Stereoselective synthesis of dienic nitrogen compounds

Article abstract of DOI:10.1055/s-2006-926303

Eight dienic nitrogen compounds were prepared starting from cyclobutene lactam 8. Dienes 12-15 were obtained by benzylation or acylation followed by methanolysis, hydrolysis or reduction. The unsubstituted lactam 8 provided diene 16. The latter was a prec

Full text of DOI:10.1055/s-2006-926303

PAPER
633
Stereoselective Synthesis of Dienic Nitrogen Compounds
D
ienic Nitrogen C
a
ompound
m
zi Aït Youcef,a Charlotte Boucheron,a Stéphane Guillarme,a Stéphanie Legoupy,*a Didier Dubreuil,b
François Huet*a
a
Laboratoire de Synthèse Organique, UCO2M, UMR CNRS 6011, Université du Maine, avenue Olivier Messiaen,
72085 Le Mans cedex 9, France
b
Laboratoire de Synthèse Organique, UMR CNRS 6513, FR CNRS 2465, 2 rue de la Houssinière, BP 92208, 44322 Nantes cedex 03,
France
Fax +33(2)43833902; E-mail: stephanie.legoupy@univ-lemans.fr; E-mail: francois.huet@univ-lemans.fr
Received 1 July 2005; revised 5 September 2005
reduction with NaBH4, did not occur. This result is coher-
Abstract: Eight dienic nitrogen compounds were prepared starting
ent with the absence of ‘push–pull’ character of this diene.
from cyclobutene lactam 8. Dienes 12–15 were obtained by benzyl-
As to isomerization of 3 to the E,E-isomer, it did not occur
either. This result is not surprising when taking into ac-
count the better stability of 2Z,3E-dienic diacid mo-
noesters with respect to the 2E,2E-derivatives showing
the preference of a CO2H group for the 2Z-position.12
ation or acylation followed by methanolysis, hydrolysis or reduc-
tion. The unsubstituted lactam 8 provided diene 16. The latter was
a precursor for the mono and biacylated products 17–19.
Key words: electrocyclic reactions, lactams, ring opening, dienes,
torquoselectivity
NHBoc
NBoc
a
In the course of the past two decades, dienamides have
emerged as reactive dienes in Diels–Alder reactions, espe-
cially for the synthesis of alkaloids.1 Stereocontrolled
preparation of dienamides can be achieved by various
methods such as acylation of enamines,2 thermal rear-
rangement of propargylic trichloroacetamides or Curtius
rearrangement of dienyl azides,3 anionization and alkyla-
tion of a-carbamidosulfones,4 deprotonation and silyla-
tion of a vinylogous amide,5 reaction involving ynamide-
titanium alkoxide complexes,6 condensation of nitrogen
compound with an aldehyde,7 and cross coupling reac-
tions.8
O
2
1
c
d
CH2OH
b
NHBoc
NHBoc
NHBoc
d
4
3
5
CO2H
CO2Me
MeO2C
RO2C
Ref. 11
CO2H
e
RO2C
7
6
CO2H
The thermal ring opening of cyclobutene derivatives,
leading to 1,3-diene compounds, has been studied exten-
sively by both experimentalists and theoreticians. In the
case of dissymmetric cyclobutenes, two conrotatory open-
ings are possible each yielding a different geometrical iso-
mer. Houk et al. predicted that p-donors such as nitrogen
substituents should exclusively lead to outward rotation.9
This theoretical prediction was confirmed by experimen-
tal work from our laboratory.10 In more recent work11 we
pointed out new results equally consistent with conrotato-
ry openings of cyclobutene derivatives and exclusive out-
ward rotation of nitrogen substituents in the case of
obtaining dienes 2, 3 and 4 (Scheme 1). In contrast, the
E,E-diene 5 was formed when the ring opening was car-
ried out in basic medium. We suppose that, in this case, di-
ene 4 is the primary product. Then isomerization occurs to
the more stable diene 5, in basic medium. Compound 4
was obtained only in practically neutral medium and we
also checked that it isomerized to 5 on basic treatment. On
the other hand, isomerization of 2, which was obtained by
Ref. 12
Scheme 1 Reagents and conditions : (a) NaBH4, MeOH –20 °C, se-
paration of the reduction products, then heating in refluxing toluene
for 10 min; (b) H2O, LiOH, THF; (c) MeOH, NaN3, DMF; (d) MeOH,
LiOH; (e) H2O, 80 °C.
