Tertiary 3-aminopropenones and 3-aminopropenoates: Their preparation, with and without Lewis acids, from secondary amines and 1,3-diketo compounds

Article abstract of DOI:10.1055/s-2007-965916

A direct method for the preparation of tertiary 3-aminopropenones and 3-aminopropenoates from β-diketones and β-keto esters, and secondary amines has been developed. The reaction is performed without solvent in the presence or absence of Lewis acid as catalyst, depending on the reactivity of both the amine and the diketo substrate. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-965916

PAPER
731
Tertiary 3-Aminopropenones and 3-Aminopropenoates: Their Preparation,
with and without Lewis Acids, from Secondary Amines and 1,3-Diketo
Compounds
T
ertiary 3-Amino
a
propenone
m
s
and 3-Aminoprope
a
noates ndeep Kaur Vohra, Jean-Luc Renaud, Christian Bruneau*
Catalyse et Organométalliques, UMR 6226: Sciences Chimiques de Rennes, CNRS-Université de Rennes 1, Campus de Beaulieu,
35042 Rennes Cedex, France
Fax +33(2)23236939; E-mail: christian.bruneau@univ-rennes1.fr
Received 22 November 2006; revised 5 December 2006
methyl group of 3-aminobut-2-enoates and their nucleo-
Abstract: A direct method for the preparation of tertiary 3-amino-
philic C2 atom have made possible the preparation of six-
propenones and 3-aminopropenoates from b-diketones and b-keto
membered rings upon reaction with various potential 1,3-
esters, and secondary amines has been developed. The reaction is
performed without solvent in the presence or absence of Lewis acid
dielectrophiles such as 2-nitroprop-2-en-1-yl esters,13
as catalyst, depending on the reactivity of both the amine and the hexafluoroacetylacetone,14 or b-trifluoroacetylvinyl
ethers.15 In tertiary b-enamino esters derived from 3-oxo-
diketo substrate.
butanoates, the methyl group connected to the carbon–
carbon double bond is able to react with electrophilic cen-
ters such as methyl trifluoropyruvate to generate b-amino
alcohols,16 and with chlorodiphenyl phosphine to give b-
phosphinoenamine derivatives.17 The electron richness of
the double bond of push–pull enamino esters makes pos-
sible the direct introduction of a cyano group upon reac-
tion with isocyanatophosphoryl dichloride,18 and the
direct difluorination to form a,a-difluoro-b-keto esters or
a,a-difluoro-b-diketones after hydrolysis.19 b-Enamino
esters are also precursors of b-keto esters and b-diketones
resulting from the reactivity of their polarized carbon–car-
bon double bond as exemplified by their reaction with
NsONHCO2Et {N-[(4-nitrobenzenesulfonyl)oxy]carbam-
ate},20 and 1,4-dibromobutene.21 The hydrogenation of b-
enamino esters to produce b-amino esters has been per-
formed under stoichiometric conditions with sodium tri-
acetoxyborohydride for instance,22 as well as under
catalytic conditions in the presence of hydrogen and opti-
cally active transition-metal catalysts.2 The double bond
of b-enamino esters is cleaved by perfluoroalkanesulfonyl
azides to give N-perfluoroalkanesulfonyl amidines and a
diazo ester.23 The unique reactivity of tertiary enamino es-
ters with alkynylcarbene tungsten complexes proceeds via
a metathetic process, whereas secondary homologues are
involved in a Michael-type addition.24
Key words: catalysis, Lewis acid, enaminones, enamino esters, nu-
cleophilic addition
3-Aminopropenones and 3-aminopropenoates are reac-
tive multifunctional molecules and represent a class of
useful intermediates for the synthesis of biologically ac-
tive compounds.1 Therefore, they are valuable intermedi-
ates for the preparation of a- and b-amino acid
compounds,2 alkaloids,3 and peptides.4 They have also
found many applications in heterocyclic synthesis.3e,5
A
variety of products arising from b-enamino ketones and
esters have revealed biological activity as anti-inflamma-
tory,6 antitumor,6a,7 and anticonvulsant agents.6a,8 As far
as tertiary enamine derivatives are concerned, profit has
been taken from the absence of a reactive NH function and
the combined push–pull effect of the amino and keto
groups, which enhances the reactivity of the carbon–car-
bon double bond, to achieve a variety of reactions, which
are not possible from secondary and primary enamine de-
rivatives.
