Aldol-type condensation reactions of lithium eneselenolates generated from selenoamides with aldehydes

Article abstract of DOI:10.1039/b100198l

Aldol-type condensation reactions of α-monosubstituted selenoamides with a variety of aldehydes are examined to furnish β-hydroxy selenoamides in good to high yields. The use of selenoamides derived from dibenzylamine exhibits high stereoselectivity. As for the reaction with aliphatic aldehydes selenoamides show better yields and selectivity compared with ordinary amides. Conversion of the resulting β-hydroxy selenoamides to 1,3-amino alcohols is also described.

Full text of DOI:10.1039/b100198l

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Aldol-type condensation reactions of lithium eneselenolates
generated from selenoamides with aldehydes
Toshiaki Murai, Akiko Suzuki and Shinzi Kato*
1
Department of Chemistry, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193,
Japan
Received (in Cambridge, UK) 2nd January 2001, Accepted 17th July 2001
First published as an Advance Article on the web 19th September 2001
Aldol-type condensation reactions of α-monosubstituted selenoamides with a variety of aldehydes are examined to
furnish β-hydroxy selenoamides in good to high yields. The use of selenoamides derived from dibenzylamine exhibits
high stereoselectivity. As for the reaction with aliphatic aldehydes selenoamides show better yields and selectivity
compared with ordinary amides. Conversion of the resulting β-hydroxy selenoamides to 1,3-amino alcohols is
also described.
Introduction
Aldol condensation reactions of lithium enolates1 have been
studied in great depth. Similar reactions using lithium thioenol-
ates have also been explored.2 In contrast, much less attention
has been paid to the chemistry of the selenium counterparts of
enolates, i.e., eneselenolates. However, recent studies on the
organoselenium compounds3 have proved their importance in a
variety of fields such as material chemistry, biological chemistry
and organic synthesis. As a result, synthetic reactions leading to
new types of organoselenium compounds are in demand, and
eneselenolates can be key reactive species in such reactions.
Generation of metal eneselenolates has been generally attained
by the insertion reaction of a selenium atom into vinyl metallic
species.4 In contrast, only limited examples of the deproton-
ation of selenocarbonyl compounds have been studied5 despite
the recent ongoing progress of their chemistry.6 This is partly
because of the instability of enolizable selenocarbonyl com-
Scheme 1
pounds and of the lack of methods for their simple synthesis.
reaction, selenoamides bearing a variety of amino groups were
Very recently, we established efficient methods for the synthesis
synthesized according to the literature7d and were treated with
of selenoamides [RC(Se)NRЈ2]7 and selenothioic acid S-esters
LDA and aldehyde 3a. As a result, the use of N,N-dibenzyl-
pent-4-eneselenoamide 1b gave β-hydroxy selenoamide 4b in
[RC(Se)SRЈ]8 starting from terminal acetylenes. Deprotonation
of the obtained selenocarbonyl compounds9,10 proceeded in a
83% yield with better diastereoselectivity.
similar way to that of ordinary carbonyl and thiocarbonyl
Then, a wide range of aldehydes 3 were employed as sub-
strates for the aldol condensation reaction of selenoamide 1b
(Scheme 2). The results are summarized in Table 1. Initially,
compounds. The reaction of lithium eneselenolates of a
selenoacetamide with aldehydes took place accompanied by
dehydration to give α,β-unsaturated selenoamides, and β-
α,β-unsaturated aldehydes 3b–3f were treated with lithium
hydroxy selenoamides were not obtained as products.9a We have
eneselenolate 2b (entries 1–7). In all cases the 1,2-addition of
2b to aldehydes 3b–3f proceeded smoothly to give the products
4c–4g in moderate to good yields with selectivities from 71 : 29
further disclosed that Michael addition of lithium eneselenol-
ates of α-monosubstituted selenoamides to α,β-unsaturated
ketones and esters was complete within a few seconds with high
efficiency.9b We report herein aldol-type condensation reactions
of lithium eneselenolates of α-monosubstituted selenoamides
and their stereoselectivity. The conversion of the resulting β-
hydroxy selenoamides to 1,3-amino alcohols is also described.
Results and discussion
At the outset, the reaction of lithium eneselenolates generated
from pent-4-eneselenoamides 1 with crotonaldehyde 3a was
carried out in Et2O (Scheme 1). The reaction of 2a with 3a was
complete within a few seconds to give 1,2-adduct 4a in 70%
yield as a stable mixture of two diastereomers in a ratio of
55 : 45. No product derived from the Michael addition of 2a
to 3a was detected. To improve the stereoselectivity of the
Scheme 2
DOI: 10.1039/b100198l
J. Chem. Soc., Perkin Trans. 1, 2001, 2711–2716
2711
This journal is © The Royal Society of Chemistry 2001

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Table 1 Reaction of pent-4-eneselenoamide 1b with aldehydes 3a
Entry
1
Aldehyde
Product yield (%)b
Diastereomer ratio (threo : erythro)c
4c 70
88 : 12
2
4d 81
93 : 7
3
4
4e 78
4f 57
74 : 26
77 : 23
5
6
4f 64d
4g 81
68 : 32
71 : 29
7
8
4g 45d
4h 84
4 : 96
89 : 11
9
4i 87
94 : 6
10
11
12
4j 27e
4k 29
4l 49
>99 : <1
95 : 5
83 : 17
a Selenoamide 1b (1 mmol) was treated with LDA (1.2 mmol) in Et2O or THF (5 mL) at 0 ЊC for min, then to the reaction mixture was added an
aldehyde 3 (1.2 mmol) at Ϫ78 ЊC and stirred for 10 min at Ϫ78 ЊC. b Isolated yield. c The ratio of diastereomers was determined by 1H NMR
spectroscopy of crude products. d The reaction was carried out in the presence of TMEDA (2.4 mmol). e After the addition of aldehyde 3i the
reaction mixture was stirred for 10 min at Ϫ78 ЊC, raised to 0 ЊC, and stirred for 5 min at 0 ЊC.
