Regio-and stereocontrolled synthesis of (Z)-α-(phenylseleno)sulfinyl and-sulfonyl alkenes via sulfenic acids, and a study of their reactivity

Article abstract of DOI:10.1002/ejoc.201100759

A general procedure for the synthesis of α-(phenylseleno)sulfinyl and-sulfonyl alkenes has been described. 1-(Phenylseleno)ethenyl sulfoxides were prepared by the syn-addition of in situ-generated sulfenic acids on to the triple bond of suitably substituted (phenylseleno)acetylenes. 1-(Phenylseleninyl)ethenyl sulfones were obtained by further oxidation of their sulfinyl analogues. The mild conditions of the sulfenic acid/(phenylseleno) alkyne syn-addition and its stereospecificity and regioselectivity allowed us to obtain electron-poor alkenes with a well defined stereochemistry and sensitive substituents at the double bond. Chiral (Z)-1-[(2,3,4,6-tetra-O-acetyl-β-D- glucopyranosyl)sulfinyl]-1-(phenylseleno)-1-hexene was also obtained via the enantiopure2,3,4,6-tetra-O-acetylglucosulfenic acid. The reactivity of α-(phenylseleninyl)sulfinyl and-sulfonyl alkenes has been evaluated in nucleophilic additions to the electron-poor double bond, conducted with hard nucleophiles such as piperidine and phenol.

Full text of DOI:10.1002/ejoc.201100759

FULL PAPER
DOI: 10.1002/ejoc.201100759
Regio- and Stereocontrolled Synthesis of (Z)-α-(Phenylseleno)sulfinyl and
-sulfonyl Alkenes via Sulfenic Acids, and a Study of their Reactivity
Maria Chiara Aversa,[a] Anna Barattucci,[a] Paola Bonaccorsi,*[a] and Andrea Temperini*[b]
Dedicated to Professor Gianfranco Scorrano on the occasion of his 72nd birthday
Keywords: Sulfur / Selenium / Sulfenic acids / Alkenes / Michael addition
A general procedure for the synthesis of α-(phenylseleno)-
tron-poor alkenes with a well defined stereochemistry and
sulfinyl and -sulfonyl alkenes has been described. 1-(Phen-
sensitive substituents at the double bond. Chiral (Z)-1-
ylseleno)ethenyl sulfoxides were prepared by the syn-ad- [(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)sulfinyl]-1-(phen-
dition of in situ-generated sulfenic acids on to the triple bond
of suitably substituted (phenylseleno)acetylenes. 1-(Phenyl-
ylseleno)-1-hexene was also obtained via the enantiopure
2,3,4,6-tetra-O-acetylglucosulfenic acid. The reactivity of α-
seleninyl)ethenyl sulfones were obtained by further oxi- (phenylseleninyl)sulfinyl and -sulfonyl alkenes has been
dation of their sulfinyl analogues. The mild conditions of the
sulfenic acid/(phenylseleno)alkyne syn-addition and its ste-
evaluated in nucleophilic additions to the electron-poor
double bond, conducted with hard nucleophiles such as
reospecificity and regioselectivity allowed us to obtain elec- piperidine and phenol.
these substrates act as good nucleophilic acceptors for
Introduction
amines[5] or enamines[6] affording, in the latter case, the cor-
responding ketones. A radical cyclization route to pyrroli-
dines has been recently described, based on Michael-type
addition of allyl or propargylamines to α-(phenylseleno)-
sulfonyl alkenes.[7] A general procedure for the synthesis of
2-alkynylcyclopropanes has also been described, using α-
(phenylseleno)sulfonyl enynes as starting materials.[8]
Not many synthetic approaches to seleno- and sulfur-
substituted alkenes are reported in the literature. In particu-
lar, α-(phenylseleno)sulfinyl and -sulfonyl alkenes are usu-
ally obtained following three main procedures, two of which
are comparable. They are based on the addition of a phen-
ylselenenyl halide to a vinyl sulfone or sulfoxide in the pres-
ence[7] or absence[9] of zinc chloride. Subsequent dehydro-
halogenation with a base affords the desired compounds. In
a recent methodology, the cis-carbocupration of acetylenic
sulfoxides, followed by electrophilic reaction with phenyl-
selenenyl bromide, led to α-(phenylseleno)-p-tolylsulfinyl alk-
enes in good yields.[10]
In this paper we present a new approach to the synthesis
of α-(phenylseleno)sulfinyl and -sulfonyl alkenes by the syn-
addition of transient sulfenic acids to the triple bond of
variously substituted (phenylseleno)acetylenes.[11] The syn-
addition of sulfenic acids to the triple bond constitutes a
general stereocontrolled methodology to obtain vinyl sulf-
oxides.[12] Enantiopure sulfenic acids can be generated from
suitable enantiopure sulfinyl precursors and their addition
to unsaturated bonds produces diastereomeric mixtures of
sulfoxides that can usually be separated by simple column
The stereocontrolled synthesis of electron-poor alkenes
