A recyclable biphasic system for stereoselective and easily handled hydrochalcogenations

Article abstract of DOI:10.1002/ejoc.201402668

Vinyl selenides and vinyl sulfides were prepared by hydrochalcogenation of alkynes with selenols and thiols generated in situ by the reduction of the corresponding diselenides and disulfides with elemental zinc in a biphasic acidic medium. The yields, ste

Full text of DOI:10.1002/ejoc.201402668

FULL PAPER
DOI: 10.1002/ejoc.201402668
A Recyclable Biphasic System for Stereoselective and Easily Handled
Hydrochalcogenations
Caterina Tidei,[a][‡] Luca Sancineto,[a][‡] Luana Bagnoli,[a] Benedetta Battistelli,[a]
Francesca Marini,[a] and Claudio Santi*[a]
Dedicated to C.I.N.M.P.I.S. on the occasion of its 20th anniversary
Keywords: Waste prevention / Chalcogens / Selenium / Sulfur / Zinc / Alkynes
Vinyl selenides and vinyl sulfides were prepared by hydro- disulfides with elemental zinc in a biphasic acidic medium.
chalcogenation of alkynes with selenols and thiols generated
in situ by the reduction of the corresponding diselenides and
The yields, stereoselectivity as well as the possibility of re-
using the aqueous medium up to ten times are discussed.
terials that are not readily available;[8] the hydrochalco-
genation of alkynes represents the most direct and conve-
nient method for their preparation. The first example, re-
ported by Sharpless and Laurer, involved the use of a boron
complex [Na(PhSeB(OEt)3)] as nucleophile, which was gen-
erated in situ by reduction of diphenyl diselenide with so-
dium borohydride in ethanol.[9] The nucleophilic addition
of PhSeH to alkynes leads to the selective formation of the
Z-anti-Markovnikov isomer but the reaction proceeds very
slowly and requires several days to reach completion at
room temperature. Higher temperature (120 °C) can be
used to increase the reaction rate but, in this case, a drastic
loss of stereoselectivity was generally observed.[10]
When the chalcogen is a sulfur atom, the reaction can be
accelerated by the inclusion of radical activators, affording
diastereomeric mixtures of E/Z isomers with a slight excess
of the E isomer.[8]
Selenols, even more than thiols, are known as unpleasant
and malodorous compounds and their stability in air is
strongly limited by rapid oxidation to the corresponding
diselenides. For these reasons the latter compounds are
preferentially used as precursors for the preparation of sele-
nols in situ by using several methods for the reductive cleav-
age of the selenium–selenium bond including LiAlH4,
NaBH4, Na/NH3, Bu3SnH, Zn/NaOH, Zn/AlCl3, and Zn/
RuCl3.[11]
Introduction
The chemistry of organochalcogen compounds has de-
veloped rapidly over the past few years, and organoselen-
ium as well as organosulfur derivatives are now powerful
tools in the hands of chemists as reagents, catalysts, and
intermediates. A number of books and paper reviews have
recently appeared that describe the synthesis and the
synthetic application of a large series of organochalcogen-
ides,[1a–i] as well as their biological activity.[1j–1l] Among
these compounds, vinyl selenides and sulfides play an im-
portant role as starting materials for the stereoselective
preparation of functionalized alkenes and other deriva-
tives.[2] Although a series of methods are available for their
preparation, the development of new efficient, stereoselec-
tive, and environmentally friendly procedures remain an
interesting target especially methodologies involving nucle-
ophilic selenium reagents. In this context, we recently intro-
duced the synthesis of phenylchalcogen zinc halides.[3] This
class of bench-stable reagents could be successfully em-
ployed in nucleophilic substitution of alkyl, vinyl, and acyl
halides,[4] Michael-type addition reactions,[5] ring opening
of epoxides,[4a] as well as thiol oxidation,[6] showing, in all
the cases, an interesting rate acceleration when effected in
on-water conditions at room temperature.[7]
Many syntheses of vinyl sulfides, selenides, and tellurides
involve the use of expensive catalysts or require starting ma-
We recently demonstrated that in a biphasic acidic sys-
tem, zinc reduces diselenides to form aliphatic and aromatic
selenols that can be trapped by electrophiles such as epox-
ides, alkyl halides,[12] and, as reported by Braga and co-
workers, unprotected aziridines.[13]
[a] Department of Pharmaceutical Sciences, University of Perugia,
Via del Liceo 1, 06100 Perugia, Italy
E-mail: claudio.santi@unipg.it
http://www.unipg.it/pagina-personale?matricola=004434
[‡] These two authors contributed equally to this work.
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402668.
Very recently, the same protocol has been applied to the
solid-phase synthesis of cysteine- and selenocysteine-con-
5968
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 5968–5975

Stereoselective Hydrochalcogenations
taining peptides starting from the corresponding dichalco- tocol; hydrotelluration of alkynes is known to proceed
genide precursors.[14]
slowly in ethanol heated to reflux with a reaction time that
Here, we report an extension of our methodology for the strongly depends on the substrate (ranging from 2 to
synthesis of vinyl selenides and vinyl sulfides through 72 h).[15]
stereoselective hydrochalcogenation of terminal and in-
When the hydroselenenylation of phenylacetylene 1a was
ternal alkynes, highlighting the possibility of increasing the performed using diselenide 11,[16] vinyl selenide 13a was iso-
green aspects of the process by reducing waste production lated in good yield and Z/E ratio, indicating that the reac-
through the efficient reuse (5–10 times) of the aqueous reac- tivity as well as the stereoselectivity was only slightly ef-
tion medium.
fected by steric bulk and by the inductive effect of the iso-
propyl groups. Similarly, the presence of electron-with-
drawing groups such as the trifluoromethyl moiety in dis-
elenide 12,[17] seems to be well tolerated, affording the de-
sired vinyl selenide 14a in good yield (66%) and only
slightly reduced Z/E ratio, (83:17, Scheme 2) highlighting
the broad and general applicability of the proposed proto-
col.
Results and Discussion
We started our investigation by evaluating the hydro-
chalcogenation of phenylacetylene 1a by using PhSeH (5),
PhSH (6), and PhTeH (7) generated in situ by zinc re-
duction of the corresponding dichalcogenides 2–4 in the bi-
phasic system. Compounds 2–4 are commercially available
and were treated with an excess of zinc shavings (10 equiv.
relative to dichalcogenide) in a 1:1 mixture of HCl (aq.
10%) and Et2O at room temperature. The decoloration of
the organic layer indicated complete formation of chalco-
genols 5 and 7, whereas in the case of colorless disulfide
2, we chose an initial arbitrary reduction time of 15 min.
According to our previously proposed mechanism,[12] di-
chalcogenides are reduced by zinc under acidic conditions
to give a metal chalcogenate complex that can be proton-
ated to afford simultaneously the reactive chalcogenols and
the Lewis acid ZnCl2; the species are distributed in the bi-
phasic system on the basis of their relative solubility. After
the formation of the chalcogenol, 1a (1 equiv.) was added
and the biphasic mixture was stirred at 800 rpm for 1 h in
a closed vial (Scheme 1). The reactions afforded, in the case
Scheme 2. Hydroselenenylation by using diselenides 11 and 12.