of TMEDA to the reaction mixture lowered the selectivity. For
example, the diastereoselectivity of the product 4f decreased to
68 : 32 from 77 : 23 (entry 5). As an exceptional case the reac-
tion with (E)-α-methylcinnamaldehyde 3f in the presence of
TMEDA gave the anti isomer of the product 4g with a selec-
tivity of 4 : 96 (entry 7). The stereoselectivity of the reaction
with aliphatic and aromatic aldehydes was also examined. The
use of acetaldehyde 3g and isobutyraldehyde 3h as aliphatic
aldehydes gave β-hydroxy selenoamides 4h and 4i with high
stereoselectivity and in good yields (entries 8 and 9). The
reaction of aromatic aldehydes 3i and 3k also showed high
stereoselectivities, although the yields of the products 4j–4l
were moderate (entries 10–12). The applicability of the dia-
stereoselective aldol-type condensation of selenoamides was
further examined. N,N-Dibenzyl-α-phenyl(selenoacetamide)
1c was treated with LDA and aldehyde 3h to give the corre-
sponding β-hydroxy selenoamide 4m in 86% yield as a mixture
of diastereomers in a ratio of 77 : 23 (Scheme 3).
To compare the reactivity and selectivity of lithium ene-
selenolates 2b with those of the lithium enolate generated from
Fig. 1 ORTEP drawing of compound 4d with atomic-numbering
amide 5 the enolate was treated with aldehydes. The results are
scheme.
summarized in Table 2. In the reaction of the lithium enolate
generated from 5 with aldehydes 3a and 3c both the yields
to 93 : 7 (entries 1–4, 6). The α,β-unsaturated aldehydes with
substituents at the β-position exhibited low selectivity, whereas
aldehyde 3c gave a highly stereoselective reaction. The X-ray
structure of the crystalline product 4d confirmed that the syn
isomer of 4d was selectively formed (Fig. 1). The stereo-
chemistry of all other products 4 was determined on the basis
of the similarities of 1H NMR and 13C NMR chemical shifts.11
The effect of an additive on the diastereoselectivity in the
aldol reaction of 2 was next examined. However, the addition
and diastereoselectivity of the products 6a and 6b were nearly
equal to those obtained with lithium eneselenolate 2b (entries 1
and 2). On the other hand, in the reaction with aldehydes 3g
and 3h, selenoamide 1b gave both higher yields and better
diastereoselectivity.
Finally, β-hydroxy selenoamides were converted to 1,3-amino
alcohols, which have been one of the most important classes of
compounds in organic synthesis,12 by reduction with LiAlH4
(Scheme 4). When β-hydroxy selenoamide 4d was treated with
2712
J. Chem. Soc., Perkin Trans. 1, 2001, 2711–2716

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Table 2 Reaction of amide 5 with aldehydes 3a
Entry
1
Aldehyde
Product yield (%)b
76
Diastereomer ratio (syn : anti)c
80 : 20
2
62
99 : 1
3
4
27
74 : 26
75 : 25
40d
a Amide 5 (1 mmol) was treated with LDA (1.2 mmol) in Et2O (5 mL) at 0 ЊC for 10 min, then to the reaction mixture was added an aldehyde 3
(1.2 mmol) at Ϫ78 ЊC and stirred for 10 min at Ϫ78–0 ЊC. b Isolated yield. c The ratio of diastereomers was determined by 1H NMR. d The starting
material 5 was recovered in 17% recovery.
was treated with LiAlH4 to furnish TMS-protected 1,3-amino
alcohol 10a in high yield. A similar transformation of 4i was
successful to give 10b quantitatively via siloxy selenoamides 9b.
In these cases the stereochemistry of the starting β-hydroxy
selenoamides was retained.
In summary, the aldol-type condensation reaction of lithium
eneselenolates generated from pent-4-eneselenoamides has pro-
vided a new route to β-hydroxy selenoamides. The highly stereo-
selective reaction was attained with N,N-dibenzyl selenoamide
1b. In particular, the use of aliphatic aldehydes gave products
with better diastereoselectivities and yields than those of the
reaction of these aldehydes with ordinary amides. Reduction of
the obtained β-hydroxy selenoamides with LiAlH4 successfully
led to 1,3-amino alcohols.
Scheme 3
Experimental
General
IR spectra were obtained on a Perkin-Elmer FT-IR 1640 spec-
1
trophotometer. H NMR spectra were measured on a JEOL
α-400 (399.7 MHz) for samples in CDCl3. Chemical shifts of
protons are reported in δ-values referred to tetramethylsilane as
internal standard, and the following abbreviations are used;
s: singlet, d: doublet, m: multiplet. J-values are given in Hz
13C NMR spectra were measured on a JEOL α-400 (100.4
MHz). Mass spectra (MS) were taken on Shimadzu GCMS
QP1000 (EI mode) or GCMS 9020DF high-resolution mass
spectrometers. High-resolution mass spectra were taken on the
9020DF spectrometer. Elemental analyses were carried out by
the Elemental Analysis Center of Kyoto University. High-
performance liquid chromatography (HPLC) was performed
using a Japan Analytical Industry LC-908 recycling prepar-
ative HPLC coupled to RI indicator and UV detecter (256 nm).
The selenoamides 1 were prepared by the procedure in the
literature.7 Other substrates were commercially available.