has always represented an interesting topic in organic syn-
thesis because of the potential of the reactive double bond
in nucleophilic additions, 1,3-dipolar and Diels–Alder cy-
cloadditions, because of the nature of the electron-with-
drawing (EW) groups present on the unsaturated system,
which can control the stereoselectivity of such reactions. In
particular, α,β-unsaturated sulfoxides[1] as well as electron-
deficient vinylic selenides[2] show many types of reactivity
for the ability of these heteroatoms to stabilize both nega-
tive and positive charges, because they are good leaving
groups and can be subjected to a number of transforma-
tions. Furthermore, the sulfinyl group has been shown to
be one of the most efficient chiral auxiliaries for accessing
optically active vinyl sulfoxides in stereocontrolled synthe-
ses.[3] Vinylic selenides, on the other hand, represent inter-
esting substrates with which cross-coupling reactions with
various organometallic reactions can be carried out.[4]
The idea of localizing two heteroatoms, such as selenium
and sulfur, in different oxidation states on a double bond
has been already exploited and described in few papers, and
[a] Dipartimento di Chimica organica e biologica, Università degli
Studi di Messina,
Viale F. Stagno d’Alcontres 31, 98166 Messina, Italy
Fax: +39-090-393895
E-mail: pbonaccorsi@unime.it
[b] Dipartimento di Chimica e Tecnologia del Farmaco, Università
degli Studi di Perugia,
Via del liceo 1, 06123 Perugia, Italy
5668
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Synthesis of (Z)-α-(Phenylseleno)sulfinyl and -sulfonyl Alkenes
chromatography.[13] We have used this route to obtain op- ospecific reaction,[17] which, in these cases, generally led to
tically pure active derivatives. Furthermore, the reactivity of the exclusive formation of (Z)-alkenes. It is also a regiose-
such electron-poor alkenes has been exploited and dis- lective addition when substituents are present on the unsat-
cussed with regard to accessing substituted vinyl sulfoxides urated bond; it usually follows the Markovnikov rule[15b,18]
with controlled stereochemistry at the double bond.
that the sulfinyl group adds on to the most electrophilic
unsaturated carbon atom. The regiochemistry of this ad-
dition was determined on the basis of NOESY experiments
on 9: a positive cross peak was observed between the H-2
and H2-3 resonances (Figure 1). The (Z)-configuration in 9
comes from the stereospecificity of the sulfenic acid syn-
addition. Analogously, the structures of 12–14 were une-
quivocally attributed. The geminal or vicinal spin–spin cou-
pling of the olefinic protons distinguishes 10 from 15 (Ex-
perimental Section). Finally, the carbon resonance of SCSe
in 11 (142.8 or 142.1 ppm) was in the range 143.8–
142.3 ppm, characterizing the corresponding nucleus in
strictly related 9, 13 and 14.
Results and Discussion
Synthesis
A general procedure for the synthesis of (phenylseleno)-
sulfinyl alkenes is shown in Scheme 1. The key step of the
pathway is the in situ generation of sulfenic acid 2 from a
suitable sulfinyl precursor, and its syn-addition to the triple
bond of variously substituted (phenylseleno)acetylenes 3–8,
which were prepared according to literature pro-
cedures.[11,14] In sulfoxides 1a–c[15] the different alkyl moie-
ties linked to the sulfur atom, with at least one EW group
on the β-carbon atom, allow the generation of the transient
sulfenic acid 2 by thermal β-syn-elimination at different
temperatures.[16] We thermolyzed each of the three sulfox-
ides 1, in the presence of the same sulfenic acid acceptor 3,
to find the best sulfenic acid precursor to obtain (phenyl-
seleno)sulfinyl alkenes 9–16. Sulfoxide 1c and 1-(phenyl-
seleno)-1-hexyne (3), in 1:3 molar ratio, reacted at 40 °C
(CH2Cl2) for 14 h to afford 9 in only 40% yield. The use of
precursor 1b led to 9 after 6 h in ClCH2CH2Cl (83 °C) in
75% yield. The best sulfenic acid precursor was 1a, which
afforded 9 under the same reaction conditions as those of
1b but in 85% yield. The use of tetrahydrofuran (THF,
65 °C, 12 h) as the solvent in the reaction of 1a with 3 was
less effective, and 9 was obtained in 70% yield. In all these
experiments excess 3 was recovered (75% yield) from col-
umn chromatography performed on the reaction mixture.
Table 1. Synthesis of 9–16 from 1a in ClCH2CH2Cl.
[a] Calculated with respect to 1a. Excess 3–8 was always recovered
(75% yield).
Figure 1. NOESY correlations in 9.
Scheme 1. General procedure for the synthesis of (phenylseleno)-
ethenyl sulfoxides.
