[1-(Phenylseleno)alkyl]stannanes-mixed selenium/tin analogs of acetals: preparation from α-hydroxystannanes and use for generating selenium-stabilized carbanions

Article abstract of DOI:10.1021/jo8004292

(Chemical Equation Presented) Selenium-stabilized carbanions are available by a route that does not involve acid-catalyzed formation of selenoacetals. Aldehydes are converted first into α-hydroxystannanes and then into α-(phenylseleno)stannanes. Treatment with BuLi affords selenium-stabilized carbanions by preferential Sn/Li exchange.

Full text of DOI:10.1021/jo8004292

SCHEME 1. Formation of Allylic Alcohols by Selenoxide
Fragmentation
[1-(Phenylseleno)alkyl]stannanes-Mixed
Selenium/Tin Analogs of Acetals: Preparation
from r-Hydroxystannanes and Use for
Generating Selenium-Stabilized Carbanions
Shimal C. Fernandopulle, Derrick L. J. Clive,* and
Maolin Yu
SCHEME 2. Conversion of Selenoacetals into
Selenium-Stabilized Carbanions
Chemistry Department, UniVersity of Alberta, Edmonton,
Alberta, Canada T6G 2G2
derrick.cliVe@ualberta.ca
ReceiVed February 22, 2008
SCHEME 3. Formation of r-(Phenylseleno)stannanes
for Sn/Li exchange is observed with R-halostannanes.7 However,
the compounds of type 8 had previously been made from
(phenylseleno)acetals 6 by conversion into the corresponding
selenium-stabilized carbanions 1 and quenching with Bu3SnCl.6
Our proposed route (Scheme 3) avoids the acid-catalyzed
formation of (phenylseleno)acetals and proceeds instead by way
of R-stannyl alcohols 7. These compounds are well-known, but
although they can be trapped by acylation8 or as ethers,8a,d,9,10
they have the reputation7,10,11 of being quite labile, and it was
not clear if they could be converted into the selenides 8.
In our first experiment, isovaleraldehyde was used as a test
substrate (Table 1, entry i). Reaction with Bu3SnLi was
accomplished by generating the tin reagent at 0 °C from Bu3SnH
and LDA.10,12 We also examined the effect of generating a
suitable tin reagent by other methods such as reaction of Li
with Bu3SnCl,13 reaction of (Bu3Sn)2 with BuLi,14 treatment
of Bu3SnH with i-PrMgCl,15 or the generation of what we
assume (from the stoichiometry used) to be Bu3SnCeCl2.
However, in none of these experiments was there any obvious
improvement in the yield of (phenylseleno)stannane obtained
from the crude R-stannyl alcohol (see later), and so we settled
Selenium-stabilized carbanions are available by a route that
does not involve acid-catalyzed formation of selenoacetals.
Aldehydes are converted first into R-hydroxystannanes and
then into R-(phenylseleno)stannanes. Treatment with BuLi
affords selenium-stabilized carbanions by preferential Sn/
Li exchange.
In connection with work aimed at the synthesis of the complex
natural product halichlorine,1 a need arose in this laboratory to
generate a selenium-stabilized carbanion that could be con-
densed2 with an aldehyde in order to form an allylic alcohol3
by selenoxide fragmentation (Scheme 1). The standard route to
selenium-stabilized carbanions is by the action of BuLi on
selenoacetals (6 f 1, Scheme 2).2,4 In turn, the selenoacetals
are normally made5 by reaction of an aldehyde with PhSeH in
the presence of a protic or Lewis acid. In the particular case
that prompted the present investigation, such acidic conditions
were deemed unacceptable, and so we considered a route to
selenium-stabilized carbanions that involves the use of nucleo-
philic reagents (Bu3SnLi and PhSe-) along the lines summarized
in Scheme 3. Several 1-[(phenylseleno)alkyl]stannanes of type
8 had been reported,6 and it was known that they react in the
desired manner with BuLi, the rate of attack of BuLi on tin
evidently being higher than on selenium. A similar preference
(8) E.g (a) Dussault, P. H.; Eary, C. T.; Lee, R. J.; Zope, U. R. J. Chem.
