Hydroselenation of alkynes by lithium butylselenolate: An approach in the synthesis of vinylic selenides

Article abstract of DOI:10.1021/ol0498904

Vinylic selenides were prepared in good yields by hydroselenation of alkynes with lithium butylselenolate generated by reaction of n-butyllithium with elemental selenium. The regio- and stereochemistry of the hydroselenation depend on the nature of the su

Full text of DOI:10.1021/ol0498904

ORGANIC
LETTERS
2
004
Vol. 6, No. 7
135-1138
Hydroselenation of Alkynes by Lithium
Butylselenolate: An Approach in the
Synthesis of Vinylic Selenides
1
,
†
†
†
†
Gilson Zeni,* Marcelo P. Stracke, Cristina W. Nogueira, Antonio L. Braga,
‡
§
Paulo H. Menezes, and Helio A. Stefani
Laborat o´ rio de S ´ı ntese, ReatiVidade, AValia c¸ a˜ o, Toxicol o´ gica e Farmacol o´ gica de
Organocalcogenios-CCNE-UFSM, 97105-900 Santa Maria RS, Brazil,
Departamento de Qu ´ı mica Fundamental-UFPE, Recife. Brazil, and
Faculdade de Ci eˆ ncias Farmac eˆ uticas-USP, S a˜ o Paulo, Brazil
gzeni@quimica.ufsm.br
Received January 17, 2004
ABSTRACT
Vinylic selenides were prepared in good yields by hydroselenation of alkynes with lithium butylselenolate generated by reaction of n-butyllithium
with elemental selenium. The regio- and stereochemistry of the hydroselenation depend on the nature of the substituents bonded to the
alkyne.
Organoselenium compounds have become attractive synthetic
targets because of their chemo-, regio-, and stereoselectivity
selenides after longer reaction times at room temperature.
The reaction is faster at a high temperature; however, the
mixture of Z- and E-vinylic selenides was obtained in an
1
2
reactions and their useful biological activities. On this way,
vinylic selenides play an important role in the synthesis of
organoselenium compounds, especially in the development
of many convenient methods for the stereoselective prepara-
5
almost 1:1 ratio (Scheme 1). On the other hand, the
3
tion of functionalized alkenes. Although various methods
Scheme 1
are mentioned for the preparation of vinylic selenides, a more
useful procedure has centered on the nucleophilic or elec-
trophilic organoselenium addition to terminal or internal
4
alkynes. For example, the nucleophilic addition of sele-
nophenol to alkynes affords, preferentially, the Z-vinylic
†
CCNE-UFSM.
UFPE.
USP.
‡
§
(1) (a) Organoselenium Chemistry, Topics in Current Chemistry 208;
Wirth, T., Ed.; Springer-Verlag: Heidelberg, 2000. (b) Krief, A. In
ComprehensiVe Organometallic Chemistry II; Abel, E. V., Stone, F. G. A.,
Wilkinson, G., Eds.; Pergamon Press: New York, 1995; Vol. 11, Chapter
eletrophilic addition of organoselenenyl halides to alkynes
gave a mixture of Markownikov and anti-Markownikov
1
3. (c) Paulmier, C. In Organic Chemistry Series 4. Baldwin, J. E., Ed.;
Selenium Reagents and Intermediates in Organic Synthesis; Pergamon
Press: Oxford, 1986.
(4) (a) Comasseto, J. V. J. Organomet. Chem. 1983, 253, 131-181. (b)
Barros, O. S. D.; Lang, E. S.; de Oliveira, C. A. F.; Peppe, C.; Zeni, G.
Tetrahedron Lett. 2002, 43, 7921-7923. (c) Dabdoub, M. J.; Dabdoub, V.
B.; Pereira, M. A. Tetrahedron Lett. 2001, 42, 1595-1597. (d) Dabdoub,
M. J.; Baroni, A. C. M.; Lenard a˜ o, E. J.; Gianeti, T. R.; Hurtado, G. R.
Tetrahedron 2001, 57, 4271-4276. (e) Dabdoub, M. J.; Cassol, T. M.;
Batista, A. C. F. Tetrahedron Lett. 1996, 37, 9005-9008.
(
2) (a) Mugesh, G.; du Mont, W.-W.; Sies, H. Chem. ReV. 2001, 101,
125-2179. (b) Parnham, M. J.; Graf, E. Prog. Drug Res. 1991, 36, 9-47.
c) Nogueira, C. W.; Quinhones, E. B.; Jung, E. A. C.; Zeni, G.; Rocha, J.
B. T. Inflammation Res. 2003, 52, 56-63.
3) Comasseto, J. V.; Ling, L. W.; Petragnani, N.; Stefani, H. A. Synthesis
997, 373-403.
2
(
(
1
1
0.1021/ol0498904 CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/09/2004