Compounds 9 and 12–14 were obtained with complete
Once we had chosen 1a as the best sulfinyl precursor for and expected regioselectivity (Entries 1 and 4–6, respec-
sulfenic acid 2, we decided to test the general validity of the tively). High regioselectivity was also observed in the reac-
procedure with differently substituted (phenylseleno)acetyl- tion of 2 with the unsaturated acceptor 5. Alkenes 11 and
enes 3–8, and the results are reported in Table 1. (Phenylse- 16 were obtained in a 98:2 ratio (Entry 3), confirming that
leno)sulfinyl alkenes 9–16 were obtained in very good over- electronic effects govern the regioselectivity of the reaction
all yields under mild conditions, allowing the presence of in this case. The result obtained when 2 was treated with
acid/base sensitive substituents such as SiMe3, phthalimido (ethynylseleno)benzene (4, Entry 2) can be ascribed to the
or ester groups (Entries 4–6) in the final products. The syn- absence of substituents other than the seleno group on the
addition of a sulfenic acid to an unsaturated bond is a stere- triple bond of 4 and to the consequent preferred addition
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M. C. Aversa, A. Barattucci, P. Bonaccorsi, A. Temperini
FULL PAPER
of the sulfur group to the less hindered carbon atom of the giving insignificant results when it was involved in the reac-
unsaturated skeleton.[15b]
tion with piperidine. Sulfoxide 20 and sulfone 21 reacted
Furthermore, we decided to generate enantiopure gluco- with the cyclic amine to afford 25 and 24, respectively, in
sulfenic acid 18 from the sulfinyl precursor 17 (sulfur epi- good yields as shown in Scheme 3. Vinyl sulfoxide 22 comes
meric mixture) in the presence of a (phenylseleno)acetylene from phenate addition/phenylselenenyl loss. A positive
to synthesize α-(phenylseleno)sulfinyl alkenes with con- NOESY cross peak observed between the olefinic proton
trolled stereochemistry at the sulfur atom of the sulfinyl and CH2NCH2 moiety supports the structure of sulfoxide
moiety (Scheme 2).[19] In our experience a 1,1-diethoxycar- 25. Similarly, 22 shows a positive NOESY cross peak be-
bonyl-2-methylprop-2-yl residue linked to the anomeric sul- tween the CH2C= and the ortho protons of the phenylsulf-
fur atom in glucosyl sulfoxide 17 allows us to overcome the inyl moiety.
problem of regioselectivity in the generation of sulfenic acid
18, due to the presence of two different syn-β-hydrogen
atoms with respect to the SO group.[19b] The thermolysis
was conducted at 40 °C (CH2Cl2) in the presence of alkyne
acceptor 3, leading to a mixture of the two sulfinyl epimers
19. Stereoselectivity was observed in this reaction, and epi-
mers 19 were obtained in a 1:2 ratio. Our attribution of the
sulfur configuration in the two sulfur epimers 19 comes
from the well-known influence that an anomeric configura-
tion exerts on the sulfoxide configuration in sulfinyl glyco-
sides owing to the exo-anomeric effect.[20] We have pre-
viously reported[19a] that the syn-addition to a triple bond
by a α-d-glucosulfenic acid affords a glucosyl vinyl sulfox-
ide mixture with a major amount of (RS)-configured prod-
uct stereoselectively, whereas the contrary is found when the
same reaction involves β-d-glucosulfenic acid 18.[19b] The
generation of the transient glucosulfenic acid 18 and its ad-
dition to 3 provide a significant model for the development
of a stereocontrolled synthesis of 1-(phenylseleno)-1-sulfin-
ylalkenes.
Scheme 3. Nucleophilic additions to α-(phenylseleninyl)sulfinyl
and -sulfonyl alkenes.
α-(Phenylseleno)sulfonyl and β-(phenylseleninyl)sulfonyl
alkenes have been subjected to nucleophilic additions with
cyclic and linear amines[5,7] or enamines[6] previously. This
confirmed our finding for reactive substrate 21, which gave
vinyl sulfone 24 as a unique reaction product in good yield
after the spontaneous loss of PhSeOH. To the best of our
knowledge, α-(phenylseleninyl)sulfinyl alkenes, such as 20,
have not been prepared in the past possibly because of their
poor stability. However, we found that 20 remained unal-
Scheme 2. Stereoselective synthesis of glucopyranosyl (Z)-1-(phen-
tered on the bench for a few days. This observation con-
ylseleno)alkenyl sulfoxides.
firms the (Z)-configuration of alkene 9. Otherwise, if 20,
and consequently its precursor 9, was (E)-configured the
The controlled oxidation of (Z)-[{1-(phenylseleno)-1-
PhSeOH syn-elimination would occur even at low tempera-
hexen-1-yl}sulfinyl]benzene (9) with m-chloperoxybenzoic
ture and 20 would not have been isolated.
acid (m-CPBA) led to a diastereomeric mixture of racemic
α-(phenylseleninyl)sulfinyl alkenes 20, which gave α-phenyl-
seleninyl sulfonyl alkene 21 when treated with an excess of
Results obtained from the piperidine addition to 20 ap-
pear significant and deserve comment. The reaction may
occur through a first addition step leading to the unstable
oxidant (Scheme 2).
diastereomeric mixture of α-(phenylseleninyl)sulfinyl al-
kanes 23, that spontaneously loses PhSeOH to afford 25.