General procedure for the aldol reaction of lithium eneselenolates 2
Scheme 4
A representative experimental procedure is described for the
preparation of 1-[3-hydroxy-2-(prop-2-enyl)-1-selenoxohex-4-
enyl]pyrrolidine 4a. To a THF solution (5 mL) of diisoprop-
ylamine (0.17 mL, 1.2 mmol) was added BuLi (1.6 M hexane
solution; 0.75 mL, 1.2 mmol) at 0 ЊC, and the mixture was
LiAlH4, it gave amino alcohol 7a in low yield (18%) along with
a 57% yield of alkenylamine 8, the result of the retro-aldol
reaction of 4d. Then, β-siloxy selenoamide 9a derived from 4d
J. Chem. Soc., Perkin Trans. 1, 2001, 2711–2716
2713

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stirred for 10 min at this temperature. Pent-4-eneselenoamide
1a (0.216 g, 1.0 mmol) was added, and the mixture was stirred
for 10 min at 0 ЊC. Then, crotonaldehyde 3a (0.1 mL, 1.2 mmol)
and water (1 mL) were added successively at Ϫ78 ЊC. The result-
ing mixture was poured into saturated aq. NaCl, and extracted
with Et2O three times. The organic layer was dried over Na2SO4
and concentrated in vacuo. The residue was purified by column
chromatography (SiO2; hexane–Et2O = 3 : 1) to give 4a (0.201 g,
70%, diastereomer ratio syn : anti = 55 : 45) as a yellow oil, Rf =
0.46, 0.58 (hexane–Et2O = 1 : 3); δH (400 MHz; CDCl3) 1.72
(3 H, d, J 6.6, CH3), 2.00–2.20 (4 H, m, CH2), 2.50–2.60 (1 H,
(1 H, s, CH ᎐C), 5.46–5.60 (1 H, m, ᎐CH), 6.46 (1 H, d, J 14.6,
᎐ ᎐
2
NCH2), 7.05–7.45 (10 H, m, Ph); δC (100 MHz; CDCl3) syn
isomer 19.3, 34.5, 52.3, 54.4, 60.8, 74.6, 112.8, 118.0, 125.7,
128.1, 128.3, 128.3, 128.9, 129.4, 135.6, 133.8, 134.4, 143.1,
216.2; νmax/cmϪ1 3276, 1642, 1496, 1446, 1233, 1000, 912, 733,
696, 588; m/z (EI) 412 (Found: C, 66.74; H, 6.55. C23H27NOSe
requires C, 66.98; H, 6.60%).
N,N-Dibenzyl-3-hydroxy-5-phenyl-2-(prop-2-enyl)pent-4-ene-
selenoamide 4e. A yellow oil; δH (400 MHz; CDCl3) syn isomer
2.58–2.64 (1 H, m, CH2), 2.95–3.06 (1 H, m, CH2), 4.30 (1 H, d,
m, CH C᎐C), 2.80–2.90 (1 H, m, CH C᎐C), 3.08–3.15 (1 H, m,
J 5.5, OH), 4.60–5.10 (6 H, m, CHC᎐Se, CHO, NCH ), 5.45
᎐
2
᎐
᎐
2
2
CHC᎐Se), 3.50–3.70 (2 H, m, CH ), 3.80–4.00 (2 H, m, CH ),
(1 H, d, J 14.0, C᎐CH ), 5.60–5.70 (2 H, m, CH᎐, C᎐CH ), 6.32
᎐ ᎐ ᎐
2 2
᎐
2
2
4.30–4.40 (1 H, m, CHO), 4.40–4.50 (1 H, s, OH), 4.97 (1 H,
dd, J 10.4, CH ᎐), 5.11 (1 H, d, J 15.6, CH ᎐), 5.50–5.60 (1 H,
(1 H, dd, J 7.6 and 16.1, CH ᎐), 6.67 (1 H, d, J 16.1, CH᎐C),
᎐ ᎐
2
7.14–7.49 (15 H, m, Ph); δC (100 MHz; CDCl3) syn isomer 35.7,
54.7, 56.1, 60.7, 73.6, 118.0, 126.1–136.6, 215.2; anti isomer
᎐
᎐
2
2
m, CH), 5.65–5.83 (2 H, m, CH2); δC (100 MHz; CDCl3) syn
isomer 17.8, 23.9, 26.1, 34.4, 52.4, 57.7, 57.7, 73.1, 117.1, 127.5,
131.1, 135.9, 206.0; anti isomer 17.8, 23.9, 26.0, 37.9, 52.4, 57.7,
73.1, 117.4, 127.5, 131.1, 135.9, 204.4; νmax/cmϪ1 3394, 2974,
1638, 1560, 1329, 1258, 1170, 969, 920; m/z (EI) 287 (Found: C,
54.33; H, 7.26. C13H21NOSe requires C, 54.54; H, 7.39%).