With the aim of increasing the possibilities of stereochem-
ical control, we examined several parameters. The influ-
ence of the nature of substituent on the nitrogen atom
proved to be determinant. We prepared the suitable pre-
cursors from lactam 811,13 (Scheme 2). Acetylation, ben-
zylation and tosylation provided the expected products 9,
10, and 11, in 57, 78 and 64% yield, respectively.
As it was anticipated, hydrolysis of 9 provided diene 12
by a conrotatory process with outward rotation of the ni-
trogen substituent and preference of CO2H for the 2Z-po-
sition. On the other hand, we thought that the E,E-diene
would be formed by methanolysis after isomerization of
the primary diene. This isomerization was not observed
and we obtained compound 13. This unexpected result is
probably due to a moderate ‘push–pull’ character of diene
13 in which a strongly electron-withdrawing group is
present on nitrogen. In this case, isomerization was slow
and stirring in the presence of LiOH in MeOH for 48
SYNTHESIS 2006, No. 4, pp 0633–0636
x
x
.
x
x
.2
0
0
6
Advanced online publication: 19.01.2006
DOI: 10.1055/s-2006-926303; Art ID: T09505SS
© Georg Thieme Verlag Stuttgart · New York

634
R. Aït Youcef et al.
PAPER
NH2
a or b or c
NR
NH
a
8
16
O
O
8
~ quant.
9, R = Ac
57%
10, R = Bn 78%
11, R = pTs 64%
CO2Me
NAc2
NHAc
d
9
12
b
81%
18
NHAc
17
60%
CO2H
NHAc
b
CO2Me
NAcBoc
16
57%
e
c
9
13
CO2Me
19
90%
64%
CO2Me
NHBn
CO2Me
e
Scheme 3 Reagents and conditions: (a) LiOH, MeOH; (b) Ac2O,
DMAP, Et3N, CH2Cl2, 0 °C to r.t.; (c) Boc2O, DMAP, Et3N, CH2Cl2,
0 °C to r.t.
10
9
14
94%
MeO2C
NHAc
Stereochemical assignments for dienes 12–16 were based
f
1
15
on H NMR analyses. When the differences between the
62%
coupling constants for a trans- and a cis-relationship were
not sufficient, the structures were confirmed by NOE or
NOESY experiments.
CH2OH
Scheme 2 Reagents and conditions: (a) Ac2O, KOH, THF, –78 °C
to r.t.; (b) BnBr, KOH, Bu4NI, THF, –78 °C to r.t; (c) p-Ts2O, Et3N,
CH2Cl2, 0 °C to r.t.; (d) H2O, LiOH, THF; (e) MeOH, LiOH; (f)
LiAlH4, THF, –78 to –20 °C, separation of the reduction products,
then heating in refluxing toluene for 40 min.
In conclusion we have found efficient conditions to pre-
pare E,E- as well as Z,E-nitrogen dienes. We also propose
an interpretation of our previous results as well as of these
new ones. Synthetic application of the products is now in
progress.
hours led to a mixture of Z,E- and E,E-dienes in a 4:1 ra-
tio, respectively. Logically, when the acetyl group was re-
placed by a benzyl group, the E,E-diene 14 was formed.
Treatment of 9 with LiAlH4 at low temperature led to a se-
lectivity in favor of reduction of the lactam moiety with
respect to the acetyl group. A mixture of N-[4-hydroxy-
methyl)cyclobut-2-enyl]acetamide and diene 15 was thus
obtained. The latter was isolated in 62% overall yield after
isomerization of the cyclobutene compound by heating in
refluxing toluene. Methanolysis and hydrolysis of lactam
11 were also carried out. However, they did not lead to
good results and mainly formation of degradation prod-
ucts was observed.
