Synthesis of aliphatic (E)-α,β-unsaturated amides with high diastereoselectivity from α,β-epoxyamides promoted by SmI 2/HMPA

Article abstract of DOI:10.1002/ejoc.200300641

Synthesis of aliphatic (E)-α,β-unsaturated amides 2, in which the C=C bond is di- or trisubstituted, is achieved by using samarium diiodide and HMPA. The starting compounds 1 were easily prepared by the reaction of the corresponding lithium or potassium e

Full text of DOI:10.1002/ejoc.200300641

FULL PAPER
Synthesis of Aliphatic (E)-α,β-Unsaturated Amides with High
Diastereoselectivity from α,β-Epoxyamides Promoted by SmI2/HMPA
[a]
[a]
´
´
Jose M. Concellon* and Eva Bardales
Keywords: Amides / α,β-Epoxyamides / Samarium / Synthesis design
Synthesis of aliphatic (E)-α,β-unsaturated amides 2, in which
lithium or potassium enolates of α-chloroamides with alde-
the C=C bond is di- or trisubstituted, is achieved by using
hydes. A mechanism to explain this process is proposed.
samarium diiodide and HMPA. The starting compounds 1 ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
were easily prepared by the reaction of the corresponding
Germany, 2004)
Introduction
Here, we report a general synthesis of aliphatic α,β-un-
saturated amides 2 from α,β-epoxyamides with high dia-
stereoselectivity by using SmI2 in the presence of HMPA.
Samarium diiodide has been shown to be a useful reagent
in reductive elimination reactions in recent years.[1] We have
described the diastereoselective synthesis of (Z)-vinyl hal-
ides from O-acetylated 1,1-dihaloalkan-2-ols,[2] the prep-
aration of (E)-α,β-unsaturated esters[3] or amides[4] from 2-
halo-3-hydroxy esters or amides, respectively, and the for-
mation of (Z)-vinylsilanes from 1-chloro-1-trialkylsilylal-
kan-2-ols. In addition, we have described the transform-
ation of α,β-epoxy esters into (E)-α,β-unsaturated esters.[5]
In this respect, samarium diiodide has been used to trans-
form epoxides into alkenes, however, this reaction takes
place with poor diastereoselectivity,[6] and to the best of our
knowledge no general transformation of aliphatic α,β-ep-
oxyamides into the synthetically interesting aliphatic α,β-
unsaturated amides has been reported.
Results and Discussion
The disubstituted epoxyamide 1a was prepared by reac-
tion of the lithium enolate of chloroacetamide (generated
by treatment of α-chloroacetamide with LDA at Ϫ78 °C)
with cyclohexanecarbaldehyde and subsequent treatment
with sodium hydride. Trisubstituted epoxyamides 1bϪg
were obtained by reaction of the corresponding potassium
enolates of α-chloroamides (generated by treatment of α-
chloroamides with potassium hexamethyldisilazide at Ϫ78
°C) with different aldehydes at temperatures ranging from
Ϫ78 to 25 °C (Scheme 1).
α,β-Unsaturated amides are an important class of com-
pounds not only for their biological[7] and insecticidal[8] ac-
tivities but also because of their presence in the structure of
natural products.[9] However, the preparation of α,β-unsatu-
rated amides has scarcely been reported. For these reasons,
an easy and general transformation of aliphatic α,β-ep-
oxyamides into aliphatic α,β-unsaturated amides would be
desirable.
Recently, we described the transformation, with total or
high diastereoselectivity, of aromatic α,β-epoxyamides, in
which the oxirane ring is trisubstituted, into (Z)-α,β-un-
saturated amides, promoted by SmI2 in the presence of
MeOH, and the synthesis of (E)-α,β-unsaturated amides
from aromatic di- or tetrasubstituted α,β-epoxyamides by
using SmI2.[10]
Scheme 1
When the reaction conditions used to obtain aromatic
α,β-unsaturated amides from α,β-epoxyamides[10] were ap-
plied to aliphatic α,β-epoxyamides, no elimination reaction
was observed. For this reason and because the reduction
potential of SmI2 is higher in a solution of HMPA and
THF,[11] we carried out the β-elimination reaction of ali-
phatic α,β-epoxyamides by using SmI2 in the presence of
HMPA.
