Tetrabutylammonium iodide catalyzed allylic sulfonylation of Baylis-Hillman acetates with sulfonylhydrazides in water

Article abstract of DOI:10.1039/c3ob27329f

A tetrabutylammonium iodide catalyzed method for the synthesis of allyl aryl sulfone derivatives with Baylis-Hillman acetates and sulfonylhydrazides using tert-butyl hydroperoxide as an oxidation agent in water has been developed. In this process, the group eliminated from the sulfonyl precursor is molecular nitrogen.

Full text of DOI:10.1039/c3ob27329f

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Tetrabutylammonium iodide catalyzed allylic
sulfonylation of Baylis–Hillman acetates with
sulfonylhydrazides in water†
Cite this: Org. Biomol. Chem., 2013, 11,
1739
Xiaoqing Li,* Xiangsheng Xu* and Yucai Tang
Received 30th November 2012,
Accepted 18th January 2013
A tetrabutylammonium iodide catalyzed method for the synthesis of allyl aryl sulfone derivatives with
Baylis–Hillman acetates and sulfonylhydrazides using tert-butyl hydroperoxide as an oxidation agent in
water has been developed. In this process, the group eliminated from the sulfonyl precursor is molecular
nitrogen.
DOI: 10.1039/c3ob27329f
www.rsc.org/obc
Introduction
In recent years the tetrabutylammonium iodide (TBAI)/tert-
butyl hydroperoxide (TBHP) catalyzed system has become a
significant field of interest.1 The simple operation, nontoxic
and easy to handle reagents, and products free of heavy metal
impurities make it a versatile alternative for transition-metal
catalysts in numerous important organic transformations such
as C–O, C–N and C–C bond formations. However, TBAI cata-
lyzed C–S bond formation has not been considered of high
value.1n
The allyl aryl sulfone derivatives are important intermedi-
ates in organic synthesis2 and have been found to exhibit
important biological activities.3 Traditionally, they can be pre-
pared by the reaction of Baylis–Hillman adducts with sulfonyl
precursors such as sulfinates,4 arenesulfonyl cyanides,5
p-toluenesulfonylmethyl isocyanide6 and sulfinyl chlorides7
(Scheme 1). Generally, these reactions occurred in ionic liquid
or organic solvents with the elimination of undesirable bypro-
ducts from sulfonyl precursors. Thus, there is still a need for
facile and environmentally benign methods to afford allyl aryl
sulfone derivatives.
Recently, our group has developed a novel TBAI catalyzed
protocol for the direct allylic sulfonylation of α-methyl styrene
derivatives using sulfonylhydrazides as a sulfonyl precursor.1n
To the best of our knowledge, this is the first example of a
TBAI–TBHP system catalyzed C–S bond formation reaction. As
a logical extension of this catalytic method, and encouraged by
our previous work on the transformation of Baylis–Hillman
Scheme 1 Synthesis of substituted allyl sulfones.
adducts,8 we herein report a TBAI–TBHP system catalyzed
allylic sulfonylation of Baylis–Hillman acetates with sulfonyl-
hydrazides in water. A process that includes C–S bond for-
mation and C–O bond cleavage affords substituted allyl aryl
sulfones (Scheme 1).
Results and discussion
At the beginning of our study, we chose Baylis–Hillman acet-
ates 1a and TsNHNH2 (2a) as model substrates for this sulfony-
lation using the standard reaction conditions established by
our previous work (1.2 equiv. of TsNHNH2, 2 equiv. of TBHP,
and 20 mol% of TBAI in MeCN at 80 °C).1n The desired allylic
sulfone 3aa was obtained in 23% yield (Table 1, entry 1). A
similar result was obtained when EtOAc was used as the
solvent (Table 1, entry 2). To our delight, the yield increased to
66% when the reaction occurred in water. Moreover, the reac-
tion could finish within 0.5 h (Table 1, entry 3). No effect in
yield was observed with higher amounts of TsNHNH2 and
TBHP (Table 1, entry 4).
College of Chemical Engineering and Materials Science, Zhejiang University of
Technology, Hangzhou 310014, P. R. China. E-mail: xqli@zjut.edu.cn, future@zjut.
edu.cn; Fax: +86 571 88320799; Tel: +86 571 88320799
†Electronic supplementary information (ESI) available: Spectra for compounds
3. See DOI: 10.1039/c3ob27329f
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Table 1 Optimization of reaction conditionsa
Table 2 Scope of the reactiona,b,c
Entry
1a/2a
TBHP (eq.)
