Regio- and stereospecific alkyl and alkynyl substitution reactions of epoxy selenides with organoaluminums via episelenonium ions

Article abstract of DOI:10.1016/j.tetlet.2003.12.137

Regio- and stereospecific alkyl and alkynyl substitution reactions of epoxy selenides with organoaluminum reagents have been developed, which proceed via episelenonium ion intermediates to give the C2 alkyl substitution products with double inversion of t

Full text of DOI:10.1016/j.tetlet.2003.12.137

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 1911–1913
Regio- and stereospecific alkyl and alkynyl substitution reactions of
epoxy selenides with organoaluminums via episelenonium ions
Minoru Sasaki, Mitsuru Hatta, Keiji Tanino and Masaaki Miyashita*
Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan
Received 22 November 2003; revised 19 December 2003; accepted 25 December 2003
Abstract—Regio- and stereospecific alkyl and alkynyl substitution reactions of epoxy selenides with organoaluminum reagents have
been developed, which proceed via episelenonium ion intermediates to give the C2 alkyl substitution products with double inversion
of the configuration and the C1 alkynyl substitution products with migration of the arylseleno group in high yields, respectively.
Ó 2004 Elsevier Ltd. All rights reserved.
Stereoselective, epoxide-opening reactions are important
transformations in organic synthesis and are widely used
as the key reaction in natural product synthesis.
Although a variety of regio- and/or stereoselective
R'
O
R'
R'
OH
R'3Al
Al
O
2
2
1
R
SeAr
R
1
SeAr
R
+
double
R'
Se Ar
inversion
N
epoxide-opening reactions via an S 2 process have been
episelenonium ion
intermediates
2
reported so far, the stereospecific alkyl or alkynyl
substitution reaction of epoxides, which proceeds with
retention of the configuration, is scarcely known.
Recently, Saigo et al. and we have independently
Figure 1. Substitution reaction of epoxy selenides with organoalumi-
num reagents.
3;4
4;5
reported stereospecific alkyl and alkynyl substitu-
tion reactions of epoxy sulfides with organoaluminum
reagents, which proceed via episulfonium ion interme-
diates to give the substitution products with double
inversion of the configuration, that is, with retention of
tion of trans-1-arylseleno-4-benzyloxy-2,3-epoxybutane
(1) with (CH ) Al. For the purpose, three epoxy aryl-
3 3
selenides, 1a, 1b, and 1c, were prepared according to the
Grieco–Nishizawa protocol. As a result, remarkable
discrepancy was observed depending on the aryl group
on a selenium atom of 1 (Scheme 1).
8
6
;7
the configuration, respectively.
With a view to
exploiting the stereospecific substitution reaction of
epoxides with double inversion of the configuration, we
examined the reaction of epoxy selenides with organo-
aluminum reagents. We report herein the regio- and
stereospecific alkyl and alkynyl substitution reactions of
epoxy selenides with organoaluminums, which proceed
via episelenonium ion intermediates to afford the C2
alkyl substitution products with double inversion of the
configuration and the C1 alkynyl substitution products
with migration of the arylseleno group in high yields,
respectively (Fig. 1).
Thus, the reaction of 1a having a phenylseleno group
with (CH ) Al afforded the allylic alcohol 3, a reduction
3 3
product, as the major product together with a minor
amount of the methylation product 2 with double
inversion of the configuration. Notably, the reaction is
9
OH
OH
O
BnO
BnO
2
BnO
SeAr
SeAr
Me
1
2
3
To gain insight into the reaction of an epoxy selenide
with organoaluminums, we initially examined the reac-
1
1
a: Ar = phenyl
9%
90%
10%
b: = p-nitrophenyl
86%
92%
1
c: = o-nitrophenyl
trace
Keywords: Epoxide; Selenide; Substitution reaction; Organoaluminum.
*
Corresponding author. Tel.: +81-117062705; fax: +81-117064920;
e-mail: miyasita@sci.hokudai.ac.jp
Scheme 1. Reactions of 1 with (CH
)
3
)
out with (CH Al (3 equiv) in CH Cl
3
Al. The reactions were carried
at )30 °C for 30 min.
3
3
2
2
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.12.137

