Reaction of lithium eneselenolates derived from selenoamides with ketones: A highly diastereoselective synthetic route to β,β-disubstituted β-hydroxy selenoamides

Article abstract of DOI:10.1016/S0040-4039(02)02877-0

The reaction of lithium eneselenolates generated from selenoamides with a variety of ketones proceeded smoothly at -78°C to give the corresponding β,β-disubstituted β-hydroxy selenoamides in moderate to good yields. The reaction showed high diastereoselectivity. The products obtained were converted to the corresponding amides by reacting them with cyclohexene oxide.

Full text of DOI:10.1016/S0040-4039(02)02877-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 1343–1346
Reaction of lithium eneselenolates derived from selenoamides
with ketones: a highly diastereoselective synthetic route to
b,b-disubstituted b-hydroxy selenoamides
Toshiaki Murai,* Masato Ishizuka, Akiko Suzuki and Shinzi Kato
Department of Chemistry, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan
Received 20 November 2002; revised 18 December 2002; accepted 20 December 2002
Abstract—The reaction of lithium eneselenolates generated from selenoamides with a variety of ketones proceeded smoothly at
−
78°C to give the corresponding b,b-disubstituted b-hydroxy selenoamides in moderate to good yields. The reaction showed high
diastereoselectivity. The products obtained were converted to the corresponding amides by reacting them with cyclohexene oxide.
2003 Elsevier Science Ltd. All rights reserved.
©
The aldol condensation reaction of enolates from1
amides and thioamides has been studied in great detail.
On the other hand, much less attention has been paid
tures, the reaction gave a complex mixture along with
the recovered starting selenoamide 1a.
2
to the reaction of these enolates with ketones. To the
best of our knowledge, there has been no report on the
stereochemical aspects of this reaction except for the
2
d
reaction with a-tetralone.
Meanwhile, syntheses,
(1)
structure and reaction of compounds with a selenocar-
bonyl group have recently been developed in great
3
depth. Among them, selenium isologues of amides, i.e.
4
selenoamides, have received particular attention. Dur-
ing the course of our studies on the synthesis and
5
reactivity of selenoamides, we recently found that sele-
nium isologues of lithium enolates, i.e. lithium enesel-
enolates generated from selenoamides smoothly
underwent Michael addition to a,b-unsaturated
Next, a variety of selenoamides 1 and ketones 3 were
subjected to the reaction. The results are summarized in
Table 1.
5
a
ketones. We report here the addition reaction of
lithium eneselenolates to aliphatic and aromatic ketones
with high diastereoselectivity.
A similar reaction of 1a with cyclic ketones 3b and 3c
proceeded smoothly to give the corresponding
selenoamides 4b and 4c in moderate yields (entries 1
and 2). In the reaction with methyl ethyl ketone 3d, two
diastereomers of the products 4d were obtained in
nearly equal amounts (entry 3). On the other hand, the
reaction of selenoamides 1a and 1c with methyl isopro-
pyl ketone 3e showed high diastereoselectivity to give
exclusively anti isomers 4e and 4j (entries 4 and 9),
whereas the reaction with pinacolone 3f did not take
place and the starting selenoamide 1a was recovered
Initially, lithium eneselenolate 2a was generated from
selenoamide 1a and LDA at 0°C in THF (Eq. (1)). To
the reaction mixture was then added acetone 3a and
water successively at −78°C. After the usual work-up,
b,b-disubstituted b-hydroxy selenoamide6 4a was
obtained as a deep yellow oil in 70% yield. The reac-
tion must be carried out at −78°C. At higher tempera-
Keywords: selenoamides; lithium eneselenolates; b,b-disubstituted b-
hydroxy selenoamides; organoselenium compounds; diastereoselectiv-
ity.
(
entry 5). Aromatic ketones could also be used in the
reaction of lithium eneselenolates 2 (entries 6, 7, and
10). As for acetophenone 3h, anti isomers 4h and 4k
were obtained as sole products (entries 7 and 10).
*
Corresponding author. Tel.: +81-58-293-2614; fax +81-58-293-2614;
e-mail: mtoshi@cc.gifu-u.ac.jp
0
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02877-0

1
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T. Murai et al. / Tetrahedron Letters 44 (2003) 1343–1346
a
Table 1. Reaction of lithium eneselenolates 2 with ketones 3
1
3
The stereochemistry of the product 4h was un-
4k was estimated by comparing their C NMR spectra
8
equivocally determined by X-ray molecular structure
with that of 4h. To compare the stereoselectivity in the
7
analysis. The ORTEP drawing of 4h is shown in Fig.
present reaction with that of ordinary amides 5, these
compounds were reacted with LDA and ketone 3h to
give a mixture of two diastereomers, albeit in rather
low yields (Eq. (2)).
1.
The stereochemistry of the major products 4e, 4j, and

