Michael addition of various nitrogen and oxygen nucleophiles to 1,1-diethoxybut-3-yn-2-one

Article abstract of DOI:10.1055/s-0031-1289294

1,1-Diethoxybut-3-yn-2-one, a conjugated terminal acetylenic ketone, reacts with nitrogen and oxygen nucleophiles and gives Michael adducts, in most cases in good to excellent yield. In almost every case the predominant reaction is monoaddition, which lea

Full text of DOI:10.1055/s-0031-1289294

PAPER
3899
Michael Addition of Various Nitrogen and Oxygen Nucleophiles to
1,1-Diethoxybut-3-yn-2-one
Michael
A
ddition to 1,
y
1-Diethoxyb
a
ut-3-yn-2-o
g
ne marsuren Sengee, Leiv K. Sydnes*
Department of Chemistry, University of Bergen, Allégt. 41, 5007 Bergen, Norway
Fax +4755589490; E-mail: leiv.sydnes@kj.uib.no
Received 9 August 2011; revised 10 September 2011
Some time ago we reported a simple and efficient synthe-
sis of 3,3,4,4-tetraethoxybut-1-yne (TEB).5 From this
acetylene, a series of compounds containing the a,b-un-
saturated acetylenic ketone motif has been prepared by re-
Abstract: 1,1-Diethoxybut-3-yn-2-one, a conjugated terminal acet-
ylenic ketone, reacts with nitrogen and oxygen nucleophiles and
gives Michael adducts, in most cases in good to excellent yield. In
almost every case the predominant reaction is monoaddition, which
leads to formation of the corresponding b-substituted a,b-unsaturat- acting the acetylide of TEB with aldehydes and ketones,
ed ketones in a stereospecific fashion. The stereochemistry depends
on the nature of the nucleophile, the general pattern being that am-
monia and primary amines give Z-alkenones, whereas secondary
rivatives of 1, that is 2, and acylated derivatives of 2, that
amines and alcohols afford E-alkenones. Triethylamine does not
furnish a Michael addition product, but catalyzes a trimerization
followed by derivatization and deketalization, for instance
to give 1,1-diethoxybut-3-yn-2-one (1), hydroxylated de-
is 3, as outlined in Scheme 1.6 The chemical properties of
compounds 1–3 are currently under investigation and ex-
citing reactivity has been uncovered. For instance, hy-
droxy ketones 2 give Michael adducts in almost
quantitative yields when reacted with thiolates, and keto
esters 3 react with cuprates and afford furans in a com-
pletely regiospecific fashion in good to excellent yields
after a multistep transformation.
that leads to formation of a 6H-1,3-dioxine derivative. When bis-
nucleophiles, for instance hydrazine and hydroxylamine, are used,
the Michael-addition products are unstable and undergo secondary
reactions to form heterocyclic compounds, which are isolated in ex-
cellent yields.
Key words: acetylenic ketones, Michael additions, vinyl ketones,
cyclotrimerization, acetals
To get an impression of the reactivity of other nucleo-
philes toward the conjugated moiety in 1–3, we decided to
study the reaction of 1, prepared from TEB by acid-cata-
lyzed deketalization in aqueous tetrahydrofuran, with var-
ious nitrogen and oxygen nucleophiles under typical
Michael conditions. Interesting results were obtained and,
as reported here, acetylene 1 appeared to react in a fashion
that was sensitive to the nature of the nucleophile.
a,b-Unsaturated carbonyl moieties are important sub-
structures in synthesis for a number of reasons, but in par-
ticular due to their ability to react with nucleophiles in a
Michael fashion.1 Compared to conjugated olefinic ke-
tones, other conjugated unsaturated compounds have been
investigated less, not necessarily because they are less re-
active, but because the compounds are more cumbersome
to prepare. One group of compounds belonging to this cat-
egory is a,b-unsaturated acetylenic ketones,2 which ap-
pear to undergo efficient Michael addition with a variety
of nucleophiles including cuprates3 and thiolates.4
The reactions with ammonia and amines were performed
in ethanol at room temperature, and under these condi-
tions smooth and slightly exothermic reactions took place.
Ammonia and all the primary and secondary amines gave
OEt
OEt
OEt
R1
R2
R1
R2
HO
esterification
coupling
OEt
OEt
OEt
OEt
OEt
OEt
R3COO
EtO
EtO
TEB
EtO
deketalization
OEt
deketalization
deketalization
OEt
OEt
OEt
R1
R1
R2
R2
OEt
O
OEt
O
R3COO
O
HO
1
2
3
Scheme 1 Outline of syntheses of some a,b-unsaturated acetylenic ketones from 3,3,4,4-tetraethoxybut-1-yne
SYNTHESIS 2011, No. 23, pp 3899–3907
x
x.
x
x
.
2
0
1
1
Advanced online publication: 17.10.2011
DOI: 10.1055/s-0031-1289294; Art ID: Z78711SS
© Georg Thieme Verlag Stuttgart · New York

3900
M. Sengee, L. K. Sydnes
PAPER
the corresponding Michael addition products, namely the various aqueous conditions, E-to-Z isomerization took
corresponding 4-substituted 1,1-diethoxybut-3-en-2-ones place. On the basis of this observation, the reaction of 1
4, in excellent yields (Scheme 2, Table 1).
with aniline was repeated according to the general proce-
dure, but when the reaction was complete as indicated by
TLC analysis, water was added to the product mixture as
a first step in the workup. To our satisfaction this gave 1,1-
diethoxy-4-(phenylamino)but-3-en-2-one as a single iso-
mer with Z configuration [(Z)-4c] in excellent yield
(Table 1, entry 3).
R1R2N
EtO
R1R2NH
OEt
OEt
OEt
EtOH, r.t.
O
O
4
1
Scheme 2 Addition of amines to 1
Another secondary reaction was observed when a reaction
between 1 and an amine was quenched by the addition of
a significant amount of an aqueous solution of ammonium
chloride, which contains ammonia, a significantly better
nucleophile than water. Whatever amine was used, the
product obtained was the Z isomer of 4a. The yield was
generally excellent, in the case of the reaction between 1
and diethylamine, for instance, (Z)-4a was isolated in 92%
yield.
Table 1 Synthesis of 4-Amino-Substituted 1,1-Diethoxybut-3-en-
2-ones 4 by Addition of Amines R1R2NH to 1
Entry
R1
R2
4
Yielda of
(Z)-4 (%) (E)-4 (%)
Yielda of
1
2
3
4
5
6
H
H
H
H
Et
4a
4b
4c
4d
4e
4f
92
95
89
0
0
0
Me
The stereospecific formation of 4 is interesting and poten-
tially useful. We believe that the specificity is the result of
restricted mobility and conformational changes of inter-
mediates caused by the net impact of the hydrogen bond-
ing between the NH moiety and the carbonyl group, as
well as steric interactions between the substituted amino
group and the acyl group. The deviating behavior in the
case of aniline when compared to ammonia and methyl-
amine is not straightforward to explain, but it could be re-
lated to a more significant steric effect and/or an extended
chromophore and therefore more extensive conjugation
when the phenyl group is present.