Soc., Perkin Trans. 1 1999, 2189–2204. (b) Tsai, Y.-M.; Chang, S.-Y. J. Chem.
Soc., Chem. Commun. 1995, 981–982. (c) Ritter, K. Tetrahedron Lett. 1990,
31, 869–872. (d) Ye, J.; Bhatt, R. K.; Falck, J. R. J. Am. Chem. Soc. 1994, 116,
1–5.
(9) For example: (a) Linderman, R. J.; Godfrey, A.; Horne, K. Tetrahedron
1989, 45, 495–506. (b) Chan, P.C.-M.; Chong, J. M. J. Org. Chem. 1988, 53,
5584–5586. (c) Pratt, A. J.; Thomas, E. J. J. Chem. Soc., Chem. Commun. 1982,
1115–1117. (d) Linderman, R. J.; Ghannam, A. J. Am. Chem. Soc. 1990, 112,
2392–2398. (e) Candela Lena, J. I.; Rico Ferreira, M. del R.; Martin Hernando,
J. I.; Arseniyadis, S. Tetrahedron: Asymmetry 2001, 12, 3281–3291. (f)
Katsumura, S.; Fujiwara, S.; Isoe, S. Tetrahedron Lett. 1985, 26, 5827–5830.
(g) Marshall, J. A.; Gung, W. Y. Tetrahedron Lett. 1989, 30, 309–312. (h)
Crimmins, M. T.; Thomas, J. B. Tetrahedron Lett. 1989, 30, 5997–6000.
(10) Still, W. C. J. Am. Chem. Soc. 1978, 100, 1481–1487.
(1) Clive, D. L. J.; Yu, M.; Wang, J.; Yeh, V. S. C.; Kang, S. Chem. ReV.
2005, 105, 4483–4514.
(2) Review on selenium-stabilized carbanions: Clive, D. L. J. Organic
Compounds of Sulphur, Selenium, and Tellurium; Royal Society of Chemistry:
London, 1981; Vol. 6, Specialist Periodical Reports, pp 112-126.
(3) (a) Sharpless, K. B.; Lauer, R. F. J. Am. Chem. Soc. 1973, 95, 2697–
2699. Review:(b) Clive, D. L. J. Tetrahedron 1978, 34, 1049–1132.
(4) Hoffmann, R. W.; Bewersdorf, M. Liebigs Ann. Chem. 1992, 643–653.
(5) Review on the chemistry of selenoacetals: Krief, A.; Hevesi, L. Janssen
Chim. Acta 1984, 2, 3–14.
(11) Mohapatra, S.; Bandyopadhyay, A.; Barma, D. K.; Capdevilla, J. H.;
Falck, J. R. Org. Lett. 2003, 5, 4759–4762.
(12) Marshall, J. A.; Garofalo, A. W.; Hinkle, K. W. Organic Syntheses;
Wiley: New York, 2004; Collect. Vol 10, pp 496-500.
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7419–7422.
(13) Mochida, K. Bull. Chem. Soc. Jpn. 1987, 60, 3299–3306.
(14) Still, W. C. J. Am. Chem. Soc. 1977, 99, 4836–4838.
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2397–2400.
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6018 J. Org. Chem. 2008, 73, 6018–6021
10.1021/jo8004292 CCC: $40.75 2008 American Chemical Society
Published on Web 07/02/2008

TABLE 1. Conversion of Aldehydes into
provement was found. When we made the selenides in THF,
with neither pyridine nor MeCN, we usually isolated some alkyl
selenide corresponding to the desired (phenylseleno)stannane
but having the Bu3Sn unit replaced by H; however, under the
optimum conditions (THF-MeCN-pyridine), formation of this
byproduct was usually insignificant.
r-(Phenylseleno)stannanesa
The (phenylseleno)stannanes are nonpolar, and the nonpolar
byproduct, PhSeSePh, was most conveniently removed by
reaction with NaBH4 and capture of the resulting phenylselenide
anion with BrCH2CO2H. As shown in Table 1, yields of
(phenylseleno)stannanes over the two steps from the aldehyde
are usually a little above 50%; this represents our optimum
conditions. The (phenylseleno)stannane 12b was a 3:2 mixture
of diastereoisomers. Since a few examples are known in which
an aldehyde is converted in well over 70% yield via its
R-hydroxystannane into the corresponding O-acyl derivative,8a,b,d
bromide,19 or MOM ether8a,9a,c,e,f,h it is probable that in our
sequence the alcohol f selenide conversion is inefficient.
