An expeditious synthetic access to β-(Z)-[(1-propynyl)amino]enones and β-[(Z)-(1-propynyl)amino]enoates

Article abstract of DOI:10.1055/s-2003-37654

The silver nitrate promoted reaction of propargyl bromide with (Z)-4-amino-3-penten-2-ones and (Z)-3-amino-2-butenoates provides rapid access to β-(Z)-[(1-propynyl)amino]enones and β-[(Z)-(1-propynyl)amino]enoates respectively.

Full text of DOI:10.1055/s-2003-37654

PAPER
523
An Expeditious Synthetic Access to -(Z)-[(1-Propynyl)amino]enones and
-
[(Z)-(1-Propynyl)amino]enoates
A
D
n
Expeditious Sy
a
nthetic
A
cc
v
ess to
β
-(
Z
)-
i
[(1-Pr
o
d
pynyl)amino]enon
G
e
s
and Enoates ravestock,* Martin C. Dovey
School of Chemical and Physical Sciences, University of Natal, Pietermaritzburg, Private Bag X01, Scottsville 3209, South Africa.
Fax +27(33)260 5009; E-mail: GravestockD@nu.ac.za
Received 27 November 2002; revised 23 January 2003
methods to access these compounds for some time now.
Initial endeavours in this regard involved the preparation
of cyclic compounds and their subsequent transformation
Abstract: The silver nitrate promoted reaction of propargyl bro-
mide with (Z)-4-amino-3-penten-2-ones and (Z)-3-amino-2-
butenoates provides rapid access to β-(Z)-[(1-propynyl)ami-
no]enones and β-[(Z)-(1-propynyl)amino]enoates respectively.
5
into 2,3-dihydro-7(1H)-indolizinones. Attempts to ex-
tend this methodology required the preparation of their
acyclic analogues. Following the same protocols for the
preparation of the cyclic compounds mentioned above
would require synthesis of thioamide D (Scheme 1). N-
Propargylation of various secondary amides A, using pro-
pargyl bromide and sodium hydride as base, was met with
failure. Beak and Lee reported a method for the N-allyla-
tion of various secondary amides using tert-butyllithium
Key words: β-aminoenones, β-aminoenoates, ynamines, micro-
wave-mediated synthesis
Ynamines are a class of compounds whose exposure has
increased in the past 40–50 years. This stems from their
ability to function as a synthon for a variety of synthetic
protocols. They are more valuable than traditional alkynes
and are in their own right very useful compounds, due to
the electron donating ability of the nitrogen atom which
6
as base. In accordance with this method, treatment of sec-
ondary amides A with propargyl bromide and tert-butyl-
lithium afforded tertiary amides B. However, thionation
1
allows for regiospecific transformations. Ynamides are a
7
using Brillon’s method (P S , Na CO , THF) did not
4
10
2
3
subgroup of ynamines which contain an electron with-
drawing group attached to nitrogen and show greater sta-
bility than their electron rich counterparts without great
yield the desired thioamides D. Previous attempts at
thionation of N-propargyl lactams using Lawesson’s
8
2
reagent appeared to harm the alkyne functionality and,
loss of reactivity. Ynamides have received much atten-
therefore, this method was not attempted on the present
amides. Using a different approach, alkylation of second-
ary thioamides C, accessed via thionation of secondary
amides A using Brillon’s procedure, was not successful.
tion over the past decade with numerous accounts of their
3
synthesis and reactivity.
We now report our addition to this fascinating field of or-
ganonitrogen chemistry. We have prepared ynamines that
are related to the ynamides discussed above by vinylogy.
Thus in our systems (CH C≡C–N–C=C–COR′) a carbon-
3
carbon double bond is interpolated between the nitrogen
atom and the electron withdrawing ketone or ester group.
Nitrogen is thus linked conjugatively to both the alkyne
and the electron withdrawing group. The ynamine moiety
is stabilised by virtue of the conjugation of the nitrogen
lone pair with the electron-withdrawing carbonyl group.
The β-acylated enamine moiety offers attractive synthetic
potential from its ability to function both as an ambident
nucleophile and as an ambident electrophile in addition to
its ability to participate in pericyclic and radical process-
4
es. In our system the electron-withdrawing acyl group
serves to temper the reactivity of both the enamine and
ynamine functional groups and thus improves the stability
of these novel organonitrogen compounds. Our system
marries ynamines and β-acylated enamines and their syn-
ergistic chemistry promises to be rich and useful.
Scheme 1
We are particularly interested in the chemistry of N-prop-
argylated enaminones and have been developing synthetic
Another possible alternative would be to prepare second-
ary β-enaminones, which could be propargylated to give
the required compounds. Hamelin and co-workers report-
ed the synthesis of secondary and tertiary enaminoketones
by condensing β-diketones with amines, over an inert sup-
Synthesis 2003, No. 4, Print: 18 03 2003.
Art Id.1437-210X,E;2003,0,04,0523,0530,ftx,en;P06702SS.pdf.
©
Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

5
24
D. Gravestock, M. C. Dovey
PAPER
port, under microwave irradiation.9,10 Various amines 1 Treatment of (Z)-4-(methylamino)-3-penten-2-one (3a)
were reacted with acetylacetone 2a or ethyl acetoacetate with sodium hydride and propargyl bromide (Scheme 2)
2
b and enaminones 3a–k were obtained (Table 1). afforded a colorless oil which, based on LRMS and NMR
Equimolar quantities of the primary amine 1 and β-dicar- data, was not (Z)-4-[methyl(2-propynyl)amino]-3-penten-
bonyl compound (2a or 2b) were mixed and poured onto 2-one (4) as anticipated but, in fact, was the isomeric C-
a bed of silica gel. The mixture was irradiated in a domes- propargyl compound 3-[(Z)-1-(methylamino)ethylidene]-
tic microwave oven to yield analytically pure samples of 5-hexyn-2-one (5) obtained in 68% yield. Although not
the desired enaminones (3a–k). The reaction appears sen- the desired product, this is nevertheless an interesting re-
sitive to steric effects alpha to nitrogen as consistently sult in its own right and its chemistry deserves further in-
good yields (70–97%) were obtained with R = Me, n-Bu, vestigation. The reaction was repeated at –78 °C using
1
Bn and cyclohexyl while the reaction of tert-butylamine tert-butyllithium as base. GC-MS and H NMR data indi-
and acetylacetone afforded a low 6% yield of the corre- cated that 3-[(Z)-1-(methylamino)ethylidene]-5-hexyn-2-
sponding enaminone and its reaction with ethyl acetoace- one was again obtained as the major product albeit in a
1
tate failed to give any detectable condensation product.
lower yield (58% based on H NMR). Carrying out the re-
action at elevated temperature afforded the identical re-
sult.