38.7, 54.4, 55.8, 60.2, 74.7, 118.2, 126.1–135.4, 212.9; νmax
/
cmϪ1 3344, 3028, 2250, 1678, 1626, 1495, 1450, 1354, 1221,
1167, 1124, 970, 918, 845, 749, 696; m/z (EI) 475 (Found: Mϩ,
475.13881. C28H29NOSe requires M, 475.14129).
N,N-Dibenzyl-3-hydroxy-2-(prop-2-enyl)octa-4,6-dieneseleno-
amide 4f. A yellow oil; δH (400 MHz; CDCl3) syn isomer 1.64
(3 H, d, J 6.3, CH3), 2.40–2.50 (1 H, m, CH2), 2.80–2.90 (1 H,
N,N-Dibenzyl-3-hydroxy-2-(2-prop-2-enyl)hex-4-eneseleno-
amide 4b. A yellow oil; δH (400 MHz; CDCl3) syn isomer 1.58
(3 H, d, J 6.4, CH3), 2.50–2.65 (1 H, m, CH2), 2.90–3.00 (1 H, m,
m, CH ), 3.15–3.20 (1 H, m, CHC᎐Se), 4.24 (1 H, d, J 5.9,
᎐
2
CH ), 3.20–3.30 (1 H, m, CHC᎐Se), 4.24 (1 H, d, J 5.3, CHO),
4.66 (1 H, d, J 17.1, NCH2), 4.84 (1 H, s, OH), 4.89 (1 H, d,
CHO), 4.38 (1 H, s, OH), 4.50–6.00 (10 H, m, CH, NCH2), 6.23
(1 H, d, J 14.6, NCH2), 7.00–7.40 (10 H, m, Ph); anti isomer
1.70 (3 H, d, J 6.8, CH3), 2.50–2.60 (1 H, m, CH2), 3.00–3.10
᎐
2
J 14.4, NCH ), 5.01 (1 H, dd, J 1.5, and 10.7, CH ᎐C), 5.17
᎐
2
2
(1 H, d, J 18.5, CH ᎐C), 5.25 (1 H, dd, J 1.5 and 5.3, CH᎐C),
(1 H, m, CH ), 3.20–3.30 (1 H, m, CHC᎐Se), 4.31 (1 H, d, J 4.9
᎐
2
᎐
᎐
2
5.40–5.80 (3 H, m, CH, NCH2), 6.27 (1 H, d, J 14.4, NCH2),
7.00–7.40 (10 H, m, Ph); anti isomer 1.70 (3 H, d, J 6.3, 3H,
Hz, CHO), 4.50–6.00 (11 H, m, CH ᎐CH, CH᎐CH, OH,
᎐ ᎐
2
NCH2), 6.23 (1 H, d, J 14.6, NCH2), 7.00–7.40 (10 H, m, Ph); δC
(100 MHz; CDCl3) syn isomer 18.1, 35.5, 54.6, 56.0, 60.6, 73.3,
115.4–137.5, 215.3; anti isomer 13.5, 32.5, 54.4, 55.8, 60.5, 73.3,
115.4–137.5, 213.0; νmax/cmϪ1 2968, 2371, 1654, 1560, 1508,
1499, 1458, 990, 734 cmϪ1; m/z (EI) 439 (Found: Mϩ, 439.14394.
C25H29NOSe requires M, 439.14129).
CH ), 2.50–2.65 (2 H, m, CH ), 3.20–3.30 (1 H, m, CHC᎐Se),
᎐
3
2
4.46 (1 H, t, J = 6.5, CHO), 4.66 (1 H, d, J 17.1, NCH2), 4.80–
4.90 (2 H, m, OH, NCH ), 4.90–5.10 (2 H, m, CH ᎐C), 5.18–
᎐
2
2
5.22 (1 H, m, CH), 5.40–5.80 (3 H, m, CH᎐CH, NCH ), 6.27
᎐
2
(1 H, d, J 14.2, NCH2), 7.00–7.40 (10 H, m, Ph); νmax/cmϪ1 3421,
3030, 2367, 2344, 1497, 1449, 1354, 1220, 1169, 1079, 1029, 917,
734, 697; m/z (EI) 413 (Found: Mϩ, 413.12683. C23H27NOSe
requires M, 413.12565).
N,N-Dibenzyl-3-hydroxy-4-methyl-5-phenyl-2-(prop-2-enyl)-
pent-4-eneselenoamide 4g. A yellow oil; δH (400 MHz; CDCl3)
syn isomer 1.29 (3 H, s, CH3), 2.50–2.60 (1 H, m, CH2), 2.85–
N,N-Dibenzyl-3-hydroxy-2-(prop-2-enyl)pent-4-eneseleno-
amide 4c. A yellow oil; δH (400 MHz; CDCl3) syn isomer 2.45–
2.97 (1 H, m, CH ), 3.39 (1 H, dd, J 2.6 and 10.0, CH᎐CSe),
᎐
2
4.29 (1 H, s, OH), 4.65–5.20 (6 H, m, NCH ,CH ᎐C, PhCH),
᎐
2 2
2.55 (1 H, m, ᎐CH ), 2.85–2.95 (1 H, m, CH ), 3.44–3.60 (1 H,
5.50–5.75 (2 H, m, ᎐CH, CHO), 6.45 (1 H, d, J 14.4 Hz, NCH ),
᎐
᎐
2
2
2
m, CHC᎐Se), 4.25–4.30 (1 H, m, CHO), 4.66 (1 H, d, J 17.0,
NCH2), 4.81 (1 H, d, J 14.6, NCH2), 4.88 (1 H, d, J 17.0,
6.50–7.50 (15 H, m, Ph); δC (100 MHz; CDCl3) syn isomer 15.2,
34.7, 52.6, 60.8, 76.0, 118.0–134.3, 216.0; anti isomer 13.6, 39.0,
54.4, 60.5, 82.5, 117.9–134.3, 214.4; νmax/cmϪ1 3428, 3028, 2978,
1507, 1449, 1247, 1159, 1029, 742, 697; m/z (EI) 489 (Found: C,
71.39; H, 6.40. C29H31NOSe requires C, 71.30; H, 6.40%).
