Tetrabutylammonium iodide-catalyzed oxidative coupling of enamides with sulfonylhydrazides: Synthesis of β-keto-sulfones

Article abstract of DOI:10.1039/c5ob00742a

A facile synthetic route towards pharmaceutically interesting β-keto-sulfone derivatives by tetrabutylammonium iodide (TBAI)/tert-butyl hydroperoxide (TBHP) mediated oxidative coupling of readily prepared enamides with economical sulfonylhydrazides is described. The corresponding β-keto-sulfone compounds were obtained in moderate to good yields. The present method is metal-free and base-free and shows tolerance to a variety of functional groups. This journal is

Full text of DOI:10.1039/c5ob00742a

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ARTICLE TYPE
Tetrabutylammonium Iodide-Catalyzed Oxidative Coupling of
Enamides with Sulfonylhydrazides: Synthesis of β-keto-Sulfones
Yucai Tang,a Ye Zhang,a Kaifeng Wang,a Xiaoqing Li,a Xiangsheng Xu,a Xiaohua Du*a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
compounds, in which the sideꢀproducts are water and
nitrogen[Scheme 1b(II)]. Very recently, Jiang et al.15 described a
novel copperꢀcatalyzed coupling of oxime acetates with sodium
sulfinates to achieve sulfone derivatives[Scheme 1b(III)].
However, expensive and toxic metal salts are still needed in most
of these transformations. Therefore, there is still a great demand
for developing more mild, convenient and especially green and
sustainable approaches to produce βꢀketosulfones.16 It is known
that the sulfonyl radical could also be generated from the
commercially available tetrabutylammonium iodide(TBAI)/tertꢀ
butyl hydroperoxide(TBHP) catalyst system.17 We wondered
whether we could construct βꢀketosulfones through oxidative
coupling using TBAI as a catalyst and sulfonylhydrazides as
sulfonyl radical precursor. Herein, we wish to report a novel
TBAIꢀTBHP mediated oxidative coupling of enamides with
A facile synthetic route towards pharmaceutically interesting
β-keto-sulfone derivatives by tetrabutylammonium
iodide(TBAI)/tert-butyl hydroperoxide(TBHP) mediated
oxidative coupling of readily prepared enamides with
economical
sulfonylhydrazides
is
described.
The
corresponding β-keto-sulfone compounds were obtained in
moderate to good yields. The present method features metal-
free, base-free and a varity of founctional groups tolerance.
Introduction
CꢀS bond formation is of great importance in organic
synthesis because organosulfur compounds are an attractive
component of many biologically active compounds,1 and also
widely present in natural products, medical chemistry and
functional materials science.2 Given the tremendous importance
of organosulfur compounds, the development of CꢀS bond
formation has emerged as a significant field of research in
organic chemistry. Transition metalꢀcatalyzed C–S bond
formation, such as Pd,3 Cu,4 Ni,5 Fe,6 Ag7 and other metals,8
have been successfully developed. Among the very recent report,
the groups of Tian9 and Singh10 independently developed a
copper and nickel catalysed crossꢀcoupling of arylsulfonyl
hydrazides with aryl boronic acids for the synthesis of
arylsulfides. Nonetheless, these methods suffer from the use of
expensive or toxic metal salts, harsh reaction conditions, and
narrow substrate scopes. With the development of green
chemistry and increased concern over environmental issues,
metalꢀfree promoted oxidative coupling for CꢀS bond formation
are of great demanded. Although some progress has been made in
this field, 11 there still remains a great challenge in developing a
green, efficient and alternative strategy to access organosulfur
compounds.
sulfonylhydrazides
to
access
useful
βꢀketoꢀsulfone
compounds[Scheme 1b(IV)]. The present method features metalꢀ
free, baseꢀfree and
tolerance.