Table 1 Microwave Reaction Results of Primary Amines with β-
Dicarbonyl Compounds 2
Enaminones are ambident nucleophiles. They may attack
electrophiles via their nitrogen atom or the carbon atom
beta to nitrogen. The outcome of any given reaction (N-
versus C-alkylation) will be determined to a large extent
by the electronic character of the electrophile. Hard bases
prefer hard acids and soft bases prefer soft acids according
to hard and soft acid-base theory. In an ambident nucleo-
phile the more electronegative atom is a harder base than
the less electronegative atom. When applying these con-
cepts to the enaminone system we can view the carbon
atom as the soft base with the more electronegative nitro-
gen atom being the harder base. Therefore the reaction
conditions shown in Scheme 2 favoured the soft-base/soft
acid combination. The conversion (3a → 5, Scheme 2)
Entry
β-Dicarbonyl
Compound 2
R
Yield of 3a–k
11
(%)a
1
2
3
4
5
6
7
8
9
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
Me
80 (3a)
82 (3b)
76 (3c)
70 (3d)
6 (3e)
Me
n-Bu
n-Bu
t-Bu
t-Bu
presumably takes place via an S 2 mechanism whereby
N
the soft enamine attacks the soft electrophilic carbon atom
of propargyl bromide with simultaneous expulsion of bro-
mide. In order to induce attack via the more electronega-
tive nitrogen atom the electrophile must be converted into
a harder acid. This would favour the corresponding SN1
–b
c-C H
88 (3f)
76 (3g)
72 (3h)
70 (3i)
82 (3j)
97 (3k)
6
11
11
+
mechanism. Treatment of propargyl bromide with Ag
c-C H
6
should encourage the heterolytic cleavage of the carbon-
bromine bond, favouring formation of a carbocation and
thus rendering the propargyl bromide a harder acid and
therefore attack by nitrogen would be preferred. This
trend has been observed in the treatment of alkyl halides
Ph
Ph
Bn
Bn
1
1
1
0
1
2
12
with the cyanide anion. Alkyl halides treated with NaCN
give mostly nitriles (RCN), whereas alkyl halides treated
with AgCN give mostly isonitriles (RNC). It was with
these ideas in mind that the reactions summarized in
Table 2 were performed.
a
Isolated yields of pure compounds based on 2.
No condensation product was detected.
b
Scheme 2
Synthesis 2003, No. 4, 523–530 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
An Expeditious Synthetic Access to β-(Z)-[(1-Propynyl)amino]enones and Enoates
525
Table 2 Reaction Results of Enaminones 3a–k with Propargyl
Bromide
the double bond had not changed during the course of the
reaction summarized in Table 2 a NOESY experiment on
the benzyl derivative, 4-[benzyl(1-propynyl)amino]-3-
penten-2-one (6j) was performed. A correlation between
the vinyl proton at δ 6.30 and the methyl group bonded to
the double bond at δ 2.49 showed that the double bond had
maintained its Z-geometry (Figure 1). By analogy a Z-
configuration was assigned to all the other 1-propynylena-
minone products listed in Table 2. The third structure in
Figure 1 shows that if the compounds existed as the E-iso-
mers then one would not expect a correlation between
these groups (see highlighted regions).
Entry
Enamine
a–k
R
Z
Yieldof6a–k
3
(%)a
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3f
Me
COMe
16 (6a)
21 (6b)
24 (6c)
24 (6d)
25 (6f)
24 (6g)
7b (6h)
–c
Me
CO Et
2
n-Bu
n-Bu
COMe
CO Et
2
c-C H
COMe
6
11
11
3g
3h
3i
c-C H
CO Et
6
2
Figure 1
Ph
Ph
Bn
Bn
COMe
CO Et
2
Comparison of the NMR data showed some interesting ef-
fects (Figure 2). All protons of the enaminones 3a–k ex-
perienced a downfield shift when converted into the
corresponding N-(1-propynyl)enaminones 6a–k. The
most marked shift being experienced by the vinyl protons
3j
COMe
21 (6j)
b
1
0
3k
CO Et
14 (6k)
2
a
Isolated yields of pure compounds based on 3.
Starting material and product co-elute and therefore the yield is
b
13
1
(e.g. δ 4.42 in 3b versus δ 6.22 in 6b). Effects on the C
signals were more erratic. Noteworthy though is the sig-
nificant downfield shift experienced by the vinyl carbon
beta to nitrogen (e.g. δ 81.7 in 3a versus δ 106.9 in 6b) and
an even more pronounced upfield shift of the quaternary
vinyl carbon alpha to nitrogen (e.g. δ 162.6 in 3b versus δ
based on relative integral values of the vinyl protons in the H NMR
spectrum.
c
1
Trace quantity detected by H NMR spectroscopy.
Thus propargyl bromide was added to a stirred solution of
an equimolar quantity of silver nitrate in anhydrous aceto-
nitrile at ambient temperature. The appropriate enamino-
ne (0.5 equiv) was added immediately thereafter and the
mixture stirred overnight. Workup and purification af-
forded not the desired N-(2-propynyl)enaminones, but in-
stead the novel N-(1-propynyl)enaminones in moderate
yields. This result is rather surprising and further studies
to elucidate the mechanism of this reaction are currently
being undertaken. Presumably a thermodynamic driving
force for the rearrangement reaction will be the conjuga-
tion of the nitrogen atom to the alkyne group. These com-
pounds are remarkably stable – they suffer very little
degradation even when left exposed to the atmosphere for
several weeks.
1
35.2 in 6b). Comparison of the chemical shifts of the
5
alkyne carbon atoms in N-2-propynyl compound (7) and
the analogous N-1-propynyl compound (6b) reveals some
startling differences (Figure 2). The carbon atoms in the
N-1-propynyl compounds (6a–k) experience significant
downfield shifts (∆δ = 40–50). These NMR data serve as
valuable clues to the electronic changes brought about
when the enaminone system (N–C=C–COR) is bonded to
the propynyl group to form the corresponding β-(Z)-[(1-
propynyl)amino]enones (MeC≡C–N–C=C–COMe) and
β-[(Z)-(1-propynyl)amino]enoates
(MeC≡C–N–C=C–
CO Et).
2
In conclusion we have developed a convenient synthetic
access to β-(Z)-[(1-propynyl)amino]enones and β-[(Z)-
Various 2-D NMR spectra including GHMQC, GHSQC,
and COSY facilitated the unambiguous assignment of
NMR signals. A NOESY experiment on the benzyl ana-
logue, 4-(benzylamino)-3-penten-2-one (3j) showed a
correlation between the vinyl proton at δ 5.03 and the me-
thyl group at δ1.89 (Figure 1). By analogy a Z-configura-
tion was assigned to all the other enaminone products
shown in Table 1. This finding is in agreement with the re-
(
1-propynyl)amino]enoates from readily accessible and
very affordable starting materials. We have thus added
our route to the relatively few methods reported that ac-
cess functionalised ynamines. Future work involves con-
ducting studies to elucidate the mechanism of the
rearrangement reaction as well as to investigate the chem-
istry and the synthetic potential of these remarkable com-
posite functional groups.
