Manganese(III) acetate-mediated oxidative cyclization of α-methylstyrene and trans-stilbene with β-ketosulfones

Article abstract of DOI:10.3390/molecules18044293

A convenient microwave irradiation protocol was utilized for the synthesis of β-ketosulfones 1-5 in good yields. These sulfones reacted with alkenes through a radical oxidative cyclization mediated by Mn(OAc)₃. Dihydrofurans 6-10 were obtained

Full text of DOI:10.3390/molecules18044293

Molecules 2013, 18, 4293-4307; doi:10.3390/molecules18044293
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Communication
Manganese(III) Acetate-mediated Oxidative Cyclization of 
-Methylstyrene and trans-Stilbene with -Ketosulfones
Ahlem Bouhlel, Christophe Curti, Clémence Tabelé and Patrice Vanelle *
Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, Aix-Marseille Univ, CNRS,
Institut de Chimie Radicalaire ICR, UMR 7273, 27 Bd Jean Moulin, CS 30064,
13385 Marseille Cedex 05, France
* Author to whom correspondence should be addressed; E-Mail: patrice.vanelle@univ-amu.fr;
Tel.: +33-491-835-580; Fax: +33-491-794-677.
Received: 27 February 2013; in revised form: 3 April 2013 / Accepted: 4 April 2013 /
Published: 11 April 2013
Abstract: A convenient microwave irradiation protocol was utilized for the synthesis of
-ketosulfones 1–5 in good yields. These sulfones reacted with alkenes through a radical
oxidative cyclization mediated by Mn(OAc)3. Dihydrofurans 6–10 were obtained in
moderate to good yields starting from 1,1-disubstituted alkenes. Dihydrofurans 11–15 were
synthesized in moderate yields and unexpected cyclopropanes 16–19 were obtained in low
yields starting from 1,2-disubstituted alkenes. This protocol offers access to various
dihydrofurans which could be tested for their antiparasitic potential.
Keywords: manganese(III) acetate; dihydrofuran; radicals
1. Introduction
Manganese(III) acetate has received considerable attention over the past several decades, and
remains a useful tool for carbon-carbon bond formation [1–4]. Its specificity for carbonyl derivatives
allows a wide variety of radical synthetic applications, leading to various structures like pyrrolidinones [5],
-lactones [6,7], tetralins [8,9] or spirocyclic derivatives [10–12]. Within our research program
directed towards the development of original synthesis methods in medicinal chemistry [13–17], we
have explored the radical cyclization of -ketosulfones [18,19] mediated by manganese(III) acetate in
order to synthesize dihydrofurans as potential antiparasitic compounds.

Molecules 2013, 18
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The valuable antileishmanial activities of the functionalized dihydrofurans obtained call for
pharmacomodulation starting from new alkene building blocks. Dihydrofuran derivatives are known to
have other useful pharmacological properties, such as antibacterial [20–22], antifungal [20,21] and
anticancer activity [23], as well as being valuable potential intermediates in the synthesis of various
substances [24]. A wide variety of methods yielding dihydrofurans and cyclopropanes substituted by a
sulfonyl group have been developed [25–29]. We report here the reactivity of two alkenes, 
-methylstyrene and trans-stilbene, extending previous work on styrene, allylbenzene [30],
1.1-diphenylethylene and derivatives [30,31] and the ,-ethylenic ketone series [32].
2. Results and Discussion
-ketosulfones 1-5 were synthesized using previously reported methods [33,34]. As reported in the
literature [35–37], we observed formation of β-ketosulfones rather than β-ketosulfinate esters. An
aqueous solution of sodium benzene sulfinate and the corresponding 2-bromoacetophenone was
irradiated at 500 W, 100 °C in a microwave oven for 45 min to give sulfones 1–4 in good yields
(61–92%) (Scheme 1).
Scheme 1. Microwave assisted synthesisf-ketosulfones 1–4.
O
S
O
water, 100 oC
Br
SO2
Na
500 W, 45 min.
R1
O
R1
O
R1 = p-NO2, p-CN, p-Cl, m-NO2
1-4
-Ketosulfone 5 was synthesized starting with bromination of the corresponding ketone, and
substitution with benzene sodium sulfinate without further purification (Scheme 2). The -ketosulfone
derivatives thus obtained are presented in Table 1.
Scheme 2. -ketosulfone 5 microwave assisted synthesis.
O
S
a) Br2 (1 equiv.), CHCl3
b)
O
CH3
O
O
NO2
SO2
Na
(2 equiv.)
NO2
water, 100 oC, 500 W
5

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Table 1. Microwave assisted synthesis of -ketosulfones.
Entry
Product
Yields a
1
O
O
S
O
92%
O2N
NC
1
2
O
O
S
61%
O
2
3
O
O
S
89%
88%
65%
O
Cl
3
4
5
O
O
S
O2N
O
4
NO2 O
O
S
O
5
a Yield of isolated product based on the corresponding ketone.
A suspension of manganese(III) acetate in glacial acetic acid was irradiated at 200 W in a
microwave oven at 80 °C for 15 min until solubilization. -Ketosulfones 1–5 and the corresponding
alkenes were added to this solution and the mixture was then irradiated at 200 W, 80 °C for 45 min.
Using -methylstyrene as starting alkene, the desired 2,3-dihydrofuran derivatives 6–10, were
obtained (Scheme 3) in moderate yields (34–51%, Table 2), with several inseparable secondary
products. Attempts were made to increase these yields by adjusting several parameters [Cu(OAc)2,
more equivalents of alkene, more equivalents of Mn(OAc)3] without effect .
Scheme 3. Mn(OAc)3 mediated -ketosulfone reactivity in the -methylstyrene series.
R1
H3C
O
S
Mn(OAc)3 2.1 equiv.,
O
O
O
S
AcOH,
200 W, 80 oC, 45 min.
CH3
R1
O
O
3 equiv.
1-5
6-10
R1 = p-NO2, p-CN, p-Cl, m-NO2, o-NO2
The yield (43%) obtained with 1-(4-nitrophenyl)-2-(phenylsulfonyl)ethanone (1) is consistent with
previous results [30]. Dihydrofuran was obtained with a lower yield (32%) when the same
-ketosulfone reacted with styrene under the same conditions. Moreover, a better yield (48%) was
obtained in the 1,1-diphenylethylenic series. Yields obtained from radical oxidative cyclization of 