a
varity of founctional groups
βꢀketoꢀsulfones are versatile compounds owing to their
unique biological properties, which present in a large array of
natural products and important organic compounds.12 Generally,
βꢀketoꢀsulfones are prepared by the alkylation of sodium
sulfinates with αꢀhaloꢀketones or αꢀtosyloxy ketones [Scheme
1a].13 However, most of them suffer from some limitations, such
as the preꢀfunctionalized materials were required, relatively
complicated or harsh reaction conditions, and undesired
byproducts. The addition of sulfonyl radicals to carbon−carbon
multiple bonds represents a particularly useful contribution to
sulfone synthesis. 14 For example, Lei et al.14b reported an aerobic
oxidative difunctionalization of alkynes towards βꢀketosulfones
via the generation of sulfonyl radicals from sulfinic acids in the
presence of pyridine[Scheme 1b(I)]. Wang and coworkers14c
developed a copperꢀcatalyzed direct oxysulfonylation of alkenes
with dioxygen and sulfonylhydrazides to access βꢀketoꢀsulfone
Scheme 1. Traditional coupling and oxidative coupling reactions
Results and discussion
Our investigation commenced with the reaction of Nꢀ
vinylacetamide (1a) and pꢀtoluenesulfonylhydrazide (2a) in
o
CH3CN at 80 C under air atmosphere. Gratifyingly, the desired
product 3a was obtained in 44% yield under 20 mol% of TBAI
as a catalyst and 2.0 equivalents of TBHP(70 wt% in water) as an
external oxidant(Table 1, entry 1). After screening a series of
catalysts such as FeCl2•4H2O, KI, Cu(OAc)2 and I2, TBAI was
found to be most efficient (Table 1, entries 1ꢀ5). Further
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DOI: 10.1039/C5OB00742A
elaboration of the loading of 2a proved that 1.5 equivalents was
best and 80% yield was obtained (Table 1, entries 6ꢀ7). Among
the solvents screened, CH3CN was proved beneficial for this
reaction(Table 1, entries 6, 8ꢀ10). Some representative oxidants
were also examined in the presence of TBAI as catalyst and
results proved to be less effective(Table 1, entries 11ꢀ12).
Gratifyingly, a large scale reaction also proceeded smoothly,
furnishing product 3a in good yield (entry 13).
Table 1 Optimization of Reaction Conditions a
NHAc
O
Ts
Catalyst
Oxidant
Solvent, 80 oC
Ts
+
NHNH2
3a
2a
1a
Entry
1
Catalyst
TBAI
Oxidant solvent
Yield % b
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
DTBP
TBPB
TBHP
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
EtOAc
H2O
44
0
2
FeCl2•4H2O
KI
3
41
36
18
80
72
76
63
52
0
4
Cu(OAc)2
I2
5
6c
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
7d
8c
9c
10c
11c
12c
DMF
CH3CN
CH3CN
CH3CN
31
62
13e
[a]
Reaction conditions: 1a (0.25 mmol), 2a (1.2 eq), oxidant (2.0eq),
o
[b]
[c]
[a]
catalyst (0.05 mmol), solvent (2.0 mL) at 80 C. isolated yield. 1.5
Reaction conditions:1a (0.25 mmol), 2a (1.5 eq), TBAI (20 mol%),
equiv of 2a was used. [d] 2.0 equiv of 2a was used. [e]1a (8 mmol).
TBHP(2.0eq, 70% aqueous solution) in 2.0 mL of MeCN at 80 oC. isolated
[b]
yield.
To explore the substrate scope of this protocol, the optimized
reaction conditions were applied to a series of substituted Nꢀ
vinylacetamides and results are summarized in Table 2. The
substituents on the phenyl ring of the Nꢀvinylacetamide with
TsNHNH2(2a) were first tested. It was found that various
functional groups at the para –position were tolerated well under
the present oxidative conditions affording the products in good
yields(products 3bꢀ3h). Notably, halogen and nitro groups were
tolerable, which were suitable for potential further
functionalization. The reaction also proceeded smoothly with
both electronꢀwithdrawing (CF3, NO2 and halide) and electronꢀ
donating(MeO) substituents at the meta position of the aromatic
ring under the reaction conditions (products 3iꢀ3m). Nꢀ
vinylacetamide bearing ortho substituent on the aromatic ring
revealed different reactivity probably result from the electronic
effect(products 3n, 3o). In addition, the propiophenone and nꢀ
butyrophenone substituted Nꢀvinylacetamides were also applied
as substrates in this reaction, the corresponding products could be
isolated in reasonable yields(products 3pꢀ3r). Furthermore, the
dihydronaphthalenꢀderived enamide could also be used well and
afforded the desired product 3s in 27% yield.
Next, the reaction was examined with substituted
sulfonylhydrazides,
which
were
treated
with
Nꢀ
vinylacetamide(1a) under the standard reaction conditions and
the results are summarized in Table 3. Various paraꢀsubstituted
sulfonylhydrazides such as those bearing H, F, Cl, Br, CF3, or
OMe groups afforded the products 4aꢀ4f in moderate to good
yields. 2ꢀchlorobenzenesulfonohydrazide and naphthaleneꢀ2ꢀ
sulfonohydrazide could also transform into the corresponding
products in 63% and 67% yields, respectively (products 4g, 4h).