᎐
NCH ), 4.95–5.05 (3 H, m, OH, CH ᎐C), 5.07–5.10 (1 H, m,
᎐
2
2
CH ᎐C), 5.16 (1 H, dd, J 2.0 and 16.8, CH ᎐C), 5.44–5.55 (1 H,
᎐
᎐
2
2
m, C᎐CH), 5.60–5.75 (1 H, m, C᎐CH), 6.37 (1 H, d, J 14.6,
᎐
᎐
NCH2), 7.07–7.41 (10 H, m, Ph); anti isomer 2.45–2.55 (1 H, m,
CH ), 2.85–2.95 (1 H, m, CH ), 3.44–3.60 (1 H, m, CHC᎐Se),
N,N-Dibenzyl-2-(1-hydroxyethyl)pent-4-eneselenoamide 4h. A
yellow oil; δH (400 MHz; CDCl3) syn isomer 0.94 (3 H, d, J 6.8,
CH3), 2.49–2.56 (1 H, m, CH2), 2.85–2.95 (1 H, m, CH2), 3.13
᎐
2
2
4.25–4.30 (1 H, m, CHO), 4.60–5.25 (8 H, m, NCH , OH, CH ᎐
᎐
2
2
C, CH ᎐C), 5.60–5.75 (1 H, m, C᎐CH), 5.85–5.95 (1 H, m,
᎐
᎐
2
C᎐CH), 6.20 (1 H, d, J 14.6, NCH ), 7.07–7.41 (10 H, m, Ph); δ
(1 H, ddd, J 1.5, 3.4, and 10.2, CHC᎐Se), 3.88–3.93 (1 H, m,
᎐
᎐
2
C
(100 MHz; CDCl3) syn isomer 35.0, 54.7, 55.3, 60.6, 73.3, 115.8,
118.0, 126.0–134.4, 135.4, 137.8, 215.4; anti isomer 38.5, 54.4,
55.6, 59.9, 75.5, 117.5, 118.1, 126.7–134.5, 134.5, 138.5, 213.1;
MS m/z 399 (Found: Mϩ, 399.10924. C22H25NOSe requires M,
399.11001).
CHO), 4.63 (1 H, d, J 16.6, NCH2), 4.82 (1 H, d, J 14.4, NCH2),
4.88 (1 H, d, J 16.6, NCH ), 5.02 (1 H, dd, J 2.1 and 10.5, CH ᎐
᎐
2
2
C), 5.19 (1 H, dd, J 2.1 and 17.1, CH ᎐C), 5.60–5.80 (1 H, m,
᎐
2
᎐CH), 6.35 (1 H, d, J 14.4, NCH ), 7.05–7.45 (10 H, m, Ph); δ
᎐
2
C
(100 MHz; CDCl3) syn isomer 20.9, 35.0, 54.6, 55.9, 60.5, 68.9,
117.9, 125.9–134.5, 135.5, 216.4; anti isomer 20.9, 38.7, 54.2,
57.6, 59.7, 70.5, 117.9, 126.9–134.7, 134.6, 213.8; νmax/cmϪ1 3320,
2970, 1638, 1605, 1499, 1445, 1360, 1330, 1296, 1235, 1176, 995,
920, 909, 737, 697, 633, 564, 458; m/z (EI) 386 (Found: C, 65.05;
H, 6.46 C21H25NOSe requires C, 65.28; H, 6.52%).
N,N-Dibenzyl-3-hydroxy-4-methyl-2-(prop-2-enyl)pent-4-ene-
selenoamide 4d. A yellow oil; δH (400 MHz; CDCl3) syn isomer
1.17 (3 H, s, CH3), 2.40–2.48 (1 H, m, CH2), 2.85–2.95 (1 H, m,
CH ), 3.26–3.33 (1 H, dd, J 2.9 and 10.7, CHC᎐Se), 4.15 (1 H, s,
᎐
2
OH), 4.66 (1 H, d, J 17.3, NCH2), 4.76 (1 H, d, J 14.5, NCH2),
4.88 (1 H, s, OCH), 4.90–5.00 (2 H, m, NCH , CH ᎐C), 5.10–
N,N-Dibenzyl-2-(1-hydroxy-2-methylpropyl)pent-4-eneseleno-
amide 4i. A yellow oil; δH (400 MHz; CDCl3) syn isomer 0.44
(3 H, d, J 6.8, CH3), 0.93 (3 H, d, J 6.8, CH3), 1.60–1.70 (1 H,
m, CH), 2.27 (1 H, s, OH), 2.40–2.50 (1 H, m, CH2), 2.90–3.00
(1 H, m, CH2), 3.31 (1 H, d, J 8.8, CHO), 3.41 (1 H, dd, J 3.9
and 10.3, CSeCH), 4.64 (1 H, d, J 17.1, NCH2), 4.94 (1 H, d,
᎐
2
2
5.20 (2 H, m, CH ᎐C), 5.42 (1 H, s, CH ᎐C), 5.60–5.75 (1 H, m,
᎐
᎐
2
2
CH᎐C), 6.46 (1 H, d, J 14.5, NCH ), 7.05–7.45 (10 H, m, Ph);
᎐
2
anti isomer 1.27 (3 H, s, CH3), 2.24–2.34 (1 H, m, CH2), 2.60–
2.72 (1 H, m, CH ), 3.32–3.40 (1 H, m, CH᎐Se), 4.15 (1 H, s,
᎐
2
OH), 4.66–5.20 (7 H, m, NCH , OCH, CH ᎐C, CH ᎐C), 5.42
᎐
᎐
2
2
2
2714
J. Chem. Soc., Perkin Trans. 1, 2001, 2711–2716

View Article Online
J 14.6, NCH2), 5.13 (1 H, d, J 17.1, NCH2), 4.90–5.00 (2 H,
m, CH ᎐C), 5.60–5.70 (1 H, m, CH ᎐C), 6.23 (1 H, d, J 14.6,
NCH2), 7.00–7.50 (10 H, m, Ph); anti isomer 0.82 (3 H, d, J 6.8,
CH3), 1.00 (3 H, d, J 6.8, CH3), 1.95–2.05 (1 H, m, CH), 2.27
(1 H, s, OH), 2.30–2.40 (1 H, m, CH2), 2.60–2.70 (1 H, m, CH2),
3.30–3.40 (1 H, m, CHO), 3.97 (1 H, dd, J 3.2 and 8.6, CSeCH),
(100 MHz; CDCl3) syn isomer 19.1, 19.3, 29.7, 54.9, 57.4, 60.2,
79.5, 125.5–134.5, 213.4; anti isomer 14.7, 21.0, 27.8, 54.2, 59.9,
60.5, 79.9, 125.5–134.5, 211.5; νmax/cmϪ1 3374, 2960, 1496, 1450,
1354, 1221, 1165, 1078, 1030, 999, 733, 696; m/z 450 (EI)
(Found: C, 69.07; H, 6.44. C26H29NOSe requires C, 69.32; H,
6.49%).