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-ketosulfones directly depend on the stability of the carbon centered radical of intermediate product B
(Scheme 4). Starting from -methylstyrene, this radical stability appears to be intermediate between
the stability of the radical from styrene and the radical from 1,1-diphenylethylene.
Table 2. Oxidative cyclizations mediated by Mn(OAc)3.
Entry
-ketosulfone/alkene
1/-methylstyrene
Product/Yields a
O2N
1
O
O
S
O
CH3
6
/43%
/34%
NC
2
3
2/-methylstyrene
3/-methylstyrene
O
O
S
O
CH3
7
Cl
O
O
S
O
CH3
8
/35%
NO2
4
4/-methylstyrene
O
O
S
O
CH3
9
/51%
/45%
NO2
5
6
5/-methylstyrene
1/trans-stilbene
O
O
S
O
CH3
10
O2N
O
S
O
O
O
S
O
O
NO
2 /12%
16
11
/21%
/13%
/12%
NC
7
8
2/trans-stilbene
3/trans-stilbene
O
S
O
O
O
S
O
O
CN /10%
12
17
Cl
O
S
O
O
S
O
O
O
Cl /5%
13
18

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Table 2. Cont.
Entry
-ketosulfone/alkene
Product/Yields a
NO2
9
4/trans-stilbene
O
S
O
O
O
S
O
NO2
O
19
14
/13%
/25%
NO2
O
10
5/trans-stilbene
O
S
O
15
/23%
a Yield of isolated product based on the corresponding sulfone.
Scheme 4. Suggested mechanismfthe reaction of -ketosulfones and Mn(OAc)3.
R3
R2
Mn3+
Mn2+
Mn3+
O
O
S
O
O
O
S
O
S
O
O
R3
O
R3
R1
R1
R1
R2
R2
Mn2+
R2 = -CH3, -H
R3 = -H, -Ph
A
B
C
R2 = -H
R3 = -Ph
Mn3+
O
R2
O
R1
O
S
O
S
O
O
R3
S
R1
O
O
O
R1
1-5
6-15
16-19
Using trans-stilbene as starting alkene, 2,3-dihydrofuran derivatives 11–15 were obtained
(Scheme 5) in moderate yields (12–25%, Table 2) and original cyclopropanes 16–19 were also
obtained in low yields (5–13%). With 1-(4-nitrophenyl)-2-(phenylsulfonyl)ethanone (1) 24% of the
starting material was recovered, along with several inseparable products. Dihydrofuran and
cyclopropane yields were slightly increased by using 3 equiv. of Mn(OAc)3, but not by using
Cu(OAc)2 or more equivalents of alkene.

Molecules 2013, 18
Scheme 5. Mn(OAc)3 mediated reactivity of -ketosulfones in the trans-stilbene series.
4298
R1
O
S
Mn(OAc)3 3 equiv.,
O
S
O
O
O
O
S
AcOH,
200 W, 80 oC, 45 min.
R1
O
O
O
3 equiv.
R1
1-5
11-15
16-19
R1 = p-NO2, p-CN, p-Cl, m-NO2, o-NO2
1
From analysis of the H-NMR spectra of synthesized products 11–19 and comparison with the
previously reported results, we conclude that dihydrofuran and cyclopropane derivatives were obtained
diastereoselectively from -ketosulfones 1–4 as the corresponding trans isomers.
Both protons of the dihydrofuran rings in 11–14 display two doublets at mean values of 5.50 and
4.50 ppm, with a vicinal coupling constant J between 5.0 and 5.6 Hz. For cis-2,3-dihydrofuran, the
vicinal coupling constant of the two methine protons proved to be J = 7–10 Hz, while for trans-2,3-
dihydrofuran the vicinal coupling constant J = 4–7 Hz [38]. Moreover, these results agree with previous
studies reporting trans-dihydrofuran diastereoselective synthesis via Mn(OAc)3 mediated radical
oxidative cyclizations starting from 1,2-disubstituted alkenes and -ketonitriles [39,40] or -ketoesters [41].
One of these studies [40] showed that the stereochemistry of Mn(OAc)3 mediated oxidative
cyclizations is not influenced by the stereochemistry of the starting alkene (cis or trans-stilbene).
To our knowledge, few studies have reported intramolecular cyclopropanation under Mn(OAc)3
reactivity [42–45], and only one reported intermolecular reactions between oxabenzonorbornadiene
and dimedone [46]. As Mn(OAc)3-mediated intermolecular cyclopropanation with trans-stilbene or a
similar 1,2-disubstituted alkene has never been reported, the structure of cyclopropane 16 was
established by X-ray diffraction analysis (Figure 1). As specified in previous studies [44], Mn(OAc)3
mediated cyclopropanation should come from the cation C (Schem 4), which reacted rapidly with the
enolic form of -ketosulfone to close the cyclopropane ring.
Figure 1. ORTEP view of compound 16.