All moisture-sensitive reactions were carried out in oven-dried
glassware (100 °C) under N2. Commercially available reagents and
solvents were purified and dried, when necessary, by standard
methods just prior to use. IR spectra were scanned on a FTIR spec-
trophotometer. All melting points are uncorrected. 1H and 13C NMR
spectra were recorded at 400 and 100.6 MHz, respectively. Chemi-
cal shifts are reported in ppm downfield from TMS which was used
as an internal reference. Elemental analyses were obtained from the
Service de Microanalyse, CNRS ICSN, Gif-sur-Yvette. High-reso-
lution mass measurements were performed at the CRMPO, Rennes.
N-Acetyl-2-azabicyclo[2.2.0]hex-5-en-3-one (9)
Ac2O (0.45 mL, 4.76 mmol), and KOH (0.285 g, 5.07 mmol), were
added to a solution of lactam 8 (0.300 g, 3.15 mmol) in anhyd THF
(15 mL) at –78 °C. The mixture was stirred for 16 h while the tem-
perature was slowly allowed to warm to 20 °C. A solution of 1 M
aq HCl (3 mL) was then added, and the solvents were evaporated.
The residue was dissolved in CH2Cl2 (10 mL), successively washed
with H2O (5 mL) and brine (5 mL), dried (MgSO4) and concentrat-
ed. The residue was purified by column chromatography (silica gel,
cyclohexane–EtOAc, 7:3) to give compound 9 (0.246 g, 57%) as a
colorless oil.
At this point of our work, access to E,E-dienes was limit-
ed. We thought that, if our hypotheses were good, it would
be possible to prepare one of them from the unsubstituted
lactam 8, as in this case there would not be restriction to
isomerization. We were pleased to obtain the anticipated
result and diene 16, which is poorly stable, was available
in nearly quantitative yield by treatment with MeOH,
LiOH (Scheme 3). This good result made it possible to se-
lectively prepare an E,E-aminodiene 17 bearing an elec-
tron-withdrawing group on the nitrogen atom by a
strategy based on acetylation after, instead of before, the
ring-opening process. This diene, an isomer of 13, was
available by acetylation of 16. We also showed that it was
possible to introduce a second group [Ac (18) or Boc (19)]
on nitrogen atom of dienamide 17.
IR (KBr): 3014, 1702, 1544, 1310 cm–1.
1H NMR (CDCl3): d = 6.66 (dd, 1 H, H-5, J = 2.7, 1.0 Hz), 6.59–
6.56 (m, 1 H, H-6), 4.75 (dd, 1 H, H-1, J = 2.7, 2.2 Hz), 4.21–4.18
(m, 1 H, H-4), 2.36 (s, 3 H, COCH3).
13C NMR (CDCl3): d = 168.7, 166.7, 142.3, 140.3, 56.7, 51.9, 23.1.
HRMS (EI): m/z calcd for [(C7H7NO2) – CH2CO]+: 95.0371; found:
95.0374.
Synthesis 2006, No. 4, 633–636 © Thieme Stuttgart · New York

PAPER
Dienic Nitrogen Compounds
635
N-Benzyl-2-azabicyclo[2.2.0]hex-5-en-3-one (10)
r.t. for 3 h, and the solvent was removed in vacuo. The residue was
dissolved in EtOAc (5 mL), successively washed with H2O (2 mL)
and brine (2 mL), dried (MgSO4), and concentrated in vacuo. The
residue was purified by column chromatography (silica gel, cyclo-
hexane–EtOAc, 3:2) to give compound 13 (0.072 g, 90%) as a yel-
low oil.
