Visible-light-induced direct oxysulfonylation of alkynes with sulfonyl chlorides and HCl

Article abstract of DOI:10.1016/j.tetlet.2017.09.083

A mild, practical and efficient strategy to prepare β-keto sulfones has been developed by visible-light-induced reactions. This reaction involved Ir(dtbbpy)(ppy)₂PF₆-catalyzed direct functionalization of alkynes with sulfonyl chloride and HCl using air as the oxidant. HCl not only acted as a hydrogen source in the proton transfer process, but also played a vital role in the reaction process.

Full text of DOI:10.1016/j.tetlet.2017.09.083

Accepted Manuscript
Visible-Light-Induced Direct Oxysulfonylation of Alkynes with Sulfonyl
Chlorides and HCl
Tengfei Niu, Dingyun Jiang, Bangqing Ni
PII:
S0040-4039(17)31250-9
https://doi.org/10.1016/j.tetlet.2017.09.083
TETL 49353
DOI:
Reference:
Tetrahedron Letters
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26 September 2017
29 September 2017
Please cite this article as: Niu, T., Jiang, D., Ni, B., Visible-Light-Induced Direct Oxysulfonylation of Alkynes with
Sulfonyl Chlorides and HCl, Tetrahedron Letters (2017), doi: https://doi.org/10.1016/j.tetlet.2017.09.083
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Visible-Light-Induced Direct
Oxysulfonylation of Alkynes with Sulfonyl
Chlorides and HCl
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Tengfei Niu,* Dingyun Jiang, Bangqing Ni*

1
Tetrahedron Letters
journal homepage: www.els evier.com
Visible-Light-Induced Direct Oxysulfonylation of Alkynes with Sulfonyl
Chlorides and HCl
Tengfei Niu,* Dingyun Jiang, Bangqing 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; byron_ni@yeah.net
ARTICLE INFO
ABSTRACT
Article history:
Received
A mild, practical and efficient strategy to prepare β-keto sulfones has been developed by visible-
light-induced reactions. This reaction involved Ir(dtbbpy)(ppy)2PF6-catalyzed direct
functionalization of alkynes with sulfonyl chloride and HCl using air as the oxidant. HCl not
only acted as a hydrogen source in the proton transfer process, but also played a vital role in the
reaction process.
Received in revised form
Accepted
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Visible-light promoted reaction
Oxidative difunctionalization
Alkynes
Sulfonyl chlorides
β-Keto sulfones
β-Keto sulfones are of great importance due to their wide
applications in pharmaceutical industry and material science.
They have shown a wide range of biological properties including
antifungal, antibacterial and nonnucleoside inhibitors properties.1
Moreover, β-keto sulfones are valuable building blocks for
construction of biologically active heterocycles.2 During the past
few decades, numerous methods have been developed to build
these useful structures.
visible-light-promoted protocol to β-keto sulfones through direct
oxysulfonylation of alkenes with sulfonyl chlorides.15 Although
these methods provide attractive routes to β-keto sulfones,
however, most of them focus on alkenes, the direct
oxysulfonylation of alkynes has been elusive.
Traditional approaches to access these compounds are via
direct alkylation of sodium sulfinates with acyl halides.3
Alternatively, sulfonylation of enol acetates,4 vinyl azides,5 silyl
enolate,6 arylpropiolic acids7 as well as 1,3-dicarbonyl
compounds8 with sodium sulfinate, sulfonylhydrazides and sulfur
dioxide are also useful routes to synthesize β-keto sulfones.
Recently, oxysulfonylation of an unsaturated bond has attracted
Scheme 1 Methods for the synthesis of β-keto sulfones
much
attention
due
to
its
efficiency, simplicity
and atom economy (Scheme 1). In 2013, Yang and Wang
reported a copper-catalyzed oxysulfonylation reaction of alkenes
with sulfonylhydrazides for the synthesis of β-keto sulfones.9
Yadav and co-workers disclosed a AgNO3/K2S2O8 catalyzed
oxidative difunctionalization of alkenes with thiophenols.10 Later,
this group developed another direct oxysulfonylation of alkenes
with sodium sulfinate under similar conditions.11 In 2016, Chen
et al. demonstrated an oxysulfonylation reaction between
sulfonyl chlorides and alkenes using tert-butyl hydroperoxide
(TBHP) as the oxidant under basic conditions.12 Recently,
extensive attentions have been paid to the visible-light-induced
carbonylation of alkenes and alkynes, owing to its low cost,
energy efficiency and environmental friendliness.13 In this
context, Yang group14 described visible-light-induced synthesis
of β-keto sulfones from sulfinic acids. Our group developed a
The challenge for the direct oxysulfonylation of alkynes lies
in how to generate the oxidized vinyl radical and trap the
corresponding oxidized electrophilic cation by H-atom. The
sequential single electron transfer (SET) and proton transfer (PT)
to sulfonyl radical intermediate could be an ideal route to achieve
this goal. In 2013, Lei et al. developed a aerobic oxidative
difunctionalization of terminal alkynes with sulfinic acids in the
presence of 4 equiv. of pyridine.16 Alternatively, Cai and co-
works demonstrated
a
visible-light-induced
oxidative
difunctionalization between alkynes and sulfonylhydrazides in
the presence of 4 equiv. of NaOAc and 1 equiv. of KI.17
Although the oxysulfonylation of alkynes have been achieved in
existing literature, only sulfonylating reagents those with active
H proton produced the desired products. Using sulfonylating