adducts, depending on the nature of the substituents at the
6
triple bond (Scheme 1). Conversely, vinylic selenides can
Table 1. Hydroselenation of Internal Alkynes
be prepared by palladium-catalyzed hydroselenation of
alkynes to afford the Markownikov adduct in good yields.
7
There are some limitations associated with the methodolo-
gies to prepare vinylic selenides illustrated above; procedures
8
9
described employ diorganoyl diselenides or selenophenol
as starting materials, which are volatile and unstable and have
an unpleasant odor. Also, the preparation of these compounds
is complex.
We now wish to report our results on the preparation of
vinylic selenides via hydroselenation of terminal and internal
alkynes, avoiding the previous preparation of diorganoyl
disselenides or selenophenol. Thus, a solution of alkyne in
deoxygenated ethanol was added dropwise to a solution
containing n-BuSeLi (generated in situ by addition of
n-butyllithium to a suspension of elemental selenium and
THF at room temperature). The resulting solution was
refluxed for 24 h and monitored by TLC to produce the
desired vinylic selenides in good yields and high regio- and
stereoselectivity (Scheme 2).10
Scheme 2
Our investigation began with the addition of lithium
n-butylselenolate to internal alkynes, and the results are
shown in Table 1. The hydroselenation of symmetrical
internal alkynes (entries a-e) readily produces, stereoselec-
tively, the Z-vinylic selenides 2a-e in good yields, except
for dibutylacetylene, which did not give the desired vinylic
selenides (Table 1, entry e). Under the same reaction
conditions, the hydroselenation of unsymmetrical internal
alkynes (Table 1, entries f-i) produced the corresponding
vinylic selenides in good yields and in high stereo- and
regioselectivity. The regio-and stereoselectivities obtained
in the products described in Table 1 could be justified by
a
Yields are given for isolated products. b The reaction produced a 1:1
mixture of Z- and E-isomers.
both steric and electronic effects of the substituents on the
triple bond. We have also therefore performed a series of
reactions to test whether unsymmetrical internal alkynes
bearing a heteroatom such as Si, Te, Sn, Se, S, or P would
react in the same fashion with lithium butyl selenenolate
(
1
Table 1, entries j-p). As a result, the phenylthio acetylene
j gave the Z-vinylic selenides 2j with the addition of the
organoselenium group at the â-position relative to methylthio
substituent as a single regio-, and stereoisomer in 59% yield
(Table 1, entry j). The hydroselenation of 1-alkynylphos-
phonate (Table 1, entry l) gave regioselectively the â-bu-
tylseleno vinyl phosphonate in 64% yield. However, con-
siderable loss of stereoselectivity was verified (the Z- and
E-â-butylseleno vinyl phosphonates were obtained in a 1:1
ratio). The hydroselenation did not proceed with unsym-
metrical internal alkynes bearing an organoselenium, tel-
lurium, tin, or silicon group bonded directly at the triple bond
(Table 1, entries m-p). In these cases we observed only the
cleavage of the carbon-heteroatom bond. Thus, the products
were phenylacetylene together with organoselenium com-
pounds 3 containing the heteroatom bonded directly at the
selenium atom, probably as the result of a direct attack of
n-BuSeLi to the heteroatom (Se, Si, Sn, Te) (Scheme 3).
Next we decided to expand the scope of this method to
include terminal alkynes. Thus, a solution of 1-alkyne in
(
5) Comasseto, J. V.; Ferreira, J. T. B. J. Organomet. Chem. 1981, 216,
2
87-294.
(6) (a) Filer, C. N.; Ahern, D.; Fazio, R.; Shelton, E. J. J. Org. Chem.
1
980, 45, 1313-1315. (b) Garratt, D. G.; Beaulieu, P. L.; Morisset, U. M.
Can. J. Chem. 1981, 59, 927-934.
(
7) Kuniyasu, H.; Ogawa, A.; Sato, K. I.; Ryu, I.; Sonoda, N. Tetrahedron
Lett. 1992, 33, 5525-5528.
8) (a) Krief, A.; Derock, M. Tetrahedron Lett. 2002, 43, 3083-3086.
b) Back, T. G. Organoselenium Chemistry: A Practical Approach; Oxford
University Press: Oxford, 1999.
(
(
(
9) Gosselck, J. Angew. Chem., Int. Ed. Engl. 1963, 2, 660-669.
(10) Typical Procedure for Hydroselenation of Alkynes by BuSeLi.
To a suspension of elemental selenium (0.079 g; 1 mmol) in dry THF (5
mL) under argon and with magnetic stirring was added n-butyllithium (0.4
mL of a 2.5 M solution in hexane; 1 mmol). A yellow solution was formed.
To this solution was added the appropriate alkyne (1 mmol) in deoxygenated
ethanol (5 mL). The mixture was then heated at reflux for 24 h. After this
time, the mixture was cooled to room temperature and treated with NH4Cl
(10 mL) solution and ethyl acetate (100 mL). The organic phase was
separated, dried over MgSO4, and concentrated under vacuum. The residue
was purified by flash chromatography and eluted with hexane or hexane/
ethyl acetate (80:20).
1136
Org. Lett., Vol. 6, No. 7, 2004