However, alkyl sulfonylhydrazide was not suitable for this
reaction and corresponding ketone was detected(product 4i).
Table 3. Scope of the reaction with sulfonylhydrazides a,b
NHAc
O
O
R3
TBAI (20mol%)
S
R3 SO2NHNH2
O
+
TBHP (2.0 eq.)
MeCN , 80oC
2
4a 4i
-
Table 2. Scope of the reaction with enamides a,b
2
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O
O
S
O
Cl
O
O
S
O
O
O
S
R
O
4g
: 63%
, 4a
R=H : 73%
, 4b
R=Cl
: 65%
: 72%
O
O
4i
: 0%
O
, 4c
R=Br
S
, 4d
R=OCH3
: 44%
, 4e
R=F : 52%
, 4f
R=CF3 : 46%
4h
: 67%
[a] Reaction conditions: 1a (0.25 mmol), 2a (1.5 eq), TBAI (20 mol%), TBHP(2.0
eq, 70% aqueous solution) in 2.0 mL of MeCN at 80 oC. [b] isolated yield. [c] not
detected.
In order to better understand the mechanism of this
transformation, additional experiments were carried out. No
compound 3a were formed when 1.0 equivalents of I2 and
PhI(OAc)2 were added to the reaction in the absence of TBHP.
The results exclude the possibility that the in situ generated I2 or
I3+ are involved in the oxidative NꢀS bond cleavage of
sulfonylhydrazides.11b,11f In addition, when the reaction of 1a
with TsNHNH2 was performed in the presence of TEMPO, a
common radical scavenger, the desired coupling product 3a was
sharply decreased to 15% yield, which indicated that a radical
process might involved in the present transformation.
Scheme 3. Proposed preliminary mechanisms
Conclusion
I2 (1.0 eq)
3a
In summary, we have developed a novel protocol for direct
synthesis of βꢀketoꢀsulfone derivatives starting from readily
MeCN , 80 o
C
( n.d )
prepared
enamides
and
commercially
available
NHAc
sulfonylhydrazides. The reported reactions employ cheap and
convenient TBAI/TBHP as the catalystꢀoxidation system, which
makes this transformation more environmentally benign. In
addition, this reaction tolerates a variety of functional groups and
the corresponding βꢀketoꢀsulfone compounds were obtained in
moderate to good yields. Further investigations of this reaction
system are under way in our laboratory.
PhI(OAc)2 (1.0 eq)
MeCN , 80 o
3a
+
TsNHNH2
C
( n.d )
1a
2a
standard conditions
3a
TEMPO(50mol%)
(15%)
Scheme 2. control experiment
Experimental Section
General Procedures: All reagents and solvents were purchased
from commercial suppliers and used without purifications.
Melting points are uncorrected. The 1H NMR and 13C NMR
spectra were recorded at 25 °C in CDCl3 at 500 and 125 MHz or
100 MHz, respectively, with TMS as the internal standard.
Chemical shifts (δ) are expressed in ppm and coupling constants
J are given in Hz. The enamides were synthesized according to
literature method.19
Based on the experimental results and previously reported
results,17
probable mechanistic explanation for this
a
transformation is shown in Scheme 3. Initially, TBAIꢀassisted
decomposition of TBHP generated the tertꢀbutoxyl radical and
tertꢀbutylperoxy radicals, which abstracted hydrogen of
carbazates to form sulfonyl radicals with the release of molecular
nitrogen.17,18 The addition of resultant sulfonyl radicals to alkenes
and subsequent furnish a carbonꢀcentered radical intermediate(I).
Futher oxidation leads to the corresponding carbocation
intermediate(II), which following by hydrolysis reaction afford
βꢀketoꢀsulfones.
Typical Procedure for the synthesis of βꢀketoꢀsulfones: To a
stirred solution of enamide (0.25 mmol), TsNHNH2 (0.375
mmol) and TBAI (0.05 mmol) in MeCN (2 mL) was added
TBHP (0.5 mmol, 70% aqueous solution) at room temperature.
o
The mixture was heated at 80 C for 12 h and cooled down to
room temperature. The excess solvent was removed under
vacuum, and the residue was directly purified by silica gel
column chromatography to afford desired βꢀketoꢀsulfones .