On the basis of these preliminary results and considering
of selenol 5 and thiol 6, the stereoselective and almost that the main target of our work was the development of a
quantitative formation of vinyl selenide (Z)-8a and vinyl simple, cost-effective and environmentally friendly protocol
sulfide (Z)-9a, respectively.
for the synthesis of vinyl chalcogenides, we decided to inves-
Under similar conditions, the decoloration of the ethe- tigate further the reactivity of the commercially available
real solution of diphenyl ditelluride 4, led us to suppose dichalcogenides 2 and 3.
that it was reduced to the corresponding tellurol 7 but we
To explore the scope of the hydroselenenylation reaction,
did not observed any reaction with alkyne 1a even after a range of functionalized alkynes 1a–f were subjected to the
extended reaction time (48 h). This result is not surprising best reaction conditions optimized for 1a; the results are
considering the mild reaction conditions applied in our pro- summarized in Table 1.
Scheme 1. Hydrochalcogenation reactions.
Eur. J. Org. Chem. 2014, 5968–5975
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5969

C. Santi et al.
FULL PAPER
Table 1. Hydroselenenylation of alkynes 1a–f.
of PhSeH to the triple bond with the stereoselective forma-
tion of the Z isomer (Z)-8a–f.
The isomeric ratios were determined by 1H NMR
analysis of the freshly obtained crude material, and the re-
ported yields were calculated based on the amount of iso-
lated products. The structures were assigned, after chroma-
tographic purification, on the basis of the GC–MS, 1H and
13C NMR analyses; in some cases, the E and Z isomers
were not separated and the relative spectra were assigned
by comparison with previously reported data, as indicated
in the Supporting Information. The geometries of the tri-
substituted olefins 8d and 8f were confirmed based on the
results of NOESY experiments.
By using a similar protocol and the same alkynes 1a–f,
we also explored the scope of the hydrothiolation reaction.
The results, reported in Table 2, were obtained by reducing
the commercially available colorless diphenyl disulfide by
using the previously discussed conditions for 15 min and
then adding the substrate, allowing the reaction to proceed
at room temperature for 1 h.
Table 2. Hydrothiolation of alkynes 1a–f.
[a] Reaction time 24 h. [b] The isomeric ratios were determined by
1H NMR analysis of the crude mixture.
In most cases, the reaction was found to be very fast at
room temperature, affording the addition products 8a–f in
1 h in moderate (entries d and f) to good yields (entries a–
c and e). In the case of nonterminal alkynes, 1d and 1f,
after 1 h, a large amount of starting material was recovered.
To increase the conversion, the reaction time was extended
to 24 h, which led to a clear enhancement of the yields,
albeit accompanied by a slightly detrimental effect on the
stereoselectivity (Table 1 entries d and f). This can reason-
ably be assumed to be due to a partial isomerization of
the initially formed Z isomer under the applied reaction
conditions. When the substrate is a terminal alkyne, this
isomerization should be much more favored due to the
higher thermodynamic stability of the E isomer compared
with the Z isomer. By carrying out the hydroselenenylation
of 1a with a reaction time of 24 h, vinyl selenide 8a was
isolated in a Z/E ratio of 61:39, confirming that the isomer-
ization occurs during the reaction (Table 1, entry a).
For the same selenide [(Z)-8a], a spontaneous and almost
complete isomerization to the E isomer was also observed
after storage at room temperature for several days (see the
Supporting Information).
[a] The isomeric ratios were determined by 1H NMR analysis of
the crude material.
These reactions proceeded in moderate to good yields
Interestingly, functional groups that are potentially sus- and were found to be generally less stereoselective than the
ceptible to radical reduction (e.g., 1d) or hydrolysis (e.g., corresponding hydroselenenylations, leading to vinyl sulf-
1e and 1f) were found to be compatible with the proposed ides (Z)-9a–f as the major isomer.
protocol, affording the corresponding vinyl selenides in
In the case of substrate 1d, the 1H NMR spectrum of the
good yields and stereoselectivity. It is reasonable to specu- crude material revealed the formation of a complex mixture
late that the selenium–carbon bond is not cleaved by zinc, of addition products (four broad singlets from 7 to
whereas the biphasic system and the relatively low tempera- 6.5 ppm), which were not separated by chromatography. Be-
ture (room temperature) prevent hydrolysis even in the pres- sides the desired products 9d, GC–MS analysis indicated
ence of HCl and water.
the presence of olefins 1,2-disubstituted with PhSe groups
In all cases, the reaction proceeded according to an anti- (m/z 396) and PhS groups (m/z 300), probably arising from
Markovnikov orientation, mainly based on a trans addition a competitive chalcogen to chalcogen reaction that affords
5970
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 5968–5975

Stereoselective Hydrochalcogenations
the formation of both PhSeH and PhSH in situ through the results reported in Table 3 the amount of zinc chloride
intermediate PhSeSPh.
seems to effectively enhance the formation of the E isomer.
It is interesting to observe that in the biphasic medium,
PhSH affords the E isomer as the major product (Table 3,
entry e). This suggests that, under the conditions depicted
in Table 3, entries a–d, the reactive species is not simply the
benzenethiol but, probably, its complex with the metal.
Similar investigations have also been carried out for the
hydroselenenylation of 1a, but different combinations of re-
duction conditions [Zn (5 equiv.), 3 h; Zn (10 equiv.), 3 h;
Zn (20 equiv.), 1 h; Zn (50 equiv.), 1 h; Zn (150 equiv.),
15 min] afforded in all the cases the quantitative formation
of 8a in a Z/E ratio of 90:10. This indicated that the hydro-
selenylation reaction was not influenced by the amount of
zinc chloride eventually formed.
Neither hydroselenenylation nor hydrothiolation of pyr-
idyl derivative 1g proceeded in the biphasic system of HCl
(aq. 10%)/Et2O, therefore the reaction was attempted using
acetic acid as reaction medium. In both cases, the initially
formed conjugated vinyl chalcogenides (8g and 9g) could
be reduced by Zn/AcOH[18,19] in a homogeneous solution
leading to the saturated 2-phenylselenenylethyl pyridine 15
and the 2-phenylmercaptoethyl pyridine 16, respectively, as
the main product (Scheme 3).
The geometry of (Z)-9f was confirmed by the observa-
tion of an Overhauser correlation between the olefinic pro-
ton and the OMe group.
A considerable amount of disulfide 3 was recovered from
all the reactions after chromatographic purification; to
achieve complete formation of the reactive thiol 6, the reac-
tion was repeated by using different reduction time before
the addition of 1a. Interestingly, we observed that when the
phenylacetylene was added to the biphasic system 15 min
later than the disulfide 3, the anti-Markovnikov vinyl
selenide 9a was obtained in a Z/E ratio of 88:12 (Table 3
entry a). For longer reduction times of 1 and 3 h, respec-
tively, reduced selectivity was observed, affording 9a in
Z/E ratios of 80:20 and 71:29, respectively (Table 3, en-
tries b and c).