1912
M. Sasaki et al. / Tetrahedron Letters 45 (2004) 1911–1913
in contrast with that of the corresponding epoxy sulfide
with (CH Al giving rise to the methylation product
with double inversion of the configuration exclusively.
Interestingly, we found that an aryl group bearing a
strongly electron-withdrawing substituent improved the
ratio of 2 and 3 dramatically. For example, the reaction
OH
Me2AlC CTMS
CH2Cl2
O
BnO
3 3
)
BnO
1
C CTMS
SeAr
SeAr
-30˚C, 30 min
1
c
4
92%
Scheme 2. The reaction of 1c with an ethynylaluminum reagent.
3 3
of p-nitrophenylselenenyl epoxide 1b with (CH ) Al
afforded 2 and 3 in 86% and 10% yields, respectively,
and o-nitrophenylselenenyl epoxide 1c gave the meth-
ylation product 2 exclusively in 92% yield. These results
suggest that a nitro group plays an important role to
prevent the b-elimination pathway by destabilizing the
Interestingly, the reaction occurred regioselectively at
the C1 position through migration of the arylseleno
10
group to give the substitution product 4 in 92% yield.
None of the C2 alkynyl substitution product with dou-
ble inversion of the configuration was obtained. This
result is in sharp contrast with that of the reaction of
epoxy sulfides with the same aluminum reagent giving
þ
ArSe species. Thus, o-nitrophenylselenenyl epoxide
was found to be best substrate for the present reaction.
The intriguing preliminary results led us to examine the
reactions of various trans- and cis-o-nitrophenylselene-
5
rise to the C2 alkynylation products stereoselectively.
nyl epoxides with (CH
in Table 1.
3
)
3
Al. The results are summarized
Therefore, we investigated the reaction of various 1-o-
nitrophenylselenenyl epoxides with dimethyl[2-(tri-
methylsilyl)ethynyl]aluminum. The results are summa-
rized in Table 2.
As can be seen from the table, all the reactions pro-
ceeded stereospecifically to give the single methyl sub-
stitution products, respectively, with double inversion of
the configuration in high yields. Thus, syn-substitution
products are stereospecifically obtainable from trans-
epoxy selenides, while anti-substitution products are
exclusively produced from cis-epoxy selenides by the
present method.
As shown, all reactions other than entry 4 proceeded
stereospecifically through migration of the arylseleno
group to give the C1 alkynylation products as a single
product, respectively, regardless of the stereochemistry
of the epoxides. These results demonstrate that the
reaction of an epoxy selenide with an organoaluminum
reagent proceeds regio- and stereospecifically via an
episelenonium ion intermediate and the reaction with
In turn, we focused on the alkynyl substitution reaction
of epoxy selenides with alkynylaluminum reagents to
explore another synthetic utility via episelenonium ions.
First, we examined the reaction of 1c with dimethyl[2-
3 3
(CH ) Al gives the C2 methyl substitution product with
double inversion of the configuration, while the reaction
with an alkynylaluminum reagent affords the C1 sub-
stitution product with migration of the arylseleno group,
as a single product, respectively (Fig. 2).
(
(
trimethylsilyl)ethynyl]aluminum as a model reaction
Scheme 2).
Table 1. C2-selective alkyl substitution reactions of epoxy selenides
a;b
Table 2. Alkynyl substitution reactions of epoxy selenides with
a;b
dimethyl[2-(trimethylsilyl)ethynyl]aluminum
with (CH
3
)
3
Al
c
d
c
d
Entry
Substrate
Product
Yield (%)
89
Entry Substrate
Product
Yield (%)
87
O
OH
O
OH
nPr
SeAr
nPr
SeAr
1
2
3
1
2
3
4
nPr
nPr
SeAr
C CTMS
Me
OH
SeAr
OH
O
O
92
77
82
92
80
83
BnO
SeAr
BnO
BnO
SeAr
BnO
SeAr
C
CTMS
Me
SeAr
O
OH
O
OH
SeAr
SeAr
SeAr
SeAr
nPr
nPr
nPr
nPr
SeAr
C
CTMS
Me
SeAr
OH SeAr
OH SeAr
4
O
O
BnO
BnO
BnO
BnO
Me
C
CTMS
a
a
An epoxy selenide was treated with (CH
30 °C for 30 min.
3
)
3
Al (3 equiv) in CH
2
Cl
2
at
An epoxy selenide was treated with the aluminum reagent (3 equiv) in
CH Cl
at )30 °C for 30 min.
)
2
2
b
c
b
c
Ar ¼ o-Nitrophenyl.
Ar ¼ o-Nitrophenyl.
All products were obtained as a single stereoisomer, respectively.
Isolated yield.
All products were obtained as a single stereoisomer, respectively.
Isolated yield.
d
d

