New elements on the behaviour of a bissulfinylmethyl radical

Article abstract of DOI:10.1071/CH12545

In this article, we have studied the generation of a bissulfinylmethyl radical from the corresponding TEMPO and phenylselenyl bissulfoxide precursors. No univocal formation of the bissulfinylmethyl radical has been observed. Instead, complex mixtures have been obtained in thermal or photochemical conditions, showing prominent C-S homolytic bond cleavage.

Full text of DOI:10.1071/CH12545

RESEARCH FRONT
CSIRO PUBLISHING
Aust. J. Chem. 2013, 66, 346–353
Full Paper
http://dx.doi.org/10.1071/CH12545
New Elements on the Behaviour of a Bissulfinylmethyl
Radical*
A
A
A
Rocio Martinez Mallorquin, Guillaume Vincent, Etienne Derat,
A
A B
,
A B
,
Max Malacria, Jean-Philippe Goddard,
and Louis Fensterbank
A
Institut Parisien de Chimie Mole´culaire (UMR CNRS 7201) – FR2769 UPMC Univ
Paris 06, 4 place Jussieu, C. 229, 75005 Paris, France.
Corresponding authors. Email: jean-philippe.goddard@upmc.fr;
louis.fensterbank@upmc.fr
B
In this article, we have studied the generation of a bissulfinylmethyl radical from the corresponding TEMPO and
phenylselenyl bissulfoxide precursors. No univocal formation of the bissulfinylmethyl radical has been observed. Instead,
complex mixtures have been obtained in thermal or photochemical conditions, showing prominent C–S homolytic bond
cleavage.
Manuscript received: 13 December 2012.
Manuscript accepted: 1 February 2013.
Published online: 7 March 2013.
Introduction
is the thermal or photochemical homolysis of a weak carbon-
heteroatom (C–X) bond from a bis-sulfinyl derivative III.
Inspiration was provided from the work of Byers who
described the homolytic addition of phenylselenomalonates to
alkenes upon sunlamp photolysis, involving the related malonyl
radical.[2] The corresponding thermal process has also been
proposed by Studer and has consisted of replacing the phenyl-
selenyl group by a 2,2,6,6-tetramethylpiperidin-1-oxyl moiety.
Intra- and intermolecular reactions of such derivatives have
been investigated and the group transfer resulting products
have been isolated in good yields.[3] So, we decided to transpose
such group transfer processes from bis-sulfinyl systems III,
bearing in mind the potential stereoselectivity control in addi-
tion reactions given its C2-symmetric nature. Previous reports
from literature underscore the interest in developing one-carbon
radical equivalents based on dithiane derivatives.[4]
Due to its high synthetic potential as a chiral acyl radical
equivalent, we have recently focussed on the generation of
bissulfinylmethyl radical I. Two different ways have been
investigated (Fig. 1). The first one consists in a single electron
transfer (SET) oxidation of the corresponding anion. We could
prove its viability by the formation of the TEMPO adduct 2
resulting from the ferrocenium promoted SET oxidation of the
lithium carbanion II and subsequent TEMPO trapping
(Scheme 1).[1] The second route that we focus on in this report
O
S
O
S
p-Tol
p-Tol
O
S
O
S
O
S
O
S
I
p-Tol
p-Tol
p-Tol
p-Tol
ꢀ
II
III
Homolysis
X
Results and Discussion
Set oxidation
We synthesised TEMPO adduct 2, and then investigated its
reactivity under thermal conditions. Thus, compound 2 was
heated in a sealed tube at 1008C with benzene as solvent
(Scheme 2), in the dark to avoid any potential photochemical
processes. A total conversion was observed and four major
compounds were isolated after chromatography. Besides,
p-tolyl disulfide (23 % yield), presumably originating from the
dimerisation of the corresponding thiyl radical, a predominant
thiosulfonyl product 3 was obtained in 47 % yield. Its presence is
diagnostic of the sulfinyl radical formation that dimerises, fol-
lowed by rearrangement.[5] From 3, the homolytic cleavage of
the S–S bond can liberate a sulfonyl and a thiyl radical. In these
conditions, formation of two tetramethylpiperidinyl derivatives
Fig. 1. Alternative routes to bissulfinylmethyl radical (I).
O
S
O
S
O
S
O
S
1. n-BuLi, THF, ꢀ40°C
p-Tol
p-Tol
p-Tol
p-Tol
2. FcPF6
,
TEMPO, ꢀ40°C
OTMP
1
2, 39 %
Fe ꢁ PF6ꢀ
O
FcPF6 :
OTMP :
N
Scheme 1. Formation of bis-sulfinyl radical (I) by a redox process.
*Dedicated to the memory of Athelstan Beckwith, one of the pioneers who brought radical chemistry to organic synthesis.
Journal compilation Ó CSIRO 2013
www.publish.csiro.au/journals/ajc

Radical Chemistry
347
O
O
S
(p-TolS)2
p-Tol
Sp-Tol
O
S
O
S
23 %
3, 47 %
100ꢂC, 17 h
ꢁ
p-Tol
p-Tol
Benzene
O
O
OTMP
S
N
N
2
p-Tol
H
4, 15 %
5, 12 %
Path A
ꢀ
ꢀ
O
O
Δ
2
ꢁ
S
ꢁ
ꢁ
ꢁ
N
S
SOp-Tol
4 and 5
p-Tol
p-Tol
B
O
C
O
A
N
SO2p-Tol
SOp-Tol
ꢁ
Sp-Tol
O
S
O
ꢁ
O
O
S
N
p-TolS
N
p-Tol
p-Tol
D
Path B
Scheme 2. Thermolysis of the TEMPO bissulfinylmethyl derivative 2.