Benzyl bromide (0.217 g, 1.26 mmol), KOH (0.095 g, 1.26 mmol),
and Bu4NI (0.040 g, 0.11 mmol) were added to a solution of lactam
8 (0.100 g, 1.05 mmol) in anhyd THF (8 mL) at –78 °C. The mixture
was stirred for 16 h while the temperature was slowly allowed to
warm to 20 °C. A solution of 1 M aq HCl (2 mL) was then added,
and the solvent was evaporated. The residue was dissolved in
CH2Cl2 (10 mL), successively washed with H2O (1 mL) and brine
(1 mL), dried (MgSO4) and concentrated. The residue was purified
by column chromatography (silica gel, cyclohexane–EtOAc, 3:2) to
give compound 10 (0.151 g, 78%) as an orange oil.
IR (KBr): 3352, 1683, 1578, 1433, 1250, 1128 cm–1.
1H NMR (CDCl3): d = 8.32 (d, 1 H, NH, J = 10.8 Hz), 7.33 (dd, 1
H, H-5, J = 14.2, 10.8 Hz), 7.18 (dd, H, H-4, J = 14.2, 11.3 Hz),
6.62 (t, 1 H, H-3, J = 11.3 Hz), 5.57 (d, 1 H, H-2, J = 11.3 Hz), 3.71
(s, 3 H, OCH3), 2.12 (s, 3 H, COCH3).
13C NMR (CDCl3): d = 168.1, 167.6, 144.1, 133.8, 113.7, 109.2,
51.1, 23.3.
IR (KBr): 3022, 1742, 1597, 1455 cm–1.
1H NMR (CDCl3): d = 7.37–7.27 (m, 3 H, C6H5), 7.26–7.22 (m, 2
H, C6H5), 6.46–6.43 (m, 1 H, H-5), 6.13 (t, 1 H, H-6, J = 2.5 Hz),
4.33 (AB system, 2 H, CH2Ph, J = 3.4 Hz), 4.20 (t, 1 H, H-1, J = 2.5
Hz), 4.17–4.15 (m, 1 H, H-4).
Anal. Calcd for C8H11NO3·0.1H2O: C, 56.20; H, 6.60; N, 8.19.
Found: C, 55.01; H, 6.63; N, 8.19.
13C NMR (CDCl3): d = 169.4, 141.2, 138.8, 134.9, 128.7, 128.3,
(2E,4E)-5-Benzylaminopenta-2,4-dienoic Acid Methyl Ester
(14)
127.8, 57.7, 53.8, 47.6.
HRMS (EI): m/z calcd for [C12H11NO]+: 185.0841; found:
185.0846.
LiOH (0.156 g, 6.53 mmol) was added to a solution of lactam 10
(0.400 g, 2.18 mmol) in anhyd MeOH (30 mL). The mixture was
stirred at r.t. for 4 h, and the solvent was removed in vacuo. The res-
idue was dissolved in EtOAc (10 mL), successively washed with
H2O (4 mL) and brine (4 mL), dried (MgSO4), and concentrated in
vacuo to give compound 14 (0.444 g, 94%) as an orange solid (1H
NMR estimated purity >95%). Degradation was observed in the
course of column chromatography on silica gel; mp 72–74 °C.
N-Tosyl-2-azabicyclo[2.2.0]hex-5-en-3-one (11)
Et3N (1.31 mL, 9.42 mmol) and p-toluenesulfonic anhydride (2.250
g, 6.90 mmol) were added to a cooled (0 °C) solution of lactam 8
(0.580 g, 6.10 mmol) in CH2Cl2 (25 mL). The mixture was stirred
for 3 h at r.t. and then diluted with CH2Cl2 (10 mL). The solution
was successively washed with 1 M aq HCl (3 mL), H2O (4 mL), and
brine (4 mL), dried (MgSO4), and concentrated. The residue was
purified by column chromatography (silica gel, cyclohexane–
EtOAc, 85:15, then 80:20) to give compound 11 (0.979 g, 64%) as
a white powder; mp 106–108 °C.