Table 3. Influence of ZnCl2 on the hydrothiolation 1a.
The workup of the reactions reported in Tables 1 and 2
was straightforward; it involved simply separation of the
organic layer from the biphasic medium followed by the
evaporation of the diethyl ether under reduced pressure.
The acidic water and the unreacted zinc could be recovered
and reused for subsequent reactions.
Considering the growing interest in synthetic procedures
that minimize the amount of waste production, we investi-
gated the recyclability of this aqueous medium by measur-
ing the efficiency in terms of chemical yields for the hydro-
selenenylation of 1a for a number of subsequent reactions.
We started the recycling investigation by using diluted
Entry Reagents (equiv.)[a]
Reduction time
[min]
Yield
[%]
Z/E[b]
a
b
c
d
e
f
(PhS)2 (0.5), Zn (5)
(PhS)2 (0.5), Zn (5)
(PhS)2 (0.5), Zn (5)
(PhS)2 (0.5), Zn (20)
PhSH (1)
15
60
180
15
–
75
74
88
70
99
99
88:12
80:20
71:29
73:27
27:73
15:85
PhSH (1), ZnCl2 (10)
–
[a] Reactions performed at room temp. with HCl (aqueous, 10%)/
Et2O. [b] The isomeric ratios were determined by 1H NMR spectro-
scopic analysis of the crude mixture.
These results led us to suppose that the E-selectivity is
probably favored by the ZnCl2 produced as side product by conditions (0.1 mmol) of diphenyl diselenide in the biphasic
the oxidation of the zinc in the presence of aqueous hydro- system HCl(aq.10%)/Et2O (2+2 mL), to obtain rapid re-
chloric acid. To test this hypothesis, we effected the hydro- duction of the diselenide in the presence of a large excess
thiolation of 1a by using a larger amount of elemental zinc of zinc (30 mmol) minimizing the uncontrolled side reaction
(Table 3, entry d) as well as by using commercially available of zinc with aqueous HCl. The reuse of the aqueous me-
PhSH in the absence and presence of ZnCl2 in the biphasic dium, as it is, afforded the hydroselenenylation of 0.2 mmol
acidic medium (Table 3, entries e and f). On the basis of the 1a (method A) in good yield for three cycles, with a rapid
1
Scheme 3. Hydrochalcogenation of 1g; the mixtures were not separated and were analyzed by H NMR and GC–MS.
Eur. J. Org. Chem. 2014, 5968–5975
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5971

C. Santi et al.
FULL PAPER
and progressive decrement starting from the fourth cycle. ration of benzenselenol and benzenthiol in situ starting
We supposed that the loss of performance was correlated from the corresponding commercially available dichalco-
to the consumption of the hydrochloric acid. The addition genides. These reagents react readily in a biphasic system
of 0.2 mmol HCl after each reaction (Method B) balanced with variously substituted alkynes, leading to the stereose-
the stoichiometric consumption without considering the lective formation of vinyl selenides and sulfides in good
side reaction of zinc with HCl. This allowed good conver- yields. Interestingly, the presence of the metal forces the re-
sion of 1a into 8a for ten consecutive cycles, as summarized action to form predominantly the Z isomer for both hydro-
in Figure 1 (overall yield 88%).
selenenylation and hydrothiolation, with higher stereoselec-
tivity observed with selenium. The recyclability of the aque-
ous reaction medium together with the unreacted zinc has
been investigated and optimized, which represents an inter-
esting aspect of the proposed protocol in terms of waste
minimization, and reaction design and efficiency.
Experimental Section
General Experimental: Reactions were conducted in closed vials
and were stirred with Teflon-coated magnetic stirring bars. Solvents
and reagents were used as received unless otherwise noted. Analyti-
cal thin-layer chromatography (TLC) was performed on silica gel
60 F254 precoated aluminum foil sheets and visualized by UV irra-
diation or by KMnO4 staining. Silica gel Kieselgel 60 (70–
230 mesh) was used for column chromatography. NMR experi-
ments were conducted at 25 °C with a Bruker DPX 200 spectrome-
ter operating at 200 MHz for 1H, 50.31 MHz for 13C, and
94.07 MHz for 19F experiments or with a Bruker DRX spectrome-
1
ter operating at 400 MHz for H and 100.62 MHz for 13C experi-
ments. 1H and 13C chemical shifts (δ) are reported in parts per
million (ppm), relative to TMS (δ = 0.0 ppm) and the residual sol-
vent peak of CDCl3 (δ = 7.26 and 77.00 ppm in 1H and 13C NMR,
respectively). Data are reported as: chemical shift (multiplicity, cou-
pling constants where applicable, number of hydrogen atoms, and
assignment where possible). Abbreviations are: s (singlet), d (doub-
let), t (triplet), q (quartet), dd (doublet of doublet), dt (double of
triplet), tt (triplet of triplet), m (multiplet), br. s (broad signal).
Coupling constant (J) quoted in Hertz (Hz) to the nearest 0.1 Hz.
GC–MS analyses were carried out with an HP-6890 gas chromato-
graph (dimethyl silicone column, 12.5 m) equipped with an HP-
5973 mass-selective detector. Alkynes 1a–c and 1f are commercially
available and were used without further purification, 1-phenyl-
selenyl-1-hexyne (1e) and 2-ethinyl-pyridine (1g) were synthesized
according to a reported procedure.[20]
Figure 1. Recyclability of the unreacted zinc in the aqueous reac-
tion medium.
Interestingly the Z/E ratio remained almost unaltered in
all the cycles (90:10), confirming that zinc chloride has no
effect on the stereoselectivity when the chalcogen is selen-
ium.
With the optimized conditions in hand, the scalability of
the protocol was evaluated by effecting in five cycles the
one-gram-scale synthesis of 8a. Each cycle was performed
with diphenyl diselenide 2 (0.5 mmol) and 1a (1 mmol) in
Et2O (2 mL), recycling the mixture of aqueous HCl (2 mL)
and unreacted zinc. The diethyl ether used as organic me-
dium in the biphasic system and for the extraction of the
products could be almost quantitatively recovered by distil-
Elemental analyses were carried out with a Carlo–Erba 1106 ele-
mental analyzer.