T. Murai et al. / Tetrahedron Letters 44 (2003) 1343–1346
1345
complex mixture instead of 6b. The procedure for the
deoxygenation of oxiranes to give olefins with
11
selenoamides was then used for the conversion of
b,b-disubstituted b-hydroxy selenoamides 4. The reac-
tion of 4h and 4j with cyclohexene oxide proceeded
with high efficiency to give the corresponding amides 6b
12
and 6c in high yields (Eq. (4)).
Figure 1. ORTEP drawings of 4h. Selected bond lengths (A),
,
angles (°), and torsion angles (°): Se(1)ꢀC(1)=1.834(5);
C(1)ꢀN(1)=1.318(7). Se(1)ꢀC(1)ꢀN(1)=120.2(4); Se(1)ꢀC(1)ꢀ
C(6)=121.0(4). Se(1)ꢀC(1)ꢀC(6)ꢀC(7)=60.4(6); C(1)ꢀC(6)ꢀ
C(7)ꢀO(1)=70.1(6).
(4)
In summary, we have demonstrated the addition reac-
tion of lithium eneselenolates to ketones. The b,b-di-
substituted b-hydroxy selenoamides were obtained in
moderate to good yields, and the reaction exhibited
high stereoselectivity. Further studies on the present
reaction and the synthetic application of the resulting
selenoamides obtained are underway.
(
2)
The difference in the stereochemical course of the reac-
tion between selenoamides 1 and amides 5 may exit
because the reaction of 1 is thermodynamically con-
trolled, and may give more stable products out of two
possible diastereomers. The following result may indi-
Acknowledgements
This work was supported in part by a Grant-in-Aid for
Scientific Research (C) (No. 12650852) from the Min-
istry of Education, Culture, Sports, Science and Tech-
nology, Japan.
9
rectly support this notion. In the reduction of b,b-di-
substituted b-hydroxy selenoamide 4e, the corresponding
amine was not formed. Instead, alcohol 8 and amine 9
were obtained as products in high yields (Eq. (3)).
References
1
2
3
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These products are formed by reduction of the corre-
sponding ketone 3e and lithium eneselenolate 2a, which
were derived from the cleavage of 4e via 7.
Finally, the conversion of b-hydroxy selenoamides 4 to
amides was examined. Although the conversion of
10
selenoamides to amides with per acids is well known,
®
the reaction of 4h with MCPBA or Oxone gave a

1
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T. Murai et al. / Tetrahedron Letters 44 (2003) 1343–1346
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2
4
099; (c) Koketsu, M.; Takenaka, Y.; Ishihara, H. Syn-
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15
21
W
thesis 2001, 38, 503; (d) Zhang, P.-F.; Chen. Z.-C. J.
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Koketsu, M.; Fukuta, Y.; Nada, F. J. Am. Chem. Soc.
space group P2 /c (c14), a=8.804(2), b=13.605(3), c=
1
3
12.211(1)
A
,
,
i=91.74(1)°, V=1461.8(4)
A
,
,
Z=4,
−
3
−1
Dcalcd=1.410 g cm , v (Mo Ka)=25.58 cm , T=296 K,
2
001, 123, 8408; (f) Koketsu, M.; Takenaka, Y.; Hira-
R=0.143, R =0.057, 1271 reflections, GOF=1.00. Crys-
1
matsu, S.; Ishihara, H. Heterocycles 2001, 55, 1181; (g)
Bhattacharyya, P.; Woollins, J. D. Tetrahedron Lett.
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2
001, 42, 5949; (h) Koketsu, M.; Okayama, Y.; Aoki, H.;
Ishihara, H. Heteroatom Chem. 2002, 13, 195; (i) Zhao,
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anti isomers were observed in higher fields than those of
syn isomers.
3
383.
. (a) Murai, T.; Suzuki, A.; Ezaka, T.; Kato, S. Org. Lett.
000, 2, 311; (b) Murai, T.; Mutoh, Y.; Kato, S. Org.
5
9. As in the reduction of amides, the reaction of
2
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4
5c
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11. Ogawa, A.; Miyake, J.; Murai, S.; Sonoda, N. Tetra-
6
. Typical experimental procedure for the reaction of a
lithium eneselenolate with a ketone: In a 20-mL two-
necked flask, to a THF solution (2 mL) of LDA (1.2
mmol) was added selenoamide 1a (0.19 g, 1.0 mmol) at
hedron Lett. 1985, 26, 669.
12. As an alternative procedure for the synthesis of b,b-di-
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0
°C, and the mixture was stirred at 0°C for 10 min under
a nitrogen atmosphere. Acetone (3a) (0.15 mL, 2 mmol)
was then added to the reaction mixture, followed by
water. The reaction mixture was poured onto water and
extracted with Et O (20 mL). The organic layer was dried
2
over MgSO and concentrated in vacuo. The residue was
4