᎐
2
᎐
2
4.60–5.40 (4 H, m, NCH , CH ᎐C), 5.33 (1 H, d, J 14.4, NCH ),
᎐
2
2
2
5.50–5.60 (1 H, m, ᎐CH), 6.52 (1 H, d, J 14.4, NCH ), 7.00–7.50
(10 H, m, Ph); δC (100 MHz; CDCl3) 18.6, 19.8, 31.5, 35.0,
N,N-Dibenzyl-4-methyl-2-(prop-2-enyl)-3-(trimethylsiloxy)-
pent-4-enamine 10a. A solution of selenoamide 4d (0.124 g,
0.3 mmol), HMDS (0.06 mL, 0.3 mmol) and a catalytic amount
of trimethylsilyl chloride was stirred under reflux for 20 h. The
reaction mixture was concentrated in vacuo. To a THF solution
of the reaction mixture was added LiAlH4 (0.023 mg, 0.60
mmol) at 0 ЊC. The reaction mixture was stirred under reflux for
20 h. The residue was poured into saturated aq. NaCl, and
extracted with Et2O three times. The organic layer was dried
over Na2SO4 and concentrated in vacuo to give 10a (0.142 g,
<100%) as a colourless oil, Rf = 0.88 (hexane–Et2O 1 : 1);
δH (400 MHz; CDCl3) 0.00 [9 H, s, (CH3)3SiO], 1.60 [3 H, s,
᎐
2
51.7, 54.2, 60.5, 77.9, 117.7, 125.7–134.5, 135.8, 216.7; νmax
/
cmϪ1 3854, 3650, 2959, 1654, 1560, 1498, 1225, 734, 697 cmϪ1;
m/z (EI) 414 (Found: C, 66.55; H, 7.10. C23H29NOSe requires
C, 66.66; H, 7.05%).
N,N-Dibenzyl-2-[(4-dimethylaminophenyl)hydroxymethyl]-
prop-4-eneselenoamide 4j. A yellow solid; δH (400 MHz; CDCl3)
2.30–2.40 (1 H, m, CH2), 2.55–2.65 (1 H, m, 1H, CH2), 2.93
(6 H, s, CH ), 3.45–3.55 (1 H, m, CHC᎐Se), 3.78–3.84 (1 H, m,
᎐
3
OH), 4.61 (1 H, d, J 16.6, NCH2), 4.72 (1 H, d, J 16.6, NCH2),
4.88 (1 H, d, J 10.2, CH ᎐), 4.96 (1 H, d, J 17.1, CH ᎐C),
C᎐C(CH )], 1.75–1.85 (1 H, m, CH), 2.05–2.40 (4 H, m, CH ),
᎐
3 2
᎐
᎐
2
2
5.00–5.10 (1 H, m, CHO), 5.40–5.60 (3 H, m, NCH , C᎐CH),
3.27 (2 H, d, J 13.7, NCH2), 3.66 (2 H, d, J 13.7, NCH2), 3.91
(1 H, d, J 6.4, CHO), 4.70–4.90 (4 H, m, CH ᎐C), 5.50–5.65
᎐
2
6.65–7.40 (14 H, m, ArH); δC (100 MHz; CDCl3) 39.0, 40.6,
54.2, 58.0, 60.2, 77.1, 112.5, 117.8, 126.7, 127.8, 128.2, 128.7,
129.1, 134.2, 134.6, 134.7, 213.8; νmax/cmϪ1 3854, 3650, 3451,
2902, 1612, 1506, 1449, 1348, 1252, 1166, 1028, 821, 740, 697,
572, 464; m/z (EI) 492 (Found: Mϩ, 492.16669. C28H32NO
requires M, 492.16782).
᎐
2
(1 H, m, C᎐CH), 7.10–7.20 (10 H, m, Ph); δ (100 MHz;
᎐
C
CDCl3) 0.2, 18.0, 31.7, 39.4, 55.0, 58.8, 77.4, 112.4, 115.8,
126.9, 128.2, 129.2, 139.6, 146.3, 137.4; νmax/cmϪ1 3065, 3028,
2960, 1638, 1495, 1452, 1372, 1250, 1070, 902, 842, 747, 698;
m/z (EI) 406, 210 (Found: Mϩ, 407.26615. C26H37NOSi requires
M, 407.26426).