[a]
´
´
´
Departamento de Quımica Organica e Inorganica, Universidad
de Oviedo,
´
´
Julian Claverıa, 8, 33071 Oviedo, Spain
Fax: (internat.) ϩ34-98-5103446
E-mail: jmcg@sauron.quimica.uniovi.es
Eur. J. Org. Chem. 2004, 1523Ϫ1526
DOI: 10.1002/ejoc.200300641
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1523

´
J. M. Concellon, E. Bardales
FULL PAPER
Thus, treatment of different α,β-epoxyamides 1 with a 1H NMR spectrum (J ϭ 15.1 Hz). In the case of trisubsti-
solution of SmI2 (4 equiv.) in THF and HMPA (5 equiv.)[12] tuted α,β-unsaturated amides the stereochemistry was es-
1
for 30 min at room temperature afforded, after hydrolysis, tablished by comparison of the H NMR and 13C NMR
the corresponding α,β-unsaturated amides 2 with high dia- spectra with those of authentic samples, as reported in the
stereoselectivity and in good yields (Scheme 2, Table 1).
literature.[4]
It is noteworthy that although the starting α,β-epoxyam-
ides were mixtures of cis and trans diastereoisomers, the
corresponding α,β-unsaturated amides were obtained with
total or very high (E)-selectivity.
Different behavior was observed when α,β-epoxyamides
1, derived from ketones instead of aldehydes, and α-chlo-
roamides were used. Instead of the α,β-unsaturated amides,
β,δ-unsaturated α-hydroxyamides were obtained.[13]
The observed stereochemistry of products 2 may be ex-
plained by assuming a chelation-control model (Scheme 3).
Thus, reduction of the CαϪO bond generates the enolate
intermediate 3, in which the chelation of the SmIII center
with the carbonyl oxygen atom of the amide group pro-
duces a six-membered ring. Tentatively we propose a tran-
sition state model I with the R1 in the equatorial orientation
(to avoid 1,3-diaxial interactions). As depicted in II
(C2ϪC3 Newman projection of I) R1 and R2 show a cis
relationship. Consequently, elimination from I affords (E)-
α,β-unsaturated amides. This transition state could also ex-
plain the total or very high diastereoselectivity observed in
the β-elimination reaction from a mixture of diastereoiso-
mers of 1.
Scheme 2
Table 1. Synthesis of aliphatic (E)-α,β-unsaturated amides 2
2[a] R1
R2 R3 de (%)[b] Yield (%)[c]
2a Cyclohexyl
2b Bu
2c Bu
2d C7H15
2e Me2CϭCH(CH2)2CH(Me)CH2 Me Et
2f MeCH(Ph)
2g Cyclohexyl
H
iPr Ͼ98
40
70
82
64
85
83
91
Me Et Ͼ98
Ph Et
Me Et
83
95
94
95
93
Me Et
Me Et
[a]
All products were fully characterized by spectroscopic methods
[b]
(IR, NMR, and MS).
Determined on crude reaction products
by 1H NMR spectroscopy and GC-MS. [c] Yield of isolated product
The proposed reduction of the CαϪO bond, instead of
the CβϪO bond, is supported by the fact that the treatment
of aliphatic α,β-epoxyamides with SmI2 in the presence of
water affords β-hydroxyamides.[14]
after column chromatography based on compound 1.
Conclusion
In conclusion, we present an easy and general prep-
aration of aliphatic α,β-unsaturated amides 2 with high dia-
stereoselectivity by treating α,β-epoxyamides with sam-
arium diiodide and HMPA. The reaction is general, and
the CϪC double bond of 2 can be di- or trisubstituted. A
mechanism has been proposed to explain this reaction.
Experimental Section
Scheme 3
General Remarks: Reactions requiring an inert atmosphere were
conducted under dry nitrogen, and the glassware was oven dried
(120 °C). THF was distilled from sodium/benzophenone ketyl im-
mediately prior to use. All reagents were purchased in the highest
quality available and were used without further purification. 1H
NMR spectra were recorded at 200 or 300 MHz. 13C NMR spectra
and DEPT experiments were determined at 50 or 75 MHz. GC-
MS and HRMS were measured at 70 eV. Chemical shifts are given
This proposed methodology provides a general route to
obtain α,β-unsaturated amides 2, in which R1, R2 and R3
can be varied widely. Thus linear, branched, cyclic or un-
saturated aliphatic aldehydes may be used to introduce dif-
ferent R1 groups; R2 may also be varied using different α-
chloroamides to prepare the starting compounds
(Scheme 1).