9
sults of Hamelin et al. To confirm that the geometry of
Synthesis 2003, No. 4, 523–530 ISSN 0039-7881 © Thieme Stuttgart · New York

5
26
D. Gravestock, M. C. Dovey
PAPER
Figure 2
(
Z)-4-(Butylamino)-3-acetylacetone-penten-2-one (3c)
NMR spectra were recorded using a 500 MHz Varian Unity Inova
spectrometer equipped with an Oxford magnet (11.744 T) and a
switchable 5 mm probe. H NMR spectra were recorded at 500 MHz
Butylamine and acetyl acetone were mixed and irradiated to yield
(Z)-4-(butylamino)-3-penten-2-one as a yellow oil (76%); R 0.49
(EtOAc–hexanes, 1:1).
f
1
in deuteriochloroform and referenced against the deuteriochloro-
IR (thin film, CHCl ): 3071, 2956, 2928, 2868, 1610, 1574, 1294,
1
3
3
form singlet at 7.26 ppm. C NMR spectra were recorded at 125
MHz in deuteriochloroform and referenced against the central line
of the deuteriochloroform triplet at 77.0 ppm. FTIR spectra were re-
corded as thin films (chloroform) using a Perkin Elmer Spectrum
One spectrometer. High resolution mass spectra were obtained by
the Mass Spectrometry Unit of the Cape Technikon on a double-fo-
cusing Kratos MS 80RF mass spectrometer. Low resolution (elec-
tron impact) mass spectra were recorded using a Hewlett-Packard
gas chromatographic mass spectrometer (HP5988A). Melting
points were obtained on a Kofler hot stage apparatus and are uncor-
rected. Primary amines and β-dicarbonyl compounds were obtained
from commercial suppliers. Primary amines were distilled before
–
1
7
35 cm .
1H NMR (500 MHz, CDCl
H, C=CH), 3.19 (q, 2 H, J = 7.5 Hz, NCH
1.88 (s, 3 H, CH C=C), 1.53 (m, 2 H, NCH
), 0.90 (t, 3 H, J = 7.5 Hz, CH CH ).
): δ = 10.83 (br s, 1 H, NH), 4.91 (s, 1
), 1.96 (s, 3 H, COCH ),
CH ), 1.38 (m, 2 H,
3
2
3
3
2
2
CH
CH
2
3
2
3
13
C NMR (125 MHz, CDCl ): δ = 194.5 (C=O), 163.1 (C=CH),
3
9
(
4.9 (C=CH), 42.6 (NCH ), 32.0 (NCH CH ), 28.6 (COCH ), 19.9
2
2
2
3
CH CH ), 18.7 (CH C=C), 13.6 (CH CH ).
2 3 3 2 3
+
MS (EI): m/z (%) = 155 (M , 100), 140 (85), 126 (36), 112 (51), 98
(
26), 84 (42), 70 (21).
use. THF and CH CN were distilled from sodium benzophenone
3
(
Z)-4-(t-Butylamino)-3-penten-2-one (3e)
and calcium hydride respectively before use. EtOAc and hexane, for
chromatography, were distilled before use. Thin layer chromatogra-
phy was carried out using silica gel 60 F254 aluminium backed
plates. The plates were viewed under UV irradiation (254 nm) and
developed in an iodine chamber thereafter. A 700W National do-
mestic microwave oven was used for all microwave reactions. Sili-
ca gel 60, 230–400 mesh, was used as an inert support for
microwave reactions. Silica gel 60 PF254 was used for radial chro-
matography. Reaction temperatures of –78 °C were obtained using
t-Butylamine and acetylacetone were mixed and irradiated to yield
(
(
Z)-4-(t-butylamino)-3-penten-2-one as a yellow oil (6%); R 0.47
f
EtOAc–hexanes, 1:1).
–
1
IR (thin film, CHCl ): 3070, 2950, 2935, 1610, 1591 cm .
3
1
H NMR (500 MHz, CDCl ): δ = 11.34 (br s, 1 H, NH), 4.88 (s, 1
3
H, C=CH), 2.04 (s, 3 H, COCH ), 1.97 (s, 3 H, CH C=C), 1.38 [s, 9
H, C(CH ) ].
3
3
3
3
1
3
C NMR (125 MHz, CDCl ): δ = 193.9 (C=O), 163.2 (C=CH),
a solid CO –acetone mixture.
3
2
9
6.2 (C=CH), 52.2 [C(CH ) ], 30.7 [C(CH ) ], 28.6 (COCH ), 20.4
3
3
3
3
3
(
CH C=C).
Preparation of Enaminones 3a–k via Microwave Irradiation;
General Procedure
The appropriate primary amine (3.33 mmol) was mixed with the ap-
propriate β-dicarbonyl compound (3.33 mmol) and poured onto a
bed of silica gel (1 g) in a 10mL glass vial. The mixture was placed
in a domestic microwave oven and irradiated for 3 min on the ‘low’
3
+
MS (EI): m/z (%) = 155 (M , 38), 140 (16), 84 (100).
(
Z)-4-(Cyclohexylamino)-3-penten-2-one (3f)
Cyclohexylamine and acetylacetone were mixed and irradiated to
yield (Z)-4-(cyclohexylamino)-3-penten-2-one as a yellow oil
(88%); R 0.52 (EtOAc–hexanes, 1:1).
setting. The mixture was extracted with CH Cl (10 mL), filtered
2
2
f
and the silica gel washed with Et O (2 × 10 mL). The solvent was
2
IR (thin film, CHCl ): 3080, 2934, 2857, 1610, 1580, 1300, 732
cm .
3
removed in vacuo to yield the desired vinylogous enaminone with-
out further purification. (Note: stoichiometry of certain reactions
may vary and such variations are specified in the text.)
–
1
1
H NMR (500 MHz, CDCl ): δ = 10.9 (br s, 1 H, NH), 4.85 (s, 1 H,
3
C=CH), 3.32 (m, 1 H, NCH), 1.92 (s, 3 H, COCH ), 1.88 (s, 3 H,
3
(
Z)-4-(Methylamino)-3-penten-2-one (3a)
CH C=C), 1.82–1.77, 1.72–1.67, 1.55–1.48, 1.34–1.17 (m, 10 H,
3
Methylamine and acetylacetone were mixed and irradiated to yield
NCHC H ).
5
10
(
(
Z)-4-(methylamino)-3-penten-2-one as a yellow crystalline solid
13
C NMR (125 MHz, CDCl ): δ = 194.2 (C=O), 161.7 (C=CH),
1
3
3
80%); mp 38–40 °C (Lit. mp 37–39 °C); R 0.27 (EtOAc–hex-
f
9
2
4.7 (C=CH), 51.3 (NCH), 33.6 [2 C, NCH(CH ) ], 28.5 (COCH ),
5.2 [2 C, NCH(CH ) (CH ) ], 24.2 [(CH ) CH ], 18.4 (CH C=C).
2 2 3
anes, 1:1).
2
2
2 2
2 2
2
3
–
1
IR (thin film, CHCl ): 3072, 2961, 2928, 1610, 1572, 1297 cm .
+
3
MS (EI): m/z (%) = 181 (M , 100), 166 (37), 138 (57), 100 (44), 84
(48).
1
H NMR (500 MHz, CDCl ): δ = 10.65 (br s, 1 H, NH), 4.93 (s, 1
3
H, C=CH), 2.87 (d, 3 H, J = 5.4 Hz, NCH ), 1.93 (s, 3 H, COCH ),
3
3
1
.86 (s, 3 H, CH C=C).
(Z)-4-(Benzylamino)-3-penten-2-one (3j)
3
1
3
Benzylamine and acetylacetone were mixed and irradiated to yield
C NMR (125 MHz, CDCl ): δ = 194.5 (C=O), 164.0 (C=CH),
3
(
(
Z)-4-(benzylamino)-3-penten-2-one as a yellow oil (82%); R 0.51
EtOAc–hexanes, 1:1).
f
9
4.9 (C=CH), 29.3 (COCH ), 28.5 (NCH ), 18.5 (CH C=C).