General Procedure for the Hydrochalcogenation Reaction: Diphenyl
diselenide (2) or diphenyl disulfide (3) (0.5 mmol) was poured into
a biphasic system composed of Et2O (2 mL) and HCl (aq. 10%,
2 mL) and zinc shavings (5 equiv.) were added. The mixture was
vigorously stirred (800 rpm) in a closed vial either until decol-
lation. Interestingly it was not necessary to increase the oration of the organic layer or for 15 min in the case of colorless
disulfides. Alkyne 1a–f (1 mmol) was added and the mixture was
stirred at room temperature for 1 h. The organic phase was sepa-
rated, dried with Na2SO4, filtered and the solvent was removed
under vacuum. The isomeric ratios were calculated by 1H NMR
spectroscopic analysis of the crude mixture, which was sub-
sequently purified by column chromatography on silica gel. In
some cases, isomeric mixtures could not be resolved and 1H and
13C NMR signals were assigned from the spectra of the mixtures
by comparison with the reported data. Physical and spectroscopic
data of the following products are identical to those previously re-
amount of zinc (30 mmol), and 8a (Z/E ratio 90:10) was
obtained in 95% overall yield after five cycles by the ad-
dition of 37% HCl (1 mmol) after each cycle to balance its
stoichiometric consumption (see the Supporting Infor-
mation).
Conclusions
We have demonstrated that zinc in acidic conditions
could be conveniently used as reducing agent for the prepa- ported: (E)-9a,[21] (Z)-9a,[22] (Z)-8a,[22] (E)-8a,[23] (Z)-9b,[22] (E)-
5972
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 5968–5975

Stereoselective Hydrochalcogenations
9b,[21] (E)-8b,[24] (Z)-8b,[24] (E)-9c,[25] (Z)-9c,[25] (E)-8c,[23] (Z)-8d,[26]
GC–MS: m/z (%) = 386 (83) [M+], 343 (17), 301 (28), 282 (52), 267
(E)-8d,[26] (E)-9e,[27] (Z)-9e,[27] (E)-8e,[28] (Z)-8e,[28] (E)-9f,[29] (Z)- (57), 239 (75), 211 (30), 197 (100), 183 (26), 143 (23), 128 (36), 115
9f,[29] (E)-8f,[30] (Z)-8f.[30]
(30), 104 (33), 91 (90), 77 (38). C23H30Se (385.45): calcd. C 71.67,
H 7.85; found C 71.69, H 7.79.
In the case of 2-ethinylpyridine (1g), diphenyl diselenide (2;
0.5 mmol) was poured in AcOH (2 mL), and zinc shavings
(5 equiv.) were added. The mixture was stirring in a closed vial until
the decoloration of the solution, then alkyne 1g (1 mmol) was
added and the mixture was stirred at room temperature for 4 h.
The solution was poured in NaOH (aq. 10%, 10 mL) and extracted
with diethyl ether (3ϫ 3 mL). The crude mixture was not separated
and the final ratios were determined by 1H NMR and GC–MS
analyses.
1-Styrylselenyl-3,5-bis(trifluoromethyl)benzene (14a): Isolated by
flash-chromatography (silica gel, petroleum ether) as Z/E mixture
(93:7), yield 66% (0.261 g); oil.
Major Isomer (Z)-14a: 1H NMR (200 MHz, CDCl3, 298 K, TMS):
δ = 7.85 (br. m, 2 H, CH-Ar), 7.67 (br. m, 1 H, CH-Ar), 7.35–7.20
3
(m, 5 H, CH-Ar), 7.06 (d, JH,H = 10.3 Hz, 1 H, CH=), 6.60 (d,
3JH,H = 10.3 Hz, 1 H, CH=) ppm. 19F NMR (94.07 MHz, CDCl3,
298 K, TFA
(100.62 MHz, CDCl3, 298 K, TMS): δ = 139.9, 136.5, 134.5, 132.32
= –76.55 ppm): δ =
–62.98 ppm. 13C NMR
Recycling of the Aqueous Reaction Medium: Diphenyl diselenide (2;
0.1 mmol) was poured into a biphasic solution composed by Et2O
(2 mL) and HCl (aq. 10%, 2 mL), and zinc shavings (30 mmol)
were added. The mixture was vigorously stirred (800 rpm) in a
closed vial until the decoloration of the organic layer (15 min), then
alkyne 1a (0.2 mmol) was added and the reaction was stirred at
room temperature for 1 h. The organic phase was separated, dried
with Na2SO4, filtered, and the solvent was removed and recovered
by distillation under vacuum. The water and the unreacted zinc
were reused for the subsequent cycle after the addition of HCl (aq.
37%, 0.2 mmol).
2
3
5
(q, JC,F = 33.3 Hz, Cipso), 131.76 (qq, JC,F = 3.8, JC,F = 1.2 Hz,
CH-Ar),128.5, 128.3, 128.0, 122.6 (q, 1JC,F = 228.0 Hz, CF3), 121.1
(sept, 3JC,F = 3.9 Hz, CH-Ar), 120.1 ppm. GC–MS: m/z (%) = 396
(100) [M+], 316 (82), 246 (35), 182 (16), 102 (42), 91 (23), 77 (61), 51
(24). C16H10F6Se (395.20): calcd. C 48.63, H 2.55; found C 48.62, H
2.50.
Minor Isomer (E)-14a: 19F NMR (94.07 MHz, CDCl3, 298 K, TFA
= –76.55 ppm): δ = –61.95 ppm. GC–MS: m/z (%) = 396 (100)
[M+], 316 (84), 246 (35), 182 (16), 102 (44), 91 (24), 77 (60), 51
(22).
One-Gram-Scale Synthesis of 8a Reusing Aqueous Medium: Di-
phenyl diselenide (2; 0.5 mmol) was poured into a biphasic solution
composed of Et2O (2 mL) and HCl (aq. 10%, 2 mL), and zinc shav-
ings (30 mmol) were added. The mixture was vigorously stirred
(800 rpm) in a closed vial until the decoloration of the organic layer
(15 min), then alkyne 1a (1.0 mmol) was added and the mixture
was stirred at room temperature for 1 h. The organic phase was
separated and the aqueous phase was extracted with diethyl ether
(2ϫ 2 mL). The collected organic fractions were dried with
Na2SO4, filtered, and the solvent was distilled under vacuum. The
water and the unreacted zinc were reused for four subsequent cycles
by the addition of HCl 37% (85 μL, 1.0 mmol). Compound 8a was
obtained as a pure Z/E mixture (90:10) in 95% yield without the
need for further purification.
(4-Methoxystyryl) Phenyl Selenide (8b): Isolated by flash-
chromatography (silica gel, petroleum ether) as Z/E mixture
(79:21), yield 0.197 g (68%); white solid; m.p. 66–69 °C.
Major Isomer (Z)-8b:[24] 1H NMR (200 MHz, CDCl3, 298 K,
TMS): δ = 7.74–7.55 (m, 2 H, CH-Ar), 7.42–7.27 (m, 5 H, CH-Ar),
3
6.97–6.93 (m, 3 H, CH-Ar and CH=), 6.67 (d, JH,H = 10.3 Hz, 1
H, CH=), 3.85 (s, 3 H, OCH3) ppm. 13C NMR (100.62 MHz,
CDCl3, 298 K, TMS): δ = 158.7, 132.5, 131.7, 129.9, 129.7, 129.6,
129.2, 127.3, 121.2, 113.7, 55.2 ppm. GC–MS: m/z (%) = 290 (30)
[M+], 210 (100), 195 (19), 165 (22), 89 (25), 77 (25).