O
S
O
S
O
S
O
S
O
S
O
S
Sp-Tol
O
Sp-Tol
O
Benzene
1. NaH, THF
ꢁ
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
150°C
2. PhSeCl, ꢀ20ꢂC-rt
H
SePh
SePh
SePh
6
7, 90 %
8, 5 %
1
6, 88 %
O
Scheme 3. Synthesis of the phenylselenyl precursor 6.
Sp-Tol
O
1. p-TolSNa
CCl3
CCl3
O
O
2. PhSeNa
SePh
4 and 5 were also observed from the reaction mixture. To explain
the formation of these products, we propose the following
mechanism manifold of Scheme 2. In Path A, a preliminary C–S
bond cleavage would generate radical A that can fragment to
produce an elusive formylsulfinyl derivative B and tetra-
methylpiperidyl radical C.[6] The later can recombine with the
sulfinyl radical to produce 4 while the formation of 5 remains
unclear to us but could involve B as a formyl group donor
through polar or radical addition.
7, 24 %
O
DCC
AcOEt
O
Sp-Tol
ꢁ
p-TolSH
H
OH
H
8, 89 %
Scheme 4. Reactivity of 6 under thermal conditions.
Alternatively, fragmentation to generate TEMPO could also
compete. Subsequent trapping of the thiyl radical by TEMPO, as
reported by Greci,[7] would lead to sulfenate D. The N–O
fragmentation of such adduct generates a sulfinyl radical,
resulting in a deoxygenation of the TEMPO moiety to create
concomitantly tetramethylpiperidinyl radical C. The recombi-
nation of these two species affords the previously described
compound 4.
In order to direct the homolytic cleavage towards the forma-
tion of bis-sulfinyl radical I, a C–Se bond as in 6 was preferred to
the C–O bond of 2. Seleno derivative 6 was easily prepared in
88 % yield through sodium hydride deprotonation of 1 followed
by phenylselenylchloride trapping of the corresponding carban-
ion (Scheme 3).
prepared authentic samples by independent synthesis. The first
one (Scheme 4) relies on the addition of the p-tolylthiolate and
phenylselenate anions on trisphosgene in 24 % yield and the
second one in the condensation of p-methylthiophenol and
formic acid in 89 % yield. At lower temperature, no conversion
of 6 was observed and the starting material was recovered in
good yield. The generation of 7 most likely results from the
scission of a C–S bond while the formation of 8 could be
explained by the homolytic cleavage of the C–Se bond of 7
affording an intermediate acyl radical that would be reduced by
H transfer.
Since thermolysis presumably did not allow access to the bis-
sulfinyl radical and even showed products of C–S cleavage, we
focussed on photochemical activation routinely used in radical
transformations. Thus, samples of compound 6 were irradiated
with a large spectrum sun lamp (300 W) in the presence of
1-octene as radical acceptor (Scheme 5). The temperature was
kept at 08C to avoid any thermal side reactions.
Thermolysis of 6 was tested in benzene at 1508C. A sealed-
tube was used and the reaction was conducted in the dark. A very
selective reaction occurred leading to the formation of 7 in 90 %
yield. Thioformate 8 was also observed in the reaction mixture
and isolated in 5 % yield. To confirm the structure of 7 and 8, we

348
R. M. Mallorquin et al.
A complex mixture was obtained from which it was possible
observed, indicating the formation of the sulfinyl radical. From
3, generation of a sulfonyl and a thiyl radical takes place and
these respectively add onto octene and dimerise. Traces of 12
were also recovered as well as 11 % of 7 which indicated a
fragmentation of a C–S bond of 6. It is also important to note that
the starting material 6 was recovered in 27 % yield with trace
amounts of another diastereomer formed by the epimerisation of
one sulfinyl centre under the reaction conditions.
A careful examination of this complex mixture led to the
conclusion that only 57 % of products originating from 6
(6þ1þ7þ11þ12) were obtained. In order to have more insight
into this reaction, we decided to engage a 13C-labelled analogue
of 6 that should allow us to track more easily all the different
products formed from this substrate.
to identify some constituents (Scheme 5). No traces of the
addition of the bissulfinylmethyl radical were observed. Never-
theless, three compounds (9, 10, and 11) showed the incorpo-
ration of the octyl residue, presumably by radical reactions.
The homolytic cleavage of the C–Se bond liberates the phenyl-
selenyl radical that would add onto the terminal position of
octene. An oxidative spin-trapping reaction occurs to generate
formate 11 (11 %) and 10 after hydrolysis. Compounds 9 and 10
were isolated as an inseparable mixture which rendered their
identification harder but the formation of 9 can be explained by
the addition of the sulfonyl radical onto octene followed by a
homolytic substitution on the selenium atom of 6, presumably
affording bissulfinylmethyl radical I. Traces of 3 were also
Starting from enantiopure menthylsulfinate (SS)-13 as
the source of stereogenic sulfur centres, the introduction of the
isotopic label was done by nucleophilic substitution of the
menthyl group by 13C-methylmagnesium iodide (Scheme 6).
(RS)-14-13C was obtained in 85 % yield and following our
previously reported protocol,[8] engaged in the formation of
1-13C in 82 % yield. Deprotonation of 1-13C by sodium hydride
afforded the corresponding bissulfinylmethyl anion that reacted
with phenylselenyl chloride as an electrophile and led to the
formation of 6-13C in a quantitative manner. NMR analyses
confirmed the incorporation of the isotopic label and its
abundance (.95 %).