1ꢀphenylꢀ2ꢀtosylethanone (3a) 20ꢀ23. White solid (54.8 mg, 80%); mp 102ꢀ
1
103°C; H NMR (500 MHz, CDCl3) δ 7.97 – 7.92 (m, 2H), 7.76 (d, J =
8.2 Hz, 2H), 7.64 – 7.60 (m, 1H), 7.48 (t, J = 7.8 Hz, 2H), 7.33 (d, J = 8.2
Hz, 2H), 4.72 (s, 2H), 2.44 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 188.1,
145.4, 135.8, 135.8, 134.3, 129.8, 129.3, 128.8, 128.6, 63.6, 21.7.
1ꢀ(pꢀtolyl)ꢀ2ꢀtosylethanone(3b) 20c, 20g~20i, 21~23. White solid(44.6 mg, 62%);
1
mp 104ꢀ105°C; H NMR (500 MHz, CDCl3) δ 7.85 (d, J = 8.3 Hz, 2H),
7.76 (d, J = 8.3 Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H), 7.27 (d, J = 9.4 Hz,
2H), 4.69 (s, 2H), 2.44 (s, 3H), 2.42 (s, 3H). 13C NMR (125 MHz, CDCl3)
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δ 187.7, 145.5, 145.3, 135.9, 133.4, 129.8, 129.6, 129.5, 128.6, 63.6, 21.8,
2.42 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 189.2, 158.9, 144.8, 136.7,
135.2, 131.3, 129.5, 128.6, 126.4, 120.9, 111.70, 67.5, 55.7, 21.6. HRMS
(ESI) calcd for C16H17O4S (M + H+) 305.0848, found 305.0843.
21.7.
20c, 21
1ꢀ(4ꢀfluorophenyl)ꢀ2ꢀtosylethanone(3c)
. White solid(53.3 mg,
73%); mp 128ꢀ129°C; 1H NMR (500 MHz, CDCl3) δ 8.03 – 7.98 (m, 2H),
7.75 (d, J = 8.3 Hz, 2H), 7.34 (d, J = 8.1 Hz, 2H), 7.18 – 7.13 (m, 2H),
4.69 (s, 2H), 2.45 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 186.6, 167.5(d,
J = 256.3 Hz ), 145.5, 135.7, 132.3(d, J = 2.5 Hz ), 132.2, 129.9, 128.6,
116.1(d, J = 22.5 Hz ), 63.8, 21.7.
1ꢀphenylꢀ2ꢀtosylpropanꢀ1ꢀone(3p)20b, 20c. White solid(41.8mg, 58%); mp
81ꢀ82°C; 1H NMR (500 MHz, CDCl3) δ 7.99 – 7.96 (m, 2H), 7.65 (d, J =
8.3 Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.31 (d, J =
8.1 Hz, 2H), 5.00 (dd, J = 10.9, 3.6 Hz, 1H), 2.43 (s, 3H), 2.16 (dqd, J =
15.1, 7.5, 3.6 Hz, 1H), 2.03 (ddq, J = 14.6, 11.0, 7.3 Hz, 1H), 0.88 (t, J =
7.4 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 192.6, 145.4, 136.3, 133.1,
129.8, 129.5, 129.2, 128.7, 125.6, 65.0, 21.7, 13.2.
1ꢀ(4ꢀchlorophenyl)ꢀ2ꢀtosylethanone(3d) 20c, 20i, 20j, 21, 23. White solid(48.5
mg, 63%); mp 137ꢀ138°C; 1H NMR (500 MHz, CDCl3) δ 7.90 (d, J = 8.6
Hz, 2H), 7.74 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H), 7.34 (d, J =
8.1 Hz, 2H), 4.69 (s, 2H), 2.44 (s, 3H). 13C NMR (125 MHz, CDCl3) δ
186.0, 144.5, 140.0, 134.7, 133.1, 129.8, 128.9, 128.2, 127.5, 62.7, 20.7.