Ph
0
Et
88
92
90
(CH2)4
(CH2)5
0
0
a With the exception of entry 3, the yields reported are those obtained
after non-aqueous workup (see experimental section). The yields re-
ported for aniline are after aqueous workup (see text).
It is noteworthy that 4 was the only product, even when a
significant excess of amine was used, but what is even
more interesting is that all amines except aniline gave the
Michael adduct in a stereospecific fashion; ammonia and
methylamine furnished the Z isomer only, whereas the
secondary amines gave only 4 with an E geometry
(Scheme 2, Table 1). For all the products, the stereochem-
istry is substantiated by parameters extracted from their
1H NMR spectra. Not only is the vicinal coupling constant
between the olefinic protons smaller in the Z isomers than
in the E isomers, about 7.5 Hz compared to 12.8 Hz; in ad-
dition, the proton attached to C-4 also appears at a much
lower field in (E)-4 than in (Z)-4, due to anisotropic field
effects from the carbonyl group, at about d = 7.6 ppm as
compared to d = 6.9 ppm.
When 1 was treated with tertiary amines under the condi-
tions used for the other amines investigated in this study,
no nitrogen-containing compounds were isolated; instead,
a vinyl ether was obtained as a result of ethanol addition
(vide infra). The reaction was therefore repeated by using
non-nucleophilic and non-protic solvents instead of etha-
nol, and this certainly changed the outcome. When 1 was
treated with triethylamine in hexane, a very fast and
slightly exothermic reaction occurred and led to the for-
mation of a dark, tarry material that stuck to the walls of
the reaction flask and appeared to be an intractable mix-
ture of complex, more or less polymeric products. When
hexane was replaced by diethyl ether, the outcome was to-
tally different; no colored material was formed, the exo-
thermicity was insignificant, and no product adhered to
the reaction flask. Standard workup after hydrolysis gave
one pure product only, namely 1-[2,4-bis(diethoxymeth-
yl)-2,4-diethynyl-4H-1,3-dioxin-5-yl]-2,2-diethoxyetha-
none (5), formally a trimer of 1, in 53% yield (Scheme 3).
TLC analyses under various conditions gave one spot
Unlike the other amines, aniline did not react with 1 in a
stereospecific fashion. When the reaction was performed
according to the general procedure, the 1H NMR spectrum
of the crude product gave two sets of signals for the ole-
finic protons in an approximate ratio of 11:1. The stronger
set of signals had the lower olefinic vicinal coupling, 7.8
Hz as compared to 13.0 Hz, and the proton attached to C-
4 appeared at the higher field, at d = 7.44 ppm as com-
pared to d = 8.20 ppm, and this is a clear indication of a
(Z)-4 predominance over (E)-4. Attempts to separate the
isomers under a variety of conditions were unsuccessful,
but during the experimentation to achieve separation it be-
came clear that when the crude product was exposed to
1
only, indicating a homogeneous compound, but the H-
and 13C NMR spectra gave two sets of many of the signals
that substantiate that 5 was formed as a mixture of cis and
trans isomers. According to 1H NMR spectra of the prod-
uct mixture, the isomeric ratio is 7:3, but the data do not
allow us to settle unequivocally which isomer predomi-
nates.
Synthesis 2011, No. 23, 3899–3907 © Thieme Stuttgart · New York

PAPER
Michael Addition to 1,1-Diethoxybut-3-yn-2-one
3901
OEt
in almost the same yield (48% and 45%, respectively).
Since no nitrogen-containing stable product was obtained
and since ethanol alone does not react with 1 at this tem-
perature, we conclude that triethylamine in this case acts
as a catalyst and forms intermediates that are able to give
both 6 and 7. Two such conceivable intermediates, denot-
ed A and B, are depicted in Scheme 5. Primary attack of 1
by triethylamine furnishes an allenolate zwitterion A,
which is unstable and is converted into an enolate zwitter-
ion B in the following sequence of reactions indicated by
arrows in Scheme 5: proton abstraction, ethanol attack,
and subsequent rearrangement. When zwitterion B is gen-
erated, two different reactions can occur. One transforma-
tion involves regeneration of the carbonyl group,
concomitant increased density of negative charge a to the
carbonyl group, and expulsion of triethylamine to give 6.
Alternatively, ethanol (or ethoxide that might be formed)
acts as nucleophile and attacks C-b; an SN2 reaction with
triethylamine as the leaving group takes place, and tetra-
ethoxy ketone 7 is furnished after protonation of the eno-
late moiety.
1. Et3N, Et2O
or NaH, THF
EtO
OEt
EtO
O
O
O
2. aqueous
workup
OEt
OEt
OEt
OEt
O
5
Scheme 3 Cyclotrimerization of 1
The mechanism for the transformation leading to the for-
mation of 5 is currently under investigation. Several alter-
natives for this multistep process can be envisaged, but a
crucial sequence is expected to include addition and elim-
ination of triethylamine. This sequence is quite likely,
considering the nucleophilicity of amines towards 1 (vide
supra) and the ability of trialkylamines to function as
leaving groups, but this rationale apparently does not en-
compass all aspects of the reaction, because when 1 was
reacted with sodium hydride, a reagent containing a mod-
erate nucleophile and an exceedingly bad leaving group,
trimerization still occurred and 5 was obtained in 43%
yield (Scheme 3).
EtO
5
Et
EtO
H
O
OEt
OEt
1
4
The reactions with ethanol were carried out under several
sets of conditions. When 1 was stirred in an excess of
dried, pure ethanol at room temperature, no reaction oc-
curred at all, but when the mixture was refluxed, two
products were obtained, (E)-1,1,4-triethoxybut-3-en-2-
one (6) and 1,1,4,4-tetraethoxybutan-2-one (7)
(Scheme 4). The yields were quite low, and even after 12
hours of reflux the isolated yields of 6 and 7 were not bet-
ter than 33% and 22%, respectively.
+
3
NEt3
O–
O
Et3N
2
1
A
OEt
OEt
EtO
6
7
Et3+N
–O
B
Scheme 5 Proposed intermediates in triethylamine-catalyzed addi-
tion of ethanol to 1
EtO
EtO
OEt
OEt
EtO
EtO
OEt
OEt
OEt
a) or b) or c)
+
As reported in previous publications, acid-catalyzed
deprotection of the acetal function in 1 has so far been un-
successful. Although the reason for this is not fully under-
stood, a probable explanation can be that interactions
between the acetal moiety and the conjugated carbonyl
group render both sites so electron deficient that protona-
tion becomes less favorable. If this rationale is correct, the
carbonyl group in 1 should be more reactive towards nu-
cleophiles than the carbonyl group in alkanones. On this
basis we treated 1 with sodium hydroxide at room temper-
ature, and to our satisfaction cleavage of the bond between
the carbonyl group and the ethynyl moiety took place and
afforded 2,2-diethoxyacetic acid (8) in 86% yield
(Scheme 6). This transformation should lead to ethyne
formation, and in accordance with this, bubbling was ob-
served during the course of the reaction. No attempts were
made to trap ethyne, though.