O
S
O
S
p-Tol
p-Tol
SePh
6
1-octene
(0.8 equiv.) benzene
hν, 0ꢂC, 14h
1, 9 %
ꢁ
6, 27 %
OH
OCHO
C6H13
SePh
C6H13
The behaviour of 6-13C under photochemical activation
was first investigated without radical acceptor (Scheme 7).
ꢁ
ꢁ
PhSe
PhSe
SePh
p-TolO2S
C6H13
9
10
11, 10 %
O
S
O
S
9:10 1:0.7, 11 %
p-TolS
p-Tol
H
O
S
O
S
O
O
H
p-Tol
C6D6, hν
Conv. 50 %
O
p-Tol
p-Tol
S
ꢁ
ꢁ
1-13C, 0.5
8-13C, 0.1
H
p-TolS
p-Tol
ꢁ
SePh
1.5 h in NMR tube
H
Z, Y, X
SePh
O
p-TolS
7, 11 %
6-13C
12, traces
O
O
O
Isotopic 13C labelled :
SePh
S
Mixture of
undefined
formates, 0.4
(p-TolS)2 and (PhSe)2, 19 %
7-13C, traces
ꢁ
Sp-Tol
p-Tol
3, traces
Scheme 7. Photochemical reaction without alkene trap.
Scheme 5. Reactivity of 6 under photochemical conditions.
O
O
13CH3MgI
Toluene
LDA, THF
(Ss)-
p-Tol
S
S
p-Tol
Menthyl
3
(Rs)-14-13C, 85 %
Isotopic 13C labelled :
(Ss)-13
1H
O
S
O
S
J13C-H ꢃ 158 Hz
p-Tol
p-Tol
1-13C, 82 %
NaH, THF
PhSeCl
13C
O
S
O
S
S
S
p-Tol
p-Tol
Se
SePh
6-13C, quant
Scheme 6. 13C-labelled precursor 6-13C.

Radical Chemistry
349
Y, X
H
13
O
S
H
13
Ar
O
11.8 11.6 11.4 11.2 11.0 10.8 10.6 10.4 10.2 10.0 9.8
f1 [ppm]
O
S
O
S
O
S
O
S
p-Tol
p-Tol
p-Tol
p-Tol
13
13
SePh
O
Z
H
O
13
12.0 11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
f1 [ppm]
0
O
O
S
H
13
O
O
Y, X
S
13
S
13
p-Tol
Ar
p-Tol
SePh
H
13
S
SePh
Ar
O
O
S
O
S
p-Tol
p-Tol
13
195 194 193 192 191 190 189 188 187 186
f1 [ppm]
O
H
Z
O
13
200 190 180 170 160 150 140 130 120 110 100 90
f1 [ppm]
80
70
60
50
40
30
20
10
Fig. 2. NMR spectra of 13C-labelled derivatives.
A solution of this compound in [D6]benzene was exposed to
irradiation (sunlamp) for 1.5 h and analysed by NMR. A con-
version of 50 % was observed and a complex mixture was
obtained. As major product, we observed reduced bissulfoxide
derivative 1-13C originating from the homolytic cleavage of
the C–Se bond. The bissulfinyl derivatives were identified by
their S13CHS signal at 4.04 ppm (J ¼ 152 Hz) and 4.68 ppm
(J ¼ 158 Hz) for 1-13C and 6-13C respectively. Traces of 7-13C
were observed and confirmed the source of carbon which was
transformed into a carbonyl group. Finally, a series of formate
derivatives was also identified. 10 % of the mixture was consti-
tuted by 8-13C, presumably originating from the deselenylation
of 7-13C. It was characterised by its S13COH at 10.22 ppm
(J ¼ 212 Hz). The rest of the formate derivatives were isolated as

350
R. M. Mallorquin et al.
Path C
ꢀ
ꢀ
O
O
ꢀArSOꢀ
ArSOꢀ
O
Δ
ꢁ
6
ꢁ
ꢁ
S
S
O
ꢁ SOAr
SePh
S
Ar
Ar
S
Ar
H
F
SePh Ar
E
G
SePh
p-TolS
O
Path D
7
SePh
ꢀ
O
O
?
ꢁ
ꢁ
S
6
S
Ar
Ar
ꢀ
SePh
H
I
SePh
H
Path E
Oꢀ
Sꢁ
Oꢀ
Sꢁ
O
Sꢁ
Sꢁ
ꢁ
ꢀO-H ꢁ B-H
6
ꢁ B-H
Ar
Ar
Ar
B:
Ar
H
SePh
SePh
Oꢀ
Sꢁ
H
O
7
S
ꢀArSOH
Ar
Ar
SePh
Scheme 8. Proposed mechanisms for the formation of 8.
Ph
Ph
15-13C, 6 %
16, 15 %
E:Z 1:0.4
ꢁ
Sp-Tol
O
O
S
O
C6H5 (3 equiv.)
OH
S
ꢁ
Benzene, hν, 6h
Conv. 91 %
p-Tol
p-Tol
Sp-Tol
Ph
SePh
17, 9 %
6-13C
1-13C, 7 %
(p-TolS)2 ꢁ (PhSe)2, 28 %
Scheme 9. Reactivity of 6-13C in the presence of styrene.
an inseparable mixture and only functionally identified by NMR
(Fig. 2). The proton NMR spectrum between 8.0 and 11.8 ppm
showed a series of doublets that are characteristic of 13C–H
coupling. All the mentioned structures were also confirmed by
their 13C NMR resonances.
equivalents of styrene for 6 h (Scheme 9). A conversion of 91 %
was observed and a complex mixture was obtained. As major
constituent, the di-p-tolyldisulfide and the diphenyldiselenide
were formed in 28 %, indicating the production of the corre-
sponding thiyl and selenyl radicals. The reduced bissulfoxide
derivative 1-13C was isolated in 7 % yield. No traces of cyclo-
propane derivatives were detected but we identified other
compounds that contained the styryl moiety.