Solvent
Time (h)
Yieldb (%)
1
2
3
4
1 : 1.2
1 : 1.2
1 : 1.2
1 : 1.5
2
2
2
3
MeCN
EtOAc
H2O
10
10
0.5
0.5
23
21
66
64
H2O
a Reaction conditions: 0.5 mmol of Baylis–Hillman acetates (1a),
TsNHNH2 (2a), 20 mol% TBAI, TBHP (70% aqueous solution) in
3.0 mL of solvent. b Isolated yield.
With the optimized reaction conditions, the scope of this
transformation was then examined by using various Baylis–
Hillman acetates and sulfonylhydrazides (Table 2). Treatment
of TsNHNH2 (2a) with a series of Baylis–Hillman acetates
derived from benzaldehyde derivatives and acrylic esters (1a–
1k) furnished the corresponding products (3aa–3ka) in
44–78% yields. Generally, electron-rich Baylis–Hillman acetates
showed better reactivity and gave higher yields than electron-
deficient ones. Baylis–Hillman acetates derived from acrylo-
nitrile or cinnamaldehyde were well tolerated and the desired
sulfones 3la, 3ma and 3lb were provided in 65%, 52% and
69% yields, respectively. Heteroaryl species such as thiophenyl
underwent the desired reaction to give the corresponding
product 3na in 72% yield. Phenyl and p-bromophenyl substi-
tuted sulfonylhydrazides were also suitable partners with
Baylis–Hillman acetates to access the corresponding sulfones
(3ab, 3gb, 3hb, 3lb and 3ac, 3fc) in moderate yields. Unfortu-
nately, alkyl-substituted Baylis–Hillman acetates failed to give
the desired products which might be due to the difficulty in
the elimination of acetoxy radicals. The stereochemistry in all
cases was similar to that reported in the literature.4–6
The proposed mechanism is similar to that of our previous
study of TBAI catalyzed allylic sulfonylation of α-methyl styrene
derivatives with sulfonylhydrazides.1n As shown in Scheme 2,
initially, sulfonyl radicals were generated via TBAI–TBHP
system catalyzed hydrogen abstraction of sulfonylhydrazides
with the elimination of molecular nitrogen.9 The addition of
resultant sulfonyl radicals to the double bond of Baylis–
Hillman acetates and subsequent β-acetoxy radicals elimin-
ation10 afforded sulfones 3. Hydrogen elimination did not
happen in this process, perhaps due to the relatively higher
C–H bond energy.
a Reaction conditions: 0.5 mmol of Baylis–Hillman acetates (1),
0.6 mmol of sulfonylhydrazides (2), 20 mol% TBAI, 1 mmol of TBHP
(70% aqueous solution) in 3.0 mL of H2O at 80 °C for 0.5 h. b Isolated
yield. c Ratio of isomers was determined by 1H NMR spectroscopy of
the isolated product. d After crystallization.
available sulfonylhydrazides as a sulfonyl precursor, (2) the
group eliminated from the sulfonyl precursor is molecular
nitrogen, (3) using water as a solvent, and (4) short reaction
time. Currently, radical reactions based on the TBAI–TBHP
system catalyzed radical species generation from hydrazine
compounds are under investigation in our laboratory.
Conclusion
In summary, an environmentally friendly entry to allyl aryl sul-
fones starting from Baylis–Hillman acetates and sulfonylhydr-
azides has been developed. The protocol involves TBAI–TBHP
Experimental section
General methods
system catalyzed C–S bond formation and C–O bond cleavage. All reagents and solvents were purchased from commercial
1
This new protocol is distinguished by (1) using readily suppliers and used without purification. The H NMR and 13C
1740 | Org. Biomol. Chem., 2013, 11, 1739–1742
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4.48 (s, 2H), 4.02 (t, J = 6.8 Hz, 2H), 2.41 (s, 3H), 1.65–1.52 (m,
2H), 1.42–1.37 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H). 13C NMR
(125 MHz, CDCl3) δ 166.6, 145.7, 144.7, 136.4, 133.8, 129.6,
129.5, 129.2, 128.7, 128.5, 121.5, 65.4, 55.1, 30.5, 21.6, 19.2,
13.7. HRMS (ESI) calcd for C21H25O4S (M + H)+: 373.1474;
found: 373.1462.