Molecules 2013, 18
4299
-ketosulfone 5 led to cis-dihydrofuran 15 with vicinal coupling constant J = 8.0 Hz. o-Nitro
substitution appears to have reversed the diastereoselectivity and inhibited the cyclopropanation,
probably through the stereoelectronic effects of the nitro group during the final cyclization step.
Further research is in progress to explore this original mechanism.
3. Experimental
3.1. General
Microwave-assisted reactions were performed in a multimode microwave oven (ETHOS Synth Lab
Station, Ethos start, Milestone Inc., Rockford, IL, USA). Melting points were determined with a B-540
Büchi melting point apparatus. 1H-NMR (200 MHz) and 13C-NMR (50 MHz) spectra were recorded on
a Bruker ARX 200 spectrometer in CDCl3 or D2O at the Service Interuniversitaire de RMN de la
1
Faculté de Pharmacie de Marseille. The H chemical shifts were reported as parts per million
13
downfield from tetramethylsilane (Me4Si), and the C chemical shifts were referenced to the solvent
peaks: CDCl3 (76.9 ppm) or DMSO-d6 (39.6 ppm). Absorptions were reported with the following
notations: s, singlet; bs, broad singlet; d, doublet; t, triplet; q, quartet; m, a more complex multiplet or
overlapping multiplets. Elemental analysis and mass spectra, run on an API-QqToF mass spectrometer,
were carried out at the Spectropole de la Faculté des Sciences site Saint-Jérôme. Mass spectra, run on a
MicrOToF Q mass spectrometer, were carried out at the Plateforme Protéomique Innovation
Technologique Timone (PIT2) UMR 911 Faculté de Pharmacie. The following adsorbent was used for
flash column chromatography: silica gel 60 (Merck, particle size 0.040–0.063 nm, 70–230 mesh
ASTM). TLC were performed on 5 cm × 10 cm aluminium plates coated with silica gel 60 F-254
(Merck) in an appropriate solvent.
3.2. General Procedure for the Synthesis of -Ketosulfones 1–5
Method A, starting from -bromoacetophenone: To a solution of sodium benzene sulfinate (4.1 mmol,
2 equiv.) in water (30 mL), an ethanolic solution of the corresponding acetophenone (2.05 mmol,
1 equiv.) was added. The reaction mixture was heated under reflux in a microwave oven under
irradiation (500 W, 100 °C) during 45 min. The precipitate thus formed was filtered and crystallized
from the appropriate solvent.
Method B, starting from acetophenone: To a solution of 1-(2-nitrophenyl)ethanone (3 g, 18.00 mmol,
1 equiv.) in chloroform (15 mL), a bromine (2.9 g, 18.00 mmol, 1 equiv.) solution in chloroform (7 mL)
was slowly added. After 1 h at rt, the reaction mixture was washed 3 times with a saturated solution of
sodium thiosulfate, and concentrated under vacuum. A solution of sodium benzene sulfinate (6 g,
36.00 mmol, 2 equiv.) in water (30 mL) was added. The reaction mixture was heated under reflux in a
microwave oven under irradiation (500 W, 100 °C) during 45 min. The precipitate thus formed was
filtered and crystallized from the appropriate solvent.
1-(4-Nitrophenyl)-2-(phenylsulfonyl)ethanone (1). Colorless crystals, mp 138 °C (ethanol)
(Lit. [47,48]: 136–138 °C), yield 92%. 1H-NMR (CDCl3), δ: 8.34 (d, J = 8.9 Hz, 2H), 8.15 (d, J = 8.9 Hz,
13
2H), 7.88 (d, J = 7.2 Hz, 2H), 7.64 (m, 3H), 4.77 (s, 2H). C-NMR (CDCl3), δ: 64.0 (CH2), 124.0

Molecules 2013, 18
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(2CH), 128.5 (2CH), 129.4 (2CH), 130.5 (2CH), 134.6 (CH), 138.4 (C), 140.0 (C), 186.8 (C=O), 1C
not observed in these conditions.
4-(2-(Phenylsulfonyl)acetyl)benzonitrile (2) [19]. White solid, mp 150–151 °C (isopropanol); yield
1
61%. H-NMR (CDCl3), δ: 4.74 (s, 2H, CH2), 7.53–7.72 (m, 3H, 3CH), 7.79 (d, J = 8.3, 2H, 2CH),
13
7.85–7.89 (m, 2H, 2CH), 8.07 (d, J = 8.3, 2H, 2CH). C-NMR (CDCl3), δ: 63.7 (CH2), 117.5 (2C),
128.5 (2CH), 129.4 (2CH), 129.7 (2CH), 132.6 (2CH), 134.6(CH), 138.4 (C), 138.5 (C), 197.0 (C).
1-(4-Chlorophenyl)-2-(phenylsulfonyl)ethanone (3). White solid; mp 135–137 °C (isopropanol) (Lit. [49]:
133–135 °C); yield 89%. 1H-NMR (CDCl3) H 4.70 (s, 2H, CH2), 7.44–7.73 (m, 5H, 5CH), 7.86–7.92 (m,
13
4H, 4CH). C-NMR (CDCl3) C 63.6 (CH2), 128.5 (2CH), 129.2 (2CH), 129.3 (2CH), 130.7 (2CH),
134.0 (C), 134.4 (CH), 138.5 (C), 141.1 (C), 186.8 (C).
1-(3-Nitrophenyl)-2-(phenylsulfonyl)ethanone (4). White solid; mp 127–129 °C (isopropanol) (Lit. [50]:
128–129 °C); yield 88%. 1H-NMR (CDCl3) H 4.79 (s, 2H, CH2), 7.53–7.61 (m, 2H, 2CH), 7.67–7.77
(m, 2H, 2CH), 7.87–7.91 (m, 2H, 2CH), 8.34 (ddd, J1 = 1.1, J2 = 1.5, J3 = 7.8, 1H, CH), 8.48 (ddd, J1 = 1.1,
13
J2 = 2.1, J3 = 8.2, 1H, CH), 8.73–8.75 (m, 1H, CH). C-NMR (CDCl3) C 63.7 (CH2), 124.1 (CH),
128.4 (CH), 128.5 (2CH), 129.4 (2CH), 130.2 (CH), 134.6 (CH), 134.8 (CH), 136.8 (C), 138.3 (C),
148.5 (C), 186.2 (C).
1
1-(2-Nitrophenyl)-2-(phenylsulfonyl)ethanone (5). Yellow oil; yield 65%. H-NMR (CDCl3) H 4.61
(s, 2H, CH2), 7.54–7.70 (m, 5H, 5CH), 7.73–7.84 (m, 1H, CH), 7.88–7.92 (m, 2H, 2CH), 8.12–8.16
13
(m, 1H, CH). C-NMR (CDCl3) C 66.6 (CH2), 124.2 (CH), 128.3 (2CH), 129.0 (CH), 129.4 (2CH),
131.5 (CH), 134.4 (CH), 135.0 (CH), 136.2 (C), 138.7 (C), 145.1 (C), 189.8 (C). HMRS (ESI): m/z
calcd for C14H11NO5S M+Na+: 328.0250. Found: 328.02471.
3.3. General Procedure for the Synthesis of Dihydrofurans 6–10
A suspension of manganese(III) acetate dihydrate (1.84 g, 6.87 mmol, 2.1 equiv.) in glacial acetic
acid (30 mL) was heated under microwave irradiation (200 W, 80 °C) for 15 min, until dissolution.
Then, the reaction mixture was cooled down to 50 °C, and a solution of the corresponding -keto-
sulfone (3.27 mmol, 1 equiv.) and -methylstyrene (1.16 g, 9.81 mmol, 3 equiv.) in acetic acid (5 mL)
was added. The mixture was heated under microwave irradiation (200 W, 80 °C) for 45 min. The
reaction mixture was poured into 200 mL of cold water, and extracted with chloroform (3 × 40 mL).
The organic extracts were collected and washed with saturated aqueous NaHCO3 (3 × 40 mL) and
dried (MgSO4). Solvent evaporation was followed by column chromatography (petroleum ether/
chloroform/diethyl ether 5/4.5/0.5), and the product obtained was recrystallized from isopropanol.
2-Methyl-5-(4-nitrophenyl)-2-phenyl-4-(phenylsulfonyl)-2,3-dihydrofuran (6). White solid; mp
144–145 °C; yield 43%. 1H-NMR (CDCl3) H 1.74 (s, 3H, CH3), 3.26 (d, J = 14.8, 1H, CH2), 3.38 (d,
J = 14.8, 1H, CH2), 7.29–7.58 (m, 8H, 8CH), 7.70–7.74 (m, 2H, 2CH), 7.94 (d, J = 8.9, 2H, 2CH),
13
8.30 (d, J = 8.9, 2H, 2CH). C-NMR (CDCl3) C 29.1 (CH3), 45.8 (CH2), 89.7 (C), 112.6 (C), 123.0
(2CH), 124.0 (2CH), 126.9 (2CH), 128.0 (CH), 128.7 (2CH), 129.2 (2CH), 130.8 (2CH), 133.2 (CH),