Product 17 is reminiscent of 10 and its formation can be
explained by the addition of a thiyl radical onto styrene and a
subsequent oxidation of the resulting radical. Vinylsulfide 16
could result from the dehydration of 17. The labelled cinnamal-
dehyde 15-13C was obtained in 6 % yield. One can imagine
the addition of a one–carbon-centred radical, probably bis-
sulfoxide radical I or mono-sulfoxide radical E, onto styrene
followed by trapping and elimination.
In order to understand the observed reactivity, quantum
mechanics (QM) calculations were done. Namely, we have
calculated two bond dissociation energies (BDEs, see Fig. 3),
either for the homolytic breaking of the carbon–sulfur bond or
for the homolytic breaking of the carbon–selenium bond. The
QM calculations show that generating the sulfinyl radical is
always easier than creating the selenyl radical, whatever the
The constant presence of 7 in these reactions was puzzling.
We can propose several pathways to explain its formation. The
first one relies on the homolytic fragmentation of one C–S bond
leading to the formation of radical E and the p-tolylsulfinyl
radical. These could recombine involving the sulfinyl radical by
its oxygen-centred form to afford intermediate F (Path C,
Scheme 8). Then, an intramolecular substitution can liberate a
sulfenate anion that assists the opening of G by deprotonation
to afford 7. Alternatively, product 7 could originate from a
[1,2]-oxygen shift[9] from carbene H via I (Path D), although
no obvious mechanism appears to rationalise the generation of
H.[10] The formation of 7 could also be explained by a
Pummerer-type reaction promoted by a protic source B–H like
traces of acids or sulfenic acid (Path E).
It appeared interesting to us to probe the putative intervention
of carbene H in the reaction course by a signature reaction. We
chose the cyclopropanation of styrene as a test. Under photo-
chemical conditions, 6-13C was reacted in the presence of three

Radical Chemistry
351
O
S
O
S
(p-Tolyl)-p-toluenethiosulfonate 3[5]
R
R
(p-Tolyl)-p-toluenethiosulfonate was identified (29 mg,
47 %); IR (neat) n 2923, 1594, 1490, 1325, 1140, 1078, 1017,
SePh
808 cmꢀl; H NMR (400 MHz, CDCl3) d 7.46 (d, J ¼ 8.3 Hz,
O
S
O
S
O
S
O
S
1
C-Se
C-S
2H, arom.), 7.23 (m, 4H, arom.), 7.14 (m, 2H, arom.), 2.42 (s,
3H, p-tol), 2.38 (s, 3H, p-Tol); 13C NMR (101 MHz, CDCl3)
d 144.71, 142.17, 140.64, 136.63, 130.33, 129.50, 127.74,
124.76 (12 C arom.), 21.78 and 21.60 (2 C p-Tol); m/z (HR-
MS) 301.0331; [MþNa]þ requires 301.0327. Spectral data are
in agreement with the literature.
Homolytic
cleavage
Homolytic
cleavage
R
R
R
R
SePh
SePh
Selenyl radical Sulfinyl radical
Calculation’s level
R ꢃ Me/R ꢃ p-Tol
B3LYP/LACVP∗
B3LYP/LACV3Pꢁꢁ∗∗//B3LYP/LACVP∗ 55.24/50.35
55.46/50.82
32.81/30.98
30.65/27.91
39.55/37.84
46.91/46.81
47.91/41.57
46.95/55.45
47.94/54.45
46.90/ꢀ
N-(p-Toluenesulfinyl)-2,2,6,6-tetramethylpiperidine 4[7]
PBE0/LACVP∗
61.13/56.81
66.28/70.64
74.21/67.29
57.66/66.24
71.71/76.18
72.16/ꢀ
M06-2X/LACVP∗
M06-2X/LACV3P∗
MP2/LACVP∗
N-(p-Toluenesulfinyl)-2,2,6,6-tetramethylpiperidine 4 was
identified (9.2 mg, 15 %); IR (neat) n 2930, 1462, 1383, 1367,
1242, 1172, 1084, 1060 cmꢀl; 1H NMR (400 MHz, CDCl3)
d 7.55 (d, J ¼ 8.3 Hz, 2H, arom.), 7.24 (d, J ¼ 7.9 Hz, 2H, arom.),
2.39 (s, 3H, p-Tol), 1.28–1.83 (m, 15H, TEMPO), 0.93 (s, 3H,
TEMPO); 13C NMR (101 MHz, CDCl3) d 147.30 (C arom.),
139.58 (C arom.), 129.38 (2 CH arom.), 126.09 (2 CH arom.),
61.33 (C), 58.85 (C), 43.70 (CH2), 41.58 (CH2), 35.47 (CH3),
32.69 (CH3), 31.05 (CH3), 30.46 (CH3), 21.33 (CH3), 17.44
(CH2); m/z (HR-MS) 302.1557; [MþNa]þ requires 302.1549.
Spectral data are in agreement with the literature.
MP2/TZVP//B3LYP/LACVP∗
MP2/TZVP
Fig. 3. Calculated BDE for C–Se and C–S bonds in kcal molꢀ1
.
level of calculations used. But according to our calculations it
seems that density functional theory (DFT) calculations using
the B3LYP and PBE0 functionals underestimate the BDE for
this substrate. Taking MP2 as reference calculations (higher
levels are not feasible due to the system size), the new functional
M06–2X seems to be more accurate.
