Visible-light-promoted oxidative difunctionalization of alkenes with sulfonyl chlorides to access β-keto sulfones under aerobic conditions

Article abstract of DOI:10.1016/j.tetlet.2017.08.013

A mild, practical and efficient strategy to prepare β-keto sulfones has been developed by visible light promoted reactions. This reaction involves Ir(ppy)₂(dtbbpy)PF₆ catalyzed direct funcationalization of alkenes with sulfonyl chlorides under mild conditions. Air was used as oxidant without any additives. The transformation affords the corresponding products in moderate to high yields.

Full text of DOI:10.1016/j.tetlet.2017.08.013

Accepted Manuscript
Visible-Light-Promoted Oxidative Difunctionalization of Alkenes with Sulfon-
yl Chlorides to Access β-Keto Sulfones under Aerobic Conditions
Teng-fei Niu, Jing Cheng, Chang-li Zhuo, Ding-yun Jiang, Xing-ge Shu, Bang-
qing Ni
PII:
S0040-4039(17)31002-X
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.08.013
TETL 49203
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
13 July 2017
2 August 2017
7 August 2017
Please cite this article as: Niu, T-f., Cheng, J., Zhuo, C-l., Jiang, D-y., Shu, X-g., Ni, B-q., Visible-Light-Promoted
Oxidative Difunctionalization of Alkenes with Sulfonyl Chlorides to Access β-Keto Sulfones under Aerobic
Conditions, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/j.tetlet.2017.08.013
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Visible-Light-Promoted Oxidative
Difunctionalization of Alkenes with Sulfonyl
Chlorides to Access β-Keto Sulfones under
Aerobic Conditions
Leave this area blank for abstract info.
Teng-fei Niu*, Jing Cheng, Chang-li Zhuo, Ding-yun Jiang, Xing-ge Shu, Bang-qing Ni

1
Tetrahedron Letters
journal homepage: www.els evier.com
Visible-Light-Promoted Oxidative Difunctionalization of Alkenes with Sulfonyl
Chlorides to Access β-Keto Sulfones under Aerobic Conditions
Teng-fei Niu*, Jing Cheng, Chang-li Zhuo, Ding-yun Jiang, Xing-ge Shu, Bang-qing Ni
aAffiliation 1, Address, City and Postal Code, Country School of Chemical and Material Engineering, Jiangnan University,
Wuxi 214122, Jiangsu Province, P. R. China
E-mail: niutf@jiangnan.edu.cn
ARTICLE INFO
ABSTRACT
Article history:
Received
A mild, practical and efficient strategy to prepare β-keto sulfones has been developed by visible
light promoted reactions. This reaction involves Ir(ppy)2(dtbbpy)PF6 catalyzed direct
funcationalization of alkenes with sulfonyl chlorides under mild conditions. Air was used as
oxidant without any additives. The transformation affords the corresponding products in
moderate to high yields.
Received in revised form
Accepted
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Visible-light promoted reaction
Oxidative difunctionalization
Alkenes
Sulfonyl chlorides
β-Keto sulfones
The oxidative difunctional of alkenes or alkynes to access
difunctuonal ketone derivatives is of significant interest to
organic chemists.1 Among them β-keto sulfones have received
much more reasonable attention for its widespread presence in
pharmaceuticals, agrochemicals and biologically active
compounds. For example, β-keto sulfones derivatives could be
used in antifungal and antibacterial drugs, and are also potent
nonnucleoside inhibitors.2 Moreover, these motifs are valuable
building blocks for the construction of a variety of other
tert-butyl hydroperoxide (TBHP) as oxidant for the synthesis of
β-keto sulfones (Scheme 1, a).11 Consequently, Cai et al.
demonstrated a visible light-induced aerobic oxidative
difunctionalization of alkynes and sulfonylhydrazides with 4
equiv. of NaOAc and 1 equiv. of KI as additives (Scheme 1, b).12
Utilizing oxygen for oxidative difunctionalization is more
cheaper and environment friendly. It is well know that, sulfonyl
chlorides are common, inexpensive and readily available
sulfonylating source, which have been extensively employed for
constructing sulfone-containing compounds. In this context, Yu
chemicals,
especially biologically active heterocyclic
compounds, such as polyfunctionalized 4H-pyrans and
quinolines.3 Thus, a number of approaches have been employed
to build these structures.
Previous work
a)
EosinY
visible-light
O
O
H
Ar
S
S
Ar
+
Ar
Ar
Ar
O
O
Traditional methods for the synthesis of β-keto sulfones
involve the direct alkylation of sodium sulfinates with phenacyl
halides.4 However, the precursors are not easily available.
Alternatively, difunctionalization of alkenes or alkynes with
sulfinic acids,5 sulfonylhydrazides,6 arenesulfinate salts,7 sulfonyl
chlorides8 as well as thiophenols9 are also useful routes to
synthesize β-keto sulfones. Although these methods provided the
desired products in attractive routes, a simple and efficient way
to synthesize β-keto sulfones is still highly desirable.
TBHP, EtOH/H2O
O
b)
c)
Ru(bpy)3Cl2
visible-light
O
O
Ar
NHNH2
S
S
Ar
Ar
+
Ar
O
O2,KI,NaOAc
DMF/H2O
O
O
f ace-Ir(ppy)3
OAc
O
O
Ar
Cl
visible-light
S
S
+
Ar
Ar
O
DCM, N2
O
O
In recent years, visible light promoted oxidative
difunctionalization of alkenes and alkynes has become a
powerful tool in synthetic difunctional ketone derivatives
because of its mild conditions, high efficiency, and convenient
workup.10 Recently, tremendous progress has been made in this
respect for the formation of C–S and C–O bonds. For example, in
2016, Yang and co-workers developed a visible light promoted
oxysulfonylation reaction of alkenes with sulfinic acids by using
This work
d)
Ir(dtbbpy)(ppy)2PF6
visible-light
O
O
Cl
R2
S
R2
S
+
R1
R1
O
O
air, MeCN
O
Scheme 1 Methods for the synthesis of β-keto sulfones by visible-
light-promoted reaction.