3
3
3
+
MS (EI): m/z (%) = 113 (M , 62), 98 (100), 56 (61).
–
1
IR (thin film, CHCl ): 3027, 1607, 1572, 1289, 735 cm .
3
Synthesis 2003, No. 4, 523–530 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
An Expeditious Synthetic Access to β-(Z)-[(1-Propynyl)amino]enones and Enoates
527
1
1
H NMR (500 MHz, CDCl ): δ = 11.16 (br s, 1 H, NH), 7.33–7.22
H NMR (500 MHz, CDCl ): δ = 8.58 (br s, 1 H, NH), 4.32 (s, 1 H,
3
3
(
m, 5 H, C H ), 5.03 (s, 1 H, C=CH), 4.42 (d, 2 H, J = 6.8 Hz,
C=CH), 4.01 (q, 2 H, J = 7.5 Hz, OCH CH ), 3.25 (m, 1 H, NCH),
6
5
2
3
C H CH ), 2.01 (s, 3 H, COCH ), 1.89 (s, 3 H, CH C=C).
1.87 (s, 3 H, CH C=C), 1.83–1.77, 1.72–1.66, 1.56–1.49, and 1.32–
6
5
2
3
3
3
1
3
1.20 (m, 10 H, NCHC
5
H
10), 1.18 (t, 3 H, J = 7.5 Hz, OCH
CH ).
2 3
C NMR (125 MHz, CDCl ): δ = 195.2 (C=O), 162.9 (C=CH),
3
1
3
1
37.9 (ipso-C H ), 128.6 (2 C, m-C H ), 127.2 (p-C H ), 126.5 (2
C NMR (125 MHz, CDCl ): δ = 170.4 (C=O), 160.6 (C=CH),
6
5
6
5
6
5
3
C, o-C H ), 95.7 (C=CH), 46.5 (C H CH ), 28.7 (COCH ), 18.7
81.5 (C=CH), 57.9 (OCH CH ), 51.2 (NCH), 34.1 [2 C,
2 3
6
5
6
5
2
3
(
CH C=C).
NCH(CH ) ], 25.2 [2 C, NCH(CH ) (CH ) ], 24.5 [(CH ) CH ],
3
2 2 2 2 2 2 2 2 2
+
+
19.0 (CH C=C), 14.5 (OCH CH ).
3 2 3
MS (EI): m/z (%) = 189 (M , 69), 174 (32), 91 (C H CH , 100).
6
5
2
+
MS (EI): m/z (%) = 211 (M , 73), 166 (34), 138 (23), 130 (100), 84
(
Z)-4-(Phenylamino)-3-penten-2-one (3h)
(55).
Aniline and acetylacetone were mixed and irradiated to yield (Z)-4-
(
(
phenylamino)-3-penten-2-one as a yellow oil (72%); R 0.59
EtOAc–hexanes, 1:1).
Ethyl (Z)-3-(Benzylamino)-2-butenoate (3k)
Benzylamine (1.5 equiv) and ethyl acetoacetate were mixed and ir-
radiated to yield ethyl (Z)-3-(benzylamino)-2-butenoate as a color-
f
–
1
IR (thin film, CHCl ): 2923, 1613, 1572, 1278, 749 cm .
3
less oil (97%); R 0.54 (EtOAc–hexanes, 1:1).
f
1
H NMR (500 MHz, CDCl ): δ = 12.48 (br s, 1 H, NH), 7.33–6.69
3
–1
IR (thin film, CHCl ): 3291, 2978, 1648, 1607, 1171, 784 cm .
3
(
3
m, 5 H, C H ), 5.19 (s, 1 H, C=CH), 2.10 (s, 3 H, COCH ), 1.98 (s,
6
5
3
1
H, CH C=C).
H NMR (500 MHz, CDCl ): δ = 8.97 (br s, 1 H, NH), 7.34–7.24
3
3
1
3
(m, 5 H, C
6 5
H ), 4.54 (s, 1 H, C=CH), 4.40 (d, 2 H, J = 7.5 Hz,
C NMR (125 MHz, CDCl ): δ = 196.4 (C=O), 160.5 (C=CH),
3
C H CH ), 4.10 (q, 2 H, J = 7.1 Hz, OCH CH ), 1.89 (s, 3 H,
6
5
2
2
3
1
39.0 (ipso-C H ), 129.3 (2C, m-C H ), 125.8 (p-C H ), 125.0 (2 C,
6
5
6
5
6
5
CH C=C), 1.25 (t, 3 H, J = 7.0 Hz, OCH CH ).
3
2
3
o-C H ), 97.9 (C=CH), 29.4 (COCH ), 20.1 (CH C=C).
6
5
3
3
13C NMR (125 MHz, CDCl
): δ = 170.3 (C=O), 161.6 (C=CH),
+
3
MS (EI): m/z (%) = 175 (M , 41), 161 (100), 132 (32), 77 (22).
1
38.5 (ipso-C H ), 128.5 (2 C, m-C H ), 127.1 (p-C H ), 126.5 (2
6 5 6 5 6 5
C, o-C H ), 83.0 (C=CH), 58.1 (OCH CH ), 46.5 (NCH ), 19.1
6
5
2
3
2
Ethyl (Z)-3-(Methylamino)-2-butenoate (3b)
Methylamine (2 equiv) and ethyl acetoacetate were mixed and irra-
diated to yield ethyl (Z)-3-(methylamino)-2-butenoate as a colorless
(
CH C=C), 14.4 (OCH CH ).
3 2 3
+
MS (EI): m/z (%) = 219 (M , 46), 190 (22), 172 (48), 146 (32), 91
oil (82%); R 0.58 (EtOAc–hexanes, 1:1).
(100).
f
IR (thin film, CHCl ): 3296, 2978, 2934, 1651, 1610, 1273, 1166,
3
-
1
Ethyl (Z)-3-(Phenylamino)-2-butenoate (3i)
Aniline (1.5 equiv) and ethyl acetoacetate were mixed and irradiat-
ed to yield ethyl (Z)-3-(phenylamino)-2-butenoate as a colorless oil
7
81 cm .
1
H NMR (500 MHz, CDCl ): δ = 8.43 (br s, 1 H, NH), 4.42 (s, 1 H,
3
C=CH), 4.03 (q, 2 H, J = 7.0 Hz, OCH CH ), 2.86 (d, 3 H, J = 5.5
2
3
(70%); R 0.68 (EtOAc–hexanes, 1:1).
f
Hz, NCH ), 1.87 (s, 3 H, CH C=C), 1.20 (t, 3 H, J = 7.0 Hz,
3
3
–1
IR (thin film, CHCl ): 3258, 2972, 1651, 1613, 1270, 1157 cm .
3
OCH CH ).