N-Formyl-2,2,6,6-tetramethylpiperidine 5[12]
N-Formyl-2,2,6,6-tetramethylpiperidine was characterised
as a colourless oil (4.4 mg, 12 %); IR (neat) n 2932, 1671,
1463, 1363, 1312, 1257, 1169, 1134, 804 cmꢀl; 1H NMR
(400 MHz, CDCl3) d 8.54 (s, 1H, H-C(O)-N), 1.60 (s, 6H,
CH2), 1.50 (s, 6H, CH3), 1.43 (s, 6H, CH3); 13C NMR
(101 MHz, CDCl3) d 164.75 (CH(O)), 55.94 (C), 55.45 (C),
41.41 (CH2), 40.20 (CH2), 32.60 (CH3), 31.06 (CH3), 30.47
(CH3), 28.13 (CH3), 16.48 (CH2); m/z (HR-MS) 192.1361;
[MþNa]þ requires 192.1359. Spectral data are in agreement
with the literature.
Conclusion
In conclusion, we investigated the behaviour of bissulfinyl
derivatives under thermal and photochemical conditions. The
nitrosamine and the selenide substituted bissulfoxides did not
allow, under these conditions, a selective homolytic cleavage
towards the formation of the targeted radical. Nevertheless,
some very interesting transformations have been highlighted
either by radical trapping with alkene or isotopic labelling
experiments. A rationalisation of these homolysis processes has
been realised with the help of DFT calculations that compared
the strength of the C–Se and the C–S bond. Under thermal
conditions, the more labile C–S bond is cleaved selectively
while the photochemical conditions did not give as clear results.
Synthesis of 1-(phenylseleno)-1,1-(SsSs)-bis(p-tolylsulfinyl)
methane 6
A portion of NaH (60 % by wt in mineral oil, 0.55 g, 13.7 mmol,
1.7 equiv.) was suspended in THF (20 mL) under argon and
cooled to 08C. A solution of bis-sulfoxide 1 (4.0 g, 13.7 mmol,
1.7 equiv.) in THF (30 mL) was added dropwise via syringe.
After 1 h stirring, the mixture was cooled to ꢀ258C. A portion of
PhSeCl (1.57 g, 8.2 mmol, 1.0 equiv.) was then added, the
mixture was stirred overnight and gradually warmed to room
temperature. 10 mL of diethyl ether was added, and the resulting
mixture was washed successively with HCl (1.0 M, 3 ꢁ 5 mL
portions), water (2 ꢁ 5 mL), and brine (5 mL). The combined
extracts were dried (MgSO4) and evaporated under reduced
pressure. The residue was purified by column chromatography
on silica gel (AcOEt : light petroleum ¼ 6 : 4) to afford
1-(phenylseleno)-1,1-bis(p-tolylsulfinyl)-methane 6 as white
crystals (3.18 g, 88 %); mp 112–1138C; [a]2D0 þ36 (c 0.14,
CHCl3); IR (neat) n 3053, 2920, 2240, 1594, 1084, 1048,
809 cmꢀ1; 1H NMR (400 MHz, CDCl3) d 7.68 (d, J ¼ 8 Hz, 2 H,
arom.), 7.58 (d, J ¼ 8 Hz, 2 H, arom.), 7.34 (d, J ¼ 8 Hz,
2 H, arom.), 7.24 (d, J ¼ 8 Hz, 2 H, arom.), 7.09 (t, J ¼ 7.3 Hz,
1 H, arom.), 6.82 (m, 2H, arom.), 6.29 (m, 2 H, arom.), 4.57 (s,
1 H, CH-Se), 2.43 (s, 3 H, p-Tol), 2.39 (s, 3 H, p-Tol); 13C NMR
(101 MHz, CDCl3) d 143.12 (C arom.), 142.34 (C arom.),
138.19 (C arom.), 137.51 (C arom.), 134.33 (2 CH arom.),
129.76 (2 CH arom.), 129.65 (2 CH arom.), 128.71 (2 CH
Experimental
Thermolysis of TEMPO Derivative 2
1-(Bis((Ss,Ss)-p-tolylsulfinyl)methoxy)-2,2,6,6-tetramethylpiperidine
2 (100 mg, 0.22 mmol) was dissolved in 2 mL of benzene in a
sealed tube. The resulting solution was degassed with bubbling
Ar for 15 min before thermolysis at 1008C for 17 h in a sand bath
protected from light. The reaction mixture was then allowed to
cool to room temperature (rt) and the solvent was removed under
vacuum. The crude product was purified by flash chromato-
graphy on silica gel.
[11]
1,2-Di-p-tolyldisulfane (p-TolS)2
1,2-Di-p-tolyldisulfane was identified (12.6 mg, 23 %); IR
(neat) n 2921, 1489, 1302, 1179, 1078, 1015, 803 cmꢀl; 1H NMR
(400 MHz, CDCl3) d 7.38 (d, J ¼ 8.2 Hz, 4H), 7.10 (d, J ¼
7.9 Hz, 4H), 2.32 (s, 6H); 13C NMR (101 MHz, CDCl3)
d 137.60 (2 C arom.), 134.07 (2 C arom.), 129.94 (4 CH arom.),
128.72 (4 CH arom.), 21.20 (2 p-Tol). Spectral data are in
agreement with the literature.

352
R. M. Mallorquin et al.
arom.), 128. 32 (C arom.), 126.90 (C arom.), 126.59 (2 CH
arom.), 125.34 (2 CH arom.), 97.66 (CH-Se), 21.54 (p-Tol),
21.49 (p-Tol); m/z (HR-MS) 470.9953; [MþNa]þ requires
470.9962.