2
Tetrahedron
visible-light-promoted directed
and zhang reported
a
Table 1.Screening of the Reaction Conditions.a
sulfonylation with enol acetates and sulfonyl chlorides (Scheme 1,
c).13 Give the importance of β-keto sulfones, and in continuation
of our interest in photoredox difunctionalization reactions,14
herein we reported a Ir(ppy)2(dtbbpy)PF6-catalyzed visible-light-
induced oxidative difunctionalization of alkenes with sulfonyl
chlorides using air under mild conditions without any other
additives (scheme 1d).
O
photocatalyst
Cl
air, solvent
O
S
S
O
+
O
O
blue LED, rt
O2N
O2N
1a
2a
3aa
Entry Photocatalyst (mol%)
Solvent Yield(%)b
1
Ru(bpy)3Cl2·6H2O (2)
Ir(ppy)3 (2)
MeCN
MeCN
MeCN
58
In an initial attempt, 4-nitrobenzenesulfonyl chloride 1a and
styrene 2a were chosen as the model substrates. To our delight
58% yield of desired product 3aa was obtained in the presence of
Ru(bpy)3Cl2·6H2O in MeCN at ambient temperature under air
after 8 hours (Table 1, entry 1). In order to obtain the optimum
yield, a wide variety of photocatalysts were screened. The typical
metal photocatalysts Ir(ppy)3 showed less catalytic activities
(Table 1, entry 2). However, trace amount of 3aa was obtained
when organic photocatalysts such as Eosin Y, 9-mesityl-10-
methylacridinium, Rhodamine B and Eosin B were used (Table 1,
entries 3–6). The best result was obtained when
Ir(ppy)2(dtbbpy)PF6 was used which provided 3aa in 80% yield
(Table 1, entry 7). Reducing the amount of Ir(ppy)2(dtbbpy)PF6 to
1 mol% led to a similar yield (Table 1, entry 8). Thus 1 mol% of
Ir(ppy)2(dtbbpy)PF6 was used as the photocatalyst. Furthermore,
different solvents including MeOH, DMSO, DMF and CH2Cl2
were tested, and the results showed that MeCN was the best
choice (Table 1, entries 9-12). No improvement of the yield was
observed when the reaction was carried out under oxygen instead
of air (Table 1, entry 13). It was worth noting that the reaction
did not occur in the absence of the photocatalyst or visible light
(Table 1, entries 14 and 15).
2
35
3
Eosin Y (3)
trace
trace
trace
trace
80
4
9-Mesityl-10-methylacridinium(2) MeCN
5
Rhodamine B (3)
MeCN
MeCN
MeCN
MeCN
MeOH
DMSO
DMF
6
Eosin B(3)
7
Ir(ppy)2(dtbbpy)PF6(2)
Ir(ppy)2(dtbbpy)PF6(1)
Ir(ppy)2(dtbbpy)PF6(1)
Ir(ppy)2(dtbbpy)PF6(1)
Ir(ppy)2(dtbbpy)PF6(1)
Ir(ppy)2(dtbbpy)PF6(1)
Ir(ppy)2(dtbbpy)PF6(1)
no
8
76
9
50
10
11
12
13c
14
15e
trace
trace
CH2Cl2 32
MeCN
MeCN
MeCN
76
NRd
NR
Ir(ppy)2(dtbbpy) PF6(1)
aReaction conditions:1a (0.5 mmol), 2a (0.6mmol)and photocatalyst
in indicated solvent (2 mL) were irradiated with a 5 W blue LED at
rt for 8 h under open air. isolated yield. c reaction was carried out
b
under oxygen. d no reaction. e In the dark.
With these results in hand, the scope and generality of the