Thus, b-enamino esters react with heteroallenes such as
vinyl ketenes9 and isocyanates10 to form aromatic com-
pounds and heterocycles, and undergo 1,3-dipolar cy-
cloaddition with imidoyl chlorides leading to isoxazole
derivatives.11 1,2-Dinucleophiles such as hydrazines en-
able a cyclization reaction to occur upon double addition
to the two nucleophilic sites at positions 1 and 3 to deliver
pyrazole compounds.12 [4+2]-Cycloaddition reactions be-
tween 2-vinylindoles acting as heterodienes and 3-amino-
propenoates can be triggered by anodic oxidation or
photoelectron transfer, which induces the formation of re-
active radical cations.8 All these transformations take
place with elimination of the amino group of the enamine
functionality. Formal [3+3] cycloadditions involving the
Many synthetic methods for the preparation of 3-amino-
propenones and 3-aminopropenoates containing a second-
ary amino group have been reported. Thus, the addition of
metal ester or amide enolates to nitriles,25 tosylimines,26
and imidazoyl halides27 is a possible way to couple the
amino with the keto group via construction of the carbon–
carbon double bond. Other routes based on the same strat-
egy are represented by the reaction of carboxylic acid de-
rivatives with enamines28 or ketimines,29 and the reaction
of active methylene compounds with amide acetals.12b,30
Secondary b-enamino esters themselves have been used
as precursors of b-enaminones upon reaction with an ex-
cess of organolithium reagents.31 The Michael addition of
secondary amines to but-2-ynoates is another method
SYNTHESIS 2007, No. 5, pp 0731–0738
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x
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x
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Advanced online publication: 08.02.2007
DOI: 10.1055/s-2007-965916; Art ID: Z24106SS
© Georg Thieme Verlag Stuttgart · New York

732
R. K. Vohra et al.
PAPER
which provides b-enamino esters in good yields.8e–g,20 In tracted with dichloromethane, purified over alumina by
the presence of a stoichiometric amount of zinc salt, the flash chromatography (eluent: heptane–ethyl acetate, 7:3)
Michael-type reaction proceeds with propiolate esters and to give the corresponding enaminone 3. It is important to
tertiary amines to give tertiary enamino esters.32 Simple note that the chromatographic purification over silica led
condensation of amines with b-diketones or b-keto esters to a high level of decomposition of the final compound
is probably the most straightforward route to b-enamin- and that the use of alumina is highly recommended. The
ones and b-enamino esters, but it is mainly used for prima- cyclic amines, pyrrolidine and morpholine were also very
ry amines.33 It was initially performed with azeotropic reactive as they led to the formation of the enaminones 1
removal of water but it is interesting to note that primary and 2 in quantitative yields at room temperature (Table 1).
amines also react in ionic liquids without elimination of The steric hindrance of the secondary amine has a detri-
the formed water,34 and even in water as solvent.35 A va- mental effect, while diethylamine, dibenzylamine and di-
riety of Brønsted acids such as HCl,36 H2SO4,37 acetic ac- isopropylamine were not reactive under these simple
id,38 and p-toluenesulfonic acid39 have been used as conditions. The catalytic activities of various Lewis acids
catalysts. Improved procedures have been established such as CeCl3·7H2O, FeCl3·6H2O and Zn(OAc)2·2H2O
with different processes such as chemical activation by were thus tested in the reaction with these reluctant sec-
trimethylsilyl triflate,40 NaAuCl4,41 alumina,42 silica,43 K- ondary amines. At room temperature, diethylamine react-
10 montmorillonite,44 and natural clays;45 sometimes in ed slowly to give moderate yields of 4 (41–73%
association with microwave38,43 or ultrasound activa- depending on the Lewis acid). The reactivity of dibenzy-
tion.46 More recently, Lewis acids have revealed their po- lamine was even lower as heating at 50 °C over two days
tential to promote this transformation and have made was necessary to obtain a low conversion to 5 (27–42%).
possible selective catalytic reactions under milder condi- The more bulky diisopropylamine was completely inert
tions. Zn(ClO4)2·6H2O,47 Bi(O2CCF3)3 in water48 or in even at 50 °C in the presence of a Lewis acid. From pri-
ionic liquid,49 CeCl3·7H2O,50 and InBr351 were found to be mary amines, it is established that the hydrogen bonding
very active for the direct synthesis of b-enaminones and interaction between the secondary amino group and the
b-enamino esters from b-diketo compounds and primary carbonyl group of the formed 3-aminopropenone or 3-
amines.
aminopropenoate favors the formation of the Z-isomers.