1H NMR (400 MHz, CDCl3) d 10.22 (s, 1H), 7.37 (d, J ¼ 8.1 Hz,
2H), 7.27 (m, 2H), 2.40 (s, 3H); 1H NMR (200 MHz,
[D6]benzene) d 9.82 (s, 1H), 7.15 (d, J ¼ 8.2 Hz, 2H), 6.87
(d, J ¼ 8.0 Hz, 2H), 2.05 (s, 3H); 13C NMR (50 MHz,
[D6]benzene) d 189.36 (C¼O), 140.07 (C arom.), 134.57 (2 CH
arom.), 130.58 (2 CH arom.), 123.55 (C arom.), 21.18 (p-Tol).
Spectral data are in agreement with the literature.
Photolysis of 6 in Benzene
The reaction was carried out using the same procedure described
by Byers.[2] Seleno-bis-sulfoxide 6 (250 mg, 0.56 mmol,
1 equiv.) and octene (0.07 mL, 0.44 mmol, 0.8 equiv.) were
dissolved in 4 mL of benzene in a 10 mL flask equipped with a
reflux condenser. The resulting solution was degassed with
bubbling Ar for 10 min and placed in an ice bath renewed con-
stantly. The photolysis was carried out for 14 h by a sunlamp
placed 15 cm from the solution. Solvent was removed and the
residue was purified by column chromatography on silica gel
(gradient elution from light petroleum : CH2Cl2 ¼ 1 : 1 to Et2O)
to yield 7 (26 mg, 11 %) and 8 (traces).
Photolysis of 6 in the Presence of Octene at 08C
The reaction was carried out using the same procedure described
by Byers.[2] Compound 6 (250 mg, 0.56 mmol, 1 equiv.) and
octene (0.07 mL, 0.44 mmol, 0.8 equiv.) were dissolved in 4 mL
of benzene in a 10 mL flask equipped with a reflux condenser.
The resulting solution was degassed with argon gas for 10 min.
The photolysis was carried out for 14 h at 08C by a sunlamp
placed 15 cm from the solution. Solvent was removed and the
residue was purified by column chromatography on silica gel
(gradient elution from light petroleum : CH2Cl2 ¼ 1 : 1 to Et2O)
to yield 3, 7, 9, 10, 11, 12 (p-TolS)2, and (PhSe)2.
Compounds 7 and 8 were independently synthesised to
confirm their structures:
Synthesis of Se-Phenyl-S-p-tolyl Carbonoselenothioate 7[13]
1-(Phenylseleno)-2-octanol 10 and
1-(p-Toluenesulfonyl)-2-(phenylseleno)-octane 9
To a solution of p-tolylthiol (400 mg, 3.3 mmol, 2 equiv.) in
anhydrous CH2Cl2 (5 mL) was added NaH (60 % by wt in
mineral oil, 129 mg, 3.2 mmol, 2 equiv.) at 08C. The resulting
solution was stirred at this temperature for 30 min. Then, this
This mixture of compounds was submitted to analysis
1
(21 mg, 10 %). The ratio of 10 : 9 appeared to be 1 : 0.7. H
NMR (400 MHz, CDCl3) d 7.63 (d, J ¼ 8.2 Hz, 2H, 9), 7.56–
7.50 (m, 2H, 10), 7.36–7.15 (m, 3H 10 þ 7H 9), 3.69–3.61 (m,
1H, 10), 3.50–3.36 (m, 3H, 9, CH2SO2p-Tol and CHSePh), 3.15
(dd, J ¼ 12.8, 3.5 Hz, 1H, 10), 2.87 (dd, J ¼ 12.7, 8.7 Hz, 1H,
10), 2.45 (s, 3H, 9, p-Tol), 2.17 (s, 1H, 10), 1.69–1.47 (m, 2H 10
and 2H 9), 1.35–1.17 (m, 8H 10 and 8H 9), 0.94–0.80 (m, 3H 10
and 3H 9); 13C NMR (101 MHz, CDCl3) d 144.82 (C arom. 9),
136.41 (C arom.), 135.02 (2 CH arom.), 133.14 (2 CH arom. 10),
130.05 (2 CH arom.), 129.46 (C arom.), 129.41 (2 CH arom.),
129.34 (2 CH arom. 10), 128.20 (CH arom. 9), 128.06 (2 CH
arom.), 127.79 (C arom.), 127.40 (CH arom. 10), 69.94 (CH-OH
10), 61.82 (CH2SO2, 9), 37.64 (CH-Se, 9), 37.43 (CH2Se 10),
36.72 (CH2), 33.68 (CH2), 31.87 (CH2), 31.75 (CH2), 29.37
(CH2), 28.94 (CH2), 27.53 (CH2), 25.91 (CH2), 22.71 (2 CH2),
21.79 (p-Tol 9), 14.22 (2 CH3).
solution was added dropwise to
a solution of bis-
(trichloromethyl)-carbamate (BTC) (380 mg, 1.3 mmol,
0.8 equiv.) in CH2Cl2 (20 mL) at room temperature. The reac-
tion mixture was stirred until completion as indicated by TLC
(16–18 h) then cooled to 08C. A solution of phenylselenol
(0.37 mL, 3.5 mmol, 2.2 equiv.) with NaH (60 % by wt in min-
eral oil, 141 mg, 3.5 mmol, 2.2 equiv.) was stirred at 08C for 1h.
This solution was added slowly to the first one, and the resulting
mixture was heated at reflux until the reaction was completed.