The exclusive formation of 25 from this elimination sug-
Reactivity
gests an interesting stereocontrol of the overall synthetic
The three alkenes 9, 20 and 21 were subjected to conju- process under study. An analysis of Newman projections
gate addition with nucleophiles, such as piperidine and phe- that allow the stereospecific syn-elimination of PhSeOH
nol. Compound 9 proved to be a poorly reactive substrate, from the intermediates 23 indicates that the diastereomeric
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Synthesis of (Z)-α-(Phenylseleno)sulfinyl and -sulfonyl Alkenes
gel Alugram Alox N/UV254. Products were visualized by UV or
with vanillin [1 g dissolved in MeOH (60 mL) and conc. H2SO4
(0.6 mL)]. Column chromatography was performed on Aldrich 60
silica gel or Fluka aluminum oxide Brockmann activity I. Melting
mixture 23 must have the two new stereogenic carbon atoms
in the relative configuration (R,S), which requires an anti-
approach in the nucleophilic addition.[21] This can include
the stereoinfluence exerted by the two chiral heteroatoms in
20 (Scheme 3). Similar considerations could support the
(E)-stereochemistry found in product 22. Moreover, the
analogous stereochemistry observed in α,β-unsaturated
sulfone 24 was confirmed by oxidation of the sulfinyl group
of 25 and seems to suggest that the stereogenic selenoxide
1
points were determined with a Kofler hotstage apparatus. H and
13C NMR spectra were recorded in CDCl3 solutions with SiMe4 as
the internal standard at 500 (or 300) and 125 (or 75) MHz respec-
1
tively, unless otherwise stated. J values are given in Hz. H NMR
peak assignments follow from COSY experiments. 13C NMR spec-
tra were acquired by the APT technique. Heteronuclear single
group is remarkably effective in inducing asymmetry, out- quantum coherence and NOESY experiments were also performed
for several compounds. The starting products 1a–c,[15] 3–7[11,14] and
weighing the influence of the sulfinyl group.
17[15c] have been reported previously. Benzoate 8 was prepared fol-
lowing the procedure previously described.[11]
Conclusions
General Procedure for the Synthesis of [{(Phenylseleno)-
ethenyl}sulfinyl]benzenes 9–16: A solution of methyl-3-(phenylsulf-
inyl)propanoate (1a) (212 mg, 1.00 mmol) and [(phenylseleno)eth-
ynyl]benzenes 3–8 (3.00 mmol) in ClCH2CH2Cl (9 mL) was heated
α-(Phenylseleno)sulfinyl alkenes 9–14 and 19 can be eas-
ily prepared by the syn-addition of in situ generated sulfenic
acids to the triple bond of suitably substituted selenoacetyl-
to reflux until complete sulfoxide disappearance as verified by TLC
enes. The stereospecificity and the regioselectivity of this (EtOAc/hexane). The solvent was removed under reduced pressure,
and the crude reaction mixture was purified by column chromatog-
raphy (silica gel, EtOAc/hexane) to give the expected
[{(phenylseleno)ethenyl}sulfinyl]benzene. Reaction times and yields
are shown in Table 1.
reaction contribute to the formation of electron-poor al-
kenes with a well defined stereochemistry at the double
bond. Moreover, the mild conditions adopted for the reac-
tion, without the use of a basic or acidic environment, al-
lows the presence of sensitive substituents on the final α-
(phenylseleno)sulfinyl alkenes. α-(Phenylseleninyl)sulfonyl
alkenes, such as 21, can be easily obtained by oxidation of
the sulfinyl analogues with complete chemoselectivity. Most
importantly, this synthetic pathway involving transient sulf-
enic acids offers easy access to enantiopure α-(phenyl-
seleno)sulfinyl alkenes via enantiopure sulfenic acids. In this
paper we have reported the synthesis of (Z)-1-(phenyl-
seleno)-1-[(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl)-
5-(Phenylseleno)-4-pentyn-1-yl Benzoate (8): Oil; yield 84%. 1H
NMR (200 MHz): δ = 7.9–8.0 (m, 2 H, CHPh), 7.3–7.5 (m, 5 H,
CHPh), 7.1–7.3 (m, 3 H, CHPh), 4.25 (t, Jvic = 6.2 Hz, 2 H, CH2O),
2.54 (t, Jvic = 6.9 Hz, 2 H, CH2Cϵ), 1.97 (tt, 2 H, CH2CH2CH2)
ppm. 13C NMR (50 MHz): δ = 166.5 (C=O), 135.3, 133.7 (2 C),
132.7, 130.3, 129.6 (2 C), 129.5 (2 C), 128.3 (2 C), 128.1, 107.2,
63.8, 62.9, 31.5, 26.8 ppm. C18H16O2Se (343.28): calcd. C 62.98, H
4.70; found C 62.84, H 4.91.