N,N-Dibenzyl-2-[hydroxy(4-nitrophenyl)methyl]prop-4-ene-
selenoamide 4k. A yellow solid; δH (400 MHz; CDCl3) syn
isomer 2.15–2.20 (1 H, m, CH2), 2.90–3.00 (1 H, m, CH2), 3.31
N,N-Dibenzyl-2-[2-methyl-1-(trimethylsiloxy)propyl]pent-4-
enamine 10b. A colourless oil; δH (400 MHz; CDCl3) 0.00 [9 H, s,
(CH3)3SiO], 0.82 (3 H, d, J 6.8, CH3), 0.82 (3 H, d, J 6.3, CH3),
1.60–2.50 (6 H, m, CH, CH2), 3.38–3.45 (1 H, m, CHO), 3.48
(2 H, d, J 13.7, NCH2), 3.57 (2 H, d, J 13.7, NCH2), 4.80–5.00
(1 H, ddd, J 1.0, 3.9, and 10.7, CHC᎐Se), 4.60 (1 H, d, J 14.6,
᎐
NCH2), 4.74 (1 H, d, J 17.1, NCH2), 4.86 (1 H, s, OH), 4.74
(1 H, d, J 17.1, NCH ), 4.96 (1 H, dd, J 2.0 and 10.2, CH ᎐C),
᎐
2
2
5.08 (1 H, dd, J 2.0 and 17.1, CH ᎐C), 5.40–5.60 (1 H, m, C᎐
(2 H, m, CH ᎐C), 5.70–5.90 (1 H, m, C᎐CH), 7.20–7.40 (10 H,
᎐ ᎐
2
᎐
᎐
2
CH), 5.81 (1 H, s, CHO), 6.55–8.00 (15 H, m, NCH2, ArH); anti
isomer 2.40–2.60 (2 H, m, CH ), 3.55–3.60 (1 H, m, CHC᎐Se),
m, Ph); δC (100 MHz; CDCl3) 0.8, 19.0, 20.2, 31.9, 32.8, 39.5,
57.3, 58.7, 79.5, 115.2, 126.9, 128.2, 129.6, 138.9, 139.5; νmax/cmϪ1
2958, 1640, 1495, 1453, 1385, 1250, 1057, 840, 746, 698; m/z
409 (EI) (Found: Mϩ, 409.27925. C26H39NOSi requires M,
409.27990).
᎐
2
4.50–5.05 (6 H, m, NCH , CH ᎐C, CHOH), 5.40–5.60 (1 H,
᎐
2
2
m, C᎐CH), 5.81 (1 H, s, CHO), 6.55–8.00 (15 H, m, NCH ,
᎐
2
ArH); δC (100 MHz; CDCl3) syn isomer 33.9, 54.9, 56.5,
61.5, 73.2, 118.8, 123.2, 125.6, 126.8, 128.2, 128.4, 128.5,
128.9, 129.7, 134.0, 134.2, 146.9, 149.1, 214.8; νmax/cmϪ1 3342,
3069, 1604, 1515, 1451, 1413, 1343, 1237, 1169, 1070, 854, 739,
694; m/z (EI) 369 (Mϩ Ϫ PhNO2) (Found: Mϩ, 494.11021.
C26H26N2O3Se requires M, 494.11074).
X-Ray structure analysis†
The measurement was carried out on a Rigaku AFC7R four-
circle diffractometer with graphite-monochromated Mo-Kα
radiation (λ = 0.710 69 Å). The structure was solved and refined
using the teXsan® crystallographic software package on an
IRIS Indigo computer. X-Ray quality crystals of 4d were
obtained by recrystallization from hexane–Et2O (1 : 1). A full-
matrix least-squares refinement was executed with non-
hydrogen atoms being anisotropic. The final least-squares cycle
included fixed hydrogen atoms at calculated positions of which
each isotropic thermal parameter was set to 1.2 times that of
the connecting atom. The crystal data are as follows: empirical
formula: C23H27NOSe; formula weight: 412.43; crystal dimen-
sions: 0.02 × 0.14 × 0.11 mm; crystal system: monoclinic;
lattice parameters: a = 7.445(2), b = 10.865(2), c = 13.339(1) Å,
space group: P21(#4); Z = 2; µ(Mo-Kα) = 17.82 cmϪ1; temper-
ature of data collection: Ϫ80 ЊC; residuals: R1; Rw = 0.049;
0.068; no. of observed reflections: 3200; Rint = 0.030.
N,N-Dibenzyl-2-[hydroxy(4-methylphenyl)methyl]prop-4-ene-
selenoamide 4l. A yellow solid; δH (400 MHz; CDCl3) syn
isomer 2.26 (3 H, s, CH3), 2.25–2.40 (1 H, m, CH2), 2.95–3.05
(1 H, m, CH ), 3.30–3.40 (1 H, m, CHC᎐Se), 4.50–5.00 (6 H,
᎐
2
m, NCH , OH, CH ᎐, CHO), 5.08 (1 H, d, J 17.1, NCH ), 5.45–
᎐
2
2
2
5.60 (1 H, m, C᎐CH), 6.52 (1 H, d, J 14.1, NCH ), 6.60–7.50
᎐
2
(14 H, m, ArH); δC (100 MHz; CDCl3) syn isomer 21.0, 34.3,
54.6, 57.3, 60.9, 74.2, 118.0–139.2, 215.8; anti isomer 21.0, 34.8,
54.46, 57.5, 60.2, 76.4, 118.1–139.2, 134.4, 213.1; νmax/cmϪ1
1499, 1442, 1418, 1358, 1236, 1169, 998, 916, 816, 735, 694, 586,
462; m/z (EI) 343 [Mϩ Ϫ (CH ᎐CHCH ϩ Ph)] (Found: Mϩ,
᎐
2
2
463.13953. C27H29NOSe requires M, 463.14129).
N,N-Dibenzyl-3-hydroxy-4-methyl-2-phenylpentaneseleno-
amide 4m. A yellow solid; δH (400 MHz; CDCl3) syn isomer 0.61
(3 H, d, J 6.3, CH3), 0.86 (3 H, d, J 6.3, CH3), 1.50–1.60 (1 H,
m, CH), 4.02 (1 H, dd, J 1.6 and 9.0, 1H, CHO), 4.23 (1 H, d,
Acknowledgements
This research was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, Sports and
Culture, Japan.