The solvent was removed and the residue was diluted with ethyl
acetate (40 mL) and washed with 10 % NaHCO3 (3 ꢁ 30 mL),
brine (30 ꢁ 3 mL), and then dried over anhydrous MgSO4. The
residue was purified by column chromatography on silica gel
(pentane: AcOEt ¼ 9 : 1) to afford Se-phenyl-S-p-tolyl carbo-
noselenothioate 7 as a yellow solid (276 mg, 24 %). Mp 70–
728C; IR (neat) n 3057, 2921, 1703 (C¼O), 1491, 1475, 1439,
837, 788 cmꢀ1; 1H NMR (400 MHz, CDCl3) d 7.59 (dd, J ¼ 7.9,
1.7 Hz, 2H arom.), 7.41 (m, 5H, arom.), 7.24 (d, J ¼ 7.9 Hz, 2H,
arom.), 2.39 (s, 3H, p-Tol); 13C NMR (101 MHz, CDCl3)
d 187.09 (S-C(O)-Se), 141.16 (C arom.), 136.54 (2 CH arom.),
135.57 (2 CH arom.), 130.38 (2 CH arom.), 129.61 (C arom.),
129.54 (2 CH arom.), 126.33 (C arom.), 123.86 (C arom.), 21.59
(p-Tol); m/z (HR-MS) 330.9663; [MþNa]þ requires 330.9666.
1-(Phenylselanyl)octan-2-yl Formate 11
11 was obtained in 10 % yield (14 mg); IR (neat) n 2925,
2856, 1721 (C¼O), 1578, 1167, 736 cmꢀ1; 1H NMR (400 MHz,
CDCl3) d 8.03 (s, 1H), 7.54 (m, 2H), 7.29 (m, 3H), 5.12 (dt,
J ¼ 12.2, 6.1 Hz, 1H), 3.08 (m, 2H), 1.70 (m, 2H), 1.25 (m, 8H),
0.86 (t, J ¼ 6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) d 160.75
(HC(O)O), 144.58 (C arom.), 133.15 (2 CH arom.), 129.31
(2 CH arom.), 127.44 (CH arom.), 73.55 (CH-OC(O)H), 33.82
(CH2-Se), 31.73 (CH2), 31.57 (CH2), 29.06 (CH2), 25.20 (CH2),
22.66 (CH2), 14.19 (CH3); m/z (HR-MS) 337.0676; [MþNa]þ
requires 337.0677.
Synthesis of p-Thiocresyl Formate 8[14]
The p-thiocresyl formate was synthesised following the general
procedure for the preparation of thiol formates reported by
Sprecher.[14] An ice-cold solution of dicyclohexylcarbodiimide
(2.17 g, 10.5 mmol, 1.05 equiv.) in dry ethyl acetate (15 mL) is
added with stirring to an ice-cold solution of the thiol (1.24 g,
10 mmol, 1 equiv.) and commercial 98 % formic acid
(,0.39 mL) in dry ethyl acetate (25 mL). Cooling and stirring
are continued for 2 h, while the progress of the reaction may be
monitored by TLC. The precipitated dicyclohexylurea is
removed by filtration and the solvent evaporated. The product
was purified by column chromatography on silica gel (pen-
tane : Et2O ¼ 92 : 2) affording a transparent oil (1.35 g, 89 %);
(Ss)-1-(Phenylseleno)-1-(p-tolylsulfinyl)-methane 12
The few milligrams obtained were submitted to analysis.
1H NMR (400 MHz, CDCl3) d 7.71–7.11 (m, 9H arom.), 4.11
(m, 2H), 2.43 (s, 3H); 13C NMR (101 MHz, CDCl3) d 143.88
(C arom.), 142.75 (C arom.), 136.59 (C arom.), 135.33 (CH
arom.), 133.78 (CH arom.), 130.24 (CH arom.), 129.90 (CH
arom.), 129.55 (CH arom.), 129.46 (CH arom.), 129.10
(C arom.), 128.20 (CH arom.), 126.06 (CH arom.), 125.70
(CH arom.), 125.17 (CH arom.), 52.89 (CH2), 21.61 (C p-Tol).

Radical Chemistry
353
Synthesis of 13C-Labelled Products
d 9.71 (dd, J ¼ 172.0, 7.7 Hz, 1H), 7.61 – 7.54 (m, 2H), 7.54 –
(Rs)-(p-Tolyl)-methylsulfoxide 14-13C
7.39 (m, 4H), 6.78 – 6.68 (m, 1H).
The p-tolyl methylsulfoxide 14-13C was prepared according
to a previously reported procedure using 13C-labelled methyl
iodide (99 %).[8] The product was purified by column chroma-
tography on silica gel (light petroleum : AcOEt ¼ 8 : 2) to afford
the compound as a white-yellow solid (4.18 g, 85 %). The
analyses were in agreement with the known (Rs)-(p-tolyl)-
2-Hydroxyphenylethyl p-tolyl sulfide 17[16]
(9.8 mg, 9 %). 1H NMR (400 MHz, CDCl3) d 7.28–7.38 (m,
7H), 7.14 (d, J ¼ 8.2 Hz, 2H), 4.68 (dd, J ¼ 9.7, 3.3 Hz, 1H), 3.28
(dd, J ¼ 13.8, 3.3 Hz, 1H), 3.03 (dd, J ¼ 13.8, 9.7 Hz, 1H), 2.35
(s, 3H); 13C NMR (101 MHz, CDCl3) d 142.32 (C arom.),
137.31 (C arom.), 131.24 (2 CH arom.), 131.06 (C arom.),
130.10 (2 CH arom.), 128.68 (2 CH arom.), 128.06 (CH arom.),
126.00 (2 CH arom.), 71.63 (CH-OH), 45.02 (CH2-S-Ph), 21.20
(p-Tol). Spectral data are in agreement with the literature.