(Z)-[{1-(Phenylseleno)-1-hexen-1-yl}sulfinyl]benzene (9): Racemic
mixture; colourless oil. TLC (silica gel plate, EtOAc/hexane, 5:5):
Rf = 0.74. 1H NMR: δ = 7.6–7.3 (m, 10 H, CHPh), 7.57 (s, 1 H,
sulfinyl]-1-hexene (19) as
a
diastereomeric mixture
(Scheme 2), and other interesting substrates can be pre-
pared starting from suitable precursors of enantiopure sulf-
enic acids. Initial studies on the reactivity of the unsaturated
acceptors 20 or 21 with hard nucleophiles disclose some
interesting features: it occurs with a significant stereocon-
trol, with the opportunity to obtain β-heterosubstituted
α,β-unsaturated sulfoxides, such as 22 and 25, and sulfones,
such as 24. These two classes of compounds are potentially
interesting as starting materials for further transformations,
CH2CH=), 2.2–2.1 (m,
2 H, CH2CH=), 1.2 (m, 4 H,
CH3CH2CH2), 0.80 (t, Jvic = 7.0 Hz, 3 H, CH3) ppm. 13C NMR:
δ = 143.8 and 142.9 (CSC), 133.0, 131.2, 129.6, 129.2, 128.2, and
125.3 (CHPh), 129.3 (SeCPh), 128.7 (CH2CH=), 29.8
(CH2CH2CH2), 27.6 (CH2CH=), 22.5 (CH2CH3), 13.6 (CH3) ppm.
NOESY correlation: CH2CH =/CH2CH=. C18H20OSSe (363.38):
calcd. C 59.50, H 5.55; found C 59.74, H 5.63.
[{1-(Phenylseleno)ethenyl}sulfinyl]benzene (10):[9] Racemic mixture;
yellow oil; m.p. 35 °C.[9] TLC (silica gel plate, EtOAc/hexane, 5:5):
1
for instance the alkylation/hydrolysis of the enamines 24 Rf = 0.54. H NMR: δ = 7.7–7.2 (m, 10 H, CHPh), 6.92 (d, Jgem
=
1.5 Hz, 1 H) and 6.16 (d, 1 H, CH2=) ppm. 13C NMR: δ = 146.6
(SCSe), 142.3 (SCPh), 133.2, 129.4, 129.0, 128.2, 126.3, and 126.0
(CHPh), 131.6 (SeCPh), 126.3 (CH2=) ppm. C14H12OSSe (307.27):
calcd. C 54.72, H 3.94; found C 54.67, H 4.27.
and 25 to obtain β-sulfonyl and -sulfinyl ketones, respec-
tively. Moreover, the suitable transformation of α-(phenyl-
seleno)sulfinyl alkenes, such as enantiopure sulfoxide (SS)-
19, once separated by column chromatography from its sul-
fur epimer, can be regarded as a new methodology for the
synthesis of enantiopure α,β-unsaturated sulfoxides.[22] Fol-
lowing the rationale depicted in Scheme 3, (SS)-19 could be
oxidized to an epimeric mixture of selenoxides, however, the
final product will be enantiopure, owing to the loss of sele-
nium functionality.
(Z)-[{2-Phenyl-1-(phenylseleno)ethenyl}sulfinyl]benzene (11): Race-
mic mixture; white crystals; m.p. 58 °C. TLC (silica gel plate,
EtOAc/hexane, 5:5): Rf = 0.70. H NMR: δ = 7.75 (s, 1 H, CH=),
1
7.6–7.1 (m, 15 H, CHPh) ppm. 13C NMR: δ = 142.8 and 142.1
(CSC), 133.0, 130.9, 129.5, 129.0, 128.9, 128.8, 128.6, 128.2, and
124.8 (CHPh and =CHCPh), 132.2 (=CHCPh), 129.2 (SeCPh) ppm.
C20H16OSSe (383.37): calcd. C 62.66, H 4.21; found C 62.57, H
4.46.
(Z)-[{2-(Trimethylsilyl)-1-(phenylseleno)ethenyl}sulfinyl]benzene
(12): Racemic mixture. Yellow oil. TLC (silica gel plate, EtOAc/
Experimental Section
1
General: Reactions were monitored by TLC on commercially avail-
able precoated plates Aldrich silica gel 60 F 254 or Macherey–Na-
hexane, 5:5): Rf = 0.65. H NMR: δ = 7.92 (s, 1 H, SiCH=), 7.7–
7.2 (m, 10 H, CHPh), 0.23 (s, 9 H, CH3) ppm. 13C NMR: δ = 148.0
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M. C. Aversa, A. Barattucci, P. Bonaccorsi, A. Temperini
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(SCSe), 143.2 (SiCH=), 143.0 (SCPh), 131.4, 130.3, 129.3, 128.8,
127.1, and 126.4 (CHPh), 129.7 (SeCPh), –0.49 (CH3) ppm. NOESY
correlation: SiCH =/CH3. C17H20OSSeSi (379.45): calcd. C 53.81,
H 5.31; found C 53.82, H 5.64.