IR (KBr): 3362, 1732, 1615, 1455 cm–1.
1H NMR (CDCl3): d = 7.41–7.27 (m, 6 H, 5 Harom and H-3), 6.80
(dd, 1 H, H-5, J = 12.6, 7.6 Hz), 5.48 (d, 1 H, H-2, J = 14.8 Hz),
5.35 (dd, 1 H, H-4, J = 12.6, 11.6 Hz), 4.46 (d, 1 H, NH, J = 7.6
Hz), 4.23 (AB system, 2 H, CH2 benzyl, J = 5.5 Hz), 3.68 (s, 3 H,
CH3).
13C NMR (CDCl3): d = 169.1, 147.6, 146.3, 137.5, 128.5, 127.7,
127.5, 108.0, 97.8, 50.8, 48.5.
IR (KBr): 3090, 1788, 1594, 1545, 1169, 1101 cm–1.
1H NMR (CDCl3): d = 7.84 (d, 2 H, C6H5, J = 8.6 Hz), 7.34 (d, 2 H,
C6H5, J = 8.6 Hz), 6.41 (dd, 1 H, H-5, J = 2.5, 1.2 Hz), 6.37–6.34
(m, 1 H, H-6), 4.74 (dd, 1 H, H-1, J = 3.0, 2.2 Hz), 4.27–4.25 (m, 1
H, H-4), 2.45 (s, 3 H, CH3).
HRMS: m/z calcd for [(C13H15NO2]+: 217.1102; found: 217.1101.
13C NMR (CDCl3): d = 164.5, 145.3, 141.2, 138.1, 134.9, 129.9,
127.5, 57.9, 55.1, 21.6.
(2Z,4E)-5-Acetylaminopenta-2,4-dienol (15)
A solution of compound 9 (0.295 g, 2.15 mmol) in anhyd THF (2
mL) was added to a suspension of LiAlH4 (0.245 g, 6.45 mmol) in
anhyd THF (10 mL) at –78 °C. The mixture was stirred for 6 h while
the temperature was slowly allowed to warm to –20 °C. An aq so-
lution of 2 M KOH (2.5 mL) was then added while the temperature
was slowly allowed to warm to 20 °C and then the salts were fil-
tered, and successively rinsed with Et2O (5 mL) and CH2Cl2 (5 mL).
The solvents were concentrated in vacuo and the residue was dis-
solved in CH2Cl2 (5 mL) then dried (MgSO4). The solvent was con-
centrated under reduced pressure. The mixture of N-[4-
(hydroxymethyl)cyclobut-2-enyl]acetamide and 15 in a 1:1 ratio
was refluxed in toluene for 40 min to totally convert the cyclobutene
compound into diene 15. Purification by column chromatography
on silica gel (CH2Cl2–MeOH, 95:5) provided compound 15 (0.188
g, 62%) as a pale yellow powder; mp 120–122 °C.
Anal. Calcd for C12H11NSO3: C, 57.82; H, 4.45; N, 5.62. Found: C,
57.71; H, 4.35; N, 5.61.
(2Z,4E)-5-Acetylaminopenta-2,4-dienoic Acid (12)
LiOH (0.026 g, 1.09 mmol) was added to a solution of compound 9
(0.05 g, 0.36 mmol) in THF (2 mL) and H2O (1.5 mL). The mixture
was stirred at r.t. for 16 h, and the solvent was removed in vacuo.
The aqueous layer was acidified with AcOH to pH 4 and extracted
with EtOAc (3 mL). The combined extracts were washed with brine
(2 mL), dried (MgSO4), and concentrated in vacuo. The residue was
purified by recrystallization (MeOH) to give compound 12 (0.045
g, 81%) as a yellow powder; mp 183–185 °C.
IR (KBr): 3279, 1683, 1604, 1515, 1213, 994 cm–1.