1
methylsulfoxide. H NMR (400 MHz, CDCl3) d 7.54 (d, J ¼
8.3 Hz, 2H, arom), 7.33 (d, J ¼ 7.9 Hz, 2H, arom), 2.70 (d, J ¼
138.8 Hz, 3H, 13CH3), 2.42 (s, 3 H, Tol.) with traces (1 %)
of un-labelled product.
Supplementary Material
(Ss,Ss)-1,1-Bis-(p-tolylsulfinyl)-methane 1-13
C
1H and 13C spectra of new compounds are available on the
Journal’s website.
The synthesis was carried out using the same procedure used
for the synthesis of 1,[8] starting from labelled 14-13C (2 eq.,
3.84 g, 24.9 mmol). 1,1-Bis-(p-tolylsulfinyl)-methane (13C) was
obtained after precipitation in a mixture of hexane : diethyl
ether ¼ 1 : 1 as a white solid (3.0 g, 82 %). The analyses were
in agreement with compound 1. 1H NMR (400 MHz, CDCl3) d
7.54 (d, J ¼ 8.2 Hz, 4H, arom.), 7.32 (d, J ¼ 8.2 Hz, 4H, arom.),
3.97 (d, J ¼ 149.8 Hz, 2H, CH2(SOp-Tol)2), 2.40 (s, 6H, p-Tol).
References
[1] J.-P. Goddard, C. Gomez, F. Brebion, S. Beauvie`re, L. Fensterbank,
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JO00064A023
[3] C. Wetter, K. Jantos, K. Woithe, A. Studer, Org. Lett. 2003, 5, 2899.
doi:10.1021/OL034994K
1-(Phenylseleno)-1,1-(SsSs)-bis-(p-tolylsulfinyl)-
methane 6-13C
[4] (a) A. J. Herrera, A. Studer, Synthesis 2005, 1389.
(b) M. de Greef, S. Z. Zard, Tetrahedron 2004, 60, 7781. doi:10.1016/
J.TET.2004.06.061
The synthesis was carried out using the same procedure used
for the synthesis of 6, starting from labelled 1-13C (0.67 g,
2.29 mmol). After purification by flash chromatography on
silica gel (AcOEt : light petroleum ¼ 6 : 4), 1-(phenylseleno)-
1,1-(SsSs)-bis-(p-tolylsulfinyl)-methane (13C) was obtained as
a white solid (0.631 g, quantitative yield). The analyses were in
agreement with compound 6. 1H NMR (400 MHz, [D6]benzene)
d 7.68 (d, J ¼ 8 Hz, 2 H, arom.), 7.38 (d, J ¼ 8 Hz, 2 H, arom.),
6.77–6.69 (m, 5 H, arom.), 6.57–6.50 (m, 3H, arom.), 4.77
(d, J ¼ 158.0 Hz, 1H, CH-Se), 1.99 (s, 3 H, p-Tol), 1.89 (s, 3 H,
p-Tol); m/z (HR-MS) 471.9987; [MþNa]þ requires 471.9996.
[5] (a) C. Chatgilialoglu, in The Chemistry of Sulphones and Sulphoxides
(Eds S. Patai, Z. Rappoport, C. J. M. Stirling) 1988, pp. 1081–1087
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[7] P. Carloni, E. Damiani, M. Iacussi, L. Greci, P. Stipa, D. Cauzi,
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0040-4020(95)00800-N
Photolysis of 6-13C in the Presence of Styrene
[8] F. Brebion, J. P. Goddard, L. Fensterbank, M. Malacria, Synthesis
13C Labelled seleno-bis-sulfoxide 6-13C (200 mg, 0.45 mmol,
1 equiv.) and freshly distilled styrene (0.15 mL, 1.34 mmol,
3 equiv.) were dissolved in 3.5 mL of benzene in a sealed tube.
The resulting solution was degassed with bubbling argon gas for
15 min before photolysis for 6 h by a sun-lamp placed 10 cm
from the sealed tube. The residue was purified by column
chromatography on silica gel (gradient elution using pentane :
Et2O/100 : 0 to 95 : 5) to afford 15, 16, and 17.
2005, 2449.
[9] R. A. Aitken, M. J. Drysdale, G. Ferguson, A. J. Lough, J. Chem. Soc.
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[10] For the formation of carbene intermediates under radical conditions,
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(b) J. Zakrzewski, M. Krawczyk, Heteroatom Chem. 2006, 17, 393.
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[13] S. K. Su, J. P. Zhang, X. R. Liang, Org. Prep. Proced. Int. 2006, 38,
Sulfane 16 (15 mg, 15 %) was obtained as a mixture of
1
isomers (E : Z/1.0 : 0.4); H NMR (400 MHz, CDCl3) d 7.56
404.
(m, 2H, Z), 7.44–7.20 (m, 7H E and 5H, Z), 7.19 (d, J ¼ 7.9 Hz,
2H E and 2H Z), 6.89 (d, J ¼ 15.5 Hz, 1H, E), 6.68 (d, J ¼ 15.5
Hz, 1H, E), 6.58 (d, J ¼ 10.8 Hz, 1H, Z), 6.50 (d, J ¼ 10.8 Hz,
1H, Z), 2.39 (s, 3H, E and 3H, Z). Spectral data are in agreement
with the literature.
[14] M. Sprecher, E. Nov, Synth. Commun. 1992, 22, 2949. doi:10.1080/
00397919208021120
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1217. doi:10.1016/J.TETLET.2005.11.164
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52, 3312. doi:10.1021/JO00391A025
Cinnamaldehyde 15-13C
Colourless oil (3.4 mg, 6 %); data is in agreement with the
data of a commercial sample. 1H NMR (400 MHz, CDCl3)