J 1.6, CHC᎐Se), 4.39 (1 H, d, J 15.6, NCH ), 4.49 (1 H, d,
᎐
2
J 15.6, NCH2), 4.87 (1 H, d, J 17.1, NCH2), 6.63 (1 H, d, J 17.1,
NCH2), 7.70–7.60 (15 H, m, Ph); anti isomer 0.70 (3 H, d, J 6.3
CH3), 0.93 (3 H, d, J 6.8, CH3), 1.40–1.50 (1 H, m, CH), 4.11
(1 H, d, J 9.3, CHC᎐Se), 4.56 (1 H, d, J 9.3, CHO), 4.68 (1 H, d,
J 15.6, NCH2), 4.43 (1 H, d, J 15.1, NCH2), 5.13 (1 H, d, J 15.6,
NCH2), 6.29 (1 H, d, J 15.1, NCH2), 7.70–7.60 (15 H, m, Ph); δC
᎐
† CCDC reference number 158064. See http://www.rsc.org/suppdata/
p1/b1/b100198l/ for crystallographic files in .cif or other electronic
format.
J. Chem. Soc., Perkin Trans. 1, 2001, 2711–2716
2715

View Article Online
Pergamon Press, Oxford, 1995, vol. 5, p. 565; (d ) T. Murai and
S. Kato, Top. Curr. Chem., 2000, 208, 177.
7 (a) T. Murai, T. Ezaka, N. Niwa, T. Kanda and S. Kato, Synlett,
1996, 865; (b) T. Murai, T. Ezaka, T. Kanda and S. Kato, Chem.
Commun., 1996, 1809; (c) T. Murai, T. Mori and S. Kato, Synlett,
1998, 619; (d ) T. Murai, T. Ezaka and S. Kato, Bull. Chem. Soc. Jpn.,
1998, 71, 1193.
Notes and references
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ed. B. M. Trost and I. Fleming, Pergamon Press, Oxford, 1991,
vol. 2, p. 181; (b) C. H. Heathcock, Modern Synthetic Methods,
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2 For reviews (a) P. Metzner and A. Thuillier, Sulfur Reagents in
Organic Synthesis, ed. A. R. Katritzky, O. Meth-Cohn and C. W.
Rees, Academic Press, New York, 1994; (b) P. Metzner, Top. Curr.
Chem., 1999, 204, 127.
3 For reviews (a) A. Krief, Comprehensive Organometallic Chemistry,
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Oxford, 1995, vol. 11, p. 515; (b) K. El-Bayoumy, Drugs Fut., 1997,
22, 539; (c) Organoselenium Chemistry: A Practical Approach, ed.
T. G. Back, Oxford University Press, UK, 1999.
8 T. Murai and S. Kato, Sulfur Rep., 1998, 20, 397 and references cited
therein.
9 (a) T. Murai, T. Ezaka, T. Ichimiya and S. Kato, Synlett, 1997, 775;
(b) T. Murai, A. Suzuki, T. Ezaka and S. Kato, Org. Lett., 2000, 2,
311.
10 (a) S. Kato, T. Komuro, T. Kanda, H. Ishihara and T. Murai, J. Am.
Chem. Soc., 1993, 115, 3000; (b) T. Murai, M. Fujii and S. Kato,
Chem. Lett., 1997, 545; (c) T. Murai, H. Endo, M. Ozaki and
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4 (a) J. V. Comasseto, L. W. Ling, N. Petragnani and H. A. Stefani,
Synthesis, 1997, 373; (b) K. Shimada, M. Asahida, K. Takahashi,
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5 (a) D. J. R. Barton, P.-E. Hansen and K. Picker, J. Chem. Soc.,
Perkin Trans. 1, 1977, 1723; (b) R. S. Sukhai and L. Brandsma,
Synthesis, 1979, 455; (c) M. Sekiguchi, A. Ogawa, S. Fujiwara,
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T. Kanda, T. Ezaka, T. Murai and S. Kato, Tetrahedron Lett., 1995,
36, 2807.
6 For reviews (a) F. S. Guziec, Jr. and L. J. Guziec, Comprehensive
Organic Functional Group Transformations, ed. A. R. Katritzky,
O. Meth-Cohn and C. W. Rees, Pergamon Press, Oxford, 1995,
vol. 3, p. 381; (b) A. Ishii and J. Nakayama, Comprehensive
Organic Functional Group Transformations, ed. A. R. Katritzky, O.
Meth-Cohn and C. W. Rees, Pergamon Press, Oxford, 1995, vol. 5,
p. 505; (c) C. P. Dell, Comprehensive Organic Functional Group
Transformations, ed. A. R. Katritzky, O. Meth-Cohn and C. W. Rees,
11 The protons attached to the α-carbon atom to the selenocarbonyl
group of syn isomers were observed at higher fields than those of
anti isomers. In the 13C NMR spectra, the carbon atoms of the
selenocarbonyl group of syn isomers were observed at lower fields
than those of anti isomers.
12 For recent examples of the synthesis of 1,3-amino alcohols: (a)
J. Barluenga, F. Fernández-Marí, A. L. Viado, E. Aguilar and
B. Olano, J. Org. Chem., 1996, 61, 5659; (b) B. F. Bonini, M.
Comes-Franchini, G. Mazzanti, A. Ricci and M. Sala, J. Org.
Chem., 1996, 61, 7242; (c) S. Cicchi, S. Crea, A. Goti and A. Brandi,
Tetrahedron: Asymmetry, 1997, 8, 293; (d ) C. Lutz, V. Lutz and
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Sharma, Bioorg. Med. Chem. Lett., 1998, 8, 487; ( f ) X. Li, C.-H.
Yeung, A. S. C. Chan and T.-K. Yang, Tetrahedron: Asymmetry,
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Tetrahedron, 2000, 56, 2665; (h) T.-P. Loh, J.-M. Huang S.-H. Goh
and J. J. Vittal, Org. Lett., 2000, 2, 1291.
2716
J. Chem. Soc., Perkin Trans. 1, 2001, 2711–2716