2
Tetrahedron Letters
reagents without active H proton such as sulfonyl chloride still
yield was observed when the reaction was carried out under
oxygen (Table 1, entry 16). Slightly increasing the amount of 2a
and HCl did not affect the reaction (Table 1, entries 17 and 18).
Furthermore, no desired product was observed when the reaction
was carried out in absence of photocatalyst and visible light
(Table 1, entries 19 and 20).
remains a challenge for oxysulfonylation of alkynes. Given the
importance of β-keto sulfones, and in continuation of our interest
in photoredox difunctionalization reactions,18 herein, we report a
visible-light-induced radical/oxidative addition domino process
to access β-ketosulfones by using alkyne and sulfonyl chloride as
the staring materials.
With the optimal reaction in hand, various of alkynes were
then employed to react with 1a, and the results were shown in
Table 2 (3aa-3aj). Generally, alkynes with functional groups
such as F, Cl, Br, Me and OMe were well tolerated under the
optimal reaction conditions, and the corresponding products were
obtained in moderate to good yields. Notably, substrate with a
strong electron-donating group (OMe) provided a higher yield
(Table 2, 3ag). However, cyano substituted alkyne 2k and
aliphatic alkyne such as cyclohexylacetylene 2l showed less
reactivity for the present reaction conditions, providing 27% and
36% yield of desired products respectively even 3 equiv of 1a
and HCl were used. Obviously, alkynes with para-, meta- or
ortho-fluorine substituent were unambiguously suitable for the
present reaction condition, affording the desired products 3ab,
3ac and 3ad in 70%, 66% and 61%, respectively. Besides,
heterocyclic aromatic alkyne performed well and the
corresponding product was isolated in moderated yield (Table 2,
3aj). However, internal arylalkyne 2m was unsuitable for the
present condition.
In an initial study, HCl was used as hydrogen source, 4-
nitrobenzenesulfonyl chloride 1a (0.6 mmol), phenylacetylene 2a
(0.5 mmol) were chosen as the model substrates, and air was
used as the oxidant. The model reaction was carried out in the
presence of Ru(bpy)3Cl2·6H2O (2 mol%) and HCl (1.2 equiv. 2.0
mol/L in diethyl ether) in acetonitrile under visible light
irradition with a 5W blue LED under open air. To our delight, the
reaction gave 44% yield of desired product 3aa after 8h (Table 1,
entry 1). Subsequently, various photocatalysts such as Ir(ppy)3 ,
Ir(dtbbpy)(ppy)2PF6, Eosin Y, Rhodamine B and Eosin B were
tested and a better yield was obtained when Ir(dtbbpy)(ppy)2PF6
was used (Table 1, entries 2-7). Decreasing the amount of
Ir(dtbbpy)(ppy)2PF6 to 1 mol% still led to a 74% yield (Table 1,
entry 8). Thus 1 mol% of Ir(dtbbpy)(ppy)2PF6 was used as
photocatalyst. It is worth noting that lower yield was obtained