present method were then examined. As shown in the Table 2,
diverse terminal aryl alkenes bearing a variety of electron-
donating and electron-withdrawing substituents were employed
to react with 4-nitrobenzenesulphonyl chloride 1a under the
optimized reaction conditions (3aa-3ao). Most of them delivered
the corresponding β-keto sulfone derivatives 3 smoothly in
moderate to high yields (52–88%, 3aa-3ao). The electronic
property of the substituents on the aryl rings of alkenes had a
slight influence on the reaction except substrate 2i which
provided the product 3ai in excellent yields (88%). Steric
hindrance for alkenes were not significant, and aryl alkenes with
para-, meta- or ortho-fluorine substituent were successfully
converted into the corresponding products in 71%, 68% and 62%,
respectively (3ad-3af). Aliphatic alkenes such as 1-hexene and
vinylcyclohexane afford the corresponding β-ketosulfone in 62%
and 68% yields respectively (3al and 3am). Notably, heterocyclic
alkene also survived as well in this transformation, and the
corresponding product 3an was obtained in moderated yield.
However, internal alkene such as 2-phenyl-1-propene was not
tolerated to give the desired product 3ao.
Table 2 Scope of the alkenes a
+O2N1a2R
O
O
Ir(ppy)2(dtbbpy)PF6
air, MeCN
Cl
R
S
S
O
+
O
R
O
blue LED, rt
O2N
O2N
1
2a
3
Cl
Br
O
O
S
O
S
S
O
O
O
O
O
O
O2N
O2N
O2N
(78%)
(70%)
F
3aa (76%)
3ab
3ac
F
F
O
O
S
O
S
S
O
O
O
O
O
O
O2N
O2N
O2N
3af (62%)
(71%)
3ad
(68%)
3ae
O
O
S
O
O
S
S
O
O
O
O
O
O
O2N
O2N
O2N
(76%)
(71%)
3ai (88%)
3ag
3ah
The scope of various sulfonyl chlorides was then investigated.
As can be seen in Table 3, sulfonyl chlorides with a strong
electron-withdrawing substituted group were suitable for the
present reaction conditions, affording the desired products in
moderate to good yield (3ba-3ea) . The steric hindrance of the
substituents had a significant influence on the reaction, and the 2-
nitrobenzenesulphonyl chloride gave relatively lower yield (3ca,
41%). The heterocyclic aromatic sulfonyl chloride worked well
and afforded the corresponding product in moderate yield (3fa，
56%). However, alkyl sulfonyl chlorides were inert toward this
transformation (3ga and 3ha). Besides, substrates contains only
halogen and strong electron-donating group were also unsuitable
for the present reaction conditions, providing a trace amount of
the desired products (Table 3, 3ia and 3ja).
CN
NO2
O
S
O
O
S
S
O
O
O
O
O
O
O2N
O2N
O2N
3aj (78%)
(62%)
3al
3ak (52%)
S
O
S
O
S
O
S
O
O
O
O
O
O
O2N
O2N
O2N
3am (68%)
3ao trace
3an (59%)
a
Reaction conditions: 1a (0.5 mmol),
Ir(ppy)2(dtbbpy)PF6 (1 mol%) and MeCN (2 mL), irradiated with a 5
W blue LED at rt for 8 h under open air; isolated yield.
2
(0.6mmol),