Molecules 2013, 18
4301
134.7 (C), 141.1 (C), 144.3 (C), 149.0 (C), 159.6 (C). HMRS (ESI): m/z calcd for C23H19NO5S M+H+:
422.1057. Found: 422.1058.
4-(5-Methyl-5-phenyl-3-(phenylsulfonyl)-4,5-dihydrofuran-2-yl)benzonitrile (7). White solid; mp
137–138 °C; yield 34%. 1H-NMR (CDCl3) H 1.73 (s, 3H, CH3), 3.25 (d, J = 14.7, 1H, CH2), 3.37 (d,
J = 14.7, 1H, CH2), 7.28–7.61 (m, 9H, 9CH), 7.68–7.76 (m, 3H, 3CH), 7.89 (d, J = 8.7, 2H, 2CH).
13C-NMR (CDCl3) C 29.1 (CH3), 45.8 (CH2), 89.5 (C), 112.2 (C), 114.4 (C), 118.2 (C), 124.0 (2CH),
126.8 (2CH), 127.9 (CH), 128.7 (2CH), 129.1 (2CH), 130.3 (2CH), 131.6 (2CH), 132.9 (C), 133.2
(CH), 141.1 (C), 144.4 (C), 159.9 (C). HMRS (ESI): m/z calcd for C24H19NO3S M+H+: 402.1158.
Found: 402.1157.
5-(4-Chlorophenyl)-2-methyl-2-phenyl-4-(phenylsulfonyl)-2,3-dihydrofuran (8). White solid; mp
107–109 °C; yield 35%. 1H-NMR (CDCl3) H 1.71 (s, 3H, CH3), 3.25 (d, J = 14.5, 1H, CH2), 3.36 (d,
13
J = 14.5, 1H, CH2), 7.29–7.54 (m, 10H, 10CH), 7.68–7.77 (m, 4H, 4CH). C-NMR (CDCl3) C 29.0
(CH3), 45.9 (CH2), 88.8 (C), 110.2 (C), 124.1 (2CH), 126.7 (2CH), 127.0 (C), 127.7 (CH), 128.2
(2CH), 128.6 (2CH), 129.0 (2CH), 131.0 (2CH), 132.9 (CH), 137.2 (C), 141.6 (C), 144.7 (C), 161.2
(C). HMRS (ESI): m/z calcd for C23H19ClO3S M+H+: 411.0816. Found: 411.0813.
2-Methyl-5-(3-nitrophenyl)-2-phenyl-4-(phenylsulfonyl)-2,3-dihydrofuran (9). Yellow oil; yield 51%.
1H-NMR (CDCl3) H 1.75 (s, 3H, CH3), 3.27 (d, J = 14.7, 1H, CH2), 3.41 (d, J = 14.7, 1H, CH2), 7.24–7.79
13
(m, 11H, 11CH), 8.14–8.19 (m, 1H, CH), 8.31–8.37 (m, 1H, CH), 8.55–8.57 (m, 1H, CH). C-NMR
(CDCl3) C 29.1 (CH3), 45.7 (CH2), 89.6 (C), 112.0 (C), 124.0 (2CH), 124.4 (CH), 125.5 (CH), 126.9
(2CH), 127.8 (CH), 128.4 (C), 128.7 (2CH), 129.0 (CH), 129.2 (2CH), 130.1 (C), 133.2 (CH), 135.8
(CH), 141.1 (C), 144.3 (C), 159.3 (C). HMRS (ESI): m/z calcd for C23H19NO5S M+Na+: 444.0876.
Found: 444.0880.
2-Methyl-5-(2-nitrophenyl)-2-phenyl-4-(phenylsulfonyl)-2,3-dihydrofuran (10). White solid; mp
104–105 °C; yield 45%. 1H-NMR (CDCl3) H 1.75 (s, 3H, CH3), 3.12 (d, J = 14.2, 1H, CH2), 3.37 (d,
J = 14.2, 1H, CH2), 7.31–7.36 (m, 4H, 4CH), 7.43–7.80 (m, 9H, 9CH), 8.15–8.20 (m, 1H, CH). 13C-NMR
(CDCl3) C 28.7 (CH3), 44.8 (CH2), 91.0 (C), 111.1 (C), 124.3 (2CH), 124.5 (CH), 124.8 (C), 127.1
(2CH), 127.8 (CH), 128.6 (2CH), 129.1 (2CH), 131.2 (CH), 133.0 (CH), 133.1 (2CH), 140.7 (C),
+
144.5 (C), 147.5 (C), 159.6 (C). HMRS (ESI): m/z calcd for C23H19NO5S M+NH4 : 439.1322. Found:
439.1326.
3.4. General Procedure for the Synthesis of Dihydrofurans 11–15 and Cyclopropanes 16–19
A suspension of manganese(III) acetate dihydrate (2.63 g, 9.81 mmol, 3 equiv.) in glacial acetic
acid (30 mL) was heated under microwave irradiation (200 W, 80 °C) for 15 min, until dissolution.
Then, the reaction mixture was cooled down to 50 °C, and a solution of the corresponding
-ketosulfone (3.27 mmol, 1 equiv.) and trans-stilbene (1.77 g, 9.81 mmol, 3 equiv.) in acetic acid
(5 mL) was added. The mixture was heated under microwave irradiation (200 W, 80 °C) for 45 min.
The reaction mixture was poured into 200 mL of cold water, and extracted with chloroform (3 × 40 mL).
The organic extracts were collected and washed with saturated aqueous NaHCO3 (3 × 40 mL) and