Minor Isomer (E)-8a:[24] Identified and measured on the basis of
1
some characteristic H NMR signals that did not present overlaps
3
with those of the major isomer: δ = 7.04 (d, JH,H = 15.7 Hz, 1 H,
CH=) and δ = 3.83 (s, 3 H, OCH3) ppm.
Phenyl Styryl Selenide (8a): Purified by flash-chromatography (sil-
ica gel, petroleum ether) as Z/E mixture 90:10, yield 0.215 g (95%);
colorless oil.
(Z)-(4-Bromostyryl) Phenyl Selenide [(Z)-8c)]:[23] Isolated by flash-
chromatography (silica gel, petroleum ether) as the pure Z isomer,
yield 0.294 g (87%); oil. 1H NMR (400 MHz, CDCl3, 298 K,
TMS): δ = 7.66–7.51 (m, 4 H, CH-Ar), 7.38–7.29 (m, 5 H, CH-
Ar), 6.93 (d, 3JH,H = 10.5 Hz, 1 H, CH=), 6.85 (d, 3JH,H = 10.5 Hz,
1 H, CH=) ppm. 13C NMR (100.62 MHz, CDCl3, 298 K, TMS):
δ = 136.1, 132.7, 131.4, 131.2, 129.8, 129.3, 128.8, 127.7, 125.1,
121.0 ppm. GC–MS: m/z (%) = 340 (59) [M + 2], 338 (60) [M+],
337 (73), 260 (62), 259 (50), 258 (65), 178 (100), 157 (10), 102 (68),
77 (27), 51 (26).
Major Isomer (Z)-8a:[22,23] 1H NMR (200 MHz, CDCl3, 298 K,
TMS): δ = 7.75–7.70 (m, 2 H, CH-Ar), 7.50–7.44 (m, 4 H, CH-
3
Ar), 7.40–7.30 (m, 4 H, CH-Ar), 7.07 [d, JH,H = 10.4 Hz, 1 H,
3
CH=], 6.88 (d, JH,H = 10.4 Hz, 1 H, CH=) ppm. 13C NMR
(100.62 MHz, CDCl3, 298 K, TMS): δ = 137.3, 132.7, 131.7, 130.1,
129.4, 128.4, 128.3, 127.7, 127.3, 124.0 ppm. GC–MS: m/z (%) =
260 (80) [M+], 212 (63), 179 (100), 165 (34), 102 (27), 77 (57).
Minor Isomer (E)-8a):[22,23] 1H NMR (200 MHz, CDCl3, 298 K,
1,1Ј-[(1Z)-Hex-1-ene-1,2-diylbis(seleno)]dibenzene (8d):[26] Isolated
by flash-chromatography (silica gel, petroleum ether) as pure Z iso-
3
TMS): δ = 7.75–7.25 (m, 11 H, CH-Ar and CH=), 6.95 (d, JH,H
= 15.8 Hz, 1 H, CH=) ppm.
1
mer, yield 0.178 g (45%); oil. H NMR (400 MHz, CDCl3, 298 K,
(Z)-2-Phenylvinyl 2,4,6-Triisopropylphenyl Selenide (13a): Isolated
by flash-chromatography (silica gel, petroleum ether) as pure Z iso-
TMS): δ = 7.65–7.50 (m, 4 H, CH-Ar), 7.35–7.25 (m, 6 H, CH-
3
Ar), 6.96 (s, 1 H, CH=), 2.31 (t, JH,H = 7.3 Hz, 2 H, CH2), 1.50
1
mer, yield 0.302 g (78%); oil. H NMR (400 MHz, CDCl3, 298 K,
3
3
3
(tt, JH,H = 7.3, JH,H = 7.6 Hz, 2 H, CH2), 1.26 (tq, JH,H = 7.3,
3JH,H = 7.6 Hz, 2 H, CH2), 0.85 (t, 3JH,H = 7.3 Hz, 3 H, CH3) ppm.
13C NMR (100.62 MHz, CDCl3, 298 K, TMS): δ = 136.2, 132.8,
132.5, 131.1, 129.4,129.2, 129.1, 127.9,127.3, 127.2, 39.5, 31.0,
21.8,13.7 ppm. GC–MS: m/z (%) = 396 (75) [M+], 314 (28), 234
(23), 195 (37), 183 (79), 157 (90), 129 (34), 116 (77), 77 (100).
3
3
TMS): δ = 7.58 (d, JH,H = 7.3 Hz, 2 H, CH-Ar), 7.47 (t, JH,H
=
3
7.3 Hz, 2 H, CH-Ar), 7.31 (t, JH,H = 7.5 Hz, 1 H, CH-Ar), 7.15
3
(s, 2 H, CH-Ar), 6.90 (d, JH,H = 10.5 Hz, 1 H, CH=), 6.50 (d,
3JH,H = 10.5 Hz, 1 H, CH=),3.89 (sept, JH,H = 6.8 Hz, 2 H, CH-
3
3
3
iPr), 3.03 (sept, JH,H = 6.8 Hz, 1 H, CH-iPr), 1.35 (d, JH,H
=
6.8 Hz, 6 H, CH3), 1.30 (d, JH,H = 6.8 Hz, 12 H, CH3) ppm. 13C
NMR (100.62 MHz, CDCl3, 298 K, TMS): δ = 152.6, 150.2, 137.7,
128.8, 128.4, 128.3, 127.7, 126.8, 121.9, 34.2, 34.1, 24.3, 23.9 ppm.
3
(Z)-Ethyl 3-(Phenylselanyl)acrylate (8e):[28] Isolated by flash-
chromatography (silica gel, petroleum ether/diethyl ether, 9:1) as
Eur. J. Org. Chem. 2014, 5968–5975
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5973

C. Santi et al.
FULL PAPER
pure Z isomer, yield 0.246 g (96%); oil. 1H NMR (200 MHz,
CDCl3, 298 K, TMS): δ = 7.51 (d, JH,H = 9.5 Hz, 1 H, CH=),
2-(4-Bromoyphenyl)vinyl Phenyl Sulfide (9c):[25] Isolated by flash-
chromatography (silica gel, petroleum ether) as Z/E mixture
(72:28), yield 0.171 g (59%); light-yellow oil
3
7.40–7.34 (m, 2 H, CH-Ar), 7.12–7.08 (m, 3 H, CH-Ar), 6.13 (d,
3JH,H = 9.5 Hz, 1 H, CH=), 4.03 (q, 3JH,H = 7.1 Hz, 3 H, CH2CH3),
1
Major Isomer (Z)-9c: H NMR (200 MHz, CDCl3, 298 K, TMS):
3
1.10 (t, JH,H
= 7.1 Hz, 3
H, CH2CH3) ppm. 13C NMR
3
δ = 7.44–7.20 (m, 9 H, CH-Ar), 6.57 (d, JH,H = 10.8 Hz, 1 H,
(100.62 MHz, CDCl3, 298 K, TMS): δ = 167.3, 149.9, 133.3, 132.5,
129.4, 128.2, 116.8, 60.5,14.4 ppm. GC–MS: m/z (%) = 256 (100)
[M+], 211 (46), 183 (80), 157 (56), 131 (40), 117 (36), 103 (28), 77
(54), 51 (30).