O
O
O
1
6
7
33%
17%
48%
a) EtOH, reflux
b) NaOEt, EtOH, r.t.
c) EtOH, Et3N, r.t.
22%
66%
45%
Scheme 4 Ethanol addition to 1
The sluggish reaction clearly shows that ethanol is not nu-
cleophilic enough to react efficiently with 1, and if the
yield of 6 and/or 7 is to be improved, 1 should be reacted
with ethoxide instead. This reasoning appeared to be cor-
rect; when 1 was treated with an ethanol solution of sodi-
um ethoxide for a half an hour, the yield of 7 increased to
66%, whereas that of 6 dropped to 17% (Scheme 4, meth-
od b).
The final set of conditions that led to Michael addition of
ethanol to 1 was stirring of the conjugated ketone at room
temperature in a mixture of anhydrous triethylamine and
anhydrous ethanol. After three hours all the starting mate-
rial had been consumed (TLC) and 6 and 7 were isolated
Unsaturated ketone 1 was also treated with a saturated
aqueous sodium bicarbonate solution, which is less basic
and less reactive than aqueous sodium hydroxide. The re-
action was followed by TLC, and when all the starting
material had been consumed (r.t., 12 h) the reaction was
Synthesis 2011, No. 23, 3899–3907 © Thieme Stuttgart · New York

3902
M. Sengee, L. K. Sydnes
PAPER
1. NaOH
clization and formation of heterocycles 10–12 became
possible only because the Z geometry of the primary prod-
uct enabled nucleophile Y to react with the carbonyl
group.
EtO
THF–H2O
O
OEt
OEt
OEt
2. H+
+
C2H2
HO
O
8
1
The fact that hydrazine and guanidine give aromatic prod-
ucts (a pyrazole derivative and a pyrimidine derivative,
respectively), whereas hydroxylamine does not is interest-
ing, but not really surprising. Such an outcome indicates
that the aromaticity of isoxazoles is significantly less than
that of pyrazoles and pyrimidines, and this is in accor-
dance with empirical resonance energy values published
by Katritzky et al.7 Dehydration of dihydroisoxazole 12 to
form the corresponding isoxazole should therefore not be
a favored reaction, and that was indeed the case. When 12
was refluxed in aqueous acetone under acidic conditions
(Dowex 50W), no product was detected even after 11
hours (TLC and NMR), and workup gave 12 in quantita-
tive yield.
Scheme 6 Disintegration of 1 under strong basic conditions
quenched by acid addition and workup followed. The re-
action mixture contained essentially one product only,
namely 1,3,5-tris(2,2-diethoxyacetyl)benzene (9), which
was isolated in 85% yield. The mechanism for this trans-
formation is currently under investigation.
Ketone 1 was also reacted with several compounds con-
taining more than one nucleophilic center, and these reac-
tions showed several characteristic features. Firstly, if the
centers were close to each other, either directly attached or
separated by one carbon atom, both the triple bond and the
carbonyl group were attacked, and this dual reactivity led
to the formation of cyclic structures (Scheme 7, com-
pounds 10–12). Secondly, if the nucleophiles are separat-
ed by two carbon atoms, only conjugate monoaddition
was observed; no double addition to the triple bond took
place (Scheme 7, compounds 13–16). The third trend was
revealed when the nucleophilic atoms were oxygen and
nitrogen. In this case, the more nucleophilic site, the ami-
no moiety, reacted first and gave the corresponding b-
amino-substituted a,b-unsaturated ketone 16 as the prima-
ry product by Michael addition.
When 1 was reacted with an equimolar amount of o-phe-
nylenediamine, monoaddition took place and a single
product, (Z)-4-(2-aminophenylamino)-1,1-diethoxybut-
3-en-2-one (13), formed and was isolated in 88% yield.
The product is apparently completely stable at room tem-
perature and no products due to subsequent reaction(s) of
13 with 1 were observed. However, when ethylenedi-
amine was reacted with 1 in a 1:1 ratio, products due to
both mono- and bis-addition were formed. The predomi-
nant product was monoadduct (Z)-4-(2-aminoethylami-
no)-1,1-diethoxybut-3-en-2-one (14), but a significant
amount of (3Z)-1,1-diethoxy-4-{2-[(Z)-4,4-diethoxy-3-
All amino moieties in the bis-nucleophilic reagents used
in this study are primary amines. Addition of these re-
agents to 1 are therefore expected to give the correspond-
ing alkenes with Z stereochemistry (vide supra), and this
was, indeed, the case. When 1 was treated with o-phe-
nylenediamine, ethylenediamine and 2-aminoethanol,
only Z-alkenes were detected and isolated. And when hy-
drazine, guanidine, and hydroxylamine were used, cy-
oxobut-1-enylamino]ethylamino}but-3-en-2-one
(15),
the bis-adduct corresponding of 14, was also obtained.
The relative amount of 14 appeared to be sensitive to the
reaction conditions, in particular the time of reaction,
which indicates that the compound undergoes secondary
reactions. And indeed, analysis of 14 that had been stored
OEt
OEt
OEt
N
HN
HO
N
OEt
10 (90%)
H
OH
NH2NH2
O
H2N
16 (86%)
OEt
OEt
N
guanidine
O
OEt
OEt
H2N
N
NH2
EtO
EtO
1
H2N
O
OEt
OEt
H
N
11 (95%)
NH2OH
NH2
NH2
N
H
O
OEt
OEt
OH
12 (84%)
15
N
+
O
NH2
NH
OEt
OEt
O
H2N
N
OEt
OEt
H
O
13 (88%)
14
Scheme 7 Addition of compounds containing more than two nucleophilic centers to 1
Synthesis 2011, No. 23, 3899–3907 © Thieme Stuttgart · New York

PAPER
Michael Addition to 1,1-Diethoxybut-3-yn-2-one
3903
O
O
H
N
EtO
H
N
EtO
EtO
NH2
O
OEt
OEt
EtO
+
H
N
OEt
OEt
NH2
NH2
OEt
OEt
EtO
+
H2N
H2N
N
H2N
N
H
H
N
OEt
O
H
O
15
O
–
14
Scheme 8 Conversion of 14 into 15 under solvent-free conditions
Yield: 1.25 g (80%); yellow liquid.
