Oxidative amidation of activated alkenes using Pd(OAc)2 as a catalyst precursor

Article abstract of DOI:10.1002/ejoc.201000384

A new "chloride-free" protocol was developed for oxidative amidation reactions between cyclic and acyclic amides and carbamates with activated olefins, conducted under Pd/Cu catalysis, using air as a terminal oxidant. The presence of TsOH is important for

Full text of DOI:10.1002/ejoc.201000384

FULL PAPER
DOI: 10.1002/ejoc.201000384
Oxidative Amidation of Activated Alkenes Using Pd(OAc)2 as a Catalyst
Precursor
Xinzhu Liu[a] and King Kuok (Mimi) Hii*[a]
Keywords: Homogeneous catalysis / Palladium / Amides / Alkenes / Enamines
A new “chloride-free” protocol was developed for oxidative
amidation reactions between cyclic and acyclic amides and
carbamates with activated olefins, conducted under Pd/Cu
catalysis, using air as a terminal oxidant. The presence of
TsOH is important for catalytic activity. The scope of the reac-
tion includes the addition of primary amides, carbamates, as
well as cyclic oxazolidinone and pyrrolidinone. The reactions
are found to be sensitive to steric demand of the N-nucleo-
phile, and E-selectivity can be achieved exclusively with cy-
clic N-nucleophiles. The products can be easily hydroge-
nated to afford the saturated product in high yields.
triflate at room temperature,[4b] or pTsOH under high pres-
sure.[4c] In comparison, hydroamidation reactions of α,β-
unsaturated esters require much harsher conditions; only
reported to occur at 130 °C under microwave irradiation, in
the presence of K2CO3 and tetra-n-butylammonium bro-
mide as a phase-transfer reagent.[5]
Introduction
Under certain conditions, Pd-catalysed addition of N–H
to C=C bonds can proceed via hydroamination or oxidative
amination pathways, to give amine or enamine products,
respectively.[1] Previously, we reported the use of dicationic
palladium(II) catalysts for the addition of aliphatic and aro-
matic amines to electron-deficient olefins; see Scheme 1 and
Equation (1)].[2] Prior to that, the synthesis of enamines
from reactions of olefins and secondary aromatic amines
had been reported by Hegedus and co-workers, by using a
neutral PdII catalyst and benzoquinone as an oxidant; see
Scheme 1 and Equation (2).[3]
On the other hand, oxidative amidation of electron-de-
ficient alkenes (including enones, as well as α,β-unsaturated
esters, amides and nitriles) can be achieved by Pd catalysis.
In the presence of a CuCl co-catalyst, O2 may be employed
as the terminal oxidant, effectively replacing the need for
stoichiometric oxidants such as 1,4-benzoquinone or per-
oxides (Scheme 2). First examples of these reactions were
provided by Hosokawa and Murahashi,[6] where cyclic car-
bamates and amides reacted with electron-deficient alkenes
to give E-enamides, whilst the reaction of acyclic methyl
carbamate was much slower, giving a mixture of E/Z iso-
mers. In some reactions, the addition of (highly toxic)
HMPA is necessary. More recently, a very similar protocol
has been reported for the addition of primary amides to
electron-deficient alkenes.[7] In these reactions, tetraethyl-
methylenediphosphonate (TEMDP) replaces HMPA as an
additive. Although Z-enamides were obtained as predomi-
nant products in moderate to good yields, reactions of cy-
clic N–H substrates was not described.
Scheme 1. Pd-catalysed oxidative hydroamination of electron-de-
ficient olefins (Z = CN, CO2Me).
As amides are substantially less nucleophilic than
amines, their direct addition to activated alkenes (hydro-
amidation) does not occur easily; reactions are largely lim-
ited to additions to activated α,β-unsaturated enones, which
could be catalysed by [PdCl2(NCPh)2] at 60 °C,[4a] vanadyl
[a] Department of Chemistry, Imperial College London,
Exhibition Road, South Kensington, London SW7 2AZ, U.K.
E-mail: mimi.hii@imperial.ac.uk
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000384.
Scheme 2. Pd-catalysed oxidative amidation of activated alkenes.
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X. Liu, K. K. Hii
FULL PAPER
In both of these reactions, PdCl2 precursors were used.
A general catalytic cycle was proposed (Scheme 3),[7] where
the alkene was activated by η2-coordination to the metal
centre. This allows C–N bond formation to occur via nucleo-
philic attack of the amide. Following β-hydride elimination
and release of the enamide product, the PdII precursor is
regenerated by copper(II), which is, in turn, re-oxidised
aerobically.
Scheme 4. Reaction of benzamide and butyl acrylate under Pd-cat-
alysed oxidative coupling conditions.
vious reports,[9] TsOH is most likely acting as a ligand and/
or counteranion in the process, having the unique ability to
stabilise Pd under oxidative conditions. The preparation
and use of isolated Pd(OTs)2 as a catalytic precursor for C–
H activation reactions had been described.[10]
Scheme 3. Proposed catalytic cycle.
The oxidative amidation reaction formally substitutes a
C–H bond of an alkene by a C–N bond, generating water
as the only by-product. Given that pre-activation of the al-
kene is not required, it is a more attractive strategy for en-
amide synthesis than cross-coupling reactions, where
amides and alkenyl halides/boronic acids were employed in
the presence of Cu or Pd catalysts.[8] Herein, we describe a
new catalytic protocol that allows oxidative amidation reac-
tions to be conducted in open air. In contrast to previous
reports, the procedure utilises Pd(OAc)2 as a catalyst pre-
cursor and TsOH as an additive, effectively offering “chlo-
ride-free” conditions. The new procedure allows acyclic and
cyclic amides, carbamates and imides to be employed as
substrates, without the need for additives.
Table 1. Identification necessary reaction components.[a]
Entry [Pd]/[Cu]
Additive
TsOH
Oxidant
BQ (1)
t /h
1a (2) /%[b]
– (18)[c]
1
2
3
4
Pd(OAc)2 (5)/
20
Cu(OAc)2 (5)
Pd(OAc)2 (5)/
Cu(OAc)2 (5)
Pd(OAc)2 (5)/
Cu(OAc)2 (5)
Pd(OAc)2 (5)/
Cu(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)/
Cu(OAc)2 (5)
Pd(OAc)2 (5)/
Cu(OAc)2 (5)
Pd(OAc)2 (5)/
Cu(OAc)2 (5)
Pd(OAc)2 (5)/
CuCl (5)
TsOH
none
BQ (1)
BQ (1)
none
20
26
26
30 (–)
–
TsOH
37 (3)
5
6
7
TsOH
TsOH
TsOH
BQ (1)
none
PhCO3tBu 16
26
15
12 (–)
8 (–)
8 (Ͻ1)
8
TsOH
TsOH
TsOH
H3PO4
CSA
tBuOOH
16
16
18
13
13
21 (–)
30 (1)
3 (–)
–
9
air
air
air
air
Results and Discussion
10
11
12
The work initiated with a serendipitous discovery: Under
conditions described for oxidative C–C coupling,[9]
benzamide and n-butyl acrylate did not undergo ortho-ole-
fination, but an oxidative amidation reaction to give a mix-
ture of products 1a and 2 (Scheme 4). The result was unex-
pected, given that oxidative amidation reactions were asso-
ciated entirely with the use of PdCl2 catalysts. For this
reason, we initiated a study to examine the feasibility of
a “chloride-free” catalytic protocol for these reactions. We
envisage that such a procedure may have certain advan-
tages, e.g. Pd(OAc)2 is generally more soluble than PdCl2
compounds in most organic solvents; the new procedure
may also offer complementary scope.
Pd(