1
-hexyne jointly with large amounts of dibutyl diselenide.
The effect of the hydroxyl group at the propargyl position
of 1-alkynes was also examined, and the results are sum-
marized in Table 2. The hydroselenations proceed at room
temperature, affording stereoselectively the corresponding
Z-vinylic selenides; however, a significant loss in the
regiochemistry was observed. With a bulky alkyl group in
the propargyl position (Table 2, entry g) the regioisomer 5g
was obtained as a major product with Z-stereochemistry
exclusively. However, an inversion in the regiochemistry was
observed when the hydrogen (small group) was present in
the propargyl position (Table 2, entry h). This set of
experiments demonstrated that the ratio of regioisomers is
dependent on the steric effect of the alkyl group in the
propargyl position.
Scheme 3
deoxygenated ethanol was added dropwise to a solution
containing n-BuSeLi. The resulting solution was stirred at
room temperature for the time indicated in Table 2 and
Table 2. Hydroselenation of Terminal Alkynes
Analysis of the H and 13C NMR spectra showed that all
of the vinylic selenides presented data in full agreement with
their assigned structures. The stereochemistry of the disub-
stituted vinylic selenides was easily established. As an
1
1
example, the H spectrum of compound 5a showed a doublet
centered at 6.89 ppm with a coupling constant of 9.2 Hz.
The other vinylic hydrogen resonates at 6.62 ppm as a
doublet, with a coupling constant of 9.2 Hz attributed to the
cis-related olefinic hydrogens. The geometry of the trisub-
stituted vinylic selenides was determined by NOE experi-
ments. For example, when the compound 2c was irradiated
at the signal attributed to vinylic hydrogen (6.35 ppm), an
enhancement of the allylic hydrogens (2.42 ppm) was
observed, showing a cis relationship between them.
The reaction pathway leading to vinylic selenides seems
to depend on the substitution pattern of the triple bond and
is controlled by both steric and electronic effects. We believe
that in the case of non-hydroxyled alkynes, the vinylic
selenides are formed by the addition of the selenolate anion
onto the triple bond, with subsequent trapping of the vinyl
anion with a proton from ethanol. However, in the case of
propargyl alcohols we believe that the vinylic hydrogen came
from the acidic proton of the hydroxyl group (Scheme 4).
a
b
Yields are given for isolated products. The ratios were determined
1
c
on the basis of H NMR data. Using 20 mmol scale the product was
obtained in 77% yield. The reaction was refluxed.
d
monitored by TLC to produce the desired vinylic selenides
in good yields; the results are summarized in Table 2. We
can see in Table 2 that the hydroselenation of phenylacety-
lene gave the Z-vinylic selenides 5a in good yield and in a
shorter reaction time, as an exclusive regio- and stereoisomer
Scheme 4
(Table 2, entry a). In addition, when the hydroselenation of
phenylacetylene was carried out on a large scale (20 mmol),
the product 5a was obtained in a similar yield. This result
indicates that our method can be employed in the large-scale
synthesis of vinylic selenides 5a, which are important
intermediates in organic synthesis.11 In contrast, when
To support this mechanistic description, we have carried
out the hydroselenation of phenylacetylene in MeOH-d ,
4
1
-hexyne was employed as starting material, the hydro-
where 7 was isolated as the major product (Scheme 5). We
also used the deuteration experiments to determine if the
vinylic hydrogen is donated by the alcohol or if it could come
from the hydroxyl group in the propargyl alcohols. As the
result, the hydroselenation of deuterated propargyl alcohol
selenation afforded the vinylic selenides 5b only in small
amounts, even though heating and longer reaction times were
employed (Table 2, entry b). In this case we recovered the
(11) (a) Tingoli, M.; Tiecco, M.; Testaferri, L.; Temperini, A.; Pelizzi,
8
, in the absence of a protic solvent, produces the vinylic
selenides 9 (Scheme 5). These results suggest that the
G.; Bacchi, A. Tetrahedron 1995, 51, 4691-4700. (b) Hevesi, L.; Hermans,
B.; Allard, C. Tetrahedron Lett. 1994, 35, 6729-6730.
Org. Lett., Vol. 6, No. 7, 2004
1137

