Copper catalyzed direct tert-butyl sulfonylation of alkynes with t-butylsulfinamide leading to (E)-vinyl sulfones

Article abstract of DOI:10.1039/c5ra13474a

The first copper-catalyzed tert-butyl sulfonylation reaction of alkynes with t-butylsulfinamide for the construction of (E)-vinyl sulfones has been developed. The cleavage of the N-S bond of t-butylsulfinamide, which was catalyzed by CuSO₄·5H

Full text of DOI:10.1039/c5ra13474a

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Copper catalyzed direct tert-butyl sulfonylation of alkynes with t-
butylsulfinamide leading to (E)-vinyl sulfones
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
ab
a
a
a
Zhidong Liu, Xiaolan Chen,* Jianyu Chen, Lingbo Qu,* Yingya Xia, Haitao Wu, Huili Ma,
a
c
Shaohua Zhu, Yufen Zhao
DOI: 10.1039/x0xx00000x
www.rsc.org/
Previous work
a)
R SO CH COOH
The first copper-catalyzed tert-butyl sulfonylation reaction of
alkynes with t-butylsulfinamide for the construction of (E)-vinyl
sulfones has been developed. The cleavage of N-S bond of t-
O
piperidine
(
+
R CHO
S
2
2
2
1
R1
R1
R2
R2
benzene. reflux
R1=alkyl, aryl; R2=alkyl, aryl
O
butylsulfinamide catalyzed by CuSO
this transformation.
4 2
•5H O was the key step for
O
S
H2O2, NH4Cl
(b)
R1
+
R2SH
THF, 50
℃
, 48h
O
R1=alkyl, aryl; R2=aryl
Vinyl sulfones have attracted recent attention as application in
O
1
O
S
organic synthesis and medicinal chemistry. Very recently, some
[Cu]ꢀbpy, KI 50 mol%
S
(c)
+
R1
R2
R1
R2
ONa
AcOH:DMSO=1:1
100 °C
investigations have also shown that vinyl sulfones derivatives are
O
2
3
potent antiparasitic drugs and neuroprotective agents . So far,
various methodologies have been developed to synthesize vinyl
sulfones. Traditional available methodologies generally involve: 1)
the knoevenagel condensations of aldehydes with sulfonylacetic
R1=aryl; R2=aryl, alkyl
O
O
S
CuBr (10 mol%)
S
(d)
R1
+
R1
R1
HPO(OEt)2 (10 equiv)
120 °C
O
R1= aryl, alkyl
4
5
O
S
This work
e)
acids (scheme 1-a), 2) wittig reactions, 3) the elimination from α-
O
S
CuSO4—5H2O (20 mol%)
6
(
R1
+
or β- substituted sulfones. Regrettably, these methods suffer from
H2N
O
H3PO3 (2.0 equiv)
TFA (2.0 equiv)
DMF, 100 °C
some limitations such as tedious procedures, poor selectivity or
inaccessible raw materials. In recent years, a number of studies
towards vinyl sulfones synthesis have been accomplished such as
the direct oxidation of the corresponding vinyl sulfides with
3
1
2
R1=aryl, alkyl
Scheme 1. Comparision of previous work with this work.
7
sulfonylation of alkynes using DMSO as a methyl sulfone source
oxidants (scheme 1-b), the cross-coupling reactions of sulfinate
1
7
8
9
9a
(scheme 1-d).
sulfonylation of alkenes using DMSO as a methyl sulfone source.
Our group also have developed a CuSO •5H O-H-phosphonate
Yuan’s group published an iodide-induced
salts with alkynes, alkenes (scheme 1-c) and their derivatives
1
8
1
0
11
vinyl halides , arylboronic acids , and the addition of sodium
1
2
sulfinates or 1,2-bis-(phenylsulfonyl)ethane to alkynes. Only
recently, palladium-catalyzed or iodine-catalyzed sulfonylation of
alkenes with sulfonyl hydrazides, gold-catalyzed sulfonylation of
alkynes with sulfinic acids and copper-catalyzed aerobic
decarboxylative sulfonylation of cinnamic acids with sodium
4
2
catalyzed synthesis of vinyl alkylsulfones from alkynes and widely
19
available DMSO. Despite remarkable improvement of vinyl
sulfones synthesis, the discovery of diversity of sulfone sources is
still highly desired. Herein, we disclose an efficient method for the
synthesis of (E)-vinyl sulfones from alkynes and t-butylsulfinamide,
1
3
14
15
16
,
sulfinates were developed by Jiang, lei, shi, and guo
4
using CuSO -phosphorous acid catalytic system for catalyzing the
respectively. In addition, a novel sulfone source DMSO also has
been discovered towards vinyl sulfones synthesis. For example,
Loh’s group desicribed an alternative Cu(I)-catalyzed methyl
formation of vinyl-S bond. To our knowledge, it is the first example
of using t-butylsulfinamide as the sulfur resource to prepare vinyl
sulfones.