Generation of selenium-stabilized carbanions from com-
pounds 9b-16b proceeded without incident, and only a few
experiments were needed to establish satisfactory conditions.6
These involve treatment of the R-(phenylseleno)stannane with
an excess of BuLi (2 equiv) in THF at -78 °C, usually for no
longer than 15 min (except for example x of Table 2), followed
by addition of the aldehyde (3 equiv). Yields are generally well
above 70% based on the R-(phenylseleno)stannane. In one case
(Table 2, entry xi) the intermediate carbanion was quenched
with D2O to afford the expected monodeuterated product 30 in
90% yield, indicating that selective cleavage of the C-Sn bond
occurs efficiently, at least in this case. However, a few of the
condensation yields were below 70%, and so the possibility was
considered of blocking attack of BuLi at selenium by making
the ArSe unit more hindered. To this end the known seleno-
cyanate 33 was prepared,20 but attempts to use it in place of
PhSeCN under the standard conditions17 for replacement of an
OH group gave low yields; hence the matter was not pursued.
a Yields refer to two steps from the aldehyde and are based on the
aldehyde as the limiting component.
on the LDA/Bu3SnH procedure.10,12,16 The crude R-hydroxys-
tannane 9a was then treated with PhSeCN-Bu3P17 under a
variety of conditions in attempts to optimize the yield of the
desired R-(phenylseleno)stannane 9b. Compound 9b was easily
handled and could be chromatographed over silica gel without
decomposition, unlike its precursor 9a. Attempts to chromato-
graph 9a over silica gel always resulted in significant loss (at
least 20%) of material, and TLC analysis using a plate developed
in two orthogonal directions confirmed that extensive decom-
position occurs. The alcohol f selenide conversion for 9a f
9b was tried in THF-MeCN mixtures with and without
pyridine, the yields being 33% (THF), 30% (1:3 THF-MeCN),
21% (1:0.13 THF-pyridine), and 54% (1:3:0.4 THF-MeCN-
pyridine).
As expected, the hydroxyselenides shown in Table 2 were
generally obtained as mixtures of syn and anti diastereoisomers;
in three cases the isolated hydroxyselenides (Table 2, compounds
25, 26, and 28) appeared (1H and 13C NMR) to be single
isomers.
Once we had gained some experience in making (phenylse-
leno)stannanes, we attempted to prepare the germanium analogs.
Deprotonation of Bu3GeH with LDA and addition to isovaler-
aldehyde did afford the desired R-germyl alcohol, which could
be converted into the R-germyl selenide 34,21 although the
overall yield was very low (17%). A few examples have been
reported of the formation of germyl alcohols by addition of
trialkylgermyl alkali metals to carbonyl compounds, although
Attempts were also made (using 9a) to introduce the PhSe
group via displacement of the corresponding tosylate, mesylate,
or iodide, but these experiments did not give improved yields
over the PhSeCN/Bu3P method. Instead of PhSeCN we tried
N-(phenylseleno)phthalimide-Bu3P18 (with 9a); again no im-
(19) Jeanjean, F.; Fournet, G.; Le Bars, D.; Gore´, J. Eur. J. Org. Chem. 2000,
1297–1305.
(16) For preparation of R-hydroxystannanes by use of silyl stannanes, see:
(a) Bhatt, R. K.; Ye, J.; Falck, J. R. Tetrahedron Lett. 1994, 35, 4081–4084. (b)
Busch-Petersen, J.; Bo, Y.; Corey, E. J. Tetrahedron Lett. 1999, 40, 2065–2068.