Molecules 2013, 18
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dried (MgSO4). Solvent evaporation was followed by column chromatography (petroleum ether/
chloroform/diethyl ether 5/4.5/0.5), and the products obtained were recrystallized from isopropanol.
5-(4-Nitrophenyl)-2,3-diphenyl-4-(phenylsulfonyl)-2,3-dihydrofuran (11). Yellow solid; mp 178–180 °C;
1
yield 21%. H-NMR (CDCl3) H 4.50 (d, J = 5.6, 1H, CH), 5.56 (d, J = 5.6, 1H, CH), 7.14–7.42 (m,
15H, 15CH), 8.03 (d, J = 8.8, 2H, 2CH), 8.32 (d, J = 8.8, 2H, 2CH). 13C-NMR (CDCl3) C 59.2 (CH),
92.0 (CH), 117.5 (C), 123.1 (2CH), 125.1 (2CH), 127.1 (2CH), 127.8 (2CH), 127.9 (CH), 128.6
(2CH), 129.0 (2CH), 129.1 (2CH), 129.9 (CH), 132.8 (CH), 134.7 (C), 139.6 (C), 140.3 (C), 141.4
(C), 149.2 (C), 161.9 (C). HMRS (ESI): m/z calcd for C28H21NO5S M+Na+: 506.1033. Found:
506.1032.
4-(4,5-Diphenyl-3-(phenylsulfonyl)-4,5-dihydrofuran-2-yl)benzonitrile (12). Yellow solid; mp
1
182–184 °C; yield 13%. H-NMR (CDCl3) H 4.48 (d, J = 5.5, 1H, CH), 5.54 (d, J = 5.5, 1H, CH),
7.13–7.30 (m, 8H, 8CH), 7.36–7.45 (m, 7H, 7CH), 7.76 (d, J = 8.6, 2H, 2CH), 7.98 (d, J = 8.6, 2H,
2CH). 13C-NMR (CDCl3) C 59.2 (CH), 91.8 (CH), 114.7 (C), 117.1 (C), 118.1 (C), 125.1 (2CH),
127.1 (2CH), 127.8 (2CH), 128.6 (2CH), 129.1 (2CH), 130.4 (2CH), 131.7 (2CH), 132.8 (CH), 132.9
(C), 139.7 (C), 140.5 (C), 141.4 (C), 162.2 (C). HMRS (ESI): m/z calcd for C29H21NO3S M+Na+:
486.1134. Found: 486.1131.
5-(4-Chlorophenyl)-2,3-diphenyl-4-(phenylsulfonyl)-2,3-dihydrofuran (13). White solid; mp 170–171 °C;
1
yield 12%. H-NMR (CDCl3) H 4.46 (d, J = 5.0, 1H, CH), 5.51 (d, J = 5.0, 1H, CH), 7.17–7.41 (m,
15H, 15CH), 7.45 (d, J = 8.5, 2H, 2CH), 7.82 (d, J = 8.5, 2H, 2CH). 13C-NMR (CDCl3) C 59.3 (CH),
91.3 (CH), 115.3 (C), 125.0 (2CH), 126.9 (C), 127.0 (2CH), 127.7 (CH), 127.8 (2CH), 128.4 (2CH),
128.5 (2CH), 128.8 (CH), 129.0 (4CH), 131.1 (2CH), 132.5 (CH), 137.6 (C), 140.1 (C), 141.1 (C),
141.9 (C), 163.5 (C). HMRS (ESI): m/z calcd for C28H21ClO3S M+Na+: 495.0792. Found: 495.07884.
5-(3-Nitrophenyl)-2,3-diphenyl-4-(phenylsulfonyl)-2,3-dihydrofuran (14). White solid; mp 147–148
1
°C; yield 25%. H-NMR (CDCl3) H 4.56 (d, J = 5.6, 1H, CH), 5.57 (d, J = 5.6, 1H, CH), 7.22–7.32
(m, 11H, 11CH), 7.38–7.42 (m, 4H, 4CH), 7.65–7.73 (m, 1H, CH), 8.23–8.26 (m, 1H, CH), 8.36–8.42
13
(m, 1H, CH), 8.63–8.65 (m, 1H, CH). C-NMR (CDCl3) C 59.1 (CH), 92.0 (CH), 117.0 (C), 124.7
(CH), 125.2 (2CH), 125.8 (CH), 127.2 (2CH), 127.9 (2CH), 128.7 (2CH), 129.1 (2CH), 129.2 (2CH),
129.3 (CH), 130.2 (C), 132.8 (CH), 135.8 (CH), 139.6 (C), 140.5 (C), 141.5 (C), 147.7 (C), 161.7 (C).
HMRS (ESI): m/z calcd for C28H21NO5S M+Na+: 506.1032. Found: 506.1034.
5-(2-Nitrophenyl)-2,3-diphenyl-4-(phenylsulfonyl)-2,3-dihydrofuran (15). White solid; mp 155–156 °C;
1
yield 23%. H-NMR (CDCl3) H 4.62 (d, J = 8.0, 1H, CH), 5.66 (d, J = 8.0, 1H, CH), 7.08–7.20 (m,
9H, 9CH), 7.28–7.39 (m, 6H, 6CH), 7.67–7.87 (m, 3H, 3CH), 8.24–8.18 (m, 1H, CH). 13C-NMR
(CDCl3) C 58.7 (CH), 93.8 (CH), 115.8 (C), 124.7 (CH), 125.0 (C), 125.8 (2CH), 127.2 (2CH), 127.6
(2CH), 128.5 (2CH), 128.6 (2CH), 128.8 (2CH), 128.9 (CH), 129.0 (2CH), 131.4 (CH), 132.5 (CH),
133.3 (CH), 133.4 (CH), 139.3 (C), 139.4 (C), 141.3 (C), 147.4 (C), 162.0 (C). HMRS (ESI): m/z calcd
+
for C28H21NO5S M+NH4 : 501.1479. Found: 501.1482.