1ꢀ(4ꢀbromophenyl)ꢀ2ꢀtosylethanone(3e) 20~20c, 21, 22. White solid(54.5 mg,
62%); mp 120ꢀ121°C; 1H NMR (500 MHz, CDCl3) δ 7.84 – 7.81 (m, 2H),
7.76 – 7.72 (m, 2H), 7.65 – 7.62 (m, 2H), 7.35 (d, J = 8.0 Hz, 2H), 4.67
(s, 2H), 2.46 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 187.3, 145.6, 135.6,
1ꢀ(4ꢀbromophenyl)ꢀ2ꢀtosylpropanꢀ1ꢀone(3q). White solid(33.8mg, 37%);
1
mp 130ꢀ131°C; H NMR (500 MHz, CDCl3) δ 7.87 – 7.83 (m, 2H), 7.66
– 7.60 (m, 4H), 7.32 (d, J = 8.0 Hz, 2H), 5.08 (q, J = 6.9 Hz, 1H), 2.45 (s,
3H), 1.54 (d, J = 6.9 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 191.7,
145.6, 135.1, 132.8, 132.1, 130.7, 129.8, 129.6, 129.5 , 65.2, 21.7, 13.1.
HRMS (ESI) calcd for C16H16BrO3S (M + H+) 367.0004, found 367.0001.
1ꢀphenylꢀ2ꢀtosylbutanꢀ1ꢀone(3r)20b, 20c. Colorless oil (9.8 mg, 13%); 1H
NMR (500 MHz, CDCl3) δ 7.98 (d, J = 7.3 Hz, 2H), 7.65 (d, J = 8.3 Hz,
2H), 7.61 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.31 (d, J = 8.1 Hz,
2H), 5.00 (dd, J = 10.9, 3.6 Hz, 1H), 2.43 (s, 3H), 2.16 (dqd, J = 18.7, 7.5,
3.6 Hz, 1H), 2.08 – 2.00 (m, 1H), 0.88 (t, J = 7.4 Hz, 3H).13C NMR (125
MHz, CDCl3) δ 192.8, 145.3, 137.5, 133.9, 133.8, 129.8, 129.5, 129.0,
128.8, 71.5, 22.1, 21.7, 11.5.
134.5, 132.2, 130.8, 129.92, 128.9, 128.6, 63.8, 21.7.
20c, 24
1ꢀ(4ꢀnitrophenyl)ꢀ2ꢀtosylethanone(3f)
. Yellow solid(59.0 mg,
74%); mp 144ꢀ145°C; 1H NMR (500 MHz, CDCl3) δ 8.34 (d, J = 8.8 Hz,
2H), 8.16 (d, J = 8.8 Hz, 2H), 7.75 (d, J = 8.3 Hz, 2H), 7.37 (d, J = 8.1
Hz, 2H), 4.75 (s, 2H), 2.47 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 187.0,
150.9, 145.9, 140.0, 135.4, 130.5, 130.1, 128.5, 124.0, 64.2, 21.8.
1ꢀ(4ꢀ(methylsulfonyl)phenyl)ꢀ2ꢀtosylethanone(3g). White solid(51.0mg,
58%); mp 156ꢀ157°C; 1H NMR (500 MHz, CDCl3) δ 8.16 (d, J = 8.2 Hz,
2H), 8.06 (d, J = 8.2 Hz, 2H), 7.75 (d, J = 8.1 Hz, 2H), 7.36 (d, J = 8.0
Hz, 2H), 4.77 (s, 2H), 3.10 (s, 3H), 2.46 (s, 3H). 13C NMR (125 MHz,
CDCl3) δ 187.4, 145.8, 145.1, 139.6, 135.6, 130.3, 130.0, 128.5, 127.9,
63.9, 44.2, 21.7. HRMS (ESI) calcd for C16H17S2O5 (M + H+) 353.0517,
found 353.0513.
2ꢀtosylꢀ3,4ꢀdihydronaphthalenꢀ1(2H)ꢀone(3s). White solid (20.3mg,
1
27%); mp 146ꢀ147°C; H NMR (500 MHz, CDCl3) δ 7.98 (dd, J = 7.9,
1.1 Hz, 1H), 7.80 – 7.77 (m, 2H), 7.51 (td, J = 7.5, 1.4 Hz, 1H), 7.36 (d, J
= 8.0 Hz, 2H), 7.29 (dt, J = 7.4, 4.8 Hz, 2H), 4.09 (t, J = 5.7 Hz, 1H), 3.51
(ddd, J = 16.8, 9.8, 4.7 Hz, 1H), 2.98 (dt, J = 17.0, 5.4 Hz, 1H), 2.89 –
2.82 (m, 1H), 2.65 (ddd, J = 14.8, 10.1, 5.1 Hz, 1H), 2.45 (s, 3H). 13
C
NMR (125 MHz, CDCl3) δ 188.7, 145.0, 143.6, 136.2, 134.4, 131.9,
129.6, 129.2, 128.9, 128.0, 127.0, 69.8, 26.6, 23.7, 21.7. HRMS (ESI)
calcd for C17H17O3S (M + H+) 301.0898, found 301.0894.
