel-
sen, J. Eskildsena, C. Bundgaard, Bioorg. Med. Chem. Lett. 2006, 16, 3981–
3984.
[
[
3] a) K. Ajiki, M. Hirano, K. Tanaka, Org. Lett. 2005, 7, 4193–4195; b) M.
Arisawa, T. Suzuki, T. Ishikawa, M. Yamaguchi, J. Am. Chem. Soc. 2008,
1
30, 12214–12215.
4] a) S. Zhang, P. Qian, M. Zhang, M. Hu, J. Cheng, J. Org. Chem. 2010, 75,
6732–6735; b) F. Ke, Y. Qu, Z. Jiang, Z. Li, D. Wu, X. Zhou, Org. Lett. 2011,
1
3, 454–457; c) J. H. Cheng, C. L. Yi, T. J. Liu, C. F. Lee, Chem. Commun.
2
012, 48, 8440–8442; d) S. Roy, P. Phukan, Tetrahedron Lett. 2015, 56,
[15] J. S. Swenton, B. R. Bonke, W. M. Clark, C.-P. Chen, K. V. Martin, J. Org.
Chem. 1990, 55, 2027–2034.
2426–2429; e) D. J. C. Prasad, G. Sekar, Org. Lett. 2011, 13, 1008–1011;
f) P. S. Herradura, K. A. Pendola, R. K. Guy, Org. Lett. 2000, 2, 2019–2022;
g) C. G. Bates, R. K. Gujadhur, D. Venkataraman, Org. Lett. 2002, 4, 2803–
[16] B. Stump, C. Eberle, M. Kaiser, R. Brun, R. L. K.-Siegelc, F. Diederich, Org.
Biomol. Chem. 2008, 6, 3935–3947.
[17] CCDC No. 1495949, see the Supporting Information for CIF file.
2
806; h) F. Y. Kwong, S. L. Buchwald, Org. Lett. 2002, 4, 3517–3520; i) E.
Sperotto, G. P. M. van Klink, J. G. D. Vries, G. van Koten, J. Org. Chem.
008, 73, 5625–5628; j) J. Gan, D. Ma, Org. Lett. 2009, 11, 2788–2790.
2
Received: January 5, 2017
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Full Paper
C–S Bond Coupling
A. Sharma, R. K. Peddinti* ............... 1–9
An Efficient Coupling of p-Quinone
Mono-Imine Ketals and Aryl/Alkyl
Thiols: Rapid Synthesis of Biaryl/
Aryl–Alkyl Sulfides
A regioselective synthesis of biaryl/ benzoic acid. The regioselectivity is re-
aryl–alkyl
sulfides
(4-methoxy-2- agent dependent and the reaction
sulfanyl-phenylcarbamates) has been gives the products in good to excellent
achieved in the presence of an easily yield under anti-Michael-type addition
accessible Brønsted acid, 2,4-dinitro- conditions.
DOI: 10.1002/ejoc.201700017
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