1
1
in δ (ppm) relative to TMS as internal standard in the case of H
NMR spectra and relative to CDCl3 or [D6]DMSO in the case of
The de was calculated on the crude reaction products by
13C NMR spectra.
1H NMR spectroscopy and GC-MS.
The (E) stereochemistry of the CϪC double bond of the
α,β-unsaturated amide 2a was assigned from the value of
General Procedure for the Synthesis of Compound 1a: A solution of
lithium diisopropylamide [prepared from MeLi (3.3 mL of a 1.5 
the coupling constant between the olefinic protons in the solution) in diethyl ether (5 mmol) and diisopropylamine (0.8 mL,
1524  2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2004, 1523Ϫ1526

Synthesis of Aliphatic (E)-α,β-Unsaturated Amides
FULL PAPER
5 mmol) in THF (25 mL) at 0 °C] was added dropwise to a stirred
solution of the N,N-diisopropyl chloroacetamide (0.8 g, 4.5 mmol)
in dry THF (4 mL) at Ϫ78 °C. After stirring for 10 min, a solution
of the cyclohexanecarbaldehyde (0.4 mL, 3.5 mmol) in dry THF
NMR (75 MHz, CDCl3): δ ϭ 12.3 (CH3), 12.4 (CH3), 13.9 (CH3),
14.0 (CH3), 14.1 (CH3), 15.4 (CH3), 20.5 (CH2), 22.4 (CH2), 26.1
(CH2), 27.8 (CH2), 29.0 (CH2), 29.1 (CH2), 30.0 (CH2), 31.5 (CH2),
39.1 (CH2), 39.2 (CH2), 41.0 (CH2), 41.3 (CH2), 60.8 (CH), 61.2
(4.5 mL) was added dropwise at Ϫ78 °C and the mixture was (CH), 61.9 (C), 63.9 (C), 168.5 (C), 169.9 (C) ppm. IR (film): ν˜ ϭ
stirred for 1 h. The reaction mixture was quenched with an aqueous
saturated solution of NH4Cl (20 mL) followed by extraction with
diethyl ether which provided the corresponding 2-chloro-3-
hydroxyamide, which was treated with sodium hydride (1 g,
45 mmol) at 25 °C. The mixture was stirred for 2.5 h at this tem-
perature, quenched with H2O (10 mL) and then extracted with di-
ethyl ether (3 ϫ 10 mL) to afford crude 2,3-epoxyamide 1a, which
was purified by flash column chromatography on silica gel (hexane/
EtOAc), yielding pure compound 1a.
2927, 1644, 1464, 1380, 1079 cmϪ1; Rf ϭ 0.1 (hexane/EtOAc, 5:1).
2,3-Epoxy-N,N-diethyl-2,5,9-trimethyldecan-8-enamide (1e): Yield:
90%, 632 mg. 1H NMR (200 MHz, CDCl3): δ ϭ 1.01 (d, J ϭ
6.4 Hz, 6 H), 1.15 (t, J ϭ 7.2 Hz, 6 H), 1.20 (t, J ϭ 7.1 Hz, 6 H),
1.49 (s, 6 H), 1.60 (s, 6 H), 1.68 (s, 6 H), 2.10Ϫ1.31 (m, 14 H),
13
3.68Ϫ3.03 (m, 10 H), 5.13Ϫ5.05 (m, 2 H) ppm.
C NMR
(75 MHz, CDCl3): δ ϭ 12.0 (CH3) 13.7 (CH3), 15.2 (CH3), 15.3
(CH3) 17.1 (CH3), 18.8 (CH3), 19.2 (CH3), 20.1 (CH3), 24.9 (CH3),
25.2 (CH2), 30.2 (CH), 30.6 (CH), 34.4 (CH2), 34.5 (CH2), 36.4
(CH2), 36.6 (CH2), 38.8 (CH2), 39.1 (CH2), 40.7 (CH2), 41.1 (CH2),
59.9 (C), 60.6 (CH), 60.7 (CH), 124.0 (CH), 124.1 (CH) ppm.. IR
(film): ν˜ ϭ 2968, 1635, 1434, 1380, 1076 cmϪ1; Rf ϭ 0.3 (hexane/
EtOAc, 5:1).