The spectroscopic data were in accordance with those reported in
at room temperature for a few days revealed that the com-
pound had partly undergone disproportionation and been
converted into ethylenediamine and bis-adduct 15, for in- the literature.5a
stance as indicated in Scheme 8. If this secondary reaction
Compounds 4a–f by the Addition of Ammonia or Primary or
Secondary Amines to 1; General Procedure
were irreversible, 14 would be completely consumed after
a while, but since that did not occur, 14 must be formed in
another transformation. A likely candidate is conversion
of 15 into two equivalents of 14 by reaction with ethylene-
diamine, and, sure enough, when this reaction was carried
out, 14 was obtained. Thus, the disproportionation of 14
into 15 is a reversible reaction.
A round-bottom flask was charged with a soln of 1 (0.156 g, 1.00
mmol) in EtOH (5 mL) and the appropriate amine (1.00 mmol) was
added. NH3 and MeNH2 were added as 25% and 40% aq solns, re-
spectively, whereas the other amines were added as pure liquids.
The reaction mixture was stirred at r.t. for 45 min; EtOH was then
removed by evaporation on a rotary evaporator, and the resulting
crude product was purified by flash chromatography (silica gel,
hexanes–EtOAc, 4:1). Compounds 4a–f were prepared according to
this procedure.
In summary, 1,1-diethoxybut-3-yn-2-one generally gives
stereospecific products by monoaddition of nitrogen and
oxygen nucleophiles. In the case of ethanol, bis-addition
was also observed to some extent. The title compound is
quite reactive under various basic conditions and under-
goes either cleavage of the single bond between the triple
bond and the carbonyl groups or trimerization (to 5 or 9).
When bis-nucleophiles are applied, both the triple bond
and the carbonyl group are attacked. Hydrazine, guani-
dine, and hydroxylamine furnish heterocyclic products,
whereas diamines and ethanolamine give 4-substituted
1,1-diethoxybut-3-en-2-one derivatives with Z stereo-
chemistry.
(Z)-4-Amino-1,1-diethoxybut-3-en-2-one (4a)
Yield: 0.159 g (92%); yellowish oil.
IR (film): 3550–3000 (s), 3300 (s), 3209 (s), 2976 (s), 2930 (s),
2883 (s), 1645 (s), 1614 (s), 1504 (s), 1456 (s), 1392 (m), 1371 (s),
1290 (s), 1159 (s), 1109 (s), 1062 (s), 900 (m), 836 (m), 767 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 9.27 (br s, 1 H), 6.97 (m, 1 H),
5.47 (d, J = 7.6 Hz, 1 H), 5.29 (br s, 1 H), 4.66 (s, 1 H), 3.72–3.54
(m, 4 H), 1.25 (t, J = 7.0 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 195.1, 151.7, 101.9, 91.6, 62.3,
15.2.
HRMS (DART): m/z [M + H]+ calcd for C8H16NO3: 174.1149;
found: 174.1135.
Melting points were determined on a Gallenkamp apparatus and are
uncorrected. IR spectra were recorded on a Nicolet Impact 410 IR
spectrophotometer, in most cases with the compound as a film be-
tween two NaCl plates. NMR spectra were run on a Bruker Spectro-
spin DMX 400 spectrophotometer. Chemical shifts are reported
downfield from TMS. TLC analyses of the reaction mixtures were
performed on silica gel (60 F254) on aluminum sheets with mixtures
of EtOAc and isomeric hexanes as the mobile phase. Flash chroma-
tography was carried out with silica gel (230–400 mesh) as the sta-
tionary phase and mixtures of EtOAc and isomeric hexanes as the
mobile phase; the eluent composition is given for each of the isola-
tions described below. Mass spectra were obtained on a JEOL
AccuTOF T100GC spectrometer operated in the DART+ mode at
10–15 eV.
(Z)-1,1-Diethoxy-4-(methylamino)but-3-en-2-one (4b)
Yield: 0.178 g (95%); slightly yellow liquid.
IR (film): 3550–3100 (s), 3069 (m), 2975 (s), 2930 (s), 2883 (s),
1645 (s), 1565 (s), 1503 (s), 1429 (s), 1372 (s), 1293 (s), 1240 (m),
1094 (s), 1052 (s), 976 (w), 955 (w), 881 (m), 840 (w), 798 (m), 763
(m) cm–1.
1H NMR (400 MHz, CDCl3): d = 9.91 (br s, 1 H), 6.85 (dd, J = 12.9
Hz, 7.3 Hz, 1 H), 5.39 (d, J = 7.3 Hz, 1 H), 4.66 (s, 1 H), 3.74–3.52
(m, 4 H), 3.03 (d, J = 5.0 Hz, 3 H), 1.24 (t, J = 7.0 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 193.6, 156.3, 102.2, 89.8, 62.5,
35.6, 15.4.
HRMS (DART): m/z [M + H]+ calcd for C9H18NO3: 188.1286;
found: 188.1297.
1,1-Diethoxybut-3-yn-2-one (1)
PTSA·xH2O (0.760 g, 4.0 mmol) was added to a soln of 3,3,4,4-tet-
raethoxybutyne (TEB; 2.3 g, 10.0 mmol) in a THF–H2O mixture
(7:3; 50 mL) and the mixture was heated at reflux for 4 h. The reac-
tion mixture was then allowed to cool to r.t. H2O (30 mL) and
CH2Cl2 (40 mL) were added and the organic and aqueous layers
were separated. The aqueous layer was extracted with CH2Cl2
(2 × 30 mL) and the combined organic phases were dried (MgSO4)
and filtered. The mixture was evaporated on a rotary evaporator.
The crude product was purified by flash chromatography (silica gel,
hexanes–EtOAc, 9:1).
E/Z Isomeric Mixture of 1,1-Diethoxy-4-(phenylamino)but-3-
en-2-one (4c)
Yield: 0.224 g (90%); yellow oil.
1H NMR (400 MHz, CDCl3): d = 11.76 (br d, J ª 12–12.5 Hz, 1 H),
8.20 (unresolved dd, seemingly a t with J ª 12.9 Hz) and 7.44 (dd,
J = 12.5 Hz, 7.8 Hz, 1 H, ratio 1:11), 7.35–7.30 (m, 2 H), 7.10–7.00
(m, 3 H), 5.97 (d, J = 13.0 Hz) and 5.70 (d, J = 7.8 Hz, 1 H, ratio
1:10), 4.74 and 4.70 (2s, 1 H, ratio 9.5:1), 3.76–3.58 (m, 4 H), 1.29–
1.25 (m, 6 H).
Synthesis 2011, No. 23, 3899–3907 © Thieme Stuttgart · New York

3904
M. Sengee, L. K. Sydnes
PAPER
(Z)-4c
1-[2,4-Bis(diethoxymethyl)-2,4-diethynyl-4H-1,3-dioxin-5-yl]-
2,2-diethoxyethanone (5)
The reaction was repeated according to the general procedure, but
after 45 min, H2O was added to the product mixture before workup
was carried out by extraction (CH2Cl2), drying (MgSO4), filtration,
evaporation (rotary evaporator), and flash chromatography (silica
gel, hexanes–EtOAc, 4:1).