3
CH=), 6.53 (d, JH,H = 10.8 Hz, 1 H, CH=) ppm. GC–MS: m/z
(%) = 292 (98) [M + 2], 290 (100) [M+], 247 (23), 245 (24), 211
(49), 178 (71), 134 (46), 121 (29), 102 (39), 77 (16), 51 (21).
1
Minor Isomer (E)-9c: H NMR (200 MHz, CDCl3, 298 K, TMS):
Methyl 3-Phenyl-2-(phenylseleno)acrylate (8f):[30] Isolated by flash-
chromatography (silica gel, petroleum ether) as Z/E mixture
(65:35), yield 0.159 g (50%); oil.
3
δ = 7.44–7.20 (m, 9 H, CH-Ar), 6.91 (d, JH,H = 15.6 Hz, 1 H,
3
CH=), 6.64 (d, JH,H = 15.6 Hz, 1 H, CH=) ppm. GC–MS: m/z
(%) = 292 (98) [M + 2], 290 (100) [M+], 247 (23), 245 (24), 211
(49), 178 (73), 134 (48), 121 (29), 102 (39), 77 (16), 51 (21).
1
Major Isomer (Z)-8f): H NMR (400 MHz, CDCl3, 298 K, TMS):
Mixture E/Z (E/Z)-9c: 13C NMR (100.62 MHz, CDCl3, 298 K,
TMS): δ = 135.6, 135.3, 135.2, 134.5, 131.6, 131.3, 130.1 (2 C),
130.0, 129.5, 129.1, 129.0, 127.3 (2 C), 127.1, 127.0, 125.7, 124.7,
121.0, 120.7 ppm.
Ethyl 3-(Phenylthio)acrylate (9e):[27] Isolated by flash-chromatog-
raphy (silica gel, petroleum ether/diethyl ether, 9:1) as Z/E mixture
(48:52:), yield 0.062 g (30%); light-yellow oil.
δ = 8.20 (s, 1 H, CH=), 7.75–7.60 (m, 2 H, CH-Ar), 7.45–7.40 (m,
3 H, CH-Ar), 7.40–7.30 (m, 2 H, CH-Ar), 7.25–7.20 (m, 3 H, CH-
Ar), 3.66 (s, 3 H, CH3) ppm. 13C NMR (100.62 MHz, CDCl3,
298 K, TMS): δ = 167.0, 145.4, 134.9, 131.5, 130.7, 130.2, 129.1,
128.4, 128.2, 128.0, 123.7, 52.6 ppm. GC–MS: m/z (%) = 318 (100)
[M+], 285 (10), 258 (44), 178 (96), 157 (40), 121 (98), 102 (52), 77
(50), 51 (27).
1
Minor Isomer (E)-8f): H NMR (400 MHz, CDCl3, 298 K, TMS):
1
(Z)-9e: H NMR (200 MHz, CDCl3, 298 K, TMS): δ = 7.55–7.25
δ = 7.60–7.55 (m, 2 H, CH-Ar), 7.45–7.20 (m, 8 H, CH-Ar), 7.01
(s, 1 H, CH=), 3.60 (s, 3 H, CH3) ppm. 13C NMR (100.62 MHz,
CDCl3, 298 K, TMS): δ = 167.8, 138.6, 135.4, 134.1, 129.6, 129.3,
128.6, 128.3, 128.2, 127.0, 124.1, 52.3 ppm. GC–MS: m/z (%) = 318
(100) [M+], 285 (10), 258 (37), 178 (87), 157 (34), 121 (92), 102 (45),
77 (42), 51 (21).
3
(m, 5 H, CH-Ar), 7.2 (d, JH,H = 10.1 Hz, 1 H, CH=), 5.93 (d,
3
3JH,H = 10.1 Hz, 1 H, CH=), 4.26 (q, JH,H = 7.0 Hz, 2 H, CH2-
3
CH3), 1.34 (t, JH,H = 7.0 Hz, 3 H, CH2-CH3) ppm. GC–MS: m/z
(%) = 208 (77) [M+], 163 (90), 135 (100), 109 (59), 91 (45), 77 (18),
65 (30), 51 (20).
(E)-9e: 1H NMR (200 MHz, CDCl3, 298 K, TMS): δ = 7.79 (d,
3JH,H = 15.1 Hz, 1 H, CH=), 7.55–7.25 (m, 5 H, CH-Ar), 5.65 (d,
2-[(Phenylthio)vinyl]benzene (9a): Isolated by flash-chromatography
(silica gel, petroleum ether/diethyl ether, 9:1) as Z/E mixture
(85:15:), yield 0.159 g (75%); light-yellow oil.
3
3JH,H = 15.1 Hz, 1 H, CH=), 4.18 (q, JH,H = 7.0 Hz, 2 H, CH2-
3
CH3), 1.25 (t, JH,H = 7.0 Hz, 3 H, CH2-CH3) ppm. GC–MS: m/z
Major Isomer (Z)-9a:[21,22] 1H NMR (200 MHz, CDCl3, 298 K,
(%) = 208 (77) [M+], 163 (86), 135 (100), 109 (58), 91 (45), 77 (16),
65 (29), 51 (18).
3
TMS): δ = 7.75–7.25 (m, 10 H, CH-Ar), 6.67 (d, JH,H = 10.8 Hz,
3
1 H, CH=), 6.57 (d, JH,H = 10.8 Hz, 1 H, CH=) ppm. 13C NMR
E/Z Mixture (E/Z)-9e: 13C NMR (100.62 MHz, CDCl3, 298 K,
TMS): δ = 166.6, 165.3, 149.8, 146.8, 136.2, 133.0, 131.1, 130.5,
129.7, 129.4, 129.1, 128.2, 115.7, 113.4, 60.3 (2 C), 14.3 (2 C) ppm.
Methyl 3-Phenyl-2-(phenylthio)acrylate (9f):[29] Isolated by flash-
chromatography (silica gel, petroleum ether/diethyl ether, 9:1) as Z/
E mixture (69:31:), yield 0.116 g (43%); light-yellow oil.
(100.62 MHz, CDCl3, 298 K, TMS): δ = 136.5, 136.2, 130.0, 129.2,
128.7, 128.3, 127.3, 127.2, 127.1, 126.0 ppm. GC–MS: m/z (%) =
212 (100), 178 (47), 167 (37), 134 (24), 121 (38), 91 (25), 77 (37).
51 (27).