when aqueous HCl solution (37 wt%) was used (Table 1, entry
9). Other H+ sources such as weak acid HCOOH and strong acid
H2SO4 were also screened while they exhibited poor reactivities
(Table 1, entries 10 and 11), indicating that the Cl- played an
important role in this reaction. Hereafter, a series of solvents such
as MeOH, CH2Cl2, DMSO and DMF were tried, however, lower
yields were obtained (Table 1, entries 12-15). Other control
experiments were also performed. No significant increase in the
Table 2 Reaction scope of the alkynes.a
Table 1. Optimization of reaction conditions.a
Photocatalyst
H+
Solvent
Yield
Entry
(mol%)
source
(mL)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeOH
CH2Cl2
DMSO
DMF
(%)b
44
1
2
Ru(bpy)3Cl2·6H2O (2)
Ir(ppy)3 (2)
HCl (sln)c
HCl (sln)
HCl (sln)
HCl (sln)
HCl (sln)
HCl (sln)
HCl (sln)
HCl (aq)d
HCOOH
H2SO4
53
3
Ir(dtbbpy)(ppy)2PF6(2)
Eosin Y (3)
77
4
trace
trace
trace
74
6
Rhodamine B (3)
7
Eosin B(3)
8
Ir(dtbbpy)(ppy)2PF6(1)
Ir(dtbbpy)(ppy)2PF6(1)
Ir(dtbbpy)(ppy)2PF6(1)
Ir(dtbbpy)(ppy)2PF6(1)
Ir(dtbbpy)(ppy)2PF6(1)
Ir(dtbbpy)(ppy)2PF6(1)
Ir(dtbbpy)(ppy)2PF6(1)
Ir(dtbbpy)(ppy)2PF6(1)
Ir(dtbbpy)(ppy)2PF6(1)
Ir(dtbbpy)(ppy)2PF6(1)
Ir(dtbbpy)(ppy)2PF6(1)
No
9
38
10
11
12
13
14
15
16e
17f
18g
19
20i
trace
trace
45
a
Reaction conditions: 1a (1.2 equiv), 2 (0.5 mmol) and HCl (1.2 equiv, 2.0
mol/L in diethyl ether) in MeCN (2 mL) were irradiated with a 5 W blue LED
HCl (sln)
HCl (sln)
HCl (sln)
HCl (sln)
HCl (sln)
HCl (sln)
HCl (sln)
HCl (sln)
HCl (sln)
b
under air at room temperature for 8 h. Isolated yields. 3 equiv. of 1a and
HCl were used.
51
trace
trace
74
We next tried the various of sulfonyl chlorides, however,
only sulfonyl chloride with a strong electro-withdrawing group
could smoothly converted to the corresponding products (Table
3). The steric hindrance had only a slight influence on the yields
of the reaction (Table 3, 3aa-3ca). It is worth noting that
heterocyclic aromatic sulfonyl chloride such as 3-ethynylpyridine
worked well and afforded the corresponding product 3da in 70%
yield. Nevertheless, aliphatic sulfonyl chloride 1g was inert
toward this transformation. The halogen substitution including
Cl, Br could not survived the present reaction, no reactions
occurred. Moreover, aryl sulfinic chloride bearing strong
electron-donating group such as OMe also unsuitable for the
present reaction conditions.
MeCN
MeCN
MeCN
MeCN
MeCN
70
72
NRh
NR
Ir(dtbbpy)(ppy)2PF6(1)
aReaction conditions: 1a (1.2 equiv), 2a (0.5 mmol), H+ source (1.2 equiv),
and photocatalyst in indicated solvent (2 mL) were irradiated with a 5w blue
c
LED under air at room temperature for 8h. bIsolated yields. Solution: 2.0
f
mol/L in diethyl ether. d 37 wt%. e reaction was carried out under oxygen. 2a
i
(2 equiv.) was used. g HCl (2.4 equiv.) was used. h No reaction. Reaction
without light