1H NMR (DMSO-d6): d = 11.97 (s, 1 H, OH), 10.50 (d, 1 H, NH,
J = 10.7 Hz), 7.32–7.02 (m, 2 H, H-4 and H-5), 6.70 (t, 1 H, H-3,
J = 11.1 Hz), 5.37 (d, 1 H, H-2, J = 11.1 Hz), 1.95 (s, 3 H, COCH3).
13C NMR (DMSO-d6): d = 173.2, 173.1, 149.7, 140.1, 118.5, 113.5,
27.9.
IR (KBr): 3310–3100, 1670, 1614, 1529, 1380 cm–1.
1H NMR (CD3OD): d = 6.91 (d, 1 H, H-5, J = 13.8 Hz), 6.16 (dd, 1
H, H-4, J = 13.8, 11.2 Hz), 6.03 (dd, 1 H, H-3, J = 11.2, 11.1 Hz),
5.51–5.37 (m, 1 H, H-2), 4.19 (d, 2 H, CH2, J = 6.8 Hz), 2.00 (s, 3
H, COCH3).
13C NMR (CD3OD): d = 172.2, 130.7, 130.0, 129.8, 111.4, 60.5,
24.2.
Anal. Calcd for C7H9O3N·0.05H2O: C, 53.88; H, 5.88; N, 8.98.
Found: C, 54.17; H, 6.26; N, 8.41.
(2Z,4E)-5-Acetylaminopenta-2,4-dienoic Acid Methyl Ester
(13)
Anal. Calcd for C7H11NO2: C, 59.56; H, 7.85; N, 9.92. Found: C,
59.21; H, 7.65; N, 9.68.
LiOH (0.039 g, 1.63 mmol) was added to a solution of lactam 9
(0.065 g, 0.47 mmol) in MeOH (5 mL). The mixture was stirred at
Synthesis 2006, No. 4, 633–636 © Thieme Stuttgart · New York

636
R. Aït Youcef et al.
PAPER
(2E,4E)-5-Aminopenta-2,4-dienoic Acid Methyl Ester (16)
LiOH (0.549 g, 22.9 mmol) was added to a solution of lactam 8
(0.630 g, 6.62 mmol) in anhyd MeOH (40 mL). The mixture was
stirred at r.t. for 4 h, and the solvent was removed in vacuo. The res-
idue was dissolved in EtOAc (10 mL), successively washed with
H2O (5 mL) and brine (5 mL), dried (MgSO4), and concentrated in
vacuo to give compound 16 (0.840 g, 99%) as a yellow oil (1H NMR
estimated purity >95%) which was immediately used in the next
step (degradation was observed in the course of column chromatog-
raphy on silica gel).
(2E,4E)-5-(Acetyl-tert-butoxycarbonylamino)penta-2,4-dienoic
Acid Methyl Ester (19)
Et3N (0.021 mL, 0.15 mmol), Boc2O (0.063 g, 0.29 mmol), and
DMAP (0.018 g, 0.15 mmol) were added to a cooled (0 °C) solution
of diene 17 (0.040 g, 0.23 mmol) in CH2Cl2 (2 mL). The reaction
mixture was stirred at r.t. for 16 h and then diluted with CH2Cl2 (2
mL). The solution was successively washed with 1 M aq HCl (1
mL), H2O (1 mL) and brine (1 mL), dried (MgSO4), and concentrat-
ed in vacuo. The residue was purified by column chromatography
(silica gel, cyclohexane–EtOAc, 7:3) to give compound 19 (0.040
g, 64%) as a white powder; mp 84–86 °C.
IR (KBr): 3352, 1683, 1578, 1433, 1250, 1128 cm–1.
IR (KBr): 2978, 1712, 1629, 1332, 1143 cm–1.
1H NMR (CDCl3): d = 7.32–7.28 (m, 1 H, H-2), 6.70 (dt, 1 H, H-5,
J = 12.8, 10.3 Hz), 5.50–5.48 (m, 1 H, H-3), 5.47–5.45 (m, 1 H, H-
4), 4.18 (br s, 2 H, NH2), 3.69 (s, 3 H, OCH3).