M. Sasaki et al. / Tetrahedron Letters 45 (2004) 1911–1913
1913
OH
Aid for Scientific Research on Priority Areas (A)
ÔExploitation of Multi-Element Cyclic MoleculesÕ (No.
13029003), and Sprout Research (No. 14654138) are
gratefully acknowledged. M.S. thanks JSPS for a pre-
doctoral fellowship.
path a
2
R
SeAr
Me
O
Me
R'
R': Me
R'
O
2
Al
Me2AlR'
C2 products
R
1
SeAr
a
b
R
+
OH
Ar = o-nitrophenyl
Se Ar
path b
R
1
SeAr
R'
R': alkynyl
episelenonium ions
C1 products
References and notes
Figure 2. Substitution reaction of epoxy selenides with organoalumi-
num reagents.
1. For reviews, see: (a) Klunder, J. M.; Posner, G. H. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Pergamon: Oxford, 1991; Vol. 3, pp 207–239,
Chapter 1.5; (b) Knight, D. W. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon:
Oxford, 1991; Vol. 3, pp 241–270, Chapter 1.6; (c) Garratt,
P. J. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3, pp
271–292, Chapter 1.7; (d) Posner, G. H. Org. React. 1975,
OH
H2O2
pyridine
OH
R
C
CTMS
R
C CTMS
THF
˚C to rt
SeAr
0
4
: R = BnOCH2
93% (E:Z = 95:5)
92% (E:Z = 89:11)
n
5
: R = Pr
2
2, 253–400; (e) Lipshutz, B. H.; Sengupta, S. Org. React.
Scheme 3. Conversion of the C1 alkynyl substitution products to
enyne system.
1992, 41, 135–631; (f) Hanson, R. M. Chem. Rev. 1991, 91,
437–475; (g) Bonini, C.; Righi, G. Synthesis 1994, 225–
2
38.
2
. For examples of alkyl and alkynyl substitution reactions
of epoxides with inversion of the configuration, see: (a)
Johnson, M. R.; Nakata, T.; Kishi, Y. Tetrahedron Lett.
Although the origin of the different behavior between
(
3 3
CH ) Al and an alkynylaluminum reagent is not clear,
the exceptional result of entry 4 in Table 2 indicates that
steric hindrance around the reaction site also has influ-
ence on the regioselectivity.
1
979, 20, 4343–4346; (b) Suzuki, T.; Saimoto, H.; Tom-
ioka, H.; Oshima, K.; Nozaki, H. Tetrahedron Lett. 1982,
23, 3597–3600; (c) Tius, M. A.; Fauq, A. H. J. Org. Chem.
1
983, 48, 4131–4132; (d) Flippin, L. A.; Brown, P. A.;
Jalali-Araghi, K. J. Org. Chem. 1989, 54, 3583–3596; (e)
Miyashita, M.; Hoshino, M.; Yoshikoshi, A. J. Org.
Chem. 1991, 56, 6483–6485; (f) Sasaki, M.; Tanino, K.;
Miyashita, M. Org. Lett. 2001, 3, 1765–1767.
. Liu, C.; Hashimoto, Y.; Kudo, K.; Saigo, K. Bull. Chem.
Soc. Jpn. 1996, 69, 2095–2105.
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Tetrahedron Lett. 1999, 40, 9267–9270.
5. Sasaki, M.; Tanino, K.; Miyashita, M. J. Org. Chem.
2001, 66, 5388–5394.
. For other substitution reactions of epoxy sulfides via
episulfonium ions, see: (a) Miyauchi, H.; Nakamura, T.;
Ohashi, N. Bull. Chem. Soc. Jpn. 1995, 68, 1731–1737; (b)
Hayakawa, H.; Okada, N.; Miyashita, M. Tetrahedron
Lett. 1999, 40, 3191–3194; (c) Hirai, A.; Tonooka, T.;
Wakatsuki, K.; Tanino, K.; Miyashita, M. Angew. Chem.,
Int. Ed. 2002, 41, 819–821.
. For alkyl and alkynyl substitution reactions of epoxy
amines with double inversion of the configuration, see:
Liu, C.; Hashimoto, Y.; Saigo, K. Tetrahedron Lett. 1996,
34, 6177–6180.
In order to demonstrate the synthetic potential of the
products bearing a seleno group, the alkynyl substitu-
tion products were converted to a conjugated enyne
system by elimination of the corresponding selenox-
3
4
11
ides. Thus, the products 4 and 5 were treated with
in THF containing pyridine to afford the corre-
2 2
H O
sponding enyne compound in excellent yield, respec-
tively (Scheme 3). As anticipated, the products having
an E-olefin were produced predominantly.
6
In summary, we have developed new and stereospecific
alkyl and alkynyl substitution reactions of epoxy sele-
nides with organoaluminum reagents via episelenonium
ion intermediates. The C1 alkynylation products were
efficiently converted to a conjugated enyne system by
elimination of selenoxides. Since a variety of optically
active epoxy selenides are readily available from the
corresponding epoxy alcohols, the present method pro-
vides an extremely useful methodology in organic syn-
thesis including natural product synthesis.
7
8. Grieco, P. A.; Gilman, S.; Nishizawa, M. J. Org. Chem.
976, 41, 1485–1486.
1
9
. In order to confirm the stereochemistry of the products,
authentic samples were prepared from the corresponding
1,3-diols through a selective selenylation reaction of the
primary alcohol moiety.
2
f
8
Acknowledgements
1
0. For a review of rearrangement reactions of 1-hetero-2,3-
epoxides, see: Rayner, C. M. Synlett 1997, 11–21.
Financial supports from the Ministry of Education,
Science, Sports and Culture of Japan (a Grant-in-Aid
for Scientific Research (A) (No. 12304042), a Grant-in-
11. For a review of this type of elimination reactions, see:
Reich, H. J.; Wollowitz, S. Org. React. 1993, 44, 1–296.