By reaction of 1 with Et3N: Et3N (0.101 g, 1.00 mmol) was added
dropwise to 1 (0.156 g, 1.00 mmol) dissolved in anhyd Et2O (10
mL), and the mixture was stirred at r.t. for 8 h. H2O (10 mL) was
added and the organic layer was separated. The aqueous layer was
extracted with Et2O (2 × 10 mL) and the combined organic layers
were dried (MgSO4), filtered, and subsequently concentrated on a
rotary evaporator. The crude product was purified by a flash chro-
matography (silica gel, hexanes–EtOAc, 4:1) to give a diastereo-
meric mixture of 5.
Yield: 0.222 g (89%); yellow oil.
IR (film): 3350–3150 (m), 3064 (m), 3038 (m), 2975 (s), 2929 (s),
2880 (s), 1643 (s), 1598 (s), 1573 (s), 1507 (s), 1480 (s), 1453 (m),
1367 (m), 1318 (s), 1282 (s), 1223 (s), 1179 (m), 1157 (s), 1102 (s),
1064 (s), 907 (m), 844 (w), 784 (m), 754 (s), 690 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.44 (dd, J = 12.5 Hz, 7.8 Hz, 1
H), 7.35–7.30 (m, 2 H), 7.08–7.04 (m, 3 H), 5.70 (d, J = 7.8 Hz, 1
H), 4.74 (s, 1 H), 3.76–3.58 (m, 4 H), 1.29–1.25 (m, 6 H).
13C NMR (100 MHz, CDCl3): d = 195.3, 145.9, 140.2, 129.9, 124.1,
116.6, 102.1, 93.2, 62.7, 15.4.
HRMS (DART): m/z [M + H]+ calcd for C14H20NO3: 250.1443;
found: 250.1440.
Yield: 0.083 g (53%).
By reaction of 1 with NaH: NaH (60% suspension| in mineral oil;
0.040 g, 1.0 mmol) was rinsed with pentane (1 mL) and the resulting
white solid was mixed with anhyd THF (4 mL). A soln of 1 (0.156
g, 1.00 mmol) in anhyd THF (1 mL) was then added in one portion
to the NaH suspension and the resulting mixture was stirred at r.t.
for 2 h. H2O (10 mL) and CH2Cl2 (10 mL) were added and the phas-
es were separated. The aqueous layer was extracted with CH2Cl2
(2 × 10 mL) and the combined organic phases were dried (MgSO4),
filtered, and subsequently concentrated on a rotary evaporator. The
crude product was purified by a flash chromatography (silica gel,
hexanes–EtOAc, 4:1) to give a diastereomeric mixture of 5.
(E)-4-(Diethylamino)-1,1-diethoxybut-3-en-2-one (4d)
Yield: 0.201 g (88%); yellowish liquid.
IR (film): 3100 (w), 2975 (s), 2932 (s), 2876 (s), 1656 (s), 1567 (s),
1467 (s), 1445 (s), 1380 (s), 1363 (s), 1316 (s), 1282 (s), 1174 (m),
1099 (s), 1065 (s), 1010 (s), 959 (m), 917 (m), 899 (m), 790 (m),
778 (m), 670 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.74 (d, J = 12.8 Hz, 1 H), 5.44 (d,
J = 12.8 Hz, 1 H), 4.66 (s, 1 H), 3.75–3.53 (m, 4 H), 3.32–3.24 (m,
4 H), 1.27–1.18 (m, 12 H).
13C NMR (100 MHz, CDCl3): d = 192.0, 152.5, 103.2, 90.5, 62.6,
50.4, 42.6, 15.2, 14.7, 11.5.
HRMS (DART): m/z [M + H]+ calcd for C12H24NO3: 230.1756;
found: 230.1762.
Yield: 0.067 g (43%); yellowish oil.
IR (film): 3300–3150 (s), 3107 (w), 2978 (s), 2931 (s), 2884 (s),
2122 (m), 1701 (s), 1660 (s), 1628 (s), 1481 (m), 1445 (m), 1373 (s),
1330 (s), 1293 (m), 1242 (s), 1102 (s), 1073 (s), 1013 (s), 910 (m),
819 (m), 777 (m), 752 (m), 655 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 6.11 and 6.02 (2s, 1 H, ratio 7:3),
4.75 (s, 1 H), 4.57 and 4.56 (2s, 1 H, ratio 3:7), 4.54 and 4.53 (2s, 1
H, ratio 7:3), 3.92–3.55 (m, 12 H), 2.74 and 2.73 (2s, 1 H, ratio 7:3),
2.68 and 2.62 (2s, 1 H, ratio 7:3), 1.30–1.19 (m, 18 H).
13C NMR (100 MHz, CDCl3): d = 192.2 and 192.1, (stronger (s) and
weaker (w), respectively) 162.4 and 162.2 (w and s), 108.3 and
107.4 (w and s), 104.0 and 103.6 (w and s), 102.7 and 102.6 (w and
s), 102.1, 96.0, 84.6 and 83.1 (w and s), 79.0 and 78.6 (w and s),
76.7, 75.7, 66.7 and 66.6 (s and w), 66.1, 65.6, 65.4, 65.3, 65.2,
63.0, 62.8, 15.4, 15.3, 15.2.
(E)-1,1-Diethoxy-4-(pyrrolidin-1-yl)but-3-en-2-one (4e)
Yield: 0.209 g (92%); yellowish liquid.
IR (film): 3110 (w), 2975 (s), 2929 (s), 2874 (s), 1652 (s), 1571 (s),
1481 (s), 1458 (s), 1421 (m), 1366 (s), 1339 (s), 1309 (s), 1269 (s),
1225 (m), 1172 (m), 1139 (s), 1103 (s), 1062 (s), 911 (m), 867 (m),
785 (m), 698 (m) cm–1.
HRMS (DART): m/z [M – EtO]+ calcd for C22H31O8: 423.2019;
found: 423.2023.
1H NMR (400 MHz, CDCl3): d = 7.94 (d, J = 12.7 Hz, 1 H), 5.33 (d,
J = 12.7 Hz, 1 H), 4.67 (s, 1 H), 3.73–3.58 (m, 4 H), 3.51 (t, J = 6.7
Hz, 2 H), 3.23 (t, J = 6.8 Hz, 2 H), 2.02–1.90 (m, 4 H), 1.25 (t,
J = 7.0 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 191.9, 150.2, 103.3, 91.1, 62.8,
52.5, 47.1, 25.4, 25.3, 15.4.
Compounds 6 and 7 by Ethanol Addition to 1
Method A: Compound 1 (0.156 g, 1.00 mmol) and EtOH (25 mL)
were mixed in a round-bottom flask with a condenser and the mix-
ture was heated at reflux for 12 h. The product mixture was then
cooled to r.t. EtOH was then evaporated on a rotary evaporator and
the resulting crude product was purified by flash chromatography
(silica gel, hexanes–EtOAc, 9:1).