13C NMR (CDCl3): d = 169.0, 146.8, 144.5, 109.1, 101.7, 51.0.
1H NMR (CDCl3): d = 7.31 (dd, 1 H, H-3, J = 15.2, 11.3 Hz), 7.04
(d, 1 H, H-5, J = 14.2 Hz), 6.40 (dd, 1 H, H-4, J = 14.2, 11.3 Hz),
5.88 (d, 1 H, H-2, J = 15.2 Hz), 3.74 (s, 3 H, OCH3), 2.44 (s, 3 H,
COCH3), 1.57 [s, 9 H, C(CH3)3].
13C NMR (CDCl3): d = 171.0, 167.3, 151.6, 143.4, 132.9, 120.0,
118.7, 85.2, 51.5, 27.8, 26.0.
This poorly stable compound was identified based on the NMR data
and to the full identification of its acetyl derivative 17.
(2E,4E)-5-Acetylaminopenta-2,4-dienoic Acid Methyl Ester
(17)
Anal. Calcd for C13H19NO5: C, 57.98; H, 7.11; N, 5.20. Found: C,
57.94; H, 7.03; N, 4.94.
Et3N (0.06 mL, 0.43 mmol), Ac2O (0.15 mL, 1.5 mmol), and
DMAP (0.052 g, 0.43 mmol) were added to a cooled (0 °C) solution
of diene 16 (0.110 g, 0.86 mmol) in CH2Cl2 (2 mL). The reaction
mixture was stirred at r.t. for 4 h and then diluted with CH2Cl2 (1
mL). The solution was successively washed with 1 M aq HCl (1
mL), H2O (1 mL) and brine (1 mL), dried (MgSO4), and concentrat-
ed in vacuo. The residue was purified by column chromatography
(silica gel, cyclohexane–EtOAc, 3:2) to give compound 17 (0.083
g, 57%) as a yellow powder; mp 130–132 °C.
Acknowledgment
We thank the local section of Sarthe of the Ligue Nationale contre
le Cancer for fellowships to R.A.Y. and S.G., and French Govern-
ment and Région des Pays de la Loire for financial support (CER
chimie fine et pharmacologie).
References
IR (KBr): 3304, 1710, 1681, 1614, 1252, 1238, 1136 cm–1.
(1) (a) Petrzilka, M.; Grayson, J. I. Synthesis 1981, 753.
(b) Campbell, A. L.; Lenz, G. R. Synthesis 1987, 421.
(2) (a) Oppolzer, W.; Fröstl, W. Helv. Chim. Acta 1975, 58,
587. (b) Oppolzer, W.; Fröstl, W. Helv. Chim. Acta 1975, 58,
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Acta 1975, 58, 593. (d) Oppolzer, W.; Bieber, L.; Francotte,
E. Tetrahedron Lett. 1979, 20, 981.
1H NMR (CDCl3): d = 8.40 (d, 1 H, NH, J = 10.8 Hz), 7.39–7.23
(m, 2 H, H-3 and H-5), 5.91 (dd, 1 H, H-4, J = 14.3, 11.3 Hz), 5.75
(d, 1 H, H-2, J = 15.3 Hz), 3.73 (s, 3 H, OCH3), 2.12 (s, 3 H,
COCH3).
13C NMR (CDCl3): d = 168.1, 167.8, 143.9, 133.1, 117.5, 110.2,
51.5, 23.3.
(3) (a) Overman, L. E.; Taylor, G. F.; Jessup, P. J. Tetrahedron
Lett. 1976, 3089. (b) Overman, L. E.; Taylor, G. F.; Petty, C.
B.; Jessup, P. J. Org. Chem. 1978, 43, 2164. (c) Overman,
L. E.; Taylor, G. F.; Houk, K. N.; Domelsmith, L. N. J. Am.
Chem. Soc. 1978, 100, 3182. (d) Overman, L. E.; Jessup, P.