From secondary amines, we observed the formation of
only one stereoisomer. A NOESY NMR study of com-
pound 4 clearly revealed the sole formation of the E-iso-
mer.
We have recently shown that Zn(OAc)2·2H2O is a very at-
tractive Lewis acid catalyst for the formation of b-enami-
no ketones and esters from primary amines.52 Despite the
synthetic potential of tertiary b-enamino derivatives as
shown above, very few examples of their preparation To enlarge the scope of this reaction, the condensation of
from secondary amines and b-diketo compounds are re- secondary amines with various types of b-keto ester deriv-
ported in the literature. We now show that depending on atives was studied. We observed the same order of reac-
the nature of the starting diketo compound and secondary tivity when the ethyl and benzyl 3-oxobutanoates were
amine, such direct reactions can be performed either with- treated with secondary amines in the absence of solvent
out any catalyst or in the presence of a Lewis acid under (Table 2). Quantitative formation of the b-enamino esters
neat conditions (Scheme 1).
6, 7 and 10 was observed at room temperature in short re-
action times from the cyclic pyrrolidine and morpholine.
For butylmethylamine, the reaction carried out at 25 °C
was slower but compound 8 could be obtained in 84%
yield after 16 hours at room temperature. The addition of
catalytic amounts of Lewis acid made the complete con-
version of the b-keto esters possible, and derivatives 8 and
12 were isolated in excellent yields after two days of reac-
tion at room temperature. With diethylamine, the b-enam-
ino esters 9 and 13 were also isolated in satisfactory
yields. On the other hand, no reaction was observed when
the more sterically hindered dibenzylamine and diisopro-
pylamine were used, even at 50 °C in the presence of a
Lewis acid.
no catalyst
or Lewis acid catalyst
O
O
R
O
+ R1R2NH
NR1R2
Y
Y
R
neat conditions
Scheme 1 Formation of tertiary b-enamino keto compounds from
secondary amines
Based on our initial findings that Zn(OAc)2·2H2O was an
efficient catalyst for the preparation of secondary b-enam-
ino ketones and esters from primary amines,52 we investi-
gated the reactivity of secondary amines under the same
type of catalytic conditions. Unfortunately, no reaction
occurred when pentane-2,4-dione was treated with butyl-
methylamine in dichloromethane at room temperature for
one day in the presence of the zinc salt.
Cyclic 2-ethoxycarbonylcyclopentanone and pyrrolidine
also provided the b-enamino ester 14 under neat condi-
tions without any catalyst at room temperature (Table 3).
The reactivity of morpholine was improved in the pres-
ence of CeCl3·7H2O, which provided a quantitative yield.
As was observed with the linear diketo substrates, the re-
action of butylmethylamine was promoted by addition of
a Lewis acid and the cyclic enamino ester 16 was obtained
in 84% yield in the presence of Zn(OAc)2·2H2O.
However, a successful reaction was realized when it was
performed in the absence of catalyst under neat condi-
tions. Thus, when pentane-2,4-dione (1 equiv), and butyl-
methylamine (1.5 equiv) were mixed together under argon
and stirred at room temperature overnight, complete trans-
formation took place. The crude mixture was then ex-
Synthesis 2007, No. 5, 731–738 © Thieme Stuttgart · New York

PAPER
Tertiary 3-Aminopropenones and 3-Aminopropenoates
733
Table 1 Reaction of Pentane-2,4-dione with Secondary Aminesa
O
O
O
no solvent
+ R1R2NH
NR1R2
1–5
Amine
Catalyst
no
Temp (°C)
Time (h)
1
Product
Yield (%)b
Pyrrolidine
Morpholine
25
25
25
25
25
25
25
25
50
50
50
1
2
3
4
4
4
4
5
5
5
5
99
99
99
no
16
Butylmethylamine
Diethylamine
no
16
c
no
16
–
CeCl3·7H2O
FeCl3·6H2O
Zn(OAc)2·2H2O
no
48
41
73
68
48
48
c
Dibenzylamine
24
–
CeCl3·7H2O
FeCl3·6H2O
Zn(OAc)2·2H2O
48
36
27
42
48
48
a General conditions: diketone (1 equiv), amine (1.5 equiv), catalyst (5 mol%).
b Isolated yield.
c No reaction.
