Stereoselective synthesis of (E)-1-iodo-1-selenoalkenes via hydroalumination-iodination of 1-alkynyl selenides

Article abstract of DOI:10.1016/j.tetlet.2005.05.052

syn-Hydroalumination of 2,4,6-triisopropylphenylselanyl-1-alkynes 22 with DIBAL-H, followed by Al/I exchange with I₂, afforded selectively the corresponding (E)-1-iodo-1-selenoalkenes in good yields. The sterically hindered 2,4,6-triisopropylphenyl group proved to be mandatory and prevented the formation of undesired by-products.

Full text of DOI:10.1016/j.tetlet.2005.05.052

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4883–4886
Stereoselective synthesis of (E)-1-iodo-1-selenoalkenes via
hydroalumination–iodination of 1-alkynyl selenides
*
´ ´ ´
Carlos Perez-Balado, Fabio Lucaccioni and Istvan E. Marko
´ ´
Universite catholique de Louvain, Departement de Chimie, Unite de Chimie Organique et Medicinale,
Batiment Lavoisier, Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium
´
´
ˆ
Received 29 March 2005; revised 3 May 2005; accepted 12 May 2005
Available online 4 June 2005
Abstract—syn-Hydroalumination of 2,4,6-triisopropylphenylselanyl-1-alkynes 22 with DIBAL-H, followed by Al/I exchange with
I2, afforded selectively the corresponding (E)-1-iodo-1-selenoalkenes in good yields. The sterically hindered 2,4,6-triisopropylphenyl
group proved to be mandatory and prevented the formation of undesired by-products.
Ó 2005 Elsevier Ltd. All rights reserved.
During the course of the total synthesis of polycaverno-
side A,1 a complex marine toxin, we required an expedi-
ent method for the stereoselective construction of the
trisubstituted allylsilanes 1. Whilst a few procedures ex-
ist for the assembly of 1,2 it was envisaged that the for-
mal generation of an alkene-1,1-dianion such as 2,
followed by sequential, stereocontrolled, alkylations
would lead to an efficient access to these useful allylating
agents (Fig. 1). A number of alkene-1,1-dianion equiva-
lents have already been reported in the literature.3 How-
ever, they suffer from various shortcomings, including
limited reactivity. It was thus thought that 1-iodo-1-sel-
enoalkenes 3, of defined geometry, could be interesting
equivalents of dianion 2.
ology for the stereoselective synthesis of (E)-1-iodo-1-
selenoalkenes 3, based upon the syn-hydrometallation
of 1-alkynyl selenides 5, followed by metal/iodine
exchange with I2.
At the onset of this work, the hydrozirconation of 1-
phenylselanyl-hex-1-yne
6
was performed with
Cp2Zr(H)Cl.5 The in situ generated 1-zircono-1-sele-
noalkene species 7 was subsequently captured with
various electrophiles, affording the corresponding
selenoalkenes in good to moderate yields (Scheme 1).
Deuterolysis and protonolysis experiments demon-
strated that the hydrozirconation of the C–C triple bond
occurred in a syn manner and that the Zr residue was lo-
cated on the carbon bearing the selenium moiety. Trap-
ping of 7 with I2 or NBS, at low temperature, provided a
mixture of E and Z isomers of the corresponding 1-halo-
1-selenoalkenes 8 and 11, indicating that isomerisation
of the C–C double bond takes place either during the
Zr/halogen exchange or during the work-up. Although
Although a few methodologies for the preparation of 1-
iodo-1-selenoalkenes 3 have been described,4 they usu-
ally afford 3 with moderate E/Z selectivity or require
several steps. In this letter, we wish to present some pre-
liminary results on the establishment of a novel method-
1
1
1
3
1
3
R
Si(CH )
R
R
SeR
3 3
R
SeR
ML
I
HML
2
n
3
1
SeR
R
2
R
I
n
1
3
2
4
5
Figure 1.
Keywords: Selenides; Hydroalumination; 2,4,6-Triisopropylphenyl selenide; Iodination.
*
Corresponding author. Tel.: +32 10 47 87 73; fax: +32 10 47 27 88; e-mail: marko@chim.ucl.ac.be
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.052