3
Table 3 Scope of the sulfonyl chlorides a
R2
2
O
S
Cl
Ir(ppy)2(dtbbpy)PF6
air, MeCN
R2
O
S
O
O
Cl
Ph
O
R1
Ph
2a
S
+
S
O
R
R
O
R1
blue LED, rt
O
O
1
O
S
O2
5
1
3
O
R1
Ⅲ
*
Ir
B
4
NO
O
O
2O
O2N
Cl
S
O2N
S
S
Cl
O
O
O
O
O
O
R2
O
S
Ⅳ
Ir
C
3da
O
3ba (72%)
3ca
(45%)
(41%)
O
R1
O
Ⅲ
Ir
A
6
-H+
O
O
S
R2
O
5
O
S
S
O
S
N
O
O
OH
O
O
O
R2
O
O
R1
NC
S
O
S
R2
O
O
R1
3fa (56%)
3ga trace
3ea (78%)
8
O
R1
O
7
O
S
O
S
3
O
S
O
O
O
Scheme 3 The proposed mechanism.
O
O
O
Cl
O
reduction of sulfonyl chloride 1, leading to Cl anion and sulfonyl
radical 4. Then, addition of sulfonyl radical 4 to olefins 2
provides radical 5, which is trapped by oxygen to give
intermediate 6 and 7. Ultimately, intermediate 7 undergoes 1,2-
hydrogen atom shift to generate radical 8. Subsequent SET
oxidation of intermediate 8 then racemization to lose H+
furnishes product 3.
3ha trace
3ia
3ja trace
trace
a
Reaction conditions:
Ir(ppy)2(dtbbpy)PF6 (1 mol%) and MeCN (2 mL), irradiated with a 5
W blue LED at rt for 8 h under open air; isolated yield.
1
(0.5 mmol), 2a (0.6mmol),
In order to further get insight into the reaction mechanism,
some control experiments were carried out under the standard
conditions (Scheme 2). First, 2 equivalents of free radical
scavenger, TEMPO (2,2,6,6-tetramethyl-1-piperidinyl oxyl), was
added, and the reaction was absolutely inhibited (Scheme 2, a).
The result indicated that a radical route might be involved in this
transformation. When the reaction was carried out in the presence
of a base (Na2CO3, K2HPO4, Et3N or DIPEA), no oxidation
product 3aa or coupling product 4a were observed, suggesting
that structures 4a was excluded from our transformations as a
plausible intermediate (Scheme 2b). It was worth noting that 80%
yield of 5a was obtained under nitrogen conditions, which
suggested that both free radical addition and electrophilic
addition might be involved (Scheme 2c).
In summary, we have developed an effective visible-light-
promoted reaction for the preparation of β-keto sulfones from
simple starting materials. Compared with the previous reports,8
although an expensive photocatalyst was used in this protocol,
only low amount of the catalyst (1 mol%) and the substrates (1
equiv of sulfonyl chlorides and 1.2 equiv of alkenes) were
necessary. Importantly, air was used as the oxidant without any
additives. Moreover, both aryl alkynes, aliphatic alkynes and
heterocyclic alkene were tolerated well in this transformation to
give the corresponding products in moderate to good yields
thereby providing a potential route for both academic and
industrial application.
According to the above control experiments and previous
reports11,12,13 a plausible mechanism net for the present reaction
was depicted in Scheme 3. Initially, upon the visible light
irradiation, the ground-state photocatalyst Ir(ppy)2(dtbbpy)+ (A)
was transferred to the excited state *Ir(ppy)2(dtbbpy)+ (B).
Oxidation of *Ir(ppy)2(dtbbpy)+ (B) to Ir(ppy)2(dtbbpy)2+ (C)
should be coincident with single-electron transfer (SET)
Acknowledgments
The authors gratefully acknowledge the Natural Science
Foundation of Jiangsu Province, China (BK20160164) for
financial support.
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Scheme 2 Control experiments.

4
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5
The highlights of this work are list as follows:
(1) Visible light promoted oxidative
difunctionalization of alkenes
(2) Air was used as oxidant.
(3) Mild condition, efficient strategy and easy
operation.