Table 2 Reaction of Ethyl and Benzyl 3-Oxobutanoates with Secondary Aminesa
O
O
O
no solvent
+ R1R2NH
R1R2N
OR
6–13
OR
Amine
Catalyst
Temp (°C)
Time (h)
Product
Yield (%)a
R = Et
Pyrrolidine
none
25
25
25
25
25
25
25
25
25
16
16
16
48
48
48
48
48
48
6
7
8
8
8
8
9
9
9
99
99
84
99
99
86
41
73
68
Morpholine
none
Butylmethylamine
none
CeCl3·7H2O
FeCl3·6H2O
Zn(OAc)2·2H2O
CeCl3·7H2O
FeCl3·6H2O
Zn(OAc)2·2H2O
Diethylamine
R = Bn
Pyrrolidine
Morpholine
none
25
25
25
25
25
16
16
16
16
48
10
11
11
11
12
99
91
93
84
99
CeCl3·7H2O
FeCl3·6H2O
Zn(OAc)2·2H2O
CeCl3·7H2O
Butylmethylamine
Synthesis 2007, No. 5, 731–738 © Thieme Stuttgart · New York

734
R. K. Vohra et al.
PAPER
Table 2 Reaction of Ethyl and Benzyl 3-Oxobutanoates with Secondary Aminesa (continued)
O
O
O
no solvent
+ R1R2NH
R1R2N
OR
6–13
OR
Amine
Catalyst
Temp (°C)
Time (h)
Product
12
Yield (%)a
FeCl3·6H2O
25
25
25
25
25
48
48
48
48
48
99
99
99
88
85
Zn(OAc)2·2H2O
CeCl3·7H2O
12
Diethylamine
13
FeCl3·6H2O
13
Zn(OAc)2·2H2O
13
a General conditions: b-keto ester (1 equiv), amine (1.5 equiv), catalyst (5 mol%).
b Isolated yield.
Table 3 Reaction of 2-Ethoxycarbonylcyclopentanone with Secondary Aminesa
R1R2N
O
no solvent
CO2Et
CO2Et
+ R1R2NH
14–16
Amine
Catalyst
Temp (°C)
Time (h)
16
Product
Yield (%)a
Pyrrolidine
Morpholine
none
25
25
25
25
25
25
25
14
15
15
15
16
16
16
98
99
60
51
66
68
84
CeCl3·7H2O
FeCl3·6H2O
Zn(OAc)2·2H2O
CeCl3·7H2O
FeCl3·6H2O
Zn(OAc)2·2H2O
16
16
16
Butylmethylamine
16
16
16
a General conditions: b-keto ester (1 equiv), amine (1.5 equiv), catalyst (5 mol%).
b Isolated yield.
With diethylamine, a prolonged reaction time at 50 °C presence of Lewis acid. Thus, from ethyl 3-phenyl-3-oxo-
(3 d) was necessary to obtain good conversion of the start- propanoate, which bears a less reactive carbonyl group,
ing products. However, the enamine derivative was not the complete formation of 18 under neat conditions from
obtained, but the stable nondehydrated b-hydroxy-b-ami- the reactive pyrrolidine was not possible without heating
no compound 17 was isolated in satisfactory yields and addition of catalyst (Table 4). The reaction of butyl-
(Figure 1). On the other hand, dibenzylamine and diiso- methylamine also required heating at 50 °C with a Lewis
propylamine did not react even under the more drastic acid. However, no reaction was observed with morpholine
conditions we used (50 °C, 3 d).
and diethylamine. No reaction took place when 1,3-diphe-
nylpropan-1,3-dione was used at 50 °C with different
Lewis acids in the absence of solvent, which indicates the
limitation of this direct transformation.