2
3
1H NMR (500 MHz, CDCl
m, 5 H, C H ), 4.75 (s, 1 H, C=CH), 4.19 (q, 2 H, J = 7.2 Hz,
): δ = 10.47 (br s, 1 H, NH), 7.34–6.66
3
1
3
C NMR (125 MHz, CDCl ): δ = 170.5 (C=O), 162.6 (C=CH),
3
(
6
5
8
1.7 (C=CH), 58.1 (OCH CH ), 29.4 (NCH ), 19.0 (CH C=C), 14.5
2
3
3
3
OCH CH ), 2.00 (s, 3 H, CH C=C), 1.31 (t, 3 H, J = 7.1 Hz,
2
3
3
(
OCH CH ).
2 3
OCH CH ).
2
3
+
MS (EI): m/z (%) = 143 (M , 59), 98 (100), 82 (20), 71 (57), 56 (37).
1
3
C NMR (125 MHz, CDCl ): δ = 170.1 (C=O), 158.7 (C=CH),
3
1
39.0 (ipso-C H ), 128.8 (2 C, m-C H ), 124.0 (2 C, o-C H ), 114.7
6
5
6
5
6
5
Ethyl (Z)-3-(Butylamino)-2-butenoate (3d)
Butylamine (2 equiv) and ethyl acetoacetate were mixed and irradi-
ated to yield ethyl (Z)-3-( butylamino)-2-butenoate as a colorless oil
(
(
p-C H ), 85.8 (C=CH), 58.5 (OCH CH ), 19.9 (CH C=C), 14.3
OCH CH ).
6 5 2 3 3
2
3
+
(
70%); R 0.59 (EtOAc–hexanes, 1:1).
MS (EI): m/z (%) = 205 (M , 83), 160 (57), 130 (69), 118 (100), 77
55).
f
(
IR (thin film, CHCl ): 3285, 2961, 2934, 1648, 1607, 1270, 1171,
3
–1
1
144, 781 cm .
3
-[(Z)-1-(Methylamino)ethylidene]-5-hexyn-2-one (5)
1
H NMR (500 MHz, CDCl ): δ = 8.51 (br s, 1 H, NH), 4.37 (s, 1 H,
3
NaH (102 mg, 2.12 mmol) was added to a stirred solution of (Z)-4-
(methylamino)-3-penten-2-one (200 mg, 1.77 mmol) and propargyl
bromide (0.24 ml, 0.26 g, 2.15 mmol) in anhyd THF (20 mL) at 0°C.
The reaction mixture was allowed to warm to ambient temperature
and stirred overnight. The reaction was quenched with H O (50
mL), extracted with CH Cl (3 × 50 mL). The combined organic ex-
tracts were dried (MgSO ), filtered and concentrated in vacuo. The
crude material was purified by radial chromatography (EtOAc–hex-
anes, 1:2) to yield 3-[(Z)-1-(methylamino)ethylidene]-5-hexyn-2-
one as a colorless oil (68% based on H NMR); R 0.32 (EtOAc–
C=CH), 4.03 (q, 2 H, J = 7.2 Hz, OCH CH ), 3.15 (q, 2 H, J = 6.9
2
3
Hz, NCH ), 1.86 (s, 3 H, CH C=C), 1.50 (m, 2 H, NCH CH ), 1.35
2
3
2
2
(
m, 2 H, CH CH ), 1.19 (t, 3 H, J = 7.2 Hz, OCH CH ), 0.88 (t, 3 H,
2
3
2
3
J = 7.1 Hz, CH CH ).
2
3
2
1
3
C NMR (125 MHz, CDCl ): δ = 170.5 (C=O), 161.8 (C=CH),
2
2
3
8
1.5 (C=CH), 58.0 (OCH CH ), 42.5 (NCH CH ), 32.3
4
2
3
2
2
(
NCH CH ), 19.9 (CH CH ), 19.2 (CH C=C), 14.5 (OCH CH ),
2 2 2 3 3 2 3
1
3.6 (CH CH ).
2 3
1
+
f
MS (EI): m/z (%) = 185 (M , 60), 142 (25), 130 (37), 124 (56), 84
100), 57 (67).
hexanes, 1:1).
(
–
1
IR (thin film, CHCl ): 3285, 1604, 1486, 1278, 927 cm .
3
Ethyl (Z)-3-(Cyclohexylamino)-2-butenoate (3g)
Cyclohexylamine (2 equiv) and ethyl acetoacetate were mixed and
irradiated to yield ethyl (Z)-3-(cyclohexylamino)-2-butenoate as a
1
H NMR (500 MHz, CDCl ): δ = 11.86 (br s, 1 H, NH), 3.06 (d, 2
3
H, J = 2.0 Hz, CH C≡CH), 2.90 (d, 3 H, J = 5.1 Hz, NCH ), 2.16 (s,
3
CH C≡CH).
2
3
H, COCH ), 2.03 (s, 3 H, CH C=C), 1.94 (t, 1 H, J = 2.0 Hz,
3
3
colorless oil (76%); R 0.54 (EtOAc–hexanes, 1:1).
f
2
IR (thin film, CHCl ): 3274, 2934, 2851, 1651, 1602, 1273, 781
3
–
1
cm .
Synthesis 2003, No. 4, 523–530 ISSN 0039-7881 © Thieme Stuttgart · New York

5
28
D. Gravestock, M. C. Dovey
PAPER
1
3
1
C NMR (125 MHz, CDCl ): δ = 193.7 (C=O), 164.0 (CH C=C),
H NMR (500 MHz, CDCl ): δ = 6.16 (s, 1 H, C=CH), 3.72 (t, 2 H,
3
3
3
9
9.5 (CH C=C), 83.8 (C≡CH), 67.5 (C≡CH), 29.8 (NCH ), 27.6
J = 7.8 Hz, NCH ), 2.51 (s, 3 H, CH C=C), 2.32 (s, 3 H, COCH ),
3
3
2
3
3
(
COCH ), 18.9 (CH C≡CH), 14.7 (CH C=C).
2.18 (s, 3 H, C≡CCH ), 1.56 (m, 2 H, NCH CH ), 1.34 (m, 2 H,
3
2
3
3
2
2
CH CH ), 0.93 (t, 3 H, J = 7.3 Hz, CH CH ).
2
3
2
3
3
-[(Z)-1-(Methylamino)ethylidene]-5-hexyn-2-one (5)
13
C NMR (125 MHz, CDCl ): δ = 194.7 (C=O), 134.4 (C=CH),
3
t-BuLi (3.03 mL, 5.16 mmol, 1.7 M) was added to a stirred solution
of (Z)-4-(methylamino)-3-penten-2-one (530 mg, 4.69 mmol) in an-
hyd THF (25 mL) at –78 °C and stirred at that temperature for 30
min. Propargyl bromide (0.78 mL, 0.83 g, 7.03 mmol) was added
thereafter and the mixture was stirred at –78 °C for a further 3 h, al-
lowed to warm to ambient temperature and stirred overnight. The
1
27.0 (NC≡C), 119.7 (NC≡C), 108.0 (C=CH), 43.1 (NCH ), 32.4
2
(NCH CH ), 28.3 (COCH ), 19.9 (CH CH ), 13.6 (CCH ), 12.1
2 2 3 2 3 3
(
CH C=C), 11.7 (CH CH ).
3
2
3
+
+
+
MS (EI): m/z (%) = 193 (M , 98), 178 (M – CH ,100), 150 (M –
COCH ,18), 136 (37), 122 (30), 108 (46), 43 (COCH , 28).