3-Cyclohexyl-2,3-epoxy-N,N-diisopropylpropanamide (1a): Yield:
64%, 567 mg. 1H NMR (200 MHz, CDCl3): δ ϭ 1.23 (d, J ϭ
6.7 Hz, 3 H), 1.25 (d, J ϭ 6.7 Hz, 3 H), 1.42 (d, J ϭ 6.7 Hz, 6 H),
2.06Ϫ1.57 (m, 11 H), 2.93Ϫ2.86 (m, 1 H), 3.53Ϫ3.37 (m, 1 H),
3.53 (d, J ϭ 4.4 Hz, 1 H) 4.34Ϫ4.21 (m, 1 H) ppm. 13C NMR
(75 MHz, CDCl3): δ ϭ 18.8 (CH3), 19.1 (CH3), 19.4 (CH3), 19.7
(CH3), 24.1 (CH2), 24.2 (CH2), 25.0 (CH2), 27.5 (CH2), 29.1 (CH2),
35.5 (CH), 44.6 (CH), 46.6 (CH), 53.5 (CH), 60.0 (CH), 164.2 (C)
ppm. IR (film): ν˜ ϭ 2953, 1651, 1454, 1372, 1136 2953, 1651, 1454,
1372, 1136 cmϪ1; Rf ϭ 0.2 (hexane/EtOAc, 3:1)
2,3-Epoxy-N,N-diethyl-2-methyl-4-phenylpentanamide (1f): Yield:
62%, 404 mg. 1H NMR (200 MHz, CDCl3): δ ϭ 0.95 (t, J ϭ
7.2 Hz, 6 H), 1.08 (t, J ϭ 7.2 Hz, 6 H), 1.40 (d, J ϭ 6.9 Hz, 3 H),
1.50 (d, J ϭ 6.9 Hz, 3 H), 1.54 (s, 3 H), 1.52 (s, 3 H), 3.57Ϫ2.48
(m, 12 H), 7.37Ϫ7.24 (m, 10 H) ppm. 13C NMR (75 MHz, CDCl3):
δ ϭ 12.1 (CH3), 12.3 (CH3), 13.5 (CH3), 13.9 (CH3), 15.5 (CH3),
17.4 (CH3), 18.6 (CH3), 20.6 (CH3), 39.4 (CH), 40.5 (CH2), 41.2
(CH2), 41.5 (CH2), 61.3 (C), 62.5 (C), 65.9 (CH), 67.7 (CH), 126.3
(CH), 126.5 (CH), 127.2 (CH), 127.9 (CH), 128.0 (CH), 128.1
(CH), 141.3 (C), 141.9 (C) ppm. IR (film): ν˜ ϭ 2972, 1637, 1452,
1381, 1086 cmϪ1; Rf ϭ 0.3, 0.2 (hexane/EtOAc, 3:1).
General Procedure for the Synthesis of Compounds 1bϪg: A solu-
tion of potassium hexamethyldisilazide (6.5 mL of a 0.5  solution
in toluene, 3.25 mmol) was added dropwise to a stirred solution of
the appropriate 2-chloroamide (2.5 mmol) in dry THF (4 mL) at
Ϫ78 °C. After stirring for 10 min, a solution of the corresponding
aldehyde (2.5 mmol) in dry THF (4 mL) was added dropwise at
Ϫ78 °C and the mixture was warmed to room temperature. The
resulting solution was quenched with an aqueous saturated solu-
tion of NH4Cl (10 mL) followed by extraction with diethyl ether (3
ϫ 10 mL) provided crude 2,3-epoxyamides 1bϪg, which were puri-
fied by column flash chromatography over silica gel (hexane/
EtOAc) affording pure compounds 1bϪg.