(17) Grieco, P. A.; Gilman, S.; Nishizawa, M. J. Org. Chem. 1976, 41, 1485–
1486.
(20) (a) Klapo¨tke, T. M.; Krumm, B.; Mayer, P.; Piotrowski, H.; Vogt, M. Z.
Anorg. Allg. Chem. 2003, 629, 1117–1123. (b) We made the selenocyanate from
the aryl iodide: Suzuki, H. Synthesis 1977, 640–641.
(21) For rare examples of systems with germanium and selenium attached
to the same carbon, see:(a) Ryazantsev, V. A.; Stadnichuk, M. D.; Petrov, A. A.
J. Gen. Chem. USSR 1980, 50, 1053–1059. (b) Wieber, M.; Schwarzmann, G.
Monatsh. Chem. 1969, 100, 74–78.
(18) Grieco, P. A.; Jaw, J. Y.; Claremon, D. A.; Nicolaou, K. C. J. Org.
Chem. 1981, 46, 1215–1217.
J. Org. Chem. Vol. 73, No. 15, 2008 6019

TABLE 2. Conversion of r-(Phenylseleno)stannanes into
ꢀ-Hydroxyselenides
access to these alcohols in a way that bypasses the need to
generate (phenylseleno)acetals.
Experimental Section
Tributyl[3-methyl-1-(phenylseleno)butyl]stannane (9b). BuLi
(1.6 M in hexane, 0.63 mL, 1.00 mmol) was added to a stirred and
cooled (-78 °C) solution of i-Pr2NH (0.15 mL, 1.1 mmol) in THF
(3 mL). Stirring was continued at -78 °C for 30 min, and the flask
was transferred to an ice bath. Bu3SnH (0.30 mL, 1.1 mmol) was
added, and stirring was continued for 15 min. The flask was then
transferred back to a cold bath at -78 °C and aldehyde 9 (0.055
mL, 0.50 mmol) was added dropwise. Stirring was continued at
-78 °C for 30 min, and the mixture was quenched with saturated
aqueous NH4Cl. The cold bath was removed, and the mixture was
allowed to reach room temperature (ca. 30 min). The aqueous phase
was extracted with EtOAc, and the combined organic extracts were
dried (Na2SO4) and evaporated. The crude product (9a) was left
under oilpump vacuum for 15 min and used directly in the next
step.
The above crude hydroxystannane was dissolved in 3:1
MeCN-THF (4 mL), and pyridine (0.4 mL, 5.0 mmol) was added.
The mixture was cooled to 0 °C, and PhSeCN (0.12 mL, 1.0 mmol)
and Bu3P (0.25 mL, 1.0 mmol) were added successively at a fast
dropwise rate. The ice bath was removed, and stirring was continued
for 4 h. The solvent was evaporated, and the residue was dissolved
in 4:1 THF-MeOH (5 mL). The stirred solution was cooled to 0
°C, and an excess of NaBH4 (100 mg) was added. Stirring was
continued for 20 min, an excess of BrCH2CO2H (400 mg) was
added, and the ice bath was removed. Stirring was continued for
30 min, the mixture was diluted with EtOAc, and saturated aqueous
NaHCO3 was added. The mixture was extracted with EtOAc, and
the combined organic extracts were dried (Na2SO4) and evaporated.
Flash chromatography of the residue over silica gel (1 × 25 cm),
using hexane, gave 9b (138 mg, 54%) as a colorless oil: FTIR
(CH2Cl2, cast) 3071, 2956, 2926, 2870, 2854 cm-1 1H NMR
;
(CDCl3, 300 MHz) δ 0.76-1.07 (m, 21 H), 1.25-1.40 (sextet, J
) 7.1 Hz, 6 H), 1.45-1.68 (m, 7 H), 1.77-1.83 (m, 2 H), 3.05
(dd, J ) 8.4, 7.5 Hz, 1 H), 7.2-7.29 (m, 3 H), 7.5 (dd, J ) 8.1,
1.5 Hz, 2 H); 13C NMR (CDCl3, 100 MHz) δ 9.9 (t), 13.7 (q), 22.0
(q), 22.7 (q), 23.0 (d), 27.4 (t), 28.8 (d), 29.2 (t), 45.6 (t), 126.4
(d), 128.8 (d), 132.3 (d), 132.6 (s); exact mass m/z calcd for
C23H4280Se118Sn 516.14679, found 516.14617.