3
3
3
reaction was quenched with aq NH Cl (30 mL) and extracted with
4
HRMS (EI): m/z calcd for C H NO, 193.1467; found, 193.1464.
12 19
CH Cl (3 × 50 mL). The combined organic extracts were dried
2
2
(
(
MgSO ), filtered and concentrated in vacuo. Spectroscopic data
4
(Z)-4-[Cyclohexyl(1-propynyl)amino]-3-penten-2-one (6f)
Z)-4-(Cyclohexylamino)-3-penten-2-one was treated with propar-
gyl bromide and silver nitrate to yield (Z)-4-[cyclohexyl(1-propy-
1
GC-MS and H NMR) indicated that 3-[(Z)-1-(methylamino)eth-
(
1
ylidene]-5-hexyn-2-one was the major product (58% based on H
NMR).
nyl)amino]-3-penten-2-one as a red-brown oil (25%) after radial
chromatography (EtOAc–hexanes, 1:4); R 0.56 (EtOAc–hexanes,
f
3
-[(Z)-1-(Methylamino)ethylidene]-5-hexyn-2-one (5)
1
:1).
t-BuLi (2.86 mL, 4.86 mmol, 1.7 M) was added to a stirred solution
of (Z)-4-(methylamino)-3-penten-2-one (500 mg, 4.42 mmol) in an-
hyd THF (25 mL) at –78 °C and allowed to warm to ambient tem-
perature. The mixture was heated to reflux and propargyl bromide
–
1
IR (thin film, CHCl ): 2928, 2849, 1649, 1517, 1414 cm .
3
1H NMR (500 MHz, CDCl
H, NCH), 2.62 (s, 3 H, CH
): δ = 6.17 (s, 1 H, C=CH), 3.96 (m, 1
C=C), 2.33 (s, 3 H, COCH ), 2.28 (s, 3
), 2.00–1.72, 1.41–1.17 (m, 10 H, NCHC
3
3
3
(0.74 mL, 0.79 g, 6.63 mmol) was added slowly thereafter. Reflux
H, C≡CCH
3
H10).
5
was maintained for 90 min. The reaction was quenched with aq
13
C NMR (125 MHz, CDCl ): δ = 194.9 (C=O), 134.9 (C=CH),
3
NH Cl (30 mL) and extracted with CH Cl (3 × 50 mL). The com-
4
2
2
1
27.4 (NC≡C), 109.7 (NC≡C), 106.0 (C=CH), 56.5 (NCH), 31.8 [2
bined organic extracts were dried (MgSO ), filtered and concentrat-
4
C, NCH(CH ) ], 28.5 (COCH ), 26.4 [2 C, NCH(CH ) (CH ) ],
2
2
3
2 2
2 2
1
ed in vacuo. Spectroscopic data (GC-MS and H NMR) indicated
2
5.3 [(CH ) CH ], 14.2 (C≡CCH ), 13.0 (CH C=C).
2 2 2 3 3
that 3-[(Z)-1-(methylamino)ethylidene]-5-hexyn-2-one was the ma-
+
+
1
MS (EI): m/z (%) = 219 (M , 95), 204 (M – CH , 35), 138 (28), 137
3
jor product (65% based on H NMR).
(
91), 122 (100), 55 (42), 41 (25).
Preparation of N-(1-Propynyl) Enaminones 6a–k; General Pro-
cedure
HRMS (EI): m/z calcd for C H NO, 219.1623; found, 219.1627.
1
4
21
Propargyl bromide (2 mmol) was added to a stirred solution of sil-
(Z)-4-[Benzyl(1-propynyl)amino]-3-penten-2-one (6j)
ver nitrate (2 mmol) in anhyd CH CN (10 mL) at ambient tempera-
(Z)-4-(Benzylamino)-3-penten-2-one was treated with propargyl
bromide and silver nitrate to yield (Z)-4-[benzyl(1-propynyl)ami-
no]-3-penten-2-one as a colorless oil (21%) after radial chromatog-
3
ture. The appropriate enaminone (1 mmol) was added immediately
thereafter and the mixture was stirred overnight. The reaction was
quenched with sat. aq NaHCO (20 mL) and extracted with CH Cl
3
2
2
raphy (EtOAc–hexanes, 1:3); R 0.58 (EtOAc–hexanes, 1:1).
f
(
3 × 20 mL). The combined organic extracts were dried (MgSO4),
–1
IR (thin film, CHCl ): 2912, 1651, 1522, 1415, 1242 cm .
3
filtered and concentrated in vacuo. The crude material was purified
by radial chromatography to give the desired N-(1-propynyl) enam-
inones.
1H NMR (500 MHz, CDCl
), 6.30 (s, 1 H, C=CH), 5.04 (s, 2 H, C
CH C=C), 2.40 (s, 3 H, COCH ), 2.13 (s, 3 H, C≡CCH ).
): δ = 7.33–7.23, 6.90–6.88 (m, 5 H,
CH ), 2.49 (s, 3 H,
3
C
H
H
6
5
6
5
2
3
3
3
(
(
Z)-4-[Methyl(1-propynyl)amino]-3-penten-2-one (6a)
Z)-4-(Methylamino)-3-penten-2-one was treated with propargyl
13
C NMR (125 MHz, CDCl ): δ = 195.0 (C=O), 136.7 (ipso-C H ),
3
6
5
1
35.1 (C=CH), 128.8 (2 C, m-C H ), 127.8 (NC≡C), 127.4 (p-
6 5
bromide and silver nitrate to yield (Z)-4-[methyl(1-propynyl)ami-
no]-3-penten-2-one as a white crystalline solid (mp 37–38 °C)
C H ), 125.5 (2 C, o-C H ), 120.2 (NC≡C), 108.3 (C=CH), 46.5
6
5
6
5
(
C H CH ), 28.5 (COCH ), 12.1 (C≡CCH ), 11.7 (CH C=C).
6 5 2 3 3 3
(16%) after radial chromatography (EtOAc–hexanes, 1:2); R 0.40
f
+
+
MS (EI): m/z (%) = 227 (M , 100), 212 (M – CH , 68), 91
(EtOAc–hexanes, 1:1).
3
+
(
C H CH , 80).
6 5 2
–
1
IR (thin film, CHCl ): 2933, 1646, 1522, 1410, 1229 cm .
3
HRMS (EI): m/z calcd for C H NO, 227.1310; found, 227.1302.
1
5
17
1
H NMR (500 MHz, CDCl ): δ = 6.19 (s, 1 H, C=CH), 3.38 (s, 3 H,
3
NCH ), 2.52 (s, 3 H, CH C=C), 2.34 (3 H, s, COCH ), 2.19 (s, 3 H,
C≡CCH3).
3
3
3
(Z)-4-[Phenyl(1-propynyl)amino]-3-penten-2-one (6h)
(Z)-4-(Phenylamino)-3-penten-2-one was treated with propargyl
bromide and silver nitrate to yield (Z)-4-[phenyl(1-propynyl)ami-
no]-3-penten-2-one (7%) after radial chromatography (EtOAc–hex-
1
3
C NMR (125 MHz, CDCl ): δ = 194.8 (C=O), 135.0 (C=CH),
3
1
27.6 (NC≡C), 119.7 (NC≡C), 107.7 (C=CH), 29.9 (NCH ), 28.4
3
(
COCH ), 12.2 (C≡CCH ), 11.8 (CH C=C).
anes, 1:4); R 0.59 (EtOAc–hexanes, 1:1). The desired product was
f
3
3
3
isolated as a mixture of product and starting material. The quoted
+
+
MS (EI): m/z (%) = 151 (M , 40), 136 (M – CH ,100), 56 (9).