HRMS (DART): m/z [M + H]+ calcd for C12H22NO3: 228.1560;
found: 228.1570.
Yield: (E)-6: 0.067 g (33%); 7: 0.055 g (22%).
Method B: A round-bottom flask was charged with 1 (0.156 g, 1.00
mmol), EtOH (5 mL), and NaOEt (0.054 g, 1.0 mmol). The result-
ing yellow mixture was stirred at r.t. for 30 min. The reaction was
quenched by the addition of H2O (10 mL) and the mixture was then
extracted with CH2Cl2 (3 × 10 mL). The combined organic layers
were dried (MgSO4) and concentrated under vacuum. The crude
product was purified by flash chromatography (silica gel, hexanes–
EtOAc, 9:1).
(E)-1,1-Diethoxy-4-(piperidin-1-yl)but-3-en-2-one (4f)
Yield: 0.217 g (90%); yellowish liquid.
IR (film): 3121 (m), 2974 (s), 2937 (s), 2897 (s), 2858 (s), 1655 (s),
1568 (s), 1450 (s), 1342 (m), 1327 (m), 1277 (s), 1253 (s), 1202 (s),
1162 (m), 1102 (s), 1063 (s), 1029 (s), 1003 (s), 953 (m), 905 (m),
855 (m), 823 (m), 780 (m), 671 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.69 (d, J = 12.8 Hz, 1 H), 5.47 (d,
J = 12.8 Hz, 1 H), 4.65 (s, 1 H), 3.73–3.56 (m, 4 H), 3.34–3.26 (m,
4 H), 1.66–1.61 (m, 6 H), 1.25 (t, J = 7.0 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 192.9, 153.7, 103.8, 90.1, 63.3,
55.6, 46.8, 27.1, 25.5, 24.6, 15.9.
HRMS (DART): m/z [M + H]+ calcd for C13H24NO3: 242.1756;
Yield: 6: 0.034 g (17%); 7: 0.164 g (66%).
Method C: A round-bottom flask was charged with 1 (0.156 g, 1.00
mmol) in EtOH (5 mL) and Et3N (1 mmol, 0.101 g). The resulting
mixture was stirred at r.t. for 3 h. Workup was as described for
method A.
found: 242.1771.
Yield: 6: 0.097 g (48%); 7: 0.112 g (45%).
Synthesis 2011, No. 23, 3899–3907 © Thieme Stuttgart · New York

PAPER
Michael Addition to 1,1-Diethoxybut-3-yn-2-one
3905
(E)-1,1,4-Triethoxybut-3-en-2-one (6)
Colorless liquid.
1H NMR (400 MHz, CDCl3): d = 9.10 (s, 3 H), 5.25 (s, 3 H), 3.84–
3.60 (m, 12 H), 1.28–1.22 (m, 18 H).
IR (film): 3095 (w), 2979 (s), 2931 (s), 2887 (s), 1692 (s), 1658 (s),
1633 (s), 1616 (s), 1475 (s), 1446 (s), 1396 (s), 1371 (s), 1312 (s),
1238 (s), 1156 (s), 1097 (s), 1061 (s), 904 (s), 846 (s), 816 (s), 752
(w), 676 (s), 644 (m), 626 (m) cm–1.
1H NMR (400 MHz, CDCl3): d =7.79 (d, J = 12.7 Hz, 1 H), 5.89 (d,
J = 12.7 Hz, 1 H), 4.66 (s, 1 H), 3.98 (q, J = 7.0 Hz, 2 H), 3.75–3.54
(m, 4 H), 1.36 (t, J = 7.0 Hz, 3 H), 1.26–1.23 (m, 6 H).
13C NMR (100 MHz, CDCl3): d = 194.8, 164.4, 102.9, 101.1, 67.4,
63.1, 15.3, 14.6.
HRMS (DART): m/z [M + H]+ calcd for C10H19O4: 203.1283;
found: 203.1279.
13C NMR (100 MHz, CDCl3): d = 192.7, 135.4, 134.2, 102.7, 63.5,
15.2.
HRMS (DART): m/z [M – EtO]+ calcd for C22H31O8: 423.2019;
found: 423.2019.
3-(Diethoxymethyl)-1H-pyrazole (10)
A 55% aq soln of hydrazine (0.058 g, 1.0 mmol) was added to a soln
of 1 (0.156 g, 1.00 mmol) in THF (5 mL). The mixture was stirred
at r.t. for 1 h. H2O (10 mL) and CH2Cl2 (20 mL) were added and the
organic layer was separated. The aqueous layer was extracted with
CH2Cl2 (2 × 15 mL) and the combined organic layers were dried
(MgSO4), filtered, and concentrated on a rotary evaporator.
Yield: 0.153 g (90%); slightly yellow liquid.
1,1,4,4-Tetraethoxybutan-2-one (7)
Colorless liquid.
IR (film): 3400–2900 (s), 3165 (s), 3063 (s), 2976 (s), 2931 (s),
2750 (s), 2687 (m), 1635 (w), 1540 (m), 1481 (s), 1445 (s), 1375 (s),
1336 (s), 1299 (m), 1278 (m), 1200 (s), 1162 (s), 1122 (s), 1116 (s),
1058 (s), 1032 (s), 1011 (s), 935 (s), 911 (s), 847 (s), 828 (s), 771
(s), 679 (w), 669 (w), 619 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.56 (d, J = 2.0 Hz, 1 H), 6.35 (d,
J = 2.0 Hz, 1 H), 5.69 (s, 1 H), 3.70–3.56 (m, 4 H), 1.24 (t, J = 7.1
Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 135.0, 134.9, 103.7, 97.0, 61.3,
15.4.
HRMS (DART): m/z [M + H]+ calcd for C8H15N2O2: 171.1134;
found: 171.1126.
IR (film): 2978 (s), 2932 (s), 2884 (s), 1736 (s), 1593 (m), 1481 (m),
1446 (m), 1374 (s), 1345 (s), 1321 (s), 1263 (m), 942 (w), 906 (m),
844 (m), 817 (w), 793 (w) cm–1.
1H NMR (400 MHz, CDCl3): d = 5.00 (t, J = 5.7 Hz, 1 H), 4.60 (s,
1 H), 3.69–3.54 (m, 8 H), 2.93 (d, J = 5.7 Hz, 2 H), 1.26–1.17 (m,
12 H).
13C NMR (100 MHz, CDCl3): d = 203.0, 102.5, 99.6, 63.2, 62.2,
42.5, 15.4, 15.3.
HRMS (DART): m/z [M – EtO]+ calcd for C10H19O4: 203.1283;
found: 203.1292.
2,2-Diethoxyacetic Acid (8)
2-Amino-4-(diethoxymethyl)pyrimidine (11)
A 50% aq soln of NaOH (0.16 g, 2.0 mmol) was added to 1 (0.312
g, 2.00 mmol) dissolved in a THF–H2O mixture (3:1; 16 mL) and
the reaction mixture was stirred at r.t. for 12 h. H2O (20 mL) and
CH2Cl2 (20 mL) were added and the organic layer was separated.