of 9 was verified by TLC, and the reaction was quenched by adding
a 10% aq. solution of Na2S2O3 (10 mL). The organic layer was
then separated and washed with NaHCO3 (saturated aq. solution,
2ϫ10 mL) and NaCl (saturated aq. solution, 2ϫ10 mL). The or-
ganic phase was dried with Na2SO4 and, after evaporation of the
solvent at reduced pressure, 20 was quantitatively obtained as a 1:1
diasteromeric mixture; colourless oil. TLC (silica gel plate, EtOAc/
hexane, 8:2): Rf = 0.20. 1H NMR: δ = 7.8–7.5 (m, 11 H, CHPh and
CH2CH=), 2.8–2.1 (m, 2 H, CH2CH=), 1.6–1.3 (m, 4 H,
CH3CH2CH2), 0.90 (t, Jvic = 7.2 Hz), 0.85 (t, Jvic = 6.8 Hz, 3 H,
CH3) ppm. 13C NMR: δ = 159.7, 159.5, 141.6, 141.3, and 140.3
(quaternary carbons), 133.7, 132.9, 132.5, 132.2, 131.8, 131.7,
130.3, 130.0, 129.7, 129.6, 126.1, 126.0, and 125.6 (CHPh and
CH2CH=), 32.0, 31.8, 28.1, 27.0, 22.6, and 22.5 (CH2CH2CH2),
13.6 and 13.5 (CH3) ppm. C18H20O2SSe (379.38): calcd. C 56.99,
H 5.31; found C 57.06, H 5.62.
(Z)-2-[2-(Phenylseleno)-2-(phenylsulfinyl)ethenyl]-1H-isoindole-
1,3(2H)-dione (13): Racemic mixture; yellow oil. TLC (silica gel
1
plate, EtOAc/hexane, 5:5): Rf = 0.46. H NMR: δ = 7.9–7.3 (m, 14
H, CHAr), 7.59 (s, 1 H, CH2CH=), 3.58 (t, Jvic = 7.1 Hz, 2 H,
NCH2), 2.22 (m, 2 H, CH2CH=), 1.56 (m, 2 H, CH2CH2CH2)
ppm. 13C NMR: δ = 168.1 (C=O), 142.4 and 142.3 (CSC), 134.0,
133.2, 131.3, 130.2, 129.6, 129.3, 128.3, 125.1, and 123.2 (CHAr and
CH=), 132.0 (CC=O), 128.9 (SeCPh), 37.4 (NCH2), 26.6
(CH2CH=), 25.2 (CH2CH2CH2) ppm. NOESY correlation:
CH2CH=/CH2CH=. C25H21NO3SSe (494.46): calcd. C 60.73, H
4.28, N 2.83; found C 60.49, H 4.56, N 2.92.
(Z)-[{5-(Benzoyloxy)-1-(phenylseleno)-1-penten-1-yl}sulfinyl]benzene
(14): Racemic mixture; colourless oil. TLC (silica gel plate, EtOAc/
hexane, 5:5): Rf = 0.63. 1H NMR: δ = 8.0–7.3 (m, 15 H, CHPh),
7.64 (s, 1 H, CH2CH=), 4.21 (t, Jvic = 5.9 Hz, 2 H, OCH2), 2.34
(m, 2 H, CH2CH=), 1.71 (m, 2 H, CH2CH2CH2) ppm. 13C NMR:
δ = 166.2 (C=O), 142.5 and 142.4 (CSC), 133.1, 132.9, 131.2, 130.7,
129.6, 129.5, 129.2, 128.3, 128.2, and 125.0 (CHPh and CH=), 130.0
(CC=O), 128.7 (SeCPh), 63.8 (OCH2), 26.8 (CH2CH=), 24.5
(CH2CH2CH2) ppm. NOESY correlation: CH2CH=/CH2CH=.
C24H22O3SSe (469.45): calcd. C 61.40, H 4.72; found C 61.39, H
4.97.
(Z)-[{1-(Phenylseleninyl)-1-hexen-1-yl}sulfonyl]benzene (21): A solu-
tion of m-CPBA (80 wt.-%, 89 mg, 0.41 mmol) in CH2Cl2 (5 mL)
was added dropwise to a solution of 20 (155 mg, 0.41 mmol) in
CH2Cl2 (5 mL) at room temperature. After 2 h the disappearance
of 20 was verified by TLC (silica gel plate, CH2Cl2/EtOAc, 6:4),
and the reaction was quenched with 10% aq. solution of Na2S2O3
(10 mL). The organic layer was then separated and washed with
NaHCO3 (saturated aq. solution, 2ϫ10 mL) and NaCl (saturated
aq. solution, 2ϫ10 mL). After drying the solution over Na2SO4
and removing the solvent under reduced pressure, 21 was obtained
quantitatively as racemic mixture; colourless oil. TLC (silica gel
plate, acetone/hexane, 9:1): Rf = 0.60. 1H NMR: δ = 7.8–7.4 (m,
11 H, CHPh and CH2CH=), 2.7–2.4 (m, 2 H, CH2CH=), 1.7–1.3
(m, 4 H, CH3CH2CH2), 0.83 (t, Jvic = 7.3 Hz, 3 H, CH3) ppm. 13C
NMR: δ = 153.0 (SCPh), 142.4 (CH2CH=), 139.5 and 137.6 (CSeC),
134.3, 132.2, 130.2, 129.5, 128.6, and 126.2 (CHPh), 32.3
(CH2CH2CH2), 29.0 (CH2CH=), 22.6 (CH2CH3), 13.5 (CH3) ppm.