3
1
yield is based on H NMR data.
HRMS (EI): m/z calcd for C H NO, 151.0997; found, 151.1003.
9
13
1
H NMR (500 MHz, CDCl ): δ = 7.51–7.32 (m, 5 H, C H ), 6.32 (s,
3
6
5
1
3
H, C=CH), 2.42 (s, 3 H, CH C=C), 2.30 (s, 3 H, COCH ), 1.99 (s,
H, C≡CCH3).
3
3
(
(
Z)-4-[Butyl(1-propynyl)amino]-3-penten-2-one (6c)
Z)-4-(Butylamino)-3-penten-2-one was treated with propargyl bro-
13C NMR (125 MHz, CDCl
137.6 (C=CH), 136.0 (NC≡C), 129.7 (2 C, m-C
), 128.3 (2 C, o-C ), 120.7 (NC≡C), 108.3 (C=CH), 29.4
COCH ), 13.2 (C≡CCH ), 12.9 (CH C=C).
): δ = 196.4 (C=O), 139.0 (ipso-C
H ),
6 5
mide and silver nitrate to yield (Z)-4-[butyl(1-propynyl)amino]-3-
penten-2-one as a yellow oil (24%) after radial chromatography
3
H
6 5
), 128.9 (p-
(EtOAc–hexanes, 1:4); R 0.56 (EtOAc–hexanes, 1:1).
C
(
6
H
5
H
6 5
f
–
1
3
3
3
IR (thin film, CHCl ): 2956, 2934, 1648, 1517, 1418 cm .
3
Synthesis 2003, No. 4, 523–530 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
An Expeditious Synthetic Access to β-(Z)-[(1-Propynyl)amino]enones and Enoates
529
+
+
MS (EI): m/z (%) = 213 (M , 34), 198 (M – CH , 100).
Ethyl (Z)-3-[Benzyl(1-propynyl)amino]-2-butenoate (6j)
3
Ethyl (Z)-3-(benzylamino)-2-butenoate was treated with propargyl
bromide and silver nitrate to yield ethyl (Z)-3-[benzyl(1-propy-
nyl)amino]-2-butenoate (14%) after radial chromatography
HRMS: m/z calcd for C H NO, 213.1154; found, 213.1144.
1
4
15
Ethyl (Z)-3-[Methyl(1-propynyl)amino]-2-butenoate (6b)
Ethyl (Z)-3-(methylamino)-2-butenoate was treated with propargyl
bromide and silver nitrate to yield ethyl (Z)-3-[methyl(1-propy-
nyl)amino]-2-butenoate as a colorless oil (21%) after radial chro-
(
EtOAc–hexanes, 1:4); R 0.54 (EtOAc–hexanes, 1:1). The desired
f
product was isolated as a mixture of product and starting material.
1
The quoted yield is based on H NMR data.
1
matography (EtOAc–hexanes, 1:4); R 0.59 (EtOAc–hexanes, 1:1).
H NMR (500 MHz, CDCl ): δ = 7.35–7.27 (m, 5 H, C H ), 6.37 (s,
f
3
6
5
1
H, C=CH), 5.03 (s, 2 H, C H CH ), 4.27 (q, 2 H, J = 7.1 Hz,
6 5 2
IR (thin film, CHCl ): 2983, 2923, 1695, 1533, 1415, 1223, 1061
cm .
3
–
1
OCH CH ), 2.46 (s, 3 H, CH C=C), 2.12 (s, 3 H, C≡CCH ), 1.35 (t,
3
2 3 3 3
H, J = 7.0 Hz, OCH CH ).
2 3
1
H NMR (500 MHz, CDCl ): δ = 6.22 (s, 1 H, C=CH), 4.22 (q, 2 H,
3
13
C NMR (125 MHz, CDCl ): δ = 165.6 (C=O), 136.9 (ipso-C H ),
3
6
5
J = 7.3 Hz, OCH CH ), 3.36 (s, 3 H, NCH ), 2.48 (s, 3 H, CH C=C),
2
3
3
3
1
35.4 (C=CH), 128.7 (2 C, m-C H ), 127.8 (NC≡C), 127.2 (p-
6 5
2
.16 (s, 3 H, C≡CCH ), 1.31 (t, 3 H, J = 7.2 Hz, OCH CH ).
3
2
3
C H ), 125.4 (2 C, o-C H ), 111.2 (NC≡C), 107.6 (C=CH), 59.1
(OCH CH ), 46.7 (NCH ), 14.5 (OCH CH ), 12.0 (C≡CCH ), 11.2
(CH C=C).
3
6
5
6
5
1
3
C NMR (125 MHz, CDCl ): δ = 165.6 (C=O), 135.2 (C=CH),
3
2 3 2 2 3 3
1
3
27.6 (NC≡C), 110.3 (NC≡C), 106.9 (C=CH), 58.9 (OCH CH ),
2 3
0.0 (NCH ), 14.4 (OCH CH ), 12.1 (C≡CCH ), 11.2 (CH C=C).
3
2
3
3
3
+
+
+
MS (EI): m/z (%) = 257 (M , 74), 228 (M – CH CH , 19), 212 (M
– OCH CH , 20), 91 (C H CH , 100).
2
3
+
+
MS (EI): m/z (%) = 181 (M , 80), 152 (M – CH CH , 100), 136
+
2
3
2 3 6 5 2
+
(
M – OCH CH , 58).
2 3
HRMS (EI): m/z calcd for C H NO , 257.1416; found, 257.1402.
1
6
19
2
HRMS: m/z calcd for C H NO , 181.1103; found, 181.1110.
1
0
15
2
Ethyl (Z)-3-[Phenyl(1-propynyl)amino]-2-butenoate (6i)
Ethyl (Z)-3-[Butyl(1-propynyl)amino]-2-butenoate (6d)
Ethyl (Z)-3-(phenylamino)-2-butenoate was treated with propargyl
bromide and silver nitrate to yield ethyl (Z)-3-[phenyl(1-propy-
nyl)amino]-2-butenoate in a trace quantity after radial chromatog-
raphy (EtOAc–hexanes, 1:9). The desired product was evident from
Ethyl (Z)-3-(butylamino)-2-butenoate was treated with propargyl
bromide and silver nitrate to yield ethyl (Z)-3-[butyl(1-propy-
nyl)amino]-2-butenoate as a yellow oil (24%) after radial chroma-
tography (EtOAc–hexanes, 1:4); R 0.60 (EtOAc–hexanes, 1:1).
1
f
H NMR in an amount that did not warrant further purification.
IR (thin film, CHCl ): 2961, 2928, 1698, 1533, 1421, 1229, 1061,
3
–
1
7
70 cm .