2ꢀtosylꢀ1ꢀ(4ꢀ(trifluoromethyl)phenyl)ethanone(3h)20c
.
White
1
solid(51.3mg, 60%); mp 143ꢀ144°C; H NMR (500 MHz, CDCl3) δ 8.07
(d, J = 8.2 Hz, 2H), 7.74 (d, J = 8.2 Hz, 4H), 7.34 (d, J = 8.0 Hz, 2H),
4.75 (s, 2H), 2.45 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 187.5, 145.7,
138.4, 135.6, 135.4(q, J = 32.5 Hz), 129.9, 129.8, 128.6, 125.9 (q, J = 3.8
Hz), 123.4(q, J = 271.3 Hz), 63.9, 21.7.
1ꢀphenylꢀ2ꢀ(phenylsulfonyl)ethanone(4a)20ꢀ23
.
White
solid(47.4mg,
1
73%); mp 83ꢀ84°C; H NMR (500 MHz, CDCl3) δ 7.93 (dd, J = 8.3, 1.1
Hz, 2H), 7.91 – 7.88 (m, 2H), 7.68 – 7.64 (m, 1H), 7.62 (dd, J = 10.6, 4.2
Hz, 1H), 7.54 (t, J = 7.8 Hz, 2H), 7.47 (t, J = 7.8 Hz, 2H), 4.75 (s, 2H).
13C NMR (125 MHz, CDCl3) δ 187.9, 138.8, 135.7, 134.3, 134.2, 129.3,
2ꢀtosylꢀ1ꢀ(3ꢀ(trifluoromethyl)phenyl)ethanone(3i). White solid(34.2mg,
40%); mp 165ꢀ166°C; 1H NMR (500 MHz, CDCl3) δ 8.18 (d, J = 7.9 Hz,
1H), 8.14 (s, 1H), 7.87 (d, J = 7.8 Hz, 1H), 7.75 (d, J = 8.3 Hz, 2H), 7.66
129.2, 128.9, 128.6, 63.4.
20c~20e, 20g, 20h, 20j
2ꢀ((4ꢀchlorophenyl)sulfonyl)ꢀ1ꢀphenylethanone(4b)20a,
.
(t, J = 7.8 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 4.74 (s, 2H), 2.45 (s, 3H). 13
C
White solid (47.7mg, 65%); mp 135ꢀ136°C; 1H NMR (500 MHz, CDCl3)
δ 7.93 (dt, J = 8.5, 1.5 Hz, 2H), 7.86 – 7.81 (m, 2H), 7.66 – 7.62 (m, 1H),
7.54 – 7.47 (m, 4H), 4.75 (s, 2H). 13C NMR (125 MHz, CDCl3) δ 187.9,
NMR (125 MHz, CDCl3) δ 187.1, 145.8, 136.3, 132.6, 131.53 (q, J =
25.4), 130.8(q, J = 34 Hz), 130.6(q, J = 3.8 Hz), 129.9, 128.5, 125.2 (q, J
= 275 Hz), 126.0 (q, J = 3.8 Hz), 63.8, 21.7. HRMS (ESI) calcd for
C16H14F3O3S (M + H+) 343.0616, found 343.0613.
141.1, 137.1, 135.6, 134.5, 130.2, 129.5, 129.3, 128.9, 63.3.
20c~20e, 20g, 20h, 20j
2ꢀ((4ꢀbromophenyl)sulfonyl)ꢀ1ꢀphenylethanone(4c)20a,
.
1ꢀ(3ꢀnitrophenyl)ꢀ2ꢀtosylethanone(3j). Yellow solid(62.2mg, 78%); mp
White solid (60.8mg, 72%); mp 120ꢀ121°C; 1H NMR (500 MHz, CDCl3)
δ 7.92 (d, J = 7.4 Hz, 2H), 7.75 (d, J = 8.6 Hz, 2H), 7.68 (d, J = 8.5 Hz,
2H), 7.63 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 2H), 4.75 (s, 2H). 13C
NMR (125 MHz, CDCl3) δ 187.9, 137.7, 135.6, 134.5, 132.5, 130.2,
129.7, 129.2, 128.9, 63.3.