Minor Isomer (E)-9a:[21,22] 1H NMR (200 MHz, CDCl3, 298 K,
3
TMS): δ = 7.75–7.25 (m, 10 H, CH-Ar), 6.97 (d, JH,H = 15.7 Hz,
1
3
1 H, CH=), 6.82 (d, JH,H = 15.7 Hz, 1 H, CH=) ppm. 13C NMR
Major Isomer (Z)-9e: H NMR (200 MHz, CDCl3, 298 K, TMS):
δ = 8.06 (s, 1 H, CH=), 7.78–7.72 (m, 2 H, CH-Ar), 7.32–7.14 (m,
8 H, CH-Ar), 3.59 (s, 3 H, OCH3) ppm. 13C NMR (100.62 MHz,
CDCl3, 298 K, TMS): δ = 167.6, 145.9, 135.4, 132.0, 131.2, 130.7,
129.5, 128.8, 128.6, 127.5, 124.2, 53.2 ppm. GC–MS: m/z (%) = 270
(100) [M+], 211 (69), 178 (35), 167 (23), 134 (16), 121 (64), 77 (11).
(100.62 MHz, CDCl3, 298 K, TMS): δ = 136.4, 135.2, 131.8, 129.8,
129.8, 129.0, 128.3, 127.4, 126.9, 123.4 ppm.
2-(4-Methoxyphenyl)vinyl Phenyl Sulfide (9b): Isolated by flash-
chromatography (silica gel, petroleum ether/diethyl ether, 9:1) as Z/
E mixture (72:28:), yield 0.128 g (53%); light-yellow oil.
1
Minor Isomer (E)-9e: H NMR (400 MHz, CDCl3, 298 K, TMS):
Major Isomer (Z)-9b:[21,22] 1H NMR (200 MHz, CDCl3, 298 K,
δ = 7.85–7.79 (m, 2 H, CH-Ar), 7.52–7.24 (m, 8 H, CH-Ar), 7.06
(s, 1 H, CH=),3.48 (s, 3 H, OCH3) ppm. 13C NMR (100.62 MHz,
CDCl3, 298 K, TMS): δ = 166.9, 139.0, 134.6, 134.1, 130.0, 129.8,
129.0, 128.9, 128.7, 128.5, 123.0, 52.7.2 ppm. GC–MS: m/z (%) =
270 (100) [M+], 211 (69), 178 (35), 167 (23), 134 (16), 121 (64), 77
(11).
3
TMS): δ = 7.50–7.10 (m, 5 H, CH-Ar), 7.49 (d, JH,H = 8.5 Hz, 2
3
3
H, CH-Ar), 6.93 (d, JH,H = 8.5 Hz, 2 H, CH-Ar), 6.56 (d, JH,H
3
= 10.7 Hz, 1 H, CH=), 6.37 (d, JH,H = 10.7 Hz, 1 H, CH=), 3.83
(s, 3 H, CH3O) ppm. 13C NMR (50.31 MHz, CDCl3, 298 K, TMS):
δ = 158.6, 136.4, 132.8, 130.1, 129.4, 129.0, 127.2, 127.0, 123.2,
113.7, 55.3 ppm. GC–MS: m/z (%) = 242 (100) [M+], 227 (27), 211
(33), 197 (44), 165 (31), 121 (50), 77 (20), 51 (14).
15 and 16: Identified in the spectra of the crude material.
1
2-(2-Phenylselenylethyl)pyridine (15): H NMR (200 MHz, CDCl3,
Minor Isomer (E)-9b:[21,22] 1H NMR (200 MHz, CDCl3, 298 K,
298 K, TMS): δ = 8.60–8.55 (m, 1 H, CHAr), 7.65–7.50 (m, 3 H,
3
TMS): δ = 7.40–7.10 (m, 5 H, CH-Ar), 7.38 (d, JH,H = 8.5 Hz, 2
3
CHAr), 7.40–7.20 (m, 5 H, CHAr), 3.33 (t, JH,H = 7.3 Hz, 2 H,
3
3
H, CH-Ar), 6.85 (d, JH,H = 8.5 Hz, 2 H, CH-Ar), 679 (d, JH,H
=
3
CH2-Se), 7.20 (t, JH,H = 6.3 Hz, 2 H, CH2-Pyr) ppm. GC–MS:
3
15.4 Hz, 1 H, CH=), 6.73 (d, JH,H = 15.4 Hz, 1 H, CH=), 3.80 (s,
3 H, CH3O) ppm. 13C NMR (50.31 MHz, CDCl3, 298 K, TMS): δ
= 159.4, 135.9, 132.8, 129.4, 129.2, 129.1, 127.4, 126.6, 120.0, 114.1,
55.3 ppm.
m/z (%) = 263 (18) [M+],182 (44), 106 (100), 78 (36), 51 (12).
2-(2-Phenylsulfanylethyl)pyridine (16): 1H NMR (200 MHz, CDCl3,
298 K, TMS): δ = 8.65–8.60 (m, 1 H, CHAr), 7.65–7.20 (m, 8 H,
5974
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 5968–5975

Stereoselective Hydrochalcogenations
3
3
[7] S. Narayan, J. Muldoon, M. G. Finn, V. V. Fokin, H. C. Kolb,
K. B. Sharpless, Angew. Chem. Int. Ed. 2005, 44, 3275–3279;
Angew. Chem. 2005, 117, 3339.
[8] P. H. Menezes, G. Zeni, in: Patai’s Chemistry of Functional
Groups (Ed.: Z. Rappoport), Wiley, Hoboken, USA, 2011,
DOI: 10.1002/9780470682531.pat0568.
CHAr), 3.37 (t, JH,H = 7.3 Hz, 2 H, CH2-Se), 3.12 (t, JH,H
=
7.3 Hz, 2 H, CH2-Pyr) ppm. GC–MS: m/z (%) = 215 (25) [M+], 106
(100), 93 (75), 78 (45), 51 (20).
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the H and 13C NMR are provided.
1
[9] K. B. Sharpless, K. F. Laurer, J. Am. Chem. Soc. 1973, 95,
2697–2699.
[10] J. V. Comasseto, J. T. B. Ferreira, J. Organomet. Chem. 1981,
216, 287–294.
Acknowledgments
[11] a) K. K. Bashin, N. Singh, R. Kumar, D. G. Deepali, S. K. Me-
tha, T. M. Klapoetke, M.-J. Crawford, J. Organomet. Chem.
2004, 689, 3327–3334; b) M. Yoshimatsu, T. Sato, H. Shimizu,
M. Hori, T. Kataoka, J. Org. Chem. 1994, 59, 1011–1019; c)
D. Crich, D. Grant, J. Org. Chem. 2005, 70, 2384–2386; d) I.
Andreadou, W. M. P. B. Menge, J. N. M. Commandeur, E. A.
Worthington, N. P. E. Vermeulen, J. Med. Chem. 1996, 39,
2040–2046; e) M. Sakakibara, K. Katsumata, Y. Watanabe, T.
Toru, Y. Ueno, Synthesis 1992, 377–379; f) T. Wirth, Selenium,
in: Comprehensive Organometallic Chemistry III (Eds.: R. H.
Crabtree, D. M. P. Mingos), Elsevier, Oxford, UK, 2006, vol.
9, p. 457.
Financial support from Consorzio Interuniversitario Nazionale di
Metodologie e Processi Innovativi di Sintesi (CINMPIS), Bari is
gratefully acknowledged. The authors also thank members of the
international network “SeS Redox and Catalysis” for fruitful scien-
tific discussions.