Et2N
OH
CeCl3⋅7H2O (46%)
CO2Et
FeCl3⋅6H2O (65%)
Zn(OAc)2⋅2H2O (76%)
All the enamine derivatives prepared according to the
Lewis acid free or Lewis acid catalyzed reactions have
been fully characterized by 1H and 13C NMR, and HRMS
data. The products were always obtained as a single stere-
oisomer. As compared to secondary b-enaminones and b-
enamino esters, which are stabilized in their Z-geometry
by intramolecular hydrogen bonding, we assume that the
acyclic tertiary enamine derivatives were obtained as E-
17
Figure 1 b-Amino-b-hydroxy ester 17
The formation of enamine derivatives with b-keto esters
and b-diketones substituted by an aromatic group proved
to be more difficult even at high temperature and in the
Synthesis 2007, No. 5, 731–738 © Thieme Stuttgart · New York

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Tertiary 3-Aminopropenones and 3-Aminopropenoates
735
Table 4 Reaction of Ethyl 3-Phenyl-3-oxopropanoate with Secondary Aminesa
Ph
O
O
O
no solvent
+ R1R2NH
R1R2N
Ph
OEt
OEt
18, 19
Amine
Pyrrolidine
Catalyst
Temp (°C)
Time (h)
16
Product
18
Yield (%)a
none
50
50
50
50
50
50
50
59
88
93
91
58
93
70
CeCl3·7H2O
FeCl3·6H2O
Zn(OAc)2·2H2O
CeCl3·7H2O
FeCl3·6H2O
Zn(OAc)2·2H2O
16
18
16
18
16
18
Butylmethylamine
16
19
16
19
16
19
a General conditions: b-keto ester (1 equiv), amine (1.5 equiv), catalyst (5 mol%).
b Isolated yield.
4-(Morpholin-4-yl)pent-3-en-2-one (2)
isomers as indicated in the literature and by our NMR
study on compound 4. The reactions proceed with forma-
tion of water, but its elimination by either a dehydrating
agent or a physical method is not necessary when the re-
actions are performed under neat conditions.
1H NMR (200 MHz, CDCl3): d = 2.12 (s, 3 H, COCH3), 2.50 (s, 3
H, CH3), 3.33 (t, J = 5.2 Hz, 4 H, CH2NCH2), 3.78 (t, J = 5.2 Hz, 4
H, CH2OCH2), 5.28 (s, 1 H, =CH).
13C NMR (75 MHz, CDCl3): d = 15.9, 32.5, 46.5, 66.7, 97.7, 161.3,
196.3.
The condensation of secondary amines with b-diketones
and b-keto esters to form b-enamino ketones and esters
can be efficiently performed in good to excellent yields
under solvent-free conditions. Cyclic secondary amines
readily react, whereas the reactivity of acyclic secondary
amines decreases with the steric bulk at the a-carbon of
the amino group. As far as the keto group is concerned, the
purely aliphatic MeCO and cyclic CH2CO keto groups are
much more reactive than the PhCO group. The condensa-
tion reaction can be efficiently improved by using catalyt-
ic amounts of a Lewis acid such as CeCl3·7H2O,
FeCl3·6H2O or Zn(OAc)2·2H2O.
HRMS: m/z [M+] calcd for C9H15NO2: 169.11028; found: 169.1105.
(N-Butyl-N-methylamino)pent-3-en-2-one (3)
1H NMR (200 MHz, CDCl3): d = 0.97 (t, J = 7.1 Hz, 3 H, CH3CH2),
1.31 (m, 2 H, CH2), 1.52 (m, 2 H, CH2), 2.09 (s, 3 H, COCH3), 2.52
(s, 3 H, CH3C=), 2.93 (s, 3 H, NCH3), 3.28 (t, J = 7.3 Hz, 2 H,
CH2N), 5.03 (s, 1 H, =CH).
13C NMR (75 MHz, CDCl3): d = 14.3, 15.9, 20.4, 30.4, 32.2, 38.6,
51.9, 95.2, 161.7, 195.0.
HRMS: m/z [M+] calcd for C10H19NO: 169.14666; found: 169.1460.
(N,N-Diethylamino)pent-3-en-2-one (4)
1H NMR (200 MHz, CDCl3): d = 1.19 (t, J = 7.1 Hz, 6 H, CH3CH2),
2.09 (s, 3 H, COCH3), 2.55 (s, 3 H, CH3), 3.32 (q, J = 7.1 Hz, 4 H,
CH2CH3), 5.12 (s, 1 H, =CH).
Reaction of 1,3-Dicarbonyl Compounds with Secondary
Amines; General Procedure
13C NMR (75 MHz, CDCl3): d = 13.1, 15.8, 32.3, 44.4, 94.5, 160.7,
194.7.
In a Schlenk tube, first the Lewis acid (5 mol%) (when used), then
the dicarbonyl derivative (1 equiv), and the secondary amine (1.5
equiv) were successively added under argon. The mixture was
stirred at r.t. (or at 50 °C) and the reaction was monitored by TLC
analysis. The crude mixture was dissolved in CH2Cl2 (2 mL/mmol),
and the final compound was purified over alumina by flash chroma-
tography with a 7:3 mixture of heptane–EtOAc as eluent (Tables 1–
4).