1
128ꢀ129°C; H NMR (500 MHz, CDCl3) δ 8.73 (t, J = 1.9 Hz, 1H), 8.47
(ddd, J = 8.2, 2.2, 1.0 Hz, 1H), 8.35 – 8.32 (m, 1H), 7.74 (ddd, J = 14.0,
9.3, 4.8 Hz, 3H), 7.36 (d, J = 8.0 Hz, 2H), 4.78 (s, 2H), 2.46 (s, 3H). 13C
NMR (125 MHz, CDCl3) δ 186.4, 148.5, 145.9, 136.9, 135.5, 134.9,
130.1, 130.0, 128.5, 128.4, 124.1, 63.9, 21.7. HRMS (ESI) calcd for
C15H14NO5S (M + H+) 320.0593, found 320.0590.
2ꢀ((4ꢀmethoxyphenyl)sulfonyl)ꢀ1ꢀphenylethanone(4d)20a, 20c~20e, 20g. White
1
solid (31.9mg, 44%); mp 93ꢀ94°C; H NMR (500 MHz, CDCl3) δ 7.95
1ꢀ(3ꢀbromophenyl)ꢀ2ꢀtosylethanone(3k)20c, 21. White solid(50.2mg, 57%);
(dd, J = 8.4, 1.1 Hz, 2H), 7.82 – 7.79 (m, 2H), 7.64 – 7.60 (m, 1H), 7.48
(t, J = 7.8 Hz, 2H), 7.00 – 6.97 (m, 2H), 4.71 (s, 2H), 3.88 (s, 3H).13C
NMR (100 MHz, CDCl3) δ 187.9, 163.8, 134.1, 130.7, 129.9, 129.1,
1
mp 129ꢀ130°C; H NMR (500 MHz, CDCl3) δ 8.00 (t, J = 1.8 Hz, 1H),
7.91 – 7.88 (m, 1H), 7.76 – 7.72 (m, 3H), 7.39 – 7.32 (m, 3H), 4.68 (s,
2H), 2.45 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 186.9, 145.6, 137.5,
137.1, 135.6, 132.1, 130.4, 129.9, 128.6, 128.0, 123.2, 63.7, 21.7.
128.6, 127.9, 114.2, 63.7, 55.7.
20c~20e, 20g, 20h, 20j
2ꢀ((4ꢀfluorophenyl)sulfonyl)ꢀ1ꢀphenylethanone(4e)20a,
.
1ꢀ(3ꢀchlorophenyl)ꢀ2ꢀtosylethanone(3l) 20c, 21. White solid(33.1mg, 43%);
White solid (36.1mg, 52%); mp 145ꢀ146°C; 1H NMR (500 MHz, CDCl3)
δ 7.97 – 7.87 (m, 4H), 7.63 (t, J = 6.8 Hz, 1H), 7.49 (q, J = 6.7 Hz, 2H),
7.21 (t, J = 8.4 Hz, 2H), 4.75 (s, 2H).13C NMR (100 MHz, CDCl3) δ
187.6, 165.5(d, J = 256 Hz), 135.3, 134.6, 134.3, 131.7(d, J = 10 Hz),
129.0, 128.7, 116.3(d, J = 23Hz), 63.3.
1
mp 128ꢀ129°C; H NMR (500 MHz, CDCl3) δ 7.87 – 7.83 (m, 2H), 7.77
– 7.73 (m, 2H), 7.60 – 7.56 (m, 1H), 7.46 – 7.41 (m, 1H), 7.34 (d, J = 8.0
Hz, 2H), 4.69 (s, 2H), 2.45 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 187.1,
145.6, 137.3, 135.6, 135.3, 134.2, 130.2, 129.9, 129.2, 128.6, 127.6, 63.7,
21.7.
1ꢀ(3ꢀmethoxyphenyl)ꢀ2ꢀtosylethanone(3m). Colorless oil (56.2 mg,
74%); 1H NMR (500 MHz, CDCl3) δ 7.78 – 7.75 (m, 2H), 7.52 – 7.49 (m,
1H), 7.44 – 7.42 (m, 1H), 7.37 (t, J = 8.0 Hz, 1H), 7.33 (d, J = 8.0 Hz,
2H), 7.15 (ddd, J = 8.2, 2.6, 0.7 Hz, 1H), 4.71 (s, 2H), 3.83 (s, 3H), 2.43
(s, 3H). 13C NMR (125 MHz, CDCl3) δ 187.9, 145.3, 137.1, 135.9, 129.8,
128.6, 128.2, 128.0, 122.2, 121.1, 113.0, 63.7, 55.5, 21.7. HRMS (ESI)
calcd for C16H17O4S (M + H+) 305.0848, found 305.0844.