(Z)-Ethyl 3-(p-tolyl)-2-(tosylmethyl)acrylate (3da). 1H NMR
(500 MHz, CDCl3) δ 7.90 (s, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.42
(d, J = 8.1 Hz, 2H), 7.28 (d, J = 8.1 Hz, 2H), 7.18 (d, J = 8.0 Hz,
2H), 4.49 (s, 2H), 4.04 (q, J = 7.1 Hz, 2H), 2.42 (s, 3H), 2.37 (s,
3H), 1.22 (t, J = 7.1 Hz, 3H). 13C NMR (125 MHz, CDCl3)
δ 166.7, 146.0, 144.6, 140.1, 136.6, 131.0, 129.6, 129.4, 129.4,
128.6, 120.3, 61.4, 55.3, 21.6, 21.4, 14.1. HRMS (ESI) calcd for
C20H23O4S (M + H)+: 359.1317; found: 359.1304.
(Z)-Methyl 3-(2-methoxyphenyl)-2-(tosylmethyl)acrylate (3ea).
1H NMR (500 MHz, CDCl3) δ 8.05 (s, 1H), 7.69 (d, J = 8.3 Hz,
2H), 7.58 (dd, J = 7.6, 0.9 Hz, 1H), 7.37–7.30 (m, 1H), 7.24 (d,
J = 8.0 Hz, 2H), 6.95 (t, J = 7.4 Hz, 1H), 6.83 (d, J = 8.3 Hz, 1H),
4.44 (s, 2H), 3.79 (s, 3H), 3.63 (s, 3H), 2.41 (s, 3H). 13C NMR
(125 MHz, CDCl3) δ 167.0, 157.3, 144.4, 142.2, 136.5, 131.1,
129.8, 129.5, 128.5, 122.7, 121.0, 120.6, 110.5, 55.5, 55.4, 52.2,
21.6. HRMS (ESI) calcd for C19H21O5S (M + H)+: 361.1110;
found: 361.1099.
Scheme 2 Proposed preliminary mechanisms.
(Z)-Methyl 3-(2-chlorophenyl)-2-(tosylmethyl)acrylate (3ia). 1H
NMR (500 MHz, CDCl3) δ 7.99 (s, 1H), 7.69 (d, J = 8.3 Hz, 2H),
7.65–7.60 (m, 1H), 7.40–7.24 (m, 5H), 4.37 (s, 2H), 3.65 (s, 3H),
2.42 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 166.4, 144.7, 142.8,
136.3, 134.1, 132.3, 130.5, 130.0, 129.7, 129.7, 128.4, 127.0,
123.3, 55.0, 52.5, 21.6. HRMS (ESI) calcd for C18H18ClO4S (M +
H)+: 365.0614; found: 365.0603.
NMR spectra were recorded at 25 °C in CDCl3 at 500 and
125 MHz, respectively, with TMS as the internal standard.
Chemical shifts (δ) are expressed in ppm and coupling con-
stants J are given in Hz. High resolution mass spectra (HRMS)
were obtained on a TOF MS instrument with an ESI source.
Baylis–Hillman acetates were prepared by the reported
procedure.11
General procedure for the synthesis of allyl aryl sulfone
derivatives 3. To a flask containing the Baylis–Hillman acet-
ates 1 (0.5 mmol), sulfonylhydrazides 2 (0.6 mmol), and tetra-
butylammonium iodide (0.1 mmol) in H2O (3 mL), TBHP
(70% aqueous solution) (1.0 mmol) was added. The suspen-
sion was stirred at 80 °C for 0.5 h. The mixture was then
extracted with AcOEt (4 × 10 mL) and the extract was washed
with brine, dried (anh. Na2SO4), and concentrated. The
residual was treated with silica gel chromatography (ethyl
acetate–petroleum ether) to give allyl aryl sulfones 3. The
characterization data for known compounds (3aa,5 3fa,4a
3ga,4b 3ha,5 3ka,4b 3la,4a 3ma,5 3na,4b 3ab,5 3hb,5 3lb5) are pro-
vided in the ESI.†
(Z)-Ethyl 3-phenyl-2-(tosylmethyl)acrylate (3ba). 1H NMR
(500 MHz, CDCl3) δ 7.91 (s, 1H), 7.71 (d, J = 8.3 Hz, 2H),
7.49–7.42 (m, 2H), 7.38–7.33 (m, 3H), 7.25 (d, J = 8.0 Hz, 2H),
4.48 (s, 2H), 4.07 (q, J = 7.1 Hz, 2H), 2.41 (s, 3H), 1.24 (t, J =
7.1 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 166.5, 145.8, 144.7,
136.4, 133.8, 129.6, 129.5, 129.2, 128.7, 128.5, 121.5, 61.5, 55.1,
21.6, 14.1. HRMS (ESI) calcd for C19H21O4S (M + H)+: 345.1161;
found: 245.1150.
