Silver-Catalyzed Denitrative Sulfonylation of β-Nitrostyrenes: A Convenient Approach to (E)-Vinyl Sulfones

Article abstract of DOI:10.1002/ejoc.201600237

The first utilization of β-nitrostyrenes (readily available by the Henry reaction) for a highly stereoselective, convenient, and catalytic synthesis of (E)-vinyl sulfones at room temperature was investigated. The protocol involves efficient silver-catalyz

Full text of DOI:10.1002/ejoc.201600237

DOI: 10.1002/ejoc.201600237
Full Paper
Vinyl Sulfones
Silver-Catalyzed Denitrative Sulfonylation of ꢀ-Nitrostyrenes:
A Convenient Approach to (E)-Vinyl Sulfones
Twinkle Keshari,[a] Ritu Kapoorr,[a] and Lal Dhar S. Yadav*[a]
Abstract: The first utilization of ꢀ-nitrostyrenes (readily avail- catalyzed denitrative radical cross-coupling of ꢀ-nitrostyrenes
able by the Henry reaction) for a highly stereoselective, conve-
nient, and catalytic synthesis of (E)-vinyl sulfones at room tem-
perature was investigated. The protocol involves efficient silver-
and sodium sulfinates by using potassium persulfate as an addi-
tive to complete the catalytic cycle.
Introduction
tion/elimination reaction.[23] Considering the above points and
our continued work on the functionalization of alkenes,[24] we
report herein a convenient catalytic approach to (E)-vinyl sulf-
ones from ꢀ-nitrostyrenes and sodium sulfinates (Scheme 1d).
We opted to use silver catalysis so that we could efficiently
generate sulfonyl radicals from sodium sulfinates.
Vinyl sulfones constitute an important class of compounds with
diversified biological activities and synthetic applications.[1–5]
Substituted vinyl sulfones have received overwhelming atten-
tion in medicinal chemistry and the pharmaceutical industry
owing to their wide scope of utilization as cysteine protease
inhibitors,[6] antibiotic TAN-1085,[7] and HIV-1 integrase.[8] As far
as a synthetic point of view is concerned, they act as efficient
Michael acceptors and 2π partners in cycloaddition reactions.[9]
Keeping in view the importance and further exploitation of
vinyl sulfones, many approaches are available for their synthe-
sis, and many more novel synthetic routes continue to be devel-
oped.
The literature records a number of methods for the synthesis
of vinyl sulfones that involve the direct oxidation of vinyl sulf-
ides,[10] ꢀ-elimination,[11] Knoevenagel condensation,[12] Wittig
reaction,[13] and Horner–Emmons reaction.[14] These methods
have been replaced by more efficient Pd- and Cu-catalyzed
cross-coupling reactions of vinyl halides,[15] vinyl tosylates,[16]
vinyl triflates,[17] alkenylboronic acids,[18] and alkenes.[19] Al-
though these reactions are efficient, the use of poisonous met-
als and expensive ligands makes them unsuitable from a syn-
thetic point of view. Li and co-workers developed the ammon-
ium iodide induced sulfonylation of alkenes with DMSO.[20]
However, this method is limited to the synthesis of only vinyl
methyl sulfones. We also reported the regioselective synthesis
of vinyl sulfones from epoxides.[21]
Scheme 1. Different routes for the synthesis of vinyl sulfones.
Very recently, decarboxylative sulfonylation reactions of cin-
namic acids[22] were reported, and this led us to hypothesize
that denitrative sulfonylation reactions of ꢀ-nitrostyrenes, read-
ily available by the Henry reaction, could be a convenient way
to access vinyl sulfones. In several instances, ꢀ-nitrostyrenes
have been used for denitrative C–C bond formation by an addi-
Results and Discussion
To realize our hypothesis, we commenced the study with a
model reaction of sodium p-toluenesulfinate (2a; 0.25 mmol)
and ꢀ-nitrostyrene (1a; 0.25 mmol) in the presence of AgNO3
(20 mol-%) as a catalyst and K2S2O8 (0.50 mmol) as an additive
in DMF at room temperature (Table 1). (E)-Vinyl sulfone 3a was
obtained in an excellent yield of 90 % in just 2 h. Encouraged
by this result, we switched over to optimizing the reaction con-
ditions, and different additives such as tert-butyl hydroperoxide
(TBHP), di-tert-butyl peroxide (DTBP), and (NH4)2S2O8 were
[a] Green Synthesis Lab, Department of Chemistry, University of Allahabad,
Allahabad 211002, India
E-mail: ldsyadav@hotmail.com
www.allduniv.ac.in
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201600237.
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Table 1. Optimization of the reaction conditions.[a]
Entry
Solvent
Catalyst (mol-%)
Additive (equiv.)
Yield [%][b]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
dioxane
DMSO
MeOH
CH3NO2
THF
CH3CN
toluene
DMF
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
Fe2O3 (20)
CuI (20)
FeCl3 (20)
AgOAc (20)
CuCl (20)
K2S2O8 (2)
TBHP (2)
DTBP (2)
90
27
38
54
45
26
70
40
20
50
25
65
90
75
90
26
85
22
15
–
(NH4)2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (1.0)
K2S2O8 (3)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
Cu(OAc)2 (20)
–
AgNO3 (20)
AgNO3 (20)
AgNO3 (15)
AgNO3 (25)
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
–
–
[c]
–
[a] Reaction conditions: A mixture of ꢀ-nitrostyrene (1a; 0.25 mmol), sodium p-toluenesulfinate (2a; 0.25 mmol), catalyst, and additive in solvent (3 mL) was
stirred for 2 h under N2. [b] Yield of isolated product after column chromatography. [c] Reaction was performed in the presence of O2.
tested in place of K2S2O8, but none of them was found to be ing group (e.g., CF3, Cl, or Br; see Table 2, 3a–f). Other sulfinic