[1] a) A. Krief, L. Havesi, Organoselenium Chemistry, Springer,
Berlin, 1988, vol. 1; b) A. Krief, in: Comprehensive Organome-
tallic Chemistry (Ed.: B. M. Trost), Pergamon, Oxford, UK,
1991, p. 85; c) Topics in Current Chemistry, vol. 208: Organose-
lenium Chemistry – Modern Developments in Organic Synthesis
(Ed.: T. Wirth), Springer, Berlin, 2000; d) Organoselenium
Chemistry – A Practical Approach (Ed.: T. G. Back), Oxford,
UK, New York, 2000; e) Organoselenium Chemistry – Synthesis
and Reactions (Ed: T. Wirth), Wiley-VCH, Weinheim, Ger-
many, 2011; f) T. Wirth, Angew. Chem. Int. Ed. 2000, 39, 3740–
3749; Angew. Chem. 2000, 112, 3890; g) D. M. Freudendahl, S.
Santoro, S. A. Shahzad, C. Santi, T. Wirth, Angew. Chem. Int.
Ed. 2009, 48, 8409–8411; Angew. Chem. 2009, 121, 8559–8562;
h) C. Santi, S. Santoro, B. Battistelli, Curr. Org. Chem. 2010,
14, 2442–2462; i) C. Santi, C. Tidei, in: Comprehensive Organic
Synthesis, 2nd ed., Elsevier, 2014, vol. 7, p. 605–637; j) C. Santi,
C. Tidei, C. Scalera, Curr. Chem. Biol. 2013, 7, 25–36; k) C.
Santi, F. Galli, M. Piroddi, C. Tidei, Phosphorus Sulfur Silicon
Relat. Elem. 2013, 188, 507–508; l) For a comprehensive review
on the biological activity of organoselenium derivatives, see:
A. L. Braga, J. Rafique, in: The Chemistry of Organic Selenium
and Tellurium Compounds (Ed.: Z. Rappoport), vol. 4, Wiley,
Chichester, UK, 2013, p. 989–1175.
[12] C. Santi, S. Santoro, L. Testaferri, M. Tiecco, Synlett 2008,
1471–1474.
[13] S. M. Salman, R. S. Schwab, E. E. Alberto, J. Vargas, L. Dor-
nelles, O. E. D. Rodrigues, A. L. Braga, Synlett 2011, 69–72.
[14] S. Flemer, Protein Pept. Lett. 2014, 21, 1–1.
[15] M. L. Vieira, F. K. Zinn, J. V. Comasseto, J. Braz. Chem. Soc.
2001, 12, 586–596.
[16] For the synthesis of diselenide 11, see: C. Pérez-Balado, I. E.
Markó, Tetrahedron 2006, 62, 2331–2349.
[17] For the synthesis of diselenide 12, see: H. J. Reich, J. M. Renga,
I. L. Reich, J. Am. Chem. Soc. 1975, 97, 5434–5447.
[18] C.-F. Cheng, Z.-C. Lai, Y.-J. Lee, Tetrahedron 2008, 64, 4347–
4353.
[19] T. R. Kasturi, P. V. P. Palle, J. A. Sattigeri, K. A. Kumar, Tetra-
hedron 1996, 52, 1707–1712.
[20] A. L. Braga, C. C. Silveira, A. Reckziegel, P. H. Menezes,
Tetrahedron Lett. 1993, 34, 8041–8042.
[21] C. Cao, L. R. Fraser, J. A. Love, J. Am. Chem. Soc. 2005, 127,
17614–17615.
[22] Z.-L. Wang, R.-Y. Tang, P.-S. Luo, C.-L. Deng, P. Zhong,
J.-H. Li, Tetrahedron 2008, 64, 10670–10675.
[23] A. L. Braga, T. Barcellos, M. W. Paixao, A. M. Deobald, M.
Godoi, H. A. Stefani, R. Cella, A. Sharma, Organometallics
2008, 27, 4009–4012.
[2] a) G. Perin, E. J. Lenardão, R. G. Jacob, R. B. Panatieri, Chem.
Rev. 2009, 109, 1277–1301, and references cited therein; b) J. V.
Comasseto, L. W. Ling, N. Petrignani, H. A. Stefani, Synthesis
1997, 373–403, and references cited therein.
[3] a) C. Santi, S. Santoro, B. Battistelli, L. Testaferri, M. Tiecco,
Eur. J. Org. Chem. 2008, 5387–5390; b) C. Santi, Phenyl-
selenenylzinc halides, Encyclopedia of Reagents for Organic Syn-
[24] L. Bagnoli, C. Scarponi, L. Testaferri, M. Tiecco, Tetrahedron:
Asymmetry 2009, 20, 1506–1514.
[25] S. N. Riduan, J. Y. Ying, Y. Zhang, Org. Lett. 2012, 14, 1780–
1783.
[26] A. Ogawa, H. Yokoyama, K. Yokoyama, T. Masawaki, N.
Kambe, N. Sonoda, J. Org. Chem. 1991, 56, 5721–5723.
[27] C. G. Bates, P. Saejueng, M. Q. Doherty, D. Venkataraman,
Org. Lett. 2004, 6, 5005–5008.
thesis John Wiley
book/10.1002/047084289X
&
Sons, http://onlinelibrary.wiley.com/
[3/10/2011], DOI: 10.1002/
047084289X.rn01352; c) C. Tidei, Synlett 2012, 23, 2865; d) S.
Propersi, C. Tidei, L. Bagnoli, F. Marini, L. Testaferri, C.
Santi, J. Sulfur Chem. 2013, 36, 671–676.
[4] a) S. Santoro, B. Battistelli, L. Testaferri, M. Tiecco, C. Santi,
Eur. J. Org. Chem. 2009, 4921–4925; b) C. Santi, B. Battistelli,
L. Testaferri, M. Tiecco, Green Chem. 2012, 14, 1277–1280.
[5] a) B. Battistelli, L. Testaferri, M. Tiecco, C. Santi, Eur. J. Org.
Chem. 2011, 1848–1851; b) V. L. Nunes, I. C. de Oliveira, O. S.
do Rêgo Barros, Eur. J. Org. Chem. 2014, 1825–1834.
[6] C. Tidei, M. Piroddi, F. Galli, C. Santi, Tetrahedron Lett. 2012,
53, 232–234.
[28] V. L. Nunes, I. C. de Oliveira, O. S. do Rego Barros, Eur. J.
Org. Chem. 2014, 1525–1530.
[29] D. F. Andres, E. G. Laurent, B. S. Marquet, H. Benotmane, A.
Vensadat, Tetrahedron 1995, 51, 2605–2618.
[30] Z.-Z. Huang, X. Huang, Y.-Z. Huang, J. Organomet. Chem.
1995, 490, C23–C26.
Received: May 30, 2014
Published Online: August 20, 2014
Eur. J. Org. Chem. 2014, 5968–5975
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5975