3-Cyclohexyl-2,3-epoxy-N,N-diethyl-2-methylpropanamide
(1g):
Yield: 85%, 508 mg. 1H NMR (200 MHz, CDCl3): δ ϭ 1.11 (t, J ϭ
6.9 Hz, 6 H), 1.19 (t, J ϭ 6.9 Hz, 6 H), 1.51 (s, 3 H), 1.53 (s, 3 H),
2.01Ϫ1.39 (m, 22 H), 2.57 (d, J ϭ 8.2 Hz, 1 H), 2.75 (d, J ϭ 7.4 Hz,
1 H), 3.69Ϫ3.20 (m, 8 H) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ
12.3 (CH3), 12.4 (CH3), 14.0 (CH3), 14.2 (CH3), 15.5 (CH3), 25.1
(CH2), 25.2 (CH2), 25.9 (CH2), 26.0 (CH2), 28.2 (CH2), 28.3 (CH2),
29.8 (CH2), 30.0 (CH2), 36.8 (CH), 38.6 (CH2), 39.0 (CH2), 40.9
(CH2), 41.6 (CH2), 60.9 (CH), 61.8 (CH), 65.8 (C), 67.6 (C), 169.8
(C) ppm. IR (film): ν˜ ϭ 2930, 1636, 1450, 1381, 1074 cmϪ1. Rf ϭ
0.3, 0.2 (hexane/EtOAc, 3:1).
2,3-Epoxy-N,N-diethyl-2-methylheptanamide (1b): Yield: 55%,
294 mg. 1H NMR (200 MHz, CDCl3): δ ϭ 0.96Ϫ076 (m, 6 H),
1.07 (t, J ϭ 7.1 Hz, 6 H), 1.15 (t, J ϭ 7.1 Hz, 6 H), 1.43 (s, 6 H),
1.87Ϫ1.24 (m, 8 H), 3.02Ϫ2.96 (m, 4 H), 3.59Ϫ3.12 (m, 8 H) ppm.
13C NMR (75 MHz, CDCl3): δ ϭ 12.8 (CH3), 13.4 (CH3), 14.2
(CH3), 14.4 (CH3), 14.6 (CH3), 15.8 (CH3), 15.6 (CH3), 15.9 (CH3),
25.1 (CH2), 27.9 (CH2), 28.6 (CH2), 39.5 (CH2), 41.5 (CH2), 60.6
(C), 61.0 (CH), 62.7 (C), 169.9 (C), 170.0 (C) ppm. IR (film): ν˜ ϭ
2959, 1639, 1467, 1382, 1073 cmϪ1; Rf ϭ 0.2 (hexane/EtOAc, 3:1)
General Procedure for the Synthesis of Compounds 2: A solution of
SmI2 (1.6 mmol) in THF (19 mL) and HMPA (2 mmol) was added,
under nitrogen, to a stirred solution of the appropriate epoxyamide
1 (0.4 mmol) in THF (4 mL) at room temperature. After stirring
for 30 min the reaction was quenched with aqueous HCl (20 mL
of a 0.1  solution) followed by extraction with diethyl ether (3 ϫ
10 mL) affording crude α,β-unsaturated amide 2, which was puri-
fied by column flash chromatography over silica gel (hexane/
EtOAc, 10:1).
2,3-Epoxy-N,N-diethyl-2-phenylheptanamide (1c): Yield: 74%,
1
509 mg. H NMR (300 MHz, CDCl3): δ ϭ 0.72 (t, J ϭ 7.1 Hz, 3
H), 0.80 (t, J ϭ 7.1 Hz, 3 H), 0.86 (t, J ϭ 7.1 Hz, 3 H), 0.97 (t,
J ϭ 7.1 Hz, 3 H), 1.03 (t, J ϭ 7.1 Hz, 3 H), 1.10 (t, J ϭ 7.1 Hz, 3
H), 1.55Ϫ1.15 (m, 12 H), 3.46Ϫ2.88 (m, 10 H), 7.45Ϫ7.23 (m, 10
H) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 12.2 (CH3), 12.4 (CH3),
13.2 (CH3), 13.6 (CH3), 13.7 (CH3), 13.9 (CH3), 21.9 (CH2), 22.3
(CH2), 26.5 (CH2), 27.8 (CH2), 28.3 (CH2), 30.7 (CH2), 39.2 (CH2),
39.3 (CH2), 40.8 (CH2), 41.4 (CH2), 64.0 (C), 64.9 (CH), 65.9 (C),
68.2 (CH), 124.7 (CH), 126.0 (CH), 127.7 (CH), 127.8 (CH), 127.9
(CH) ppm. IR (film): ν˜ ϭ 2940, 1644, 1463, 1380, 1032 cmϪ1; Rf ϭ
0.4, 0.3 (hexane/EtOAc, 5:1)
(E)-3-Cyclohexyl-N,N-diisopropylpropenamide (2a): Yield: 40%,
38 mg. 1H NMR (200 MHz, CDCl3): δ ϭ 2.22Ϫ1.08 (m, 23 H),
4.12Ϫ3.58 (m, 2 H), 6.14 (d, J ϭ 15.1 Hz, 1 H), 6.74 (dd, J ϭ 15.1,
7.4 Hz, 1 H) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 20.3 (CH3),
21.2 (CH3), 25.8 (CH2), 25.9 (CH2), 32.1 (CH2), 40.6 (CH), 45.5
(CH), 48.1 (CH), 120.5 (CH), 149.5 (CH), 166.7 (C) ppm. MS
(70 eV): m/z (%) ϭ237 [M]ϩ (2), 222 (5), 194 (26), 124 (62), 55
(100). IR (film): ν˜ ϭ 2926, 1654, 1438, 1337 cmϪ1. Rf ϭ 0.2 (hex-
ane/EtOAc, 3:1).