J. J. Am. Chem. Soc. 1978, 100, 5179.
(4) Berthon, L.; Uguen, D. Tetrahedron Lett. 1985, 26, 3975.
(5) Kozmin, S. A.; Rawal, V. H. J. Org. Chem. 1997, 62, 5252.
(6) Tanaka, R.; Hirano, S.; Urabe, H.; Sato, F. Org. Lett. 2003,
5, 67.
(7) (a) Behr, J.-B.; Defoin, A.; Pires, J.; Streith, J.; Macko, L.;
Zehnder, M. Tetrahedron 1996, 52, 3283. (b) Zezza, C. A.;
Smith, M. B. J. Org. Chem. 1988, 53, 1161. (c) McAlonan,
H.; Murphy, J. P.; Nieuwenhuyzen, M.; Reynolds, K.;
Sarma, P. K. S.; Stevenson, P. J.; Thompson, N. J. Chem.
Soc., Perkin Trans. 1 2002, 69.
Anal. Calcd for C8H11NO3·0.1H2O: C, 56.20; H, 6.60; N, 8.19.
Found: C, 56.06; H, 6.41; N, 7.89.
(2E,4E)-5-Diacetylaminopenta-2,4-dienoic Acid Methyl Ester
(18)
Et3N (0.015 mL, 0.10 mmol), Ac2O (0.024 mL, 0.24 mmol), and
DMAP (0.012 g, 0.10 mmol) were added to a cooled (0 °C) solution
of diene 17 (0.035 g, 0.20 mmol) in CH2Cl2 (3 mL). The reaction
mixture was stirred at r.t. for 4 h and then diluted with CH2Cl2 (1
mL). The solution was successively washed with 1 M aq HCl (1
mL), H2O (1 mL), and brine (1 mL), dried (MgSO4) and concentrat-
ed in vacuo. The residue was purified by column chromatography
(silica gel, cyclohexane–EtOAc, 3:2) to give compound 18 (0.025
g, 60%) as a yellow solid; mp 59–61 °C.
IR (KBr): 2955, 1708, 1633, 1427, 1367, 1323 cm–1.
(8) (a) Barluenga, J.; Fernandez, M. A.; Aznar, F.; Valdés, C.
Chem. Commun. 2004, 1400. (b) Barluenga, J.; Rodriguez,
F.; Alvarez-Rodrigo, L.; Fañanás, F. J. Chem. Eur. J. 2004,
10, 101. (c) Commins, D. L.; Joseph, S. P.; Chen, X.
Tetrahedron Lett. 1995, 36, 9141.
(9) Niwayama, S.; Kallel, E. A.; Spelmeyer, D. C.; Sheu, C.;
Houk, K. N. J. Org. Chem. 1996, 61, 2813.
1H NMR (CDCl3): d = 7.36 (dd, 1 H, H-3, J = 15.2, 11.2 Hz), 6.84
(d, 1 H, H-5, J = 14.0 Hz), 6.19 (dd, 1 H, H-4, J = 14.0, 11.2 Hz),
5.96 (d, 1 H, H-2, J = 15.2 Hz), 3.77 (s, 3 H, OCH3), 2.39 (s, 6 H, 2
COCH3).
13C NMR (CDCl3): d = 172.1, 166.8, 140.7, 134.0, 126.4, 122.7,
51.7, 26.0.
(10) Gourdel-Martin, M.-E.; Huet, F. Tetrahedron Lett. 1996, 37,
7745.
Anal. Calcd for C10H13NO4: C, 56.87; H, 6.20; N, 6.63. Found: C,
56.52; H, 6.04; N, 6.41.
(11) Gauvry, N.; Huet, F. J. Org. Chem. 2001, 66, 583.
(12) Jaroszewski, J. W.; Grossen, P.; Mohr, P.; Tamm, C. Helv.
Chim. Acta 1986, 69, 718.
(13) Dilling, W. L. Org. Photochem. Synth. 1976, 2, 5.
Synthesis 2006, No. 4, 633–636 © Thieme Stuttgart · New York