Y. Chen, L. Xu, B. Wang et al.
Tetrahedron Letters 65 (2021) 152794
product (Table 1, Entry 19). Alternatively, no product was formed
under nitrogen atmosphere (Table 1, Entry 18). Using pure oxygen
as the terminal oxidant provided a comparable result to that of the
reaction with air (Table 1, Entry 17). After further screening of tem-
perature, reaction time, the reaction of sodium benzenesulfinate 1a
and styrene 2a to give 3a in 94% yield using the conditions: CuCl2
(0.05 mmol), HOAc (1.0 mL), in PEG400 (1 mL) with stirring at
60 °C open to air for 6 h (Table 1, Entry 6 and Table S1, Entry
13–14). The mild reaction conditions, including shorter reaction
times (6 h), operational simplicity (open air), cost-effectiveness
and excellent yields (94%), make this protocol an alternative
method for the facile construction of numerous b-ketosulfones.
Furthermore, having identified the optimized conditions, we
investigated the scope of the reaction with respect to 2a and differ-
ent styrenes. As shown in Table 2, a range of vinylarenes, with
either electron-donating groups (R1 = Me, OMe, N, N-dimethy) or
electron-withdrawing groups (R1 = F, Cl, Br) on aromatic ring, were
viable in this transformation (Table 2, 3b-g). Electron-donating
vinylarenes (Table 2, 3b-d) displayed higher reactivity than those
bearing electron-with-drawing groups (Table 2, 3e-g). Signifi-
cantly, several functional groups (nitro, 3,4-dichloro) were well
tolerated (Table 2, 3 h-k), affording the corresponding b-ketosul-
fones in good to excellent yield. Interestingly, a nitro substituent,
which is usually unfavorable in the transformation with aerobic
oxidative cross-coupling reaction, was also well tolerated, afford-
ing the corresponding 3 h-3j in good yields. It was observed that
the electronic variation at the ortho-, meta-, para-substituents of
the aryl ring vinylarenes did not affect the transformation, gave
the corresponding 3 h, 3i and 3j in 88%, 86% and 84% yield, respec-
tively. It should be noted that 2-vinylnaphthalene was also found
to be compatible with this transformation, albeit in slightly lower
yield (Table 2, 3 l, 3u).
Additionally, to highlight the wide functional group tolerance of
this process, sulfinate salts with aliphatic and alkyl groups were
investigated under standard conditions. To our satisfaction, a vari-
ety of aryl sulfinate salts, bearing either electron-donating groups
(Table 2, 3 m-t) or electron-withdrawing groups (Table 2, 3u, 3v)
on the aryl ring, reacted smoothly with vinylarenes, affording the
corresponding b-ketosulfones in good to excellent yield. As can
be seen in Table 2, sodium p-toluenesulfinate displayed higher
reactivity than sodium 4-chlorobenzene sulfinate, although afford-
ing the corresponding b-ketosulfones in good to excellent yield. It
was interesting to note that sodium methane sulfinate, an aliphatic
sodium sulfinate, was also suitable substrate for this transforma-
tion (Table 2, 3w-z and 3Ⅰ-Ⅴ). The reaction proceeded efficiently
to afford their corresponding b-ketosulfones products in moderate
to good yields even for the substrates vinylarenes bearing func-
tional groups such as halide, Me, OMe, and nitro, especially, F, Cl
and Br group, thus further enhancing the scope of our reaction.
Because of the steric hindrance effect of ortho-position substitu-
tion, 80% of 3Ⅴwas formed, which is in contrast with the case for
3Ⅱ, where the chloro group is located on the para position of the
phenyl ring. This similar effect was then confirmed when meta-
nitro substituted vinylarene afforded 81% yield (Table 2, 3IV).
To gain preliminary mechanistic information about this proto-
col, a series of experiments were carried out to provide insight
Table 2
Substrate Scope for the Synthesis of Various b-ketosulfones under air condition
.
Entry
R1
R2
3
Yield of 3 [%]
1
2
3
4
5
6
7
8
H
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
Phenyl
4-CH3-Phenyl
4-CH3-Phenyl
4-CH3-phenyl
4-CH3-phenyl
4-CH3-Phenyl
4-CH3-Phenyl
4-CH3-Phenyl
4-CH3-Phenyl
4-Cl-Phenyl
4-Cl-Phenyl
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
3a
3b
3c
3d
3e
3f
3 g
3 h
3i
94
95
96
96
90
92
92
88
86
84
91
85
95
96
97
97
91
93
90
89
86
84
85
86
86
87
84
84
84
81
80
4-CH3
4-OCH3
4-N,N-dimethy
4-F
4-Cl
4-Br
4-NO2
3-NO2
2-NO2
3,4-dichloro
Phenyl
H
4-CH3
4-OCH3
4-N,N-dimethy
4-F
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
3j
3 k
3 l
3 m
3n
3o
3p
3q
3r
4-Cl
4-Br
3s
3t
4-NO2
Phenyl
H
4-CH3-phenyl
H
4-CH3
4-OCH3
4-F
4-Cl
4-Br
3-NO2
2-Cl
3u
3v
3w
3x
3y
3z
3Ⅰ
3Ⅱ
3III
3 IV
3Ⅴ
3