´
C. Perez-Balado et al. / Tetrahedron Letters 46 (2005) 4883–4886
4884
6
high yielding reaction, needed to be suppressed. We rea-
soned that the competitive (sp)C–Se bond cleavage
could probably be prevented by selectively hindering
the selenium atom, thereby inhibiting the coordination
between the selenium substituent and the aluminium re-
agent and hence, the delivery of hydride on selenium. In
order to verify our hypothesis, 2,4,6-triisopropylphen-
ylselanyl 1-alkynes, bearing the voluminous 2,4,6-triiso-
propylphenyl (TIPP) group instead of the phenyl group,
were prepared.
Bu
SePh
Cp2Zr(H)Cl (1.2 eq), DCE, rt, 1h
Bu
H
SePh
I2, (1.3 eq),
DCE, -10°C to rt
NBS (1.3 eq)
DCE, 0°C to rt
Zr
Cl
7
D2O
aq. NH4Cl
The 2,4,6-triisopropylphenylselanyl 1-alkynes 22 were
synthesised in good yields from di-2,4,6-triisopropyl-
phenyl diselenide 19 and the corresponding terminal
alkynes.8 Diselenide 19 was readily obtained from 1-bro-
mo-2,4,6-triisopropylbenzene, by Br/Li exchange with
2 equiv of t-BuLi, followed by treatment with metallic
selenium and final oxidation of the selenol to the disele-
nide (84% yield). Addition of Br2 to 19 generated in situ
the corresponding selenyl bromide 20, which was
reacted immediately with the lithium acetylides 21,
obtained by deprotonation of the corresponding termi-
nal alkynes with n-BuLi at low temperature, to give
the desired 1-alkynyl selenides in good yields (Scheme
2).
Bu
SePh
Bu
Bu
SePh
SePh
71%
Bu
SePh
I
Br
D
8
70%
E/Z ratio: 4/1
Scheme 1.
9
10
71%
11
62%
E/Z ratio: 1.1/1
the iodoalkene 8 could be obtained in good yield and
with a reasonable E/Z ratio of 4 to 1, this was clearly
not sufficient for our purposes. Hydroalumination of 6
with DIBAL-H was then explored.
Much to our delight, when 1-(2,4,6)-triisopropylphenyl-
selenylhex-1-yne 12 was treated with DIBAL-H, fol-
lowed by quenching with dilute HCl (under the same
conditions as 6), the (Z)-alkenyl selenide 17 was ob-
tained in 95% yield. Gratifyingly, the diselenide 19 could
not be detected in the crude reaction mixture (Fig. 2).
Thus, it transpires that the steric hindrance of the TIPP
group dramatically influences the selectivity of the
hydroalumination reaction by suppressing the competi-
tive C–Se bond cleavage. The formation of the disele-
nide by-product is prevented and the hydrometallation
of the C–C triple bond becomes essentially quantitative.
The hydroalumination of phenylseleno-acetylenes, anal-
ogous to 6, has been described by the groups of Al-Has-
san and Dabdoub,6 who showed that DIBAL-H also
added in a syn manner to the C–C triple bond of these
alkynyl selenides. They also demonstrated that the alu-
minium residue was positioned on the same carbon as
the selenium substituent (Fig. 2). However, when the
hydroalumination of 1-phenylselanyl-hex-1-yne 6 was
performed with DIBAL-H, followed by quenching of
the in situ generated 1-alumino-1-selenoalkene 13 with
dilute HCl, the (Z)-alkenyl selenide 14 was obtained in
a moderate 61% yield. Besides 14, diphenyl diselenide
15 was isolated in 29% yield. The formation of diphenyl
diselenide appears to proceed via the competitive cleav-
age of the (sp)C–Se bond of 6 by hydride attack on the
selenium moiety. This generates phenylselenol and an
alkynylalane. Phenylselenol is then deprotonated by
the hydride to give phenylselenoate, which rapidly oxi-
dises to diphenyl diselenide in the presence of oxygen
during the work-up.7
Having found that the TIPP group allowed efficient
hydroalumination of 1-alkynyl selenides, we next turned
our attention to the preparation of stereodefined 1-iodo-
1-selenoalkenes by iodination of the corresponding
vinylalane intermediates 23. Addition of I2 to 23 affor-
ded the corresponding 1-iodo-1-selenoalkenes 24 in
excellent yields. In all cases, only the E isomer was ob-
tained,9 indicating that the replacement of Al by I takes
place with retention of configuration of the C–C double
bond (Table 1). The Al/I exchange requires careful con-
trol of the reaction conditions, in order for the iodin-
ation to be complete.10 If the reaction mixture is
The undesired formation of diselenide 15 was a serious
drawback in this approach and, in order to establish a
Bu
H
SeR3
Bu
H
SeR3
H
DIBAL-H (1eq)
1N HCl
Bu
R3= Ph
SeR3
(R3Se)2
+
hexane, toluene, 0º to rt
Al(i-Bu)2
R3= Ph
14 (61%)
15 (29%)
19 (0%)
6
R3= Ph
13
R3=TIPP 12
R3=TIPP 16
R3=TIPP 17 (95%)
TIPP = 2,4,6-triisopropylphenyl =
Figure 2.