Acknowledgements
1
H NMR (500 MHz, CDCl ): δ = 6.24 (s, 1 H, C=CH), 4.23 (q, 2 H,
3
J = 7.1 Hz, OCH CH ), 3.73 (t, 2 H, J = 7.4 Hz, NCH ), 2.50 (s, 3
We thank the South African National Research Foundation (NRF)
and the University of Natal for providing the funding for the rese-
arch. MCD also thanks the NRF for a grant-holder bursary. We are
grateful to Mr C. Grimmer (University of Natal) and Dr P. R. Bos-
hoff (Cape Technikon) for recording NMR spectra and mass spec-
tra, respectively.
2
3
2
H, CH C=C), 2.18 (s, 3 H, C≡CCH ), 1.58 (m, 2 H, NCH CH ),
3
3
2
2
1
.36 (m, 2 H, CH CH ), 1.31 (t, 3 H, J = 7.1 Hz, OCH CH ), 0.94
2
3
2
3
(
t, 3 H, J = 7.5 Hz, CH CH ).
2 3
1
3
C NMR (125 MHz, CDCl ): δ = 165.7 (C=O), 134.8 (C=CH),
3
1
4
1
27.2 (NC≡C), 110.5 (NC≡C), 107.4 (C=CH), 58.9 (OCH CH ),
2
3
3.4 (NCH ), 32.6 (NCH CH ), 20.0 (CH CH ), 14.5 (OCH CH ),
2
2
2
2
3
2
3
3.7 CH CH ), 12.1 (C≡CCH ), 11.2 (CH C=C).
2
3
3
3
References
+
+
MS (EI): m/z (%) = 223 (M , 100), 194 (M – CH CH , 56), 181
2
3
(
1) Zificsak, C. A.; Mulder, J. A.; Hsung, R. P.; Rameshkumar,
+
(
31), 178 (M – OCH CH , 40), 108 (20).
2 3
C.; Wei, L.-L. Tetrahedron 2001, 57, 7575.
HRMS (EI): m/z calcd for C H NO , 223.1572; found, 223.1578.
1
3
21
2
(2) (a) Majumdar, K. C.; Ghosh, S. K. Synth. Commun. 1994,
4, 217. (b) Brükner, D. Synlett 2000, 1402. (c) Wei, L.-L.;
2
Ethyl (Z)-3-[Cyclohexyl(1-propynyl)amino]-2-butenoate (6g)
Ethyl (Z)-3-(cyclohexylamino)-2-butenoate was treated with prop-
argyl bromide and silver nitrate to yield ethyl (Z)-3-[cyclohexyl(1-
propynyl)amino]-2-butenoate as a yellow oil (24%) after radial
Mulder, J. A.; Xiong, H.; Zificsak, C. A.; Douglas, C. J.;
Hsung, R. P. Tetrahedron 2001, 57, 459.
(3) (a) Witulski, B.; Stengel, T. Angew. Chem. Int. Ed. 1998, 37,
4
89. (b) Hsung, R. P.; Zificsak, C. A.; Wei, L.-L.; Douglas,
C. J.; Xiong, H.; Mulder, J. A. Org. Lett. 1999, 1, 1237.
c) Witulski, B.; Buschmann, N.; Bergsträβer, U.
chromatography (EtOAc–hexanes, 1:9); R 0.55 (EtOAc–hexanes,
f
1
:1).
(
Tetrahedron 2000, 56, 8473.
IR (thin film, CHCl ): 2928, 2857, 1698, 1530, 1421, 1220, 1185,
3
–1
(4) Michael, J. P.; de Koning, C. B.; Gravestock, D.; Hosken, G.
D.; Howard, A. S.; Jungmann, C. M.; Krause, R. W. M.;
Parsons, A. S.; Pelly, S. C.; Stanbury, T. V. Pure Appl.
Chem. 1999, 71, 979.
1
067, 770 cm .
1
H NMR (500 MHz, CDCl ): δ = 6.22 (s, 1 H, C=CH), 4.22 (q, 2 H,
3
J = 7.1 Hz, OCH CH ), 3.95 (m, 1 H, NCH), 2.60 (s, 3 H,
2
3
CH C=C), 2.27 (s, 3 H, C≡CCH ), 1.99–1.73, 1.41–1.17 (m, 10 H,
3
3
(
5) Gravestock, D.; Peirson, I. G. Tetrahedron Lett. 2000, 41,
497.
NCHC H ), 1.31 (t, 3 H, J = 7.1 Hz, OCH CH ).
5
10
2
3
3
1
3
C NMR (125 MHz, CDCl ): δ = 165.7 (C=O), 135.3 (C=CH),
(6) Beak, P.; Lee, B. J. Org. Chem. 1989, 54, 458.
(7) Brillon, D. Synth. Commun. 1990, 20, 3085.
3
1
5
27.5 (NC≡C), 110.6 (NC≡C), 108.8 (C=CH), 58.9 (OCH CH ),
2
3
6.6 (NCH), 31.9 [2 C, NCH(CH ) ], 26.4 [2 C,
(8) (a) Pedersen, B. S.; Scheibye, S.; Nilsson, N. H.; Lawesson,
S. Bull. Soc. Chim. Belg. 1978, 87, 223. (b) Thorsen, M.;
Andersen, T. P.; Pedersen, U.; Yde, B.; Lawesson, S.
Tetrahedron 1985, 41, 5633. (c) Ghattas, A. A. G.; El-
Khrisy, E. A. M.; Lawesson, S. Sulfur Lett. 1982, 1, 69.
2
2
NCH(CH ) (CH ) ], 25.4 [(CH ) CH ], 14.5 (2 C, C≡CCH ,
2
2
2 2
2 2
2
3
OCH CH ), 12.3 (CH C=C).
2
3
3
+
+
MS (EI): m/z (%) = 249 (M , 100), 220 (M – CH CH , 19), 204
2
3
+
(
M – OCH CH , 21), 167 (35), 139 (24), 138 (71), 122 (27).
2 3
(d) Yde, B.; Yousif, N. M.; Pedersen, U. S.; Thomsen, I.;
HRMS (EI): m/z calcd for C H NO , 249.1729; found, 249.1740.
1
5
23
2
Lawesson, S. Tetrahedron 1984, 40, 2047.
Synthesis 2003, No. 4, 523–530 ISSN 0039-7881 © Thieme Stuttgart · New York

5
30
D. Gravestock, M. C. Dovey
PAPER
(
9) Rechsteiner, B.; Texier-Boullet, F.; Hamelin, J. Tetrahedron
(12) (a) Austad, T.; Songstad, J.; Stangeland, L. J. Acta Chem.
Scand. 1971, 25, 2327. (b) Carretero, J. C.; García Ruano, J.
L. Tetrahedron Lett. 1985, 26, 3381.
(13) Braibante, M. E. F.; Braibante, H. S.; Missio, L.;
Andricopulo, A. Synthesis 1994, 9, 898.
Lett. 1993, 34, 5071.
(
10) For a recent review on microwave-assisted synthesis see:
Caddick, S. Tetrahedron 1995, 51, 10403.
11) Smith, M. B.; March, J. March’s Advanced Organic
Chemistry: Reactions, Mechanisms and Structure; Wiley:
New York, 2001, 5th ed., 458–461.
(
Synthesis 2003, No. 4, 523–530 ISSN 0039-7881 © Thieme Stuttgart · New York