2,7-Dimethyl-5-(phenylseleno)octan-4-ol (20). BuLi (1.6 M in
hexane, 0.12 mL, 0.19 mmol) was added dropwise to a stirred and
cooled (-78 °C) solution of 9b (49 mg, 0.095 mmol) in THF (3
mL) (Ar atmosphere). Stirring was continued for 15 min at -78
°C, and a solution of isovaleraldehyde (0.03 mL, 0.29 mmol) in
THF (1 mL) was added dropwise (ca. 1 min). Stirring was continued
for 30 min and the mixture was quenched with saturated aqueous
NH4Cl. The cooling bath was removed and stirring was continued
for 30 min. The aqueous phase was extracted with EtOAc, and the
combined organic extracts were dried (Na2SO4) and evaporated.
Flash chromatography of the residue over silica gel (0.5 × 10 cm),
using 5:95 t-BuOMe-CH2Cl2, gave 20 (19 mg, 64%) as a colorless
a Ratio of diastereoisomers is given in parentheses. b Contains slight
impurities.
1
oil: FTIR (CH2Cl2, cast) 3455, 3072, 2956, 2931, 2869 cm-1; H
NMR (CDCl3, 400 MHz) (4:1 mixture of stereoisomers) δ
0.81-0.98 (m, 12 H), 1.17-1.25 (m, 1 H), 1.33-1.53 (m, 2 H),
1.54-1.65 (m, 1 H), 1.70-1.82 (m, 1 H), 1.85-1.96 (m, 0.8 H),
1.98-2.08 (m, 0.2 H), 2.24 (d, J ) 5.6 Hz, 0.8 H), 2.30 (d, J )
5.3 Hz, 0.2 H), 3.13-3.20 (m, 0.2 H), 3.32-3.39 (m, 0.8 H),
3.55-3.63 (m, 0.2 H), 3.67-3.75 (m, 0.8), 7.25-7.30 (m, 3 H),
7.56-7.60 (m, 2 H); 13C NMR (CDCl3, 100 MHz) δ 21.4 (q), 21.6
(q), 21.8 (q), 21.9 (q), 23.1 (q), 23.3 (q), 23.3 (q), 23.5 (q), 24.8
(d), 24.9 (d), 26.2 (d), 26.3 (d), 39.0 (t), 41.2 (t), 42.5 (t), 44.0 (t),
the process can be problematic.22 This step was not investigated,
however, because germanium/lithium exchange under our usual
conditions did not appear to take place, as judged by trapping
experiments with D2O or isovaleraldehyde.
(22) (a) Kruglaya, O. A.; Bravo-Zhivotovskii, D. A.; Vyazankin, N. S. J. Gen.
Chem. USSR 1979, 46, 1847. (b) Bulten, E. J.; Noltes, J. G. J. Organomet. Chem.
1971, 29, 409–417.
Formation of allylic alcohols from ꢀ-hydroxyselenides is a
well-established reaction,3 and so the present route provides
6020 J. Org. Chem. Vol. 73, No. 15, 2008

54.7 (d), 70.7 (d), 71.5 (d), 127.5 (d), 127.6 (d), 128.7 (s), 128.9
(d), 129.0 (d), 129.3 (s), 134.5 (d), 134.9 (d); exact mass m/z calcd
for C16H26O80Se 314.11490, found 314.11466.
Supporting Information Available: NMR spectra for
9b-16b, 21-32, and 34 and experimental procedures for
10b-16b, 21-32, and 34 This material is available free of
charge via the Internet at http://pubs.acs.org.
Acknowledgment. We thank the Natural Sciences and
Engineering Research Council of Canada for financial support.
JO8004292
J. Org. Chem. Vol. 73, No. 15, 2008 6021