HRMS: m/z [M+] calcd for C9H17NO: 155.13101; found: 155.1320.
(N,N-dibenzylamino)pent-3-en-2-one (5)
1H NMR (200 MHz, CDCl3): d = 2.05 (s, 3 H, COCH3), 2.69 (s, 3
H, CH3), 4.57 (s, 4 H, CH2), 5.36 (s, 1 H, =CH), 7.17 (d, J = 6.4 Hz,
2 H, ArH), 7.30–7.43 (m, 8 H, ArH).
13C NMR (75 MHz, CDCl3): d = 16.1, 32.5, 53.2, 53.6, 96.6, 126.8,
127.4, 127.9, 128.6, 128.9, 129.4, 136.8, 140.7, 161.9, 195.9.
4-(Pyrrolidin-1-yl)pent-3-en-2-one (1)
HRMS: m/z [(M – C5H6O)+] calcd for C14H15N: 197.12045; found:
197.1217.
1H NMR (200 MHz, CDCl3): d = 1.98 (m, 4 H, CH2CH2), 2.05 (s, 3
H, COCH3), 2.58 (s, 3 H, CH3), 3.25 (m, 2 H, CHNCH), 3.48 (m, 2
H, CHNCH), 4.98 (s, 1 H, =CH).
Ethyl 3-(Pyrrolidin-1-yl)but-2-enoate (6)
13C NMR (75 MHz, CDCl3): d = 17.7, 25.5, 31.9, 48.5, 95.5, 160.3,
194.7.
1H NMR (200 MHz, CDCl3): d = 1.28 (t, J = 7.1 Hz, 3 H, CH3CH2),
1.89–1.96 (m, 4 H, CH2CH2), 2.32 (s, 3 H, =CCH3), 3.11–3.31 (m,
4 H, CH2NCH2), 4.08 (q, J = 7.1 Hz, 2 H, OCH2), 4.46 (s, 1
H, =CH).
HRMS: m/z [M+] calcd for C9H15NO: 153.11536; found: 153.1158.
Synthesis 2007, No. 5, 731–738 © Thieme Stuttgart · New York

736
R. K. Vohra et al.
PAPER
13C NMR (75 MHz, CDCl3): d = 15.2, 17.1, 25.6, 48.3, 58.5, 83.6,
160.0, 169.7.
HRMS: m/z [M+] calcd for C16H23NO2: 261.17288; found:
261.1733.
HRMS: m/z [M+] calcd for C10H17NO2: 183.12593; found:
183.1257.
Benzyl 3-(N,N-Diethylamino)but-2-enoate (13)
1H NMR (200 MHz, CDCl3): d = 1.17 [t, J = 7.1 Hz, 6 H,
(CH3CH2)2N], 2.51 (s, 3 H, CH3), 3.28 [q, J = 7.1 Hz, 4 H,
(CH3CH2)2N], 4.70 (s, 1 H, =CH), 5.12 (s, 2 H, CH2Ph), 7.33–7.40
(m, 5 H, C6H5).
Ethyl 3-(Morpholin-4-yl)but-2-enoate (7)
1H NMR (200 MHz, CDCl3): d = 1.27 (t, J = 7.1 Hz, 3 H, CH3CH2),
2.44 (s, 3 H, =CCH3), 3.24 (t, J = 4.9 Hz, 4 H, CH2NCH2), 3.75 (t,
J = 4.9 Hz, 4 H, CH2OCH2), 4.12 (q, J = 7.1 Hz, 2 H, CH2CH3),
4.82 (s, 1 H, =CH).
13C NMR (75 MHz, CDCl3): d = 13.3, 15.5, 44.4, 64.7, 82.9, 128.0,
128.4, 128.8, 138.3, 160.8, 169.7.
13C NMR (75 MHz, CDCl3): d = 15.0, 15.7, 46.8, 59.1, 66.7, 88.8,
161.7, 169.3.
HRMS: m/z [M+] calcd for C15H21NO2: 247.15723; found:
247.1581.
HRMS: m/z [M+] calcd for C10H17NO3: 199.12084; found:
199.1227.