´
C. Perez-Balado et al. / Tetrahedron Letters 46 (2005) 4883–4886
4885
Br
Li
Br2
1. t-BuLi (2 eq), -78ºC
SeBr
Se
2. Se, -78ºC to rt
3. aq NH4Cl, air, rt
Se
THF/C6H6, 0ºC
19 (84%)
20
R1
21
R1
Se
THF, 0ºC
22 (75-85%)
Scheme 2.
Table 1. Hydroalumination–iodination of 1-(2,4,6)-triisopropylphenylselenyl-1-alkynes
R
H
SeTIPP
R
H
SeTIPP
I
I2
DIBAL-H
R
SeTIPP
Al(i-Bu)2
hexane/toluene
0ºC to rt
THF
-78ºC to rt
22
24
23
Entry
1
Substrate
Product
Yielda
SeTIPP
I
92%
95%
SeTIPP
H
SeTIPP
2
3
4
SeTIPP
H
I
SeTIPP
I
SeTIPP
O
O
O
O
H
96%
82%
SeTIPP
I
SeTIPP
SeTIPP
H
H
SeTIPP
I
5
6
91%
0%
—
SeTIPP
a Isolated yields after purification by column chromatography.
stirred longer than 1 h at room temperature, some deg-
radation may occur, accompanied by the appearance of
the Z isomer. In the case of the phenyl acetylene deriv-
ative (Table 1, entry 6), the addition of DIBAL-H to the
C–C triple bond did not occur, even when the hydroalu-
mination was performed in refluxing hexane. This lack
of reactivity could be due to the generation of prohibi-
tive steric repulsions between the aryl and SeTIPP
groups during the addition of the aluminium hydride.
the replacement of Al by Br occurred with complete
scrambling of the configuration of the C–C double bond
even under carefully controlled reaction conditions. This
might be an indication that bromination and iodination
of 23 follow different mechanistic pathways.
In summary, we have developed a novel, efficient and
stereoselective methodology for the synthesis of (E)-1-
iodo-1-selenoalkenes via hydroalumination of 1-alkynyl
selenides, followed by Al/I exchange with full retention
of configuration. Steric shielding of the selenium with
a hindered 2,4,6-triisopropylphenyl substituent proved
to be mandatory and prevented the formation of
In sharp contrast, bromination of 23, either with Br2 or
NBS, afforded a 1/1 mixture of (E) and (Z)-1-bromo-1-
selenoalkenes. Although the yields were good (80–90%),