better than K2S2O8 (Table 1, Entries 1–4). Then, we proceeded salts such as sodium 2-thienylsulfinate and sodium 2-naphthyl-
to investigate the optimum amount of the additive required, sulfinate also produced the products in excellent yields (Table 2,
and it was found that 2 equiv. was sufficient, as upon decreas- see 3i and 3s). Moreover, alicyclic and aliphatic sulfinates also
ing the amount, the yield decreased, and upon increasing the reacted under the conditions to afford the products in good
amount no change in the yield was observed (Table 1, En- yields (Table 2, see 3j and 3n).
tries 12 and 13). As shown in Table 1 (Entry 1 vs. Entries 5–10),
AgNO3 proved to be the best catalyst among those tested to
give the desired product in a maximum yield of 90 %. In the
absence of a catalyst, the yield was poor (Table 1, Entry 11).
Subsequently, quantitative optimization of the catalyst showed
that 20 mol-% was the optimum catalyst loading (Table 1, En-
try 1 vs. Entries 14 and 15).
Similarly, ꢀ-nitrostyrenes bearing an electron-donating
group on the aromatic ring worked better than those bearing
an electron-withdrawing group. Unfortunately, the reaction did
not produce the desired product in the case of an alkyl-substi-
tuted ꢀ-nitroalkene (Table 2, see 3o). This is probably the case
because for ꢀ-nitrostyrenes the formation of a resonance-stabi-
lized radical is highly favored, contrary to alkyl-substituted ꢀ-
Screening of various solvents revealed DMF to be the best nitroalkenes. Moreover, α- and/or ꢀ-substituted ꢀ-nitrostyrenes
among dioxane, DMSO, MeOH, CH3NO2, THF, CH3CN, and tolu- and nitrogen-containing heterocycles were not compatible with
ene (Table 1, Entries 16–22). The formation of product 3a was the reaction conditions.
not observed if the reaction was performed in the presence of
O2 (Table 1, Entry 23).
Trace amounts or no products were observed if the radical
scavenger 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) was
Under the standardized reaction conditions, a variety of ꢀ- added to the reaction mixture, which proves that the reaction
nitrostyrenes and sodium sulfinates were explored, and the re- proceeds by a radical pathway (Scheme 2a). The formation of
sults are summarized in Table 2. Notably, sodium sulfinates 2 the p-toluenesulfonyl–TEMPO adduct was confirmed by MS
bearing an electron-donating group [e.g., Me, OMe, or C(Me)3] [HRMS (EI): calcd. for C16H25NO3S 311.1555; found 311.1552]. In
on the aromatic ring were superior for the radical addition/ the absence of the sulfinate, reactant 1a was recovered, which
elimination reaction than those bearing an electron-withdraw- implies that the self-coupling of ꢀ-nitrostyrenes does not occur
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Table 2. Synthesis of vinyl sulfones.[a]
[a] Reaction conditions: A mixture of ꢀ-nitrostyrene 1 (0.25 mmol), sodium sulfinate 2 (0.25 mmol), AgNO3 (20 mol-%), and K2S2O8 (0.50 mmol) in DMF (3 mL)
was stirred at room temperature under N2 for 2 h (for details, see the Experimental Section). [b] The yields of isolated products 3 are given in parentheses.
Scheme 2. Mechanistic investigation.
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by a radical pathway (Scheme 2b). Moreover, (E)-vinyl sulfone
was selectively obtained upon using a (Z)-ꢀ-nitrostyrene under
the standard conditions (Scheme 2c).
Acknowledgments
We sincerely thank SAIF, Punjab University, Chandigarh, for pro-
viding microanalyses and spectra. T. K. is grateful to the Council
of Scientific and Industrial Research (CSIR), New Delhi, for the
award of a Senior Research Fellowship [File No. 09/001(0370)/
2012-EMR-1], and R. K. is grateful to the Department of Science
and Technology (DST), New Delhi, for the award of a SERB-
Young Scientist position and financial assistance (Registration
No. CS-271/2014).
On the basis of the above results and literature prece-
dent,[23a,24b,24c] a plausible radical addition/elimination mecha-
nism is proposed in Scheme 3. At first, AgI triggers the forma-
tion of sulfonyl radical 2′, and the resulting Ag0 is oxidized to
AgI with the persulfate anion to complete the catalytic cycle.
The addition of the sulfonyl radical to the olefinic double bond
of ꢀ-nitrostyrene 1 generates carbon-centered radical 1′. Finally,
1′ eliminates NO2 and produces the more stable (E)-vinyl sulf-
one 3.
Keywords: Cross-coupling · Elimination · Radical reactions ·
Silver · Sulfur
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Experimental Section
General Procedure for the Denitrative Sulfonylation of ꢀ-Nitro-
styrenes with Sodium Sulfinate: A mixture of (E)-ꢀ-nitrostyrene 1
(0.25 mmol), sodium sulfinate 2 (0.25 mmol), AgNO3 (20 mol-%),
K2S2O8 (0.50 mmol), and DMF (3 mL) was stirred at room tempera-
ture under N2 in a round-bottomed flask for 2 h. Upon completion
of the reaction (monitored by TLC), water (5 mL) was added, and
the mixture was extracted with EtOAc (3 × 5 mL). The combined
organic phases were dried with anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. The resulting crude product
was purified by column chromatography (silica gel; EtOAc/n-hex-
ane, 1:4) to afford an analytically pure sample of (E)-vinyl sulfone 3.
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Received: March 1, 2016
Published Online: May 2, 2016
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