Molecules 2013, 18
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(2,3-Diphenyl-1-(phenylsulfonyl)cyclopropyl)(4-nitrophenyl)methanone (16). White solid; mp 223 °C;
1
yield 12%. H-NMR (CDCl3) H 3.70 (d, J = 9.4, 1H, CH), 4.45 (d, J = 9.4, 1H, CH), 6.94–6.99 (m,
2H, 2CH), 7.13–7.24 (m, 12H, 12CH), 7.46–7.53 (m, 1H, CH), 7.97 (d, J = 9.0, 2H, 2CH), 8.07 (d, J = 9.0,
13
2H, 2CH). C-NMR (CDCl3) C 33.7 (CH), 34.0 (CH), 63.1 (C), 122.7 (2CH), 127.5 (2CH), 127.7
(CH), 128.0 (2CH), 128.1 (2CH), 128.4 (CH), 128.5 (2CH), 128.9 (2CH), 129.9 (2CH), 131.7 (2CH),
133.4 (CH), 138.7 (C), 140.3 (C), 150.1 (C), 190.8 (C). Anal. Calcd for C28H21NO5S: C, 69.55; H,
4.38; N, 2.90. Found: C, 69.48; H, 4.46; N, 2.94.
4-(2,3-Diphenyl-1-(phenylsulfonyl)cyclopropanecarbonyl)benzonitrile (17). White solid; mp 225–227
1
°C; yield 10%. H-NMR (CDCl3) H 3.67 (d, J = 9.4, 1H, CH), 4.42 (d, J = 9.4, 1H, CH), 6.94–6.99
(m, 2H, 2CH), 7.13–7.28 (m, 12H, 12CH), 7.45–7.51 (m, 1H, CH), 7.52 (d, J = 8.4, 2H, 2CH), 7.92 (d, J =
8.4, 2H, 2CH). 13C-NMR (CDCl3) C 33.6 (CH), 33.9 (CH), 62.8 (C), 116.3 (C), 117.9 (C), 127.5
(2CH), 127.7 (CH), 128.0 (2CH), 128.1 (2CH), 128.3 (CH), 128.4 (2CH), 128.9 (2CH), 129.9 (2CH),
130.2 (C), 131.0 (2CH), 131.4 (2CH), 133.2 (C), 133.4 (CH), 138.6 (C), 138.8 (C), 190.9 (C). HMRS
(ESI): m/z calcd for C29H21NO3S M+Na+: 486.1134. Found: 486.1133.
(4-Chlorophenyl)(2,3-diphenyl-1-(phenylsulfonyl)cyclopropyl)methanone (18). White solid; mp 97–98 °C;
yield 5%. 1H-NMR (CDCl3) H 3.67 (d, J = 9.4, 1H, CH), 4.38 (d, J = 9.4, 1H, CH), 6.99–7.03 (m, 1H,
CH), 7.13–7.24 (m, 4H, 4CH), 7.42–7.53 (m, 8H, 8CH), 7.61–7.68 (m, 2H, 2CH), 7.76–7.87 (m, 2H,
2CH), 7.96 (d, J = 8.5, 2H, 2CH). 13C-NMR (CDCl3) C 33.7 (CH), 33.8 (CH), 63.0 (C), 121.5 (2CH),
127.5 (CH), 128.0 (2CH), 128.4 (C), 128.5 (2CH), 128.7 (CH), 128.9 (2CH), 129.0 (2CH), 129.9
(2CH), 130.7 (2CH), 132.2 (CH), 134.7 (C), 136.5 (C), 139.2 (C), 145.3 (2CH), 189.2 (C). 1C not observed
in these conditions. HMRS (ESI): m/z calcd for C28H21ClO3S M+Na+: 495.0792. Found: 495.0792.
(2,3-Diphenyl-1-(phenylsulfonyl)cyclopropyl)(3-nitrophenyl)methanone (19). Yellow solid; mp
1
116–118 °C; yield 13%. H-NMR (CDCl3) H 3.71 (d, J = 9.3, 1H, CH), 4.48 (d, J = 9.3, 1H, CH),
6.94–7.25 (m, 8H, 8CH), 7.39–7.95 (m, 8H, 8CH), 8.13–8.48 (m, 2H, 2CH), 8.63–8.86 (m, 1H, CH).
13C-NMR (CDCl3) C 33.3 (CH), 33.7 (CH), 62.7 (C), 120.6 (CH), 123.3 (CH), 127.1 (CH), 127.5
(2CH), 127.7 (C), 128.1 (2CH), 128.3 (C), 128.5 (CH), 128.7 (2CH), 128.9 (CH), 129.1 (2CH), 129.9
(2CH), 131.2 (CH), 132.9 (C), 134.1 (CH), 134.3 (C), 139.5 (C), 190.0 (C). HMRS (ESI): m/z calcd
+
for C28H21NO5S M+NH4 : 501.1479. Found: 501.1483.
3.5. X-ray Structure Determination of Compounds 16
Crystal data for compound 16: C28H21NO5S, M = 483.52, monoclinic, a = 13.6866(5) Å,
b = 10.2670(4) Å, c = 17.8561(9) Å, α = 90°, β = 102.777(2)°, γ = 90°, V = 2447.01(18) Å3, T = 293(2)
K, space group P21/c, Z = 4, μ(MoKα) = 0.172 mm−1, 18832 reflections measured, 5869 independent
reflections (Rint = 0.145). The final R1 values were 0.1086 (I > 2σ(I)). The final wR(F2) values were
0.1595 (I > 2σ(I)). The final R1 values were 0.2171 (all data). The final wR(F2) values were 0.2003 (all
data). The goodness of fit on F2 was 1.094. Crystallographic data (excluding structure factors) for the
structures 16 have been deposited with the Cambridge Crystallographic Data Centre (CCDC) under the
number 918793. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK, (fax: +44-(0)1223-336033 or e-mail: deposit@ccdc.cam.ac.uk).