The aqueous layer was then acidified with dilute H2SO4 to pH ~1
and extracted with EtOAc (2 × 20 mL). The combined extracts were
dried (MgSO4) and concentrated on a rotary evaporator to furnish 8.
The NMR data were in accordance with those reported in the liter-
ature.8
A 60% NaH dispersion in oil (0.040 g, 1.0 mmol) was washed with
hexane and added to a round-bottom flask where guanidine hydro-
chloride (0.096 g, 1.0 mmol) dissolved in EtOH (5 mL) was kept
under N2. The mixture was stirred at r.t. for 15 min and 1 (0.156 g,
1.00 mmol) in EtOH (1 mL) was then added. The mixture was
stirred during the addition and subsequently at r.t. for 45 min. EtOH
was then evaporated on a rotary evaporator and the resulting solid
product was recrystallized from EtOH.
Yield: 0.187 g (95%); white solid; mp 125–126 °C.
Yield: 0.254 g (86%); colorless liquid.
IR (KBr): 3600–3100 (s), 3322 (s), 3192 (s), 2979 (s), 2966 (s),
2926 (s), 2908 (s), 2898 (s), 2878 (s), 2779 (m), 2102 (w), 1998 (w),
1914 (w), 1644 (s), 1575 (s), 1488 (s), 1475 (s), 1450 (s), 1397 (s),
1367 (m), 1354 (s), 1346 (s), 1321 (s), 1209 (s), 1160 (m), 1138 (s),
1124 (s), 1116 (s), 1107 (s), 1063 (s), 1039 (s), 1015 (s), 917 (m),
881 (w), 843 (s), 796 (s), 768 (w), 732 (m), 646 (s), 634 (m), 536
(m), 464 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = 8.32 (d, J = 5.0 Hz, 1 H), 6.88 (d,
J = 5.0 Hz, 1 H), 5.28 (br s, 2 H), 5.22 (s, 1 H), 3.69–3.58 (m, 4 H),
1.25 (t, J = 7.0 Hz, 6 H).
IR (film): 3550–2500 (s), 2981 (s), 2933 (s), 2903 (s), 2629 (m),
2557 (m), 1740 (s), 1481 (m), 1445 (s), 1378 (s), 1336 (s), 1240 (s),
1166 (s), 1121 (s), 1070 (s), 948 (m), 886 (m), 845 (m), 778 (m),
659 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = 4.97 (s, 1 H), 3.76–3.66 (m, 4 H),
1.27 (t, J = 7.0 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 170.8, 97.1, 63.0, 15.1.
HRMS (DART): m/z [M + H]+ calcd for C6H13O4: 149.0814; found:
149.0821.
13C NMR (100 MHz, CDCl3): d = 167.9, 163.6, 159.7, 109.2, 101.8,
62.7, 15.8.
1,3,5-Tris(2,2-diethoxyacetyl)benzene (9)
Sat. aq NaHCO3 (10 mL) was added to 1 (0.156 g, 1.0 mmol) dis-
solved in THF (30 mL) and the mixture was stirred at r.t. for 12 h.
H2O (20 mL) and CH2Cl2 (20 mL) were added and the organic layer
was separated. The aqueous layer was extracted with CH2Cl2
(2 × 20 mL) and the combined organic layers were dried (MgSO4),
concentrated on a rotary evaporator, and then purified by flash chro-
matography (silica gel, hexanes–EtOAc, 9:1).
HRMS (DART): m/z [M + H]+ calcd for C9H16N3O2: 198.1242;
found: 198.1226.
5-(Diethoxymethyl)-5-hydroxy-4,5-dihydroisoxazole (12)
A 50% aq soln of NH2OH (0.066 g, 1.00 mmol) was added to a soln
of 1 (0.156 g, 1.00 mmol) and THF (5 mL) and the mixture was
stirred at r.t. for 1 h. EtOH was then removed on a rotary evaporator
and the resulting crude product was purified by flash chromatogra-
phy (silica gel, hexanes–EtOAc, 1:1).
Yield: 0.133 g (85%); colorless oil.
IR (film): 3094 (w), 2978 (s), 2932 (m), 2887 (s), 1696 (s), 1590 (s),
1484 (m), 1445 (s), 1373 (s), 1320 (s), 1252 (s), 1163 (s), 1109 (s),
1062 (s), 907 (s), 739 (m), 646 (s) cm–1.
Yield: 0.159 g (84%); colorless liquid.
Synthesis 2011, No. 23, 3899–3907 © Thieme Stuttgart · New York

3906
M. Sengee, L. K. Sydnes
PAPER
IR (film): 3590–3050 (s), 3077 (m), 2978 (s), 2932 (s), 2888 (s),
1607 (m), 1481 (m), 1446 (s), 1418 (s), 1372 (s), 1332 (s), 1287 (s),
1163 (s), 1068 (s), 967 (s), 868 (s), 832 (s), 801 (s), 764 (m) cm–1.
13C NMR (100 MHz, CDCl3): d = 193.8, 155.5, 102.2, 90.0, 62.6,
52.7, 42.8, 15.4.
Compound 15
Yield: 0.100 g (54%); brown solid; mp 119–120 °C.
1H NMR (400 MHz, CDCl3): d = 7.22 (dd, J = 1.8, 1.4 Hz, 1 H),
4.59 (s, 1 H), 3.87–3.59 (m, 5 H), 3.18–3.13 (dd, J = 18.5, 1.4 Hz,
1 H), 2.95–2.20 (dd, J = 18.5, 1.8 Hz, 1 H), 1.29–1.22 (m, 6 H).
13C NMR (100 MHz, CDCl3): d = 147.1, 105.6, 102.3, 65.2, 64.2,
42.9, 15.5, 15.4.
HRMS (DART): m/z [M + H]+ calcd for C8H16NO4: 190.1079;
found: 190.1071.
IR (KBr): 3300–3100 (m), 2975 (s), 2929 (s), 2872 (s), 1633 (s),
1565 (s), 1488 (s), 1455 (s), 1380 (s), 1318 (s), 1267 (s), 1230 (s),
1160 (s), 1129 (s), 1067 (s), 997 (s), 924 (s), 814 (s), 790 (s), 760 (s)
cm–1.
1H NMR (400 MHz, CDCl3): d = 9.96 (br s, 2 H), 6.77 (dd, J = 12.5,
7.4 Hz, 2 H), 5.39 (d, J = 7.4 Hz, 2 H), 4.65 (s, 2 H), 3.72–3.53 (m,
8 H), 3.37–3.35 (m, 4 H), 1.25–1.21 (m, 12 H).
13C NMR (100 MHz, CDCl3): d = 194.2, 155.0, 101.9, 90.9, 62.4,
50.1, 15.4.