We initiated this study, starting with establishing optimal
experimental conditions using the model reaction of
phenylacetylene (1a) with t-butylsulfinamide 2 in the presence of
4 2
CuSO •5H O, phosphorous acid and trifluoroacetic acid (TFA) in
DMF under open-air conditions for 12 h at 100 °C, as summarized in
Table 1. Initially, the reaction of phenylacetylene (1a) with t-
butylsulfinamide (2) was performed in DMF to examine the catalytic
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activities of several relatively cheap transition-metal salts including alkynes also gave the corresponding 3q-s in moderate to good
Cu, Ag, Pd, Ni and Fe salts (Table 1, entries 1–8). Among the above-
yields from 51% to 69%. 1,3-diethynylbenzene exhibiting the
expected 3t(53%) in moderate yield. Regrettably, 1-phenylpropyne
could not progress well, and only a trace amount of product was
obtained (3u).
a,b
Table 1．Optimization of reaction conditions
a,b
Table 2. Scope of hydrosulfonylation
a
Reaction conditions: 1a (0.5 mmol), 2 (0.6 mmol), catalyst (0-30 mol%)
b
H
3
PO
3
(0-3.0 equiv) and acid (0-3.0 equiv) at 100 °C for 12 h. Isolated yields.
a
mentioned metal salts, copper salts, especially CuSO
4
2
•5H O, turned
Reaction conditions: 1 (1.0 mmol), 2 (1.2 mmol), H
3
b
PO
3
(2.0 mmol),
4 2
•5H O (20 mol%), TFA (2.0 mmol) at 100 °C for 12 h. Isolated yields.
out to be the most effective catalyst giving a yield of 65%. (Table 1, CuSO
entries 1). Metal salts such as AgNO , Pd(OAc) , NiCl •6H O and
FeCl •6H O failed to deliver the product 3a (Table 1, entries 5-8).
The model reaction did not proceed in the absence of metals, H
or TFA (Table 1, entries 9-11). The ideal amounts of CuSO •5H
PO
6-19). The amounts shown in entry 12 brought about the most
satisfied yield. Besides TFA, other acid such as HNO and H SO
3
2
2
2
To further probe the reaction mechanism, some experiments
were subsequently carried out (Scheme 2). When the reaction was
carried out under a nitrogen atmosphere, the corresponding vinyl
sulfone 3a was not obtained (Scheme 2-a), indicating that the
copper-catalyzed hydrosulfonylation of alkynes required the
presence of oxygen. If TEMPO (2, 2, 6, 6-tetramethyl-1-
piperidinyloxy), a widely used radical scavenger, was added into the
reaction system, the reaction was completely suppressed (Scheme
3
2
3
PO
3
4
2
O,
H
3
3
and TFA were also explored (Table 1, entries 1 and 12, 13,
1
3
2
4
were also examined. The result showed that those acids failed to
produce the product 3a (Table 1, entries 14-15). Further screening
of the solvents showed that DMF was the best choice among those
tested solvents. The reaction in toluene and 1,4-dioxane failed to
generate the product 3a (Table 1, entries 21-22), while the reaction
conducted in DMSO gave a yield of 32% 3a and a yield of 43% vinyl
methyl sulfones (Table 1, entry 20). Therefore, optimal reaction
2
-b), suggesting that the reactions might undergo a radical
mechanism. The isotopic labeling experiment was also performed.
The reaction of phenylacetylene with t-butylsulfinamide in the
18
18
presence of 10 equiv H2 O afforded O-labeled 3a (Scheme 2-c),
conditions involved 2.0 equiv H
3 3 4 2
PO , 20 mol% CuSO •5H O and 2.0
equiv TFA in DMF at 100 °C for 12 h.