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4. Conclusions
Thanks to the radical reactivity of Mn(OAc)3, we synthesized 10 new functionalized dihydrofurans,
which could offer antiparasitic activities. Starting from trans-stilbene alkene, a diastereoselectivity
reversion of dihydrofuran was observed with ortho-substituted -ketosulfones. Moreover, four original
cyclopropanes were obtained in low yields. This original cyclopropanation reaction could be a very
valuable tool in organic synthesis and additional research seeking to enhance yields is currently
in progress.
Acknowledgements
This work was supported by the Centre National de la Recherche Scientifique and Aix-Marseille
University. We would like to express our thanks to Vincent Remusat for RMN spectra recording,
Thérèse Schembri and Valérie Monnier for mass spectra recording.
References
1. Melikyan, G.G. Manganese(III) mediated reactions of unsaturated systems. Synthesis 1993, 9,
833–850 and references therein.
2. Snider, B.B. Manganese(III)-based oxidative free-radical cyclizations. Chem. Rev. 1996, 96,
339–363 and references therein.
3. Demir, A.S.; Emrullahoglu, M. Manganese(III) acetate: A versatile reagent in organic chemistry.
Curr. Org. Synth. 2007, 4, 321–350 and references therein.
4. Burton, J.W. Manganese(III) Acetate, CAN, and Fe(III) Salts in Oxidative Radical Chemistry. In
Encyclopedia of Radicals in Chemistry, Biology and Materials, 1st ed.; Chatgilialoglu, C.,
Studer, A., Eds.; Wiley: Chichester, UK, 2012; Volume 2, pp. 901–943.
5. Keane, H.A.; Hess, W.; Burton, J.W. Manganese(III)-mediated radical cyclizations for the
(Z)-selective synthesis of exo-alkylidenepyrrolidinones and pyrrolidines. Chem. Commun. 2012,
48, 6496–6498.
6. Curry, L.; Hallside, M.S.; Powell, L.H.; Sprague, S.J.; Burton, J.W. Manganese(III)-mediated
oxidative free-radical cyclisations of allenyl malonates. Tetrahedron 2009, 65, 10882–10892.
7. Davies, J.J.; Krulle, T.M.; Burton, J.W. Total synthesis of 7,11-cyclobotryococca-5,12,26-triene
using an oxidative radical cyclization as key step. Org. Lett. 2010, 12, 2738–2741.
8. Citterio, A.; Sebastiano, R.; Marion, A.; Santi, R. Synthesis of substituted tetrahydronaphthalenes
by manganese(III), cerium(IV), and iron(III) oxidation of substituted diethyl .alpha.-
benzylmalonates in the presence of olefins. J. Org. Chem. 1991, 56, 5328–5335.
9. Bergamini, F.; Citterio, A.; Gatti, N.; Nicolini, M.; Santi, R.; Sebastiano, R. Metal-induced
electrochemical oxidation of diethyl benzylmalonates in the presence of alkenes and alkynes.
Synthesis of substituted tetrahydro- and dihydro-naphthalenes. J. Chem. Res. 1993, 9, 364–366.
10. Cossy, J.; Leblanc, C. New synthesis of lactams and spirolactams radical cyclization induced by
manganese(III) acetate. Tetrahedron Lett. 1989, 30, 4531–4534.
11. Mellor, J.M.; Mohammed, S. Synthesis of oxaspirolactones by manganic acetate promoted
addition to exocyclic enol lactones. Tetrahedron 1993, 49, 7547–7556.

Molecules 2013, 18
4305
12. Bouhlel, A.; Curti, C.; Bertrand, M.P.; Vanelle, P. Access to original spirocyclic derivatives via
inter- or intramolecular reaction mediated by manganese(III) acetate. Tetrahedron 2012, 68,
3596–3604.
13. Vanelle, P.; Maldonado, J.; Madadi, N.; Gueiffier, A.; Teulade, J.C.; Chapat, J.P.; Crozet, M.P.
SRN1 reactions in imidazo [1, 2-a] pyridine series. Tetrahedron Lett. 1990, 31, 3013–3016.
14. Roubaud, C.; Vanelle, P.; Maldonado, J.; Crozet, M.P. Synthèse et réactions SRN1 en série
3-nitroimidazo[1,2-a]pyrimidine. Tetrahedron 1995, 51, 9643–9656.
15. El-Kashef, H.S.; El-Emary, T.I.; Gasquet, M.; Timon-David, P.; Maldonado, J.; Vanelle, P.
New pyrazolo[3,4-b]pyrazines: synthesis and biological activity. Pharmazie 2000, 55, 572–576.
16. Gellis, A.; Kovacic, H.; Boufatah, N.; Vanelle, P. Synthesis and cytotoxicity evaluation of
some benzimidazole-4,7-diones as bioreductive anticancer agents. Eur. J. Med. Chem. 2008, 43,
1858–1864.
17. Cohen, A.; Crozet, M.D.; Rathelot, P.; Vanelle, P. An efficient aqueous microwave-assisted
Suzuki-Miyaura cross-coupling reaction in the thiazole series. Green Chem. 2009, 11, 1736–1742.
18. Paloque, L.; Bouhlel, A.; Curti, C.; Dumètre, A.; Verhaeghe, P.; Azas, N.; Vanelle, P. Synthesis
and evaluation of monoamidoxime derivatives: Toward new antileishmanial compounds. Eur. J.
Med. Chem. 2011, 46, 2984–2991.
19. Bouhlel, A.; Curti, C.; Dumètre, A.; Laget, M.; Crozet, M.D.; Azas, N.; Vanelle, P. Synthesis and
evaluation of original amidoximes as antileishmanial agents. Bioorg. Med. Chem. 2010, 18,
7310–7320.
20. Logoglu, E.; Yilmaz, M.; Katircioglu, H.; Yakut, M.; Mercan, S. Synthesis and biological activity
studies of furan derivatives. Med. Chem. Res. 2010, 19, 490–497.
21. Findik, E.; Dingil, A.; Karaman, I.; Budak, Y.; Ceylan, M. Synthesis of multi-substituted
4,5-dihydrofuran derivatives from (S)-limonene and 1,3-dicarbonyl compounds and their
biological activities. E. J. Chem. 2009, 6, S53–S58.
22. Avetisyan, A.A.; Karapetyan, L.V.; Paronikyan, R.V.; Stepanyan, H.M. Synthesis and
antibacterial activity of new 2,5-dihydrofuran derivatives. Pharm. Chem. J. 2011, 45, 156–158.
23. Zhang, Y.; Zhong, H.; Wang, T.; Geng, D.; Zhang, M.; Li, K. Synthesis of novel 2,5-dihydrofuran
derivatives and evaluation of their anticancer activity. Eur. J. Med. Chem. 2012, 48, 69–80.
24. Kilroy, T.G.; O’Sullivan, T.P.; Guiry, P.J. Synthesis of dihydrofurans substituted in the
2-position. Eur. J. Org. Chem. 2005, 23, 4929–4949.
25. Cao, W.; Zhang, H.; Chen, J.; Zhou, X.; Shao, M.; McMills, M.C. Stereoselective synthesis of
highly substituted trans-2,3-dihydrofuran and trans-2,3-cyclopropane derivatives containing
sulfonyl groups. Tetrahedron 2008, 64, 163–167.
26. Lee, J.W.; Dong, Y. I2-Induced Enoletherification of α-Allyl Substituted β-Keto Sulfones;
A route to 3-phenylsulfonyl-2,5-disubstituted Furans. Heterocycles 1990, 31, 1417–1421.
27. Feldman, K.S.; Wrobleski, M.L. Alkynyliodonium salts in organic synthesis. Dihydrofuran
formation via a formal stevens shift of a carbon substituent within a disubstituted-carbon oxonium
ylide. J. Org. Chem. 2000, 65, 8659–8668.
28. Makosza, M.; Judka, M. New reactions of γ-halo carbanions: Simple synthesis of substituted
tetrahydrofurans. Chemistry 2002, 8, 4234–4240.