1ꢀphenylꢀ2ꢀ((4ꢀ(trifluoromethyl)phenyl)sulfonyl)ethanone(4f)20c
. White
solid (37.7mg, 46%); mp 111ꢀ112°C; 1H NMR (500 MHz, CDCl3) δ 8.05
(d, J = 8.2 Hz, 2H), 7.92 (dd, J = 8.3, 1.1 Hz, 2H), 7.81 (d, J = 8.4 Hz,
2H), 7.63 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.9 Hz, 2H), 4.80 (s, 2H).13C
NMR (100 MHz, CDCl3) δ 187.4, 141.8, 135.7, 135.3 (d, J = 15.7 Hz),
134.4, 129.2, 129.0, 128.8, 126.9 (q, J = 3 Hz), 123.1(q, J = 272 Hz),
62.9.
2ꢀ((2ꢀchlorophenyl)sulfonyl)ꢀ1ꢀphenylethanone(4g)20c
.
Colorless oil
1ꢀ(2ꢀmethoxyphenyl)ꢀ2ꢀtosylethanone(3n). Yellow oil(25.1 mg, 33%);
1H NMR (500 MHz, CDCl3) δ 7.76 – 7.73 (m, 2H), 7.66 (dd, J = 7.8, 1.8
Hz, 1H), 7.49 (ddd, J = 8.5, 7.3, 1.8 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H),
7.01 – 6.96 (m, 1H), 6.90 (d, J = 8.3 Hz, 1H), 4.92 (s, 2H), 3.88 (s, 3H),
(46.3 mg, 63%); 1H NMR (500 MHz, CDCl3) δ 8.07 – 8.03 (m, 1H), 7.96
– 7.92 (m, 2H), 7.63 – 7.56 (m, 3H), 7.50 – 7.42 (m, 3H), 5.06 (s, 2H).13C
NMR (100 MHz, CDCl3) δ 187.4, 136.1, 135.5, 134.9, 134.2, 132.4,
131.8, 131.6 128.9, 128.7, 127.2, 60.8.
4
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DOI: 10.1039/C5OB00742A
20c, 20g ,20h.
2ꢀ(naphthalenꢀ2ꢀylsulfonyl)ꢀ1ꢀphenylethanone(4h)20a,
. White
Yuan, J.ꢀN. Xiang, Org. Lett. 2013, 15, 4654; (d) R.ꢀY. Tang, Y.ꢀX.
Xie, Y.ꢀL. Xie, J.ꢀN. Xiang, J.ꢀH. Li, Chem. Commun. 2011, 47,
12867; (e) F. Xiao, H. Xie, S. Liu, G. Deng, Adv. Synth. Catal.
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79, 10605.
solid (51.9mg, 67%); mp 134ꢀ135°C; 1H NMR (500 MHz, CDCl3) δ 8.46
(s, 1H), 8.00 – 7.91 (m, 5H), 7.87 (dd, J = 8.6, 1.9 Hz, 1H), 7.70 – 7.65
(m, 1H), 7.60 (ddd, J = 8.4, 5.0, 1.0 Hz, 2H), 7.45 (t, J = 7.8 Hz, 2H),
4.81 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 187.6, 135.5, 135.4, 135.3,
134.1, 131.8, 130.4, 129.4, 129.3, 129.1, 128.6,128.0, 127.8, 127.5, 122.7,
63.5.
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Financial support from the National Natural Science Foundation
of China (21102130), the 863 Program (2013AA065005) and the
Key Innovation Team of Science & Technology in Zhejiang
Province(2011R50017) is greatly appreciated.
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Notes and references
a College of chemical Engineering, Zhejiang University of Technology,
Hangzhou 310014, P. R. China. Fax: +86 571 88320799; Tel: +86 571
88320799; Eꢀmail: duxiaohua@zjut.edu.cn
†Electronic Supplementary Information (ESI) available: spectra for
compounds 3. See DOI:10.1039/b000000x/
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