C18H20O3SSe (395.37): calcd. C 54.68, H 5.10; found C 54.42, H
5.39.
(E)-[{2-(Phenylseleno)ethenyl}sulfinyl]benzene (15): Racemic mix-
ture; brown oil. TLC (silica gel plate, EtOAc/hexane, 5:5): Rf =
0.50. 1H NMR: δ = 7.71 and 6.28 (AB system, JAB = 11.3 Hz, 2
H, SCH=CHSe), 7.6–7.3 (m, 10 H, CHPh) ppm. 13C NMR: δ =
143.6 (SCPh), 134.6, 131.0, 129.8, 129.3, 129.0, and 124.5 (CHPh),
133.0 and 132.6 (SCH=CHSe), 126.6 (SeCPh) ppm. C14H12OSSe
(307.27): calcd. C 54.72, H 3.94; found C 54.75, H 4.25.
(E)-[{1-Phenyl-2-(phenylseleno)ethenyl}sulfinyl]benzene (16): Com-
pound 16 was detected during the chromatographic purification of
(E)-[(2-Phenoxy-1-hexen-1-yl)sulfinyl]benzene (22): To a solution of
NaH (60% dispersion in mineral oil, 5 mg, 0.13 mmol) in anhy-
drous THF (2 mL) was added a solution of phenol (149 mg,
1.58 mmol) in anhydrous THF (2.5 mL) under argon at room tem-
perature. After about 10 min, a solution of 20 (100 mg, 0.26 mmol)
in anhydrous THF (10 mL) was added. The reaction was followed
by TLC (alumina plate, EtOAc/hexane, 5:5) and stopped after 4 h
by washing the crude mixture with saturated aq. NaCl solution
(10 mL) and extracting the organic phase into Et2O (2ϫ10 mL).
The organic layer was dried with Na2SO4. After evaporation of the
solvent under reduced pressure, column chromatography (alumina,
EtOAc/hexane, 5:95) afforded 22 (49 mg, 0.16 mmol, yield 62%) as
a racemic mixture; colourless oil. TLC (alumina plate, EtOAc/hex-
1
its isomer 11 by observation of a typical H NMR olefinic singlet
at δ = 8.23 ppm and comparison with the spectroscopic data of
sulfoxide 15.
(Z)-1-[(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)sulfinyl]-1-(phen-
ylseleno)-1-hexene (19): A solution of 3 (712 mg, 3.00 mmol) and
17 (581 mg, 1.00 mmol) in CH2Cl2 (13 mL) was heated to reflux
overnight. The solvent was removed under vacuum, and 19 isolated
by column chromatography (silica gel, EtOAc/hexane, 1:9 up to
4:6); yield 50%, sulfur epimeric mixture; colourless oil. TLC (silica
gel plate, EtOAc/hexane, 5:5): Rf = 0.40. 1H NMR: δ = 7.6–7.3 (m,
6 H, CHPh and CH2CH=), 5.4–5.0 (m, 3 H, glucose 2–4-H), 4.37
(d, J1,2 = 9.4 Hz, 1 H, glucose 1-H), 4.18 (m, 2 H, glucose 6-H2),
3.76 (m, 1 H, glucose 5-H), 2.5–2.2 (m, 2 H, CH2CH=), 2.09, 2.04,
2.02, and 2.01 (four s, 12 H, CH3C=O), 1.7–1.3 (m, 4 H,
CH3CH2CH2), 0.98 (t, Jvic = 7.3 Hz, 3 H, CH2CH3) ppm. 13C
NMR: δ = 170.3, 170.0, 169.13, and 169.09 (C=O), 137.8 (SC),
132.7, 129.4, 129.3, and 128.1 (CHPh and CH2CH=), 128.7 (SeCPh),
90.1 (glucose C-1), 76.3, 73.5, 67.3, and 66.8 (glucose C-2–5), 61.6
(glucose C-6), 29.4 (CH2CH2CH2), 28.5 (CH2CH=), 22.5
(CH2CH3), 20.6, 20.5, 20.4, and 20.3 (CH3C=O), 13.6 (CH2CH3)
ppm. C26H34O10SSe (617.57): calcd. C 50.57, H 5.55; found C
50.54, H 5.92.