The substrate scope of alkynes and t-butylsulfinamide under the
optimized conditions was then explored as demonstrated in Table
2
. Various vinyl sulfones was efficiently obtained via the new
reaction. It can be seen that both electron-donating (OCH , CH
, n-C ) and electron-withdrawing groups (F, Cl, Br) of aryl
3
3
,
C
2
H
5
3 7
H
terminal alkynes were suitable for this protocol. Corresponding
vinyl sulfones were obtained in good to excellent yields (3a-o).
Common functionalities including halogen, methoxy, acetamide and
cyano groups were well tolerated. In addition, the reaction of 1-
ethynylcyclohexene with t-butylsulfinamide efficiently afforded the
conjugated sulfone 3p (70%). To our delight, heteroaromatic (a) 1a (1.0 mmol), 2 (1.2 mmol), H
3 3 4 2
PO (2.0 mmol), CuSO •5H O (20 mol%),
2
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PleaseRd So Cn oA t da vd aj un s ct ems argins
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DOI: 10.1039/C5RA13474A
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COMMUNICATION
+
TFA (2.0 mmol) at 100°C under nitrogen atmosphere for 12 h; (b) 1a (1.0
mmol), 2 (1.2 mmol), H PO (2.0 mmol), CuSO •5H O (20 mol%), TFA (2.0
mmol), TEMPO (3 equiv) at 100°C for 12 h. (c) 1a (1.0 mmol), 2 (1.2 mmol),
complex 10 then homolytically cleaved to complex 11, Cu and tert-
3
3
4
2
+
2+
butyl sulfonyl radical 12. Cu was oxidized back to Cu by oxygen in
air, and phosphonate ion 11 was protonated to form phosphorous
acid 4. Here, the selective addition of radical 12 to the terminal
alkyne 1, afterwards, led to the formation of vinyl radical 13. Then
vinyl radical 13 interacted with water to yield the final vinyl sulfone
1
8
H
2
O (10 equiv), H
00°C for 12 h.
Scheme 2. Experiments on the investigation of mechanism
3 3 4
PO (2.0 mmol), CuSO (20 mol%), TFA (2.0 mmol), at
1
demonstrating clearly that the additional oxygen atom of 3a
originated from H O instead of O in the air.
3
and hydroxyl radical. Meanwhile the vinyl radical 13 could react
2
2
with another phosphorous acid 4 molecule to produce the final
product 3 together with phosphite radical 14. Then phosphoric acid
Although the mechanism is not fully understood, a plausible
mechanism for the reaction is proposed in Scheme 3. Here, the
cheap and easily available phosphorous acid 4 (tetracoordinated
form) existed with its tautomer 5 (tricoordinated form). 5 and t-
1
5 might possibly be formed via termination reaction of phosphite
radical 14 and hydroxyl radical in the related reaction process.
2
+
butylsulfinamide 2 initially coordinated with Cu to form complex 6.
In the meantime, a six-membered ring was generated inside 6 Conclusions
…
through an intramolecular hydrogen bond (O-H O=S), and
In conclusion, a practical CuSO
E)-vinyl sulfones from alkynes and t-butylsulfinamide was
developed. The cleavage of N-S bond of t-butylsulfinamide
catalyzed by cheap and easily available CuSO •5H O-
4 2
•5H O catalyzed synthesis of
subsequently proton transfer from OH group to the oxygen of S=O
group, giving copper complex 7. It is worth emphasizing here that
complex 7 could resonate with 8. The two positive charges at the
(
4
2
phosphorous acid catalytic system was the key step for this
transformation. The method described in this paper open a
new door to the construction of vinyl sulfones. Studies of the
detailed mechanism of this process and its application are
currently underway in ou`r laboratory.
Acknowledgements
This work was financially supported by NSFC (no.
2
1072178), Innovation Specialist Projects of Henan Province
(no. 114200510023), Technology and Science talent Cultivation
Project in Zhengzhou City (no. 112PLJRC359), The Special Fund
for the Doctoral Program of Higher Education (no.
2
0124101110003), Foundational and Frontier Technology
Research Foundation of Henan Province for their financial
support (no. 132300410027).
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