Ethyl 2-(Pyrrolidin-1-yl)cyclopent-1-enecarboxylate (14)
1H NMR (200 MHz, CDCl3): d = 1.28 (t, J = 7.1 Hz, 3 H, CH3CH2),
1.70–1.91 (m, 6 H, CH2CH2 + CH2CH2CH2), 2.65 (q, J = 6.6 Hz, 4
H, CH2CH2CH2), 3.42–3.50 (m, 4 H, CH2NCH2), 4.15 (q, J = 7.1
Hz, 2 H, OCH2).
Ethyl 3-(N-Butyl-N-methylamino)but-2-enoate (8)
1H NMR (200 MHz, CDCl3): d = 0.98 (t, J = 7.1 Hz, 3 H, CH3CH2),
1.28 (t, J = 7.0 Hz, 3 H, CH3CH2O), 1.30 (m, 2 H, CH2), 1.50 (m, 2
H, CH2), 2.45 (s, 3 H, =CCH3), 2.86 (s, 3 H, NCH3), 3.23 (t, J = 7.3
Hz, 2 H, NCH2), 4.08 (q, J = 7.1 Hz, 2 H, CH2CH3), 4.51 (s, 1
H, =CH).
13C NMR (75 MHz, CDCl3): d = 15.2, 21.5, 26.1, 33.1, 36.6, 52.2,
59.1, 94.0, 159.9, 166.6.
HRMS: m/z [M+] calcd for C12H19NO2: 209.14158; found:
209.1413.
13C NMR (75 MHz, CDCl3): d = 14.3, 15.1, 15.5, 20.4, 30.5, 38.5,
51.9, 58.7, 84.1, 161.5, 169.8.
Ethyl 2-(Morpholin-4-yl)cyclopent-1-enecarboxylate (15)
1H NMR (200 MHz, CDCl3): d = 1.28 (t, J = 7.1 Hz, 3 H, CH3CH2),
1.80 (quint, J = 7.5 Hz, 2 H, CH2CH2CH2), 2.62 (quint, J = 7.3 Hz,
4 H, CH2CH2CH2), 3.42 (t, J = 4.7 Hz, 4 H, CH2NCH2), 3.74 (quint,
J = 4.7 Hz, 4 H, CH2OCH2), 4.28 (q, J = 7.1 Hz, 2 H, OCH2).
HRMS: m/z [M+] calcd for C11H21NO2: 199.15723; found:
199.1594.
Ethyl 3-(N,N-Diethylamino)but-2-enoate (9)
1H NMR (200 MHz, CDCl3): d = 1.16 [t, J = 7.1 Hz, 6 H,
(CH3CH2)2N], 1.27 (t, J = 7.1 Hz, 3 H, CH3CH2O), 2.49 (s, 3 H,
CH3), 3.28 (q, J = 7.1 Hz, 4 H, CH2N), 4.11 (q, J = 7.1 Hz, 2 H,
CH2O), 4.62 (s, 1 H, =CH).
13C NMR (75 MHz, CDCl3): d = 15.1, 20.6, 32.8, 35.5, 51.1, 59.4,
67.6, 98.4, 162.3, 166.3.
HRMS: m/z [M+] calcd for C12H19NO3: 225.13649; found:
225.1366.
13C NMR (75 MHz, CDCl3): d = 13.3, 15.2, 15.4, 44.4, 58.6, 83.2,
160.3, 169.9.
Ethyl 2-(N-Butyl-N-methylamino)cyclopent-1-enecarboxylate
(16)
HRMS: m/z [M+] calcd for C10H19NO2: 185.14158; found:
185.1425.
1H NMR (200 MHz, CDCl3): d = 0.94 (t, J = 7.2 Hz, 3 H, CH3CH2),
1.28 (t, J = 7.1 Hz, 3 H, CH3CH2O), 1.32 (m, 2 H, CH2), 1.52 (m, 2
H, CH2), 1.78 (quint, J = 7.5 Hz, 2 H, CH2CH2CH2), 2.58 (m, 4 H,
CH2CH2CH2), 3.00 (s, 3 H, NCH3), 3.27 (t, J = 7.3 Hz, 2 H, NCH2),
4.15 (q, J = 7.1 Hz, 2 H, OCH2).