Molecules 2013, 18
4306
29. Bernard, A.M.; Frongia, A.; Piras, P.P.; Secci, F.; Spiga, M. Regioselective synthesis of
trisubstituted 2,3-dihydrofurans from donor−acceptor cyclopropanes or from reaction of the corey
ylide with α-sulfenyl-, α-sulfinyl-, or α-sulfonylenones. Org. Lett. 2005, 7, 4565–4568.
30. Curti, C.; Crozet, M.D.; Vanelle, P. Microwave improved manganese(III) acetate based oxidative
cyclizations of alkenes with -ketosulfones. Tetrahedron 2009, 65, 200–205.
31. Qian, C.Y.; Nishino, H.; Kurosawa, K. Manganese(III)-mediated free-radical cyclization of active
methylene compounds, alkenes and molecular oxygen. Syntheses of sulfur- and phosphorous-
containing 1,2-dioxa-3-ols. J. Heterocycl. Chem. 1993, 30, 209–216.
32. Shanmugam, P.N.; Hemanth Kumar, K.I.; Perumal, P.N.T. Mn(III) acetate mediated
diasteroselective [3+2] oxidative addition of 1,3-dicarbonyl compounds with chalcones.
J. Heterocycl. Chem. 2007, 44, 827–830.
33. Sunitha, P.; Shiva Kumar, K.; Rama Rao, B.; Venkateshwarlu, G. Microwave assisted efficient
synthesis of -ketosulfones in aqueous medium. Green Chem. Lett. Rev. 2008, 1, 179–183.
34. Andreani, A.; Leoni, A.; Rambaldi, M.; Locatelli, A.; Bossa, R.; Galatulas, I.; Chiericozzi, M.;
Bissoli, M. Dihydropyridines bearing an imidazo[2,1-b]thiazole system. Eur. J. Med. Chem. 1997,
32, 151–157.
35. Suryakiran, N.; Prabhakar, P.; Rajesh, K.; Suresh, V.; Venkatesmarlu, Y. Synthesis of
-ketosulfones using ionic liquid [TPA][Pro] as an efficient and reusable reaction medium.
J. Mol. Catal. A Chem. 2007, 270, 20–204.
36. Srinivas, K.; Dubey, P.K. Zinc-mediated tandem-one-pot facile synthesis of
1-(arylsulfonyl)aryl/heteryl methanes: a case of C-S bond formation. Synth. Commun. 2011, 41,
1584–1592.
37. Meek, J.S.; Fowler, J.S. O and S methylation of the ambident p-toluene sulfinate anion.
J. Org. Chem. 1968, 33, 3422–3424.
38. Wang, Q.-F.; Hou, H.; Hui, L.; Yan, C.-G. Diastereoselective synthesis of trans-2,3-dihydrofurans
with pyridinium ylide assisted tandem reaction. J. Org. Chem. 2009, 74, 7403–7406.
39. Yilmaz, M.; Uzunalioglu, N.; Tarik Pekel, A. Manganese(III) acetate based oxidative cyclizations
of 3-oxopropanenitriles with conjugated alkenes and synthesis of 4,5-dihydrofuran-3-carbonitriles
containing heterocycles. Tetrahedron 2005, 61, 8860–8867.
40. Deliomeroglu, M.K.; Dengiz, C.; Çalişkan, R.; Balci, M. Mn(OAc)3-promoted sulfur-directed
addition of an active methylene compound to alkenes. Tetrahedron 2012, 68, 5838–5844.
41. Garzino, F.; Méou, A.; Brun, P. Asymmetric Mn(III)-based radical synthesis of functionalized
2,3-dihydrofurans. Tetrahedron Lett. 2000, 41, 9803–9807.
42. Ito, Y.; Jogo, S.; Fukuda, N.; Okumura, R.; Nishino, H. Manganese(III) acetate specific
intramolecular addition. Synthesis 2011, 9, 1365–1374.
43. Asahi, K.; Nishino, H. Synthesis of bicyclo[3.1.0]hexan-2-ones by manganese(III) oxidation in
ethanol. Synthesis 2009, 3, 409–423.
44. Oumar-Mahamat, H.; Moustrou, C.; Surzur, J.-M.; Bertrand, M.P. Lactone synthesis by
manganese(III)-mediated oxidative cyclization of allylic beta.-diesters. J. Org. Chem. 1989, 54,
5684–5688.
45. Snider, B.B.; Qinglin, C. Oxidative and dehydrative cyclizations of nitroacetate esters with
Mn(OAc)3. Tetrahedron 2002, 58, 7821–7827.

Molecules 2013, 18
4307
46. Caliskan, R.; Pekel, T.; Watson, W.H.; Balci, M. Unusual oxidative free-radical additions of
1,3-dicarbonyl compounds to benzonorbornadiene and oxabenzonorbornadiene. Tetrahedron Lett.
2005, 46, 6227–6230.
47. Borchardt, A.; Kopkowski, A.; Walilewski, W.; Zakrzewski, A. Prace Wydzialu Nauk
Technicznych seria A 1990, 18, 35–41.
48. Curti, C.; Laget, M.; Ortiz Carle, A.; Gellis, A.; Vanelle, P. Rapid synthesis of sulfone derivatives
as potential anti-infectious agents. Eur. J. Med. Chem. 2007, 42, 880–884.
49. Xiang, J.; Ipek, M.; Suri, V.; Tam, M.; Xing, Y.; Huang, N.; Zhang, Y.; Tobin, J.; Mansour, T.S.;
McKew, J. β-Keto sulfones as inhibitors of 11β-hydroxysteroid dehydrogenase type I and the
mechanism of action. Bioorg. Med. Chem. 2007, 15, 4396–4405.
50. Enders, D.; Grossmann, A.; Huang, H.; Raabe, G. Dual secondary amine/N-heterocyclic carbene
catalysis in the asymmetric Michael/Cross-Benzoin cascade reaction of β-oxo sulfones with enals.
Eur. J. Org. Chem. 2011, 23, 4298–4301.
Sample Availability: Samples of the compounds 1–18 are available from the authors.
© 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
(http://creativecommons.org/licenses/by/3.0/).