2,3-Epoxy-N,N-diethyl-2-methyldecanamide (1d): Yield: 92%,
587 mg. 1H NMR (200 MHz, CDCl3): δ ϭ 0.89Ϫ0.79 (m, 6 H),
1.08 (t, J ϭ 7.1 Hz, 6 H), 1.15 (t, J ϭ 7.1 Hz, 6 H), 1.42Ϫ1.20 (m, (E)-N,N-Diethyl-2-methylhep-2-enamide (2b): Yield: 70%, 55 mg.
24 H), 1.45 (s, 3 H), 1.50 (s, 3 H), 3.56Ϫ2.96 (m, 10 H) ppm. 13C 1H NMR (200 MHz, CDCl3): δ ϭ 0.91 (t, J ϭ 6.9 Hz, 3 H), 1.14
Eur. J. Org. Chem. 2004, 1523Ϫ1526
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1525

´
J. M. Concellon, E. Bardales
FULL PAPER
(t, J ϭ 7.2 Hz, 6 H), 1.58Ϫ1.12 (m, 4 H), 1.83 (s, 3 H), 2.14Ϫ2.03 (57), 140 (100). IR (film): ν˜ ϭ 2974, 1623, 1457, 1380 cmϪ1. Rf ϭ
(m, 2 H), 3.33 (q, J ϭ 7.2 Hz, 4 H), 5.48 (t, J ϭ 7.2 Hz, 1 H) ppm. 0.2 (hexane/EtOAc, 3:1)
13C NMR (75 MHz, CDCl3): δ ϭ 13.8 (CH3), 14.0 (CH3), 14.3
(CH3), 22.3 (CH2), 22.6 (CH3), 27.1 (CH2), 31.1 (CH2), 31.5 (CH2),
Acknowledgments
We thank the II Plan Regional de Investigacion del Principado de
129.6 (CH), 131.7 (C), 173.5 (C). MS (70 eV): m/z (%) ϭ197 (4)
[M]ϩ, 168 (6), 140 (72), 125 (49) ppm. IR (film): ν˜ ϭ 2938, 1624,
´
1458, 1431, 1380 cmϪ1. Rf ϭ 0.3 (hexane/EtOAc, 3:1)
Asturias (PB-EXP01Ϫ11) and the Ministerio de Ciencia y Tecnolo-
(E)-N,N-Diethyl-2-phenylhep-2-enamide (2c): Yield: 82%, 85 mg. 1H
NMR (300 MHz, CDCl3): δ ϭ 0.96Ϫ0.89 (m, 6 H), 1.23 (t, J ϭ
7.1 Hz, 3 H), 1.54Ϫ1.33 (m, 4 H), 2.25Ϫ2.18 (m, 2 H), 3.24 (q, J ϭ
7.1 Hz, 2 H), 3.54 (q, J ϭ 7.1 Hz, 2 H), 6.04 (t, J ϭ 7.6 Hz, 1 H),
7.39Ϫ7.21 (m, 5 H) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 12.5
(CH3), 13.6 (CH3), 13.7 (CH3), 22.3 (CH2), 29.5 (CH2), 31.2 (CH2),
38.2 (CH2), 42.3 (CH2), 125.1 (CH), 127.3 (CH), 128.4 (CH), 129.3
(CH), 136.4 (C), 137.5 (C), 169.1 (C) ppm. MS (70 eV): m/z (%) ϭ
259 (86) [M]ϩ, 230 (71), 202 (100), 159 (4), 77 (9). IR (film): ν˜ ϭ
2960, 1627, 1430, 1435, 1387 cmϪ1. Rf ϭ 0.5 (hexane/EtOAc, 1:1)
´
gıa (BQU2001Ϫ3807) for financial support. J. M. C. thanks Car-
´
´
men Fernandez-Florez for her time and E. B thanks the Principado
de Asturias for a predoctoral fellowship. We also thank Scott J. S.