Benzyl 3-(Pyrrolidin-1-yl)but-2-enoate (10)
1H NMR (200 MHz, CDCl3): d = 1.92–1.98 (m, 4 H, CH2CH2), 2.50
(s, 3 H, CH3), 3.38 (m, 4 H, CH2NCH2), 4.56 (s, 1 H, =CH), 5.12 (s,
2 H, CH2Ph), 7.28–7.40 (m, 5 H, C6H5).
13C NMR (75 MHz, CDCl3): d = 14.3, 15.1, 20.3, 21.4, 32.3, 42.3,
55.2, 94.9, 162.2, 166.4.
13C NMR (75 MHz, CDCl3): d = 17.2, 25.6, 48.4, 64.6, 83.4, 127.9,
128.4, 128.8, 138.4, 160.4, 169.4
HRMS: m/z [M+] calcd for C13H23NO2: 225.17288; found:
225.1739.
HRMS: m/z [M+] calcd for C15H19NO2: 245.14158; found:
245.1431.
Ethyl 3-(Pyrrolidin-1-yl)-3-phenylbut-2-enoate (18)
1H NMR (200 MHz, CDCl3): d = 1.20 (t, J = 7.1 Hz, 3 H, CH3CH2),
1.92 (m, 4 H, CH2CH2), 3.29 (m, 4 H, CH2NCH2), 3.98 (q, J = 7.1
Hz, 2 H, OCH2), 4.71 (s, 1 H, =CH), 7.22–7.29 (m, 2 H, C6H5),
7.36–7.46 (m, 3 H, C6H5).
Benzyl 3-(Morpholin-4-yl)but-2-enoate (11)
1H NMR (200 MHz, CDCl3): d = 2.45 (s, 3 H, CH3), 3.28 (t, J = 4.9
Hz, 4 H, CH2NCH2), 3.72 (t, J = 4.9 Hz, 4 H, CH2OCH2), 4.89 (s, 1
H, =CH), 5.13 (s, 2 H, CH2Ph), 7.35 (m, 5 H, C6H5).
13C NMR (75 MHz, CDCl3): d = 15.8, 46.8, 65.2, 66.8, 88.2, 128.2,
128.5, 128.9, 137.8, 162.2, 168.8.
13C NMR (75 MHz, CDCl3): d = 14.8, 25.7, 58.6, 85.6, 127.9,
128.4, 128.6, 138.2, 161.3, 168.4.
HRMS: m/z [M+] calcd for C15H19NO3: 261.13649; found:
261.1353.
HRMS: m/z [M+] calcd for C15H19NO2: 245.14158; found:
245.1431.
Benzyl 3-(N-Butyl-N-methylamino)but-2-enoate (12)
1H NMR (200 MHz, CDCl3): d = 0.98 (t, J = 7.1 Hz, 3 H, CH3CH2),
1.32 (m, 2 H, CH2), 1.56 (m, 2 H, CH2), 2.50 (s, 3 H, CH3C=), 2.90
(s, 3 H, NCH3), 3.24 (t, J = 7.1 Hz, 2 H, NCH2), 4.65 (s, 1 H, =CH),
5.12 (s, 2 H, CH2Ph), 7.34 (m, 5 H, C6H5).
Ethyl 3-(N-Butyl-N-methylamino)-3-phenylbut-2-enoate (19)
1H NMR (200 MHz, CDCl3): d = 0.98 (t, J = 7.1 Hz, 3 H, CH3CH2),
1.28 (t, J = 7.1 Hz, 3 H, CH3CH2O), 1.32–1.49 (m, 2 H, CH2), 1.50–
1.59 (m, 2 H, CH2), 2.50 (s, 3 H, NCH3), 2.64 (t, J = 6.9 Hz, 2 H,
NCH2), 4.02 (s, 1 H, =CH), 4.25 (q, J = 7.1 Hz, 2 H, OCH2), 7.60
(m, 5 H, C6H5).
13C NMR (75 MHz, CDCl3): d = 14.3, 15.7, 20.5, 30.5, 38.6, 52.0,
64.8, 83.8, 128.0, 128.4, 128.8, 138.3, 161.9, 169.5.
13C NMR (75 MHz, CDCl3): d = 14.8, 20.4, 30.9, 36.5, 50.9, 85.2,
126.3, 129.1, 130.9, 134.0, 167.1, 172.4, 194.5.
Synthesis 2007, No. 5, 731–738 © Thieme Stuttgart · New York

PAPER
Tertiary 3-Aminopropenones and 3-Aminopropenoates
737
HRMS: m/z [(M – H)+] calcd for C16H22NO2: 260.16505; found:
260.1641.
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