(Z)-Methyl
3-(4-isopropylphenyl)-2-(tosylmethyl)acrylate
(3ja). 1H NMR (500 MHz, CDCl3) δ 7.91 (s, 1H), 7.73 (dd, J =
8.4, 1.7 Hz, 2H), 7.45 (d, J = 8.1 Hz, 2H), 7.28–7.24 (m, 4H),
4.52 (s, 2H), 3.60 (s, 3H), 2.95–2.89 (m, 1H), 2.43 (s, 3H), 1.28
(s, 3H), 1.27 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 167.1, 151.0,
146.3, 144.6, 136.4, 131.2, 129.6, 128.6, 126.8, 120.0, 55.3, 52.3,
34.0, 23.8, 21.6. HRMS (ESI) calcd for C21H25O4S (M + H)+:
373.1474; found: 373.1462.
(Z)-Ethyl 3-(4-chlorophenyl)-2-((phenylsulfonyl)methyl)acrylate
(3gb). 1H NMR (500 MHz, CDCl3) δ 7.89 (s, 1H), 7.86 (d, J =
7.4 Hz, 2H), 7.62 (t, J = 7.5 Hz, 1H), 7.53–7.43 (m, 4H), 7.35 (d,
J = 8.5 Hz, 2H), 4.45 (s, 2H), 4.04 (q, J = 7.1 Hz, 2H), 1.22 (t, J =
7.1 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 166.1, 144.5, 139.3,
135.7, 133.8, 132.1, 130.5, 129.0, 129.0, 128.4, 121.7, 61.6, 55.0,
14.0. HRMS (ESI) calcd for C18H18ClO4S (M + H)+: 365.0614;
found: 365.0602.
(Z)-Methyl 2-(((4-bromophenyl)sulfonyl)methyl)-3-phenyl acry-
late (3ac). 1H NMR (500 MHz, CDCl3) δ 7.94 (s, 1H), 7.69–7.62
(m, 2H), 7.61–7.55 (m, 2H), 7.43–7.36 (m, 5H), 4.52 (s, 2H),
3.68 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 166.7, 146.4, 138.1,
133.5, 132.3, 130.1, 129.7, 129.2, 129.0, 128.8, 120.8, 54.9, 52.5.
HRMS (ESI) calcd for C17H16BrO4S (M + H)+: 394.9953; found:
394.9939.
(Z)-Butyl 3-phenyl-2-(tosylmethyl)acrylate (3ca). 1H NMR
(Z)-Methyl
2-(((4-bromophenyl)sulfonyl)methyl)-3-(4-chloro-
(500 MHz, CDCl3) δ 7.90 (s, 1H), 7.70 (d, J = 8.3 Hz, 2H), phenyl)acrylate (3fc). 1H NMR (500 MHz, CDCl3) δ 7.89 (s, 1H),
7.49–7.42 (m, 2H), 7.37–7.32 (m, 3H), 7.25 (d, J = 8.0 Hz, 2H), 7.71–7.65 (m, 2H), 7.65–7.60 (m, 2H), 7.45–7.35 (m, 4H), 4.46
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(s, 2H), 3.65 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 166.5, 145.1,
138.1, 136.1, 132.3, 131.9, 130.4, 130.1, 129.4, 129.1, 121.2,
55.0, 52.6. HRMS (ESI) calcd for C17H15BrClO4S (M + H)+:
428.9563; found: 428.9550.
We thank the National Natural Science Foundation of
China (21102130) and the Key Innovation Team of Science and
Technology in Zhejiang Province (2010R50018 and
2011R50017) for financial support.
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