Scheme 5
Scheme 6
that these findings would be useful in choosing a method
for the synthesis of vinylic selenides containing different
functional groups. This reaction associated with the nickel-
catalyzed cross-coupling of vinylic selenides with terminal
alkynes can contribute to an interesting alternative route
to the regio- and stereoselective preparation of functionalized
alkenes. Studies on the capture of vinyllithium intermediate
with different electrophiles are in progress in our group, and
the results will appear soon in a full paper.
hydroselenation across to the triple bond follows an anti-
pathway addition with the effective participation of ethanol
and the hydroxyl group of propargyl alcohols.
Finally, an application of our method in the preparation
of tetrasubstituted vinylic selenides from internal unsym-
metrical alkynes, based on the sequence of hydroselenation
and trapping of the vinyllithium intermediate with benz-
aldehyde, has been briefly investigated. Thus, 1.0 equiv of
1
2
1
-alkynylphosphonate 10 was reacted with 1.0 equiv of
n-BuSeLi at room temperature for 1 h. Then the solution of
.2 equiv of benzaldehyde in 2 mL of THF was added. The
Acknowledgment. We are grateful to CNPq, CAPES and
FAPERGS for financial support. CNPq is also acknowledged
for a MS fellowship (to M.P.St).
1
reaction was stirred at room temperature for 4 h to give the
tetrasubstituted vinylic selenides 11 in 78% yield (Scheme
6
).
Supporting Information Available: Spectroscopic data
for all new compounds and detailed experimental procedures.
This material is available free of charge via the Internet at
http://pubs.acs.org.
In summary, we present here the hydroselenation of
terminal or internal, unsymmetrical or symmetrical alkynes
by lithium selenolate anion. The nature of the substituents
(
steric and electronic effects) on the triple bond plays an
OL0498904
important role in the regio- and stereoselectivity of the vinylic
selenides formed. Additionally, by our method the use of
diorganoyl diselenides or selenophenol is avoided. We expect
(12) Silveira, C. C.; Braga, A. L.; Vieira, A. S.; Zeni, G. J. Org. Chem.
2003, 68, 662-665.
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Org. Lett., Vol. 6, No. 7, 2004