1
ane, 5:5): Rf = 0.60. H NMR: δ = 7.7–7.6 [m, 2 H, S(O)CHPh(or-
tho)], 7.5–7.0 (m, 9 H, CHPh and CH2C=CH), 2.17 (m, 2 H,
CH2C=), 1.4–1.0 (m, 4 H, CH3CH2CH2), 0.76 (t, Jvic = 7.0 Hz, 3
H, CH3) ppm. 13C NMR: δ = 156.6 (OCPh), 148.1 (SCH=), 142.8
(SCPh), 129.0 (CH2C=), 130.6, 129.9, 129.0, 124.9, 124.4, and 117.1
(CHPh), 30.6 (CH2CH2CH2), 22.5 (CH2CH3), 22.0 (CH2C=), 13.6
(CH3) ppm. NOESY correlation: CH2C=/S(O)CHPh(ortho).
C18H20O2S (300.42): calcd. C 71.96, H 6.71; found C 72.01, H 6.92.
(E)-[{2-(1-Piperidinyl)-1-hexen-1-yl}sulfonyl]benzene (24): To 21
(100 mg, 0.25 mmol) dissolved in anhydrous THF (1 mL) was
added piperidine (150 μL, 1.52 mmol) under argon. After 4 h the
(Z)-[{1-(Phenylseleninyl)-1-hexen-1-yl}sulfinyl]benzene (20): A solu-
tion of m-CPBA (80 wt.-%, 149 mg, 0.69 mmol) in CH2Cl2 (5 mL) total disappearance of 21 was verified by TLC (alumina plate,
was added dropwise to a solution of 9 (251 mg, 0.69 mmol) in EtOAc/hexane, 3:7). After removal of the solvent under reduced
CH2Cl2 (5 mL) at room temperature. After 2 h the disappearance
pressure, 24 was purified by column chromatography (alumina,
5672
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Eur. J. Org. Chem. 2011, 5668–5673

Synthesis of (Z)-α-(Phenylseleno)sulfinyl and -sulfonyl Alkenes
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Yellow oil. TLC (alumina plate, EtOAc/hexane, 8:2): Rf = 0.80. H
1
NMR: δ = 7.8–7.4 (m, 6 H, CHPh and NC=CH), 3.32 (m, 4 H,
CH2 NCH2 ), 2.15 (m, 2 H, CH2 C=), 1.6–1.2 (m, 10 H,
CH3CH2CH2 and NCH2CH2CH2CH2), 0.78 (t, Jvic = 7.3 Hz, 3 H,
CH3) ppm. 13C NMR: δ = 145.4 (=CHS), 143.2 (SCPh), 131.5,
128.6, and 127.1 (CHPh), 102.8 (NC), 51.6 (NCH2), 32.6, 26.1, 25.5,
24.0, and 22.5 (butyl CH2 and NCH2CH2CH2CH2), 13.6 (CH3)
ppm. C17H25NO2S (307.45): calcd. C 66.41, H 8.20, N 4.56; found
C 66.03, H 8.59, N 4.52. Sulfone 24 was obtained quantitatively by
m-CPBA oxidation of 25.
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(E)-[{2-(1-Piperidinyl)-1-hexen-1-yl}sulfinyl]benzene (25): To 20
(80 mg, 0.21 mmol) dissolved in anhydrous THF (0.8 mL) was
added piperidine (122 μL, 1.23 mmol). The reaction was performed
under argon at room temperature in the presence of 3 Å molecular
sieves. After 24 h, 20 was completely transformed, as verified by
TLC (alumina plate, acetone/hexane, 6:4). After evaporation of the
solvent under reduced pressure, the crude reaction mixture was
purified by column chromatography (alumina, acetone/hexane,
0.5:9.5), and 25 was obtained (40 mg, 0.14 mmol, yield 65%) as a
racemic mixture; yellow oil. TLC (alumina plate, acetone/hexane,
9:1): Rf = 0.80. 1H NMR: δ = 7.6–7.5 [m, 2H CHPh(ortho)] 7.4–7.3
(m, 3 H, CHPh), 6.70 (s, 1 H, NC=CH), 3.3 (m, 4 H, CH2NCH2),
2.2–1.9 (m, 2 H, CH2CH=), 1.6–0.8 (m, 10 H, CH3CH2CH2 and
NCH2CH2CH2CH2), 0.70 (t, Jvic = 7.3 Hz, 3 H, CH3) ppm. 13C
NMR: δ = 145.5 (=CHS), 145.2 (SCPh), 129.4, 128.4, and 125.1
(CHPh), 110.8 (NC), 51.3 (NCH2), 25.9, 24.1, 22.9, 22.5, and 22.4
(butyl CH2 and NCH2CH2CH2CH2), 13.5 (CH3) ppm. NOESY
correlation: NC=CH/CH2NCH2. C17H25NOS (291.45): calcd. C
70.06, H 8.65, N 4.81; found C 69.91, H, 8.97, N 4.79.
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Acknowledgments
We are grateful to the Ministero dell’Istruzione, dell’Università e
della Ricerca and the University of Messina, Italy, for financial
support (PRIN 2008).
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Received: May 30, 2011
Published Online: August 29, 2011
Eur. J. Org. Chem. 2011, 5668–5673
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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