Hartman for correcting the English.
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(E)-N,N-Diethyl-2-methyldec-2-enamide (2d): Yield: 64%, 70 mg.
1H NMR (300 MHz, [D6]DMSO, 373 K): δ ϭ 0.84 (t, J ϭ 6.7 Hz,
3 H), 1.11 (t, J ϭ 7.2 Hz, 6 H), 1.50Ϫ1.22 (m, 10 H), 1.78 (s, 3 H),
2.04 (q, J ϭ 6.9 Hz, 2 H), 3.34 (q, J ϭ 7.2 Hz, 4 H), 5.46 (dt, J ϭ
7.4, 1.5 Hz, 1 H) ppm. 13C NMR (75 MHz, [D6]DMSO, 373 K):
δ ϭ 12.8 (CH3), 13.9 (CH3), 14.2 (CH3), 22.4 (CH2), 27.3 (CH2),
28.8 (CH2), 29.0 (CH2), 29.1 (CH2), 31.6 (CH2), 41.5 (CH2), 130.3
(CH), 130.8 (C), 173.7 (C) ppm. MS (70 eV): m/z (%) ϭ 239 [M]ϩ
(2), 167 (27), 140 (100), 55 (40), 41 (40). IR (film): ν˜ ϭ 2928, 2856,
1624, 1460, 1379 cmϪ1; Rf ϭ 0.5 (hexane/EtOAc, 1:1)
´
´
´
´
J. M. Concellon, J. A. Perez-Andres, H. Rodrıguez-Solla,
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J. M. Concellon, E. Bardales, Org. Lett. 2002, 4, 189Ϫ191.
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L. Crombie, A. H. Krasinski, M. Manzoor-I-Khuda, J.
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Chem. Soc. 1963, 4970Ϫ4976.
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2083Ϫ2087.
M. Onda, Y. Konda, K. Hinottozawa, S.
[7e]
(E)-N,N-Diethyl-2,5,9-trimethyldec-2,8-dienamide (2e): Yield: 85%,
Omura, Chem. Pharm. Bull. 1982, 30, 1210Ϫ1214.
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Ojika, H. Niwa, Y. Shizuri, K. Yamada, J. Chem. Soc., Chem.
H. Cho,
1
90 mg. H NMR (300 MHz, [D6]DMSO, 373 K): δ ϭ 0.99 (d, J ϭ
[7f]
6.7 Hz, 3 H), 1.17 (t, J ϭ 7.3 Hz, 6 H), 1.68 (s, 3 H), 1.75 (s, 3 H),
1.83 (s, 3 H), 2.21Ϫ0.93 (m, 7 H), 3.41 (q, J ϭ 7.3 Hz4 H, ),
5.21Ϫ5.17 (m, 1 H), 5.53Ϫ5.48 (m, 1 H) ppm. 13C NMR (75 MHz,
[D6]DMSO, 373 K): δ ϭ 13.4 (CH3), 14.2 (CH3), 17.3 (CH3), 19.3
(CH3), 25.2 (CH2), 32.5 (CH), 34.2 (CH2), 36.4 (CH2), 40.4 (CH2),
124.6 (CH), 127.3 (CH), 130.5 (C), 132.9 (C), 172.4 (C) ppm. MS
(70 eV): m/z (%) ϭ 265 (6) [M]ϩ, 250 (10), 182 (67), 154 (12). IR
(film): ν˜ ϭ 2966, 1624, 1459, 1379 cmϪ1; Rf ϭ 0.2 (hexane/
EtOAc, 3:1).
M.
[7g]
Commun. 1982, 628Ϫ629.