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C. Perez-Balado et al. / Tetrahedron Letters 46 (2005) 4883–4886
4886
9819; (b) Huang, X.; Zhu, L.-S. Synthesis 1996, 1191; (c)
Zhu, L.-S.; Huang, Z.-Z.; Huang, X. J. Chem. Res. 1996,
112; (d) Dabdoud, M. J.; Begnini, M. L.; Guerrero, P. G.
Tetrahedron 1998, 54, 2371; (e) Dabdoub, M. J.; Begnini,
M. L.; Guerrero, P. G.; Baroni, A. C. J. Org. Chem. 2000,
65, 61.
undesired diselenides. The 2,4,6-triisopropylphenylselenyl
1-alkyne precursors are prepared in a straightforward
manner, from readily available materials. Current efforts
are now being directed towards exploring the reactivity
of (E)-1-iodo-1-selenoalkenes as potential precursors
for the stereocontrolled synthesis of trisubstituted
alkenes.
6. (a) Al-Hassan, M. I.; Al-Naijar, I. M.; Ahmad, M. M.
Spectrochim. Acta, Part A. 1986, 45, 1011; (b) Al-Hassan,
M. I. Synth. Commun. 2001, 31, 3027; (c) Dabdoub, M. J.;
Cassol, T. M.; Barbosa, S. L. Tetrahedron Lett. 1996, 37,
831.
Acknowledgements
7. Dabdoud, M. J.; Comasseto, J. V. Organometallics 1998,
7, 84.
8. Comasseto, J. V.; Silveira, C. C.; Ferreira, J. T.; Catani, V.
Synth. Commun. 1986, 16, 283.
9. I/Li exchange of 24 (R = Me) with n-BuLi, followed by
quenching with dilute acid afforded exclusively the (Z)-1-
propenyl selenide (JCH–CH = 8.8 Hz), thus confirming the
(E)-geometry of the C–C double bond of 24.
Financial support of this work by Chirotech Technology
´
Ltd., Cambridge, UK and the Universite catholique de
Louvain is gratefully acknowledged.
References and notes
10. Typical experimental procedure: Preparation of (E)-2-
(iodo-propenylselenyl)-1,3,5-triisopropyl-benzene [Table
1, entry 1]: DIBAL-H (26.4 mL, 39.6 mmol, 1.5 M in
toluene) was added dropwise to a stirred solution of prop-
1-ynyl selenide (12.1 g, 37.8 mmol) in hexane (80 mL)
cooled at 0 °C, under an argon atmosphere. The reaction
mixture was stirred for 1 h at 0 °C and then 2 h at rt. The
resulting colourless solution was cooled to À78 °C and a
solution of I2 (24 g, 94.5 mmol) in THF (45 mL) was added
dropwise via cannula. The mixture was allowed to slowly
reach 0 °C. It was then stirred for 1 h at 0 °C and finally
45 min at rt. It was poured into a mixture of EtOH
(215 mL)/EtOAc (215 mL)/H2O (108 mL) and treated with
NaBH4 until the solution became colourless or slightly
yellow. The solution was washed with aqueous 1 N HCl
(130 mL), a saturated aqueous Na2S2O3 solution (100 mL),
brine (150 mL), dried over MgSO4 and the solvents were
removed under reduced pressure. The crude product was
purified by chromatography on silica gel (hexane) to afford
15.6 g (92% yield) of the title compound as a reddish oil. 1H
NMR (CDCl3, 300 MHz) dH (ppm): 7.04 (2H, s), 6.83 (1H,
q, J = 6.9 Hz), 3.67 (2H, hep, J = 6.9 Hz), 2.91 (1H, hep,
J = 7.0 Hz), 2.75 (3H, d, J = 6.9 Hz), 1.27 (6H, d, J =
7.0 Hz), 1.23 (12H, d, J = 6.9 Hz). 13C NMR (50 MHz,
CDCl3) dC (ppm): 153.0, 150.7, 140.7, 125.8, 121.9, 82.1,
34.2, 33.9, 24.2, 23.8, 20.2 IR (neat): 3041, 2959, 2926,
1701, 1462, 1382, 1361, 1168, 1069 cmÀ1. MS (EI) m/z (%):
450 [M+Æ] (62), 324 [M+ÆÀI] (73). Anal. Calcd for
C18H27ISe: C, 48.12; H, 6.06. Found: C, 48.45; H, 6.23.
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