HRMS (DART): m/z [M – EtO]+ calcd for C16H27N2O5: 327.1920;
found: 327.1924.
Isoxazoline 12 (0.113 g, 0.56 mmol) was dissolved in a 95:5 mix-
ture of acetone and H2O (10.5 mL). Dowex 50W (0.200 g) was add-
ed to the soln and the mixture was refluxed for 11 h. The reaction
mixture was allowed to cool to r.t. Dowex 50W was removed by fil-
tration and the acetone was evaporated on a rotary evaporator. The
residue was dissolved in CH2Cl2 (20 mL) and H2O (10 mL) and the
organic layer was separated. The aqueous layer was extracted with
CH2Cl2 (2 × 10 mL) and the combined organic layers were dried
(MgSO4). The removal of the solvent on a rotary evaporator gave
12. Yield: 0.111 g (98%); colorless liquid.
Compound 14 from 15
A soln of 15 (0.037 g, 0.1 mmol) in EtOH (1 mL) was mixed with
ethylenediamine (0.006 g, 0.1 mmol) and the resulting mixture was
stirred at r.t. for 30 min. The solvent was removed under reduced
pressure and the crude reaction mixture was analyzed by 1H NMR
spectroscopy. The analysis revealed that a reaction had taken place
and the crude product contained a 5:6 mixture of 14 and unchanged
15 (ratio based on integration of relevant NMR peaks).
(Z)-4-(2-Aminophenylamino)-1,1-diethoxybut-3-en-2-one (13)
Compound 1 (0.156 g, 1.00 mmol) was added to a soln of o-phe-
nylenediamine (0.108 g, 1.00 mmol) in EtOH (5 mL) and the mix-
ture was stirred at r.t. for 1 h. The solvent was removed on a rotary
evaporator and the resulting crude product was purified by flash
chromatography (silica gel, hexanes–EtOAc, 7:3).
(Z)-1,1-Diethoxy-4-(2-hydroxyethylamino)but-3-en-2-one (16)
Ethanolamine (0.061 g, 1.00 mmol) was added to a soln of 1 (0.156
g, 1.00 mmol) in EtOH (5 mL) and the reaction mixture was stirred
at r.t. for 1 h. EtOH was removed on a rotary evaporator and the re-
sulting crude product was purified by flash chromatography (silica
gel, hexanes–EtOAc, 6:4).
Yield: 0.232 g (88%); yellowish liquid.
IR (film): 3500–3100 (s), 3430 (s), 3247 (s), 3069 (m), 3041 (m),
2975 (s), 2928 (s), 2881 (s), 1644 (s), 1595 (s), 1567 (s), 1508 (s),
1477 (s), 1463 (s), 1368 (s), 1321 (s), 1285 (s), 1206 (s), 1158 (s),
1102 (s), 1061 (s), 909 (s), 839 (m), 746 (s), 695 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.40 (dd, J = 12.5, 7.6 Hz, 1 H),
7.06–6.96 (m, 2 H), 6.83–6.77 (m, 2 H), 5.73 (d, J = 15.3 Hz, 1 H),
4.77 (s, 1 H), 3.77–3.59 (m, 6 H), 1.29–1.25 (m, 6 H).
13C NMR (100 MHz, CDCl3): d = 195.0, 148.3, 137.4, 128.3, 125.8,
120.1, 118.1, 117.4, 102.1, 93.4, 62.7, 15.4.
HRMS (DART): m/z [M – EtO]+ calcd for C12H15N2O2: 219.1133;
found: 219.1128.
Yield: 0.187 g (86%); colorless liquid.
IR (film): 3640–3000 (s), 3066 (m), 2975 (s), 2931 (s), 2880 (s),
1641 (s), 1558 (s), 1497 (s), 1447 (s), 1371 (s), 1290 (s), 1223 (m),
1160 (s), 1102 (s), 1060 (s), 962 (w), 910 (m), 842 (m), 765 (m), 673
(m) cm–1.
1H NMR (400 MHz, CDCl3): d = 10.1 (s, 1 H), 6.94 (dd, J = 12.8,
7.3 Hz, 1 H), 5.39 (d, J = 7.3 Hz, 1 H), 4.66 (s, 1 H), 3.74–3.55 (m,
6 H), 3.40–3.36 (m, 2 H), 3.14 (br s, 1 H), 1.24 (t, J = 7.0 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 193.6, 155.9, 102.0, 90.1, 62.7,
(Z)-4-(2-Aminoethylamino)-1,1-diethoxybut-3-en-2-one (14)
and (Z)-1,1-Diethoxy-4-{2-[(Z)-4,4-diethoxy-3-oxobut-1-enyl-
amino]ethylamino}but-3-en-2-one (15)
62.5, 62.2, 51.6, 15.4, 15.3.
HRMS (DART): m/z [M + H]+ calcd for C10H20NO4: 218.1392;
A soln of 1 (0.156 g, 1.00 mmol) in EtOH (5 mL) was added drop-
wise to ethylenediamine (0.060 g, 1.0 mmol) in EtOH (2 mL) for 30
min and the reaction mixture was stirred at r.t. for 15 min. The crude
product, which showed two clearly distinct spots on TLC (CHCl3–
MeOH, 9:1; Rf = 0.25 and 0.10) was concentrated on a rotary evap-
orator and the resulting brownish viscous liquid was purified by
flash chromatography (silica gel, CHCl3–MeOH, 9:1); this gave 15
as a brown solidand 14 as a slightly yellow liquid. The latter product
did not remain in the liquid state for a long time; shortly after re-
moval of the eluent, the compound solidified to a yellowish solid.
found: 218.1387.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgement
Financial support from The Norwegian Centre for International Co-
operation in Higher Education (SIU) (to MS) is acknowledged with
considerable appreciation. The Research Council of Norway
through the Research Programme for Catalysis and Synthetic Orga-
nic Chemistry (KOSK) is acknowledged with gratitude. Further-
more, support from Norsk Hydro to purchase chemicals is highly
appreciated. Valuable comments from the referees are very much
appreciated.
Compound 14
Yield: 0.085 g (39%); yellowish solid.
1H NMR (400 MHz, CDCl3): d = 10.01 (br s, 1 H), 6.90 (dd,
J = 12.8, 7.4 Hz, 1 H), 5.40 (d, J = 7.4 Hz, 1 H), 4.67 (s, 1 H), 3.72–
3.53 (m, 4 H), 3.31–3.26 (m, 2 H), 2.87 (t, J = 6.0 Hz, 2 H), 2.75 (br
s, 1 H), 1.26–1.22 (m, 6 H).
Synthesis 2011, No. 23, 3899–3907 © Thieme Stuttgart · New York

PAPER
Michael Addition to 1,1-Diethoxybut-3-yn-2-one
(5) (a) Sydnes, L. K.; Holmelid, B.; Kvernenes, O. H.;
3907
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