R. Grote, A. Zeeck, H. Drautz,
H. Zähner, J. Antibiot. 1988, 41, 1275Ϫ1276. [7h] G. Werner, H.
Hagenmaier, H. Drautz, A. Baumgartner, H. Zähner, J. Anti-
biot. 1984, 37, 110Ϫ117. [7i] S. Omura, N. Imamura, K. Hiniti-
zawa, K. Otoguro, G. Lukacs, R. Faghih, R. Tolmann, B. H.
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J. E. Baldwin, W. A. Dupont, Tetrahedron Lett. 1980, 21,
[8b]
1881Ϫ1182.
G. B. Mpango, K. K. Mahalanabis, Z. Mah-
davi-Damghani, V. Snieckus, Tetrahedron Lett. 1980, 21,
(E)-N,N-Diethyl-2-methyl-4-phenylpent-2-enamide (2f): Yield: 83%,
81 mg. 1H NMR (200 MHz, CDCl3): δ ϭ 1.27Ϫ1.01 (m, 6 H), 1.39
(d, J ϭ 6.9 Hz, 3 H), 1.91 (s, 3 H), 3.48Ϫ3.21 (m, 4 H), 3.80Ϫ3.70
(m, 1 H), 5.63 (d, J ϭ 9.4 Hz, 1 H), 7.42Ϫ7.11 (m, 5 H) ppm. 13C
NMR (50 MHz, CDCl3): δ ϭ 14.2 (CH3), 14.5 (CH3), 21.4 (CH3),
36.6 (CH2), 36.7 (CH2), 37.6 (CH), 126.0 (CH), 126.6 (CH), 128.4
(CH), 130.8 (C), 133.7 (CH), 145.3 (C), 172.9 (C) ppm. MS (70 eV):
m/z (%) ϭ 245 (33) [M]ϩ, 173 (37), 140 (100), 126 (100), 77 (19).
IR (film): ν˜ ϭ 3008, 2945, 1647 cmϪ1. Rf ϭ 0.5 (hexane/EtOAc, 1:1)
[8c]
4823Ϫ4826.
H. Greger, M. Grentz, F. Bohlmann, Phytoch-
[8d]
emistry 1981, 20, 2579Ϫ2581.
H. Greger, M. Grentz, F.
[8e]
Bohlmann, Phytochemistry 1982, 21, 1071Ϫ1074.
F.
Bohlmann, M. Gancer; M. Kruger, E. Nordhoff, Tetrahedron
1983, 39, 123Ϫ128.
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K. Takai; M. Tezuka, K. Utimoto, J. Org. Chem. 1991, 56,
5980Ϫ5982.
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[11]
[12]
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J. M. Concellon, E. Bardales, J. Org. Chem. 2003, 68,
9492Ϫ9494.
J. Inanaga, Y. Handa, T. Tabuchi, J. Otsubo, M. Yamaguchi,
T. Hanamoto, Tetrahedron Lett. 1991, 32, 6557Ϫ6558.
When the reactions were carried out with more HMPA
(HMPA/SmI2, 4:1) similar yields and diastereoselectivities
were obtained.
(E)-3-Cyclohexyl-N,N-diethyl-2-methylpropenamide (2g): Yield:
91%, 81 mg. 1H NMR (300 MHz, [D6]DMSO, 373 K): δ ϭ 1.17 (t,
J ϭ 7.0 Hz, 6 H), 1.50Ϫ1.21 (m, 5 H), 1.81Ϫ1.68 (m, 5 H), 1.84
(d, J ϭ 1.7 Hz, 3 H), 2.43Ϫ2.30 (m, 1 H), 3.39 (q, J ϭ 7.0 Hz, 4
H), 5.33 (dq, J ϭ 8.9, 1.7 Hz, 1 H) ppm. 13C NMR (75 MHz,
[D6]DMSO, 373 K): δ ϭ 13.4 (CH3), 14.0 (CH3), 25.1 (CH2), 25.6
(CH2), 32.0 (CH2), 36.0 (CH), 40.4 (CH2), 130.4 (C), 134.0 (CH),
172.5 (C) ppm. MS (70 eV): m/z (%) ϭ 223 [M]ϩ (9), 208 (2), 151
[13]
[14]
´
J. M. Concellon, P. L. Bernad, E. Bardales, Chem. Eur. J. ,
in press.
´
´
J. M. Concellon, E. Bardales, C. Gomez, Tetrahedron Lett.
2003, 44, 5323Ϫ5326.
Received October 9, 2003
1526
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 1523Ϫ1526