3
Table 3. Substrate scope of the sulfonyl chlorides.a
between intermediatesⅡ and Ⅲ affords radical Ⅳ, which
further undergo SET with Ir2+ complex to afford intermediate Ⅴ.
Finally, Ⅴundergoes PT to produce Ⅵ, which isomerizes and
furnishes final product 3. Due to the electronic effect of the
substituents, sulfinic chloride with electron-donating group such
as OMe cannot be easily actived at the SET process to generate
sulfonyl radical in this system.
O
Ph
R
S
Cl
2
O
Cl
1
O
S
Cl2
+
R
Ref 19
O
Ⅰ
Cl
Ir3+
*
O
S
R
Ph
Ⅱ
O
Ir2+
O2
O
Ir3+
Ph
O
O
S
R
S
Ph
R
O
O
Ⅲ
O
O
Ⅱ
Ⅳ
O
S
O
S
O
S
a
H+
Ph
Ph
OH
Ph
Reaction conditions: 1 (1.2 equiv), 2a (0.5 mmol) and HCl (1.2 equiv, 2.0
mol/L in diethyl ether) in MeCN (2 mL) were irradiated with a 5 W blue LED
under air at room temperature for 8 h. Isolated yields.
R
R
R
O
O
O
O
O
3
Ⅴ
Ⅵ
In order to gain some insight into the mechanism, several
control experiments were therefore performed. First, radical
trapping experiment was conducted by employing 2,2,6,6-
tetramethyl-1-piperidinyloxy (TEMPO), and the reaction was
absolutely inhibited (Scheme 2, a) indicating the reaction might
undergo a radical pathway. Next, no ATRA (atom-transfer
radical addition)-type product 4aa or coupling product 5aa were
observed under the standard condition, suggesting that both
structures 4aa and 5aa were excluded from our transformations
as a plausible intermediate (Scheme 2b). Additionally, no
conversion was observed when sodium benzenesulfinate 4a with
phenylacetylene 2a were reacted under the standard conditions
(Scheme 2, c), suggesting the nucleophilic addition by sulfonyl
anions may not occurred in this process.
Scheme 3 Proposed mechanism.
In conclusion, we have developed a visible-light-induced
radical strategy for the oxysulfonylation of alkynes with sulfonyl
chlorides and HCl to preparation of β-keto sulfones. The reaction
proceeded smoothly at room temperature by using air as the
oxidant. A series of functional groups survived the reaction
conditions to afford the corresponding products in moderate to
good yields. Preliminary mechanism revealed that HCl not only
acted as a hydrogen source to in the proton transfer process, but
also plays a vital role in the activity of sulfonyl chloride.
Compared with the previous reports,16, 17 although only electro-
withdrawing group substitued sulfonyl chlorides was used in this
protocol, only low amount of the catalyst (1 mol%) and the
substrates (1.2 equiv of sulfonyl chlorides, 1 equiv of alkenes and
1.2 equiv of HCl) were necessary. Importantly, air was used as
the oxidant without any other additives. The mild, efficient and
practical synthetic method described in this study could be a
superior alternative for the synthesis of a variety of biologically
and chemically significant β-keto sulfones.
Acknowledgments
The authors gratefully acknowledge the Natural Science
Foundation of Jiangsu Province, China (BK20160164) for
financial support.
References and notes
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Scheme 2 Control experiments.
Based on both of the above control experiments and previous
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was depicted in Scheme 3. Initially, upon the visible light
irradiation, the ground-state photocatalyst Ir(ppy)2(dtbbppy)PF6
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5
The highlights of this work are list as follows:
(1) Visible light promoted oxidative
difunctionalization of alkynes
(2) Air was used as oxidant.
(3) H+ was used as a hydrogen source
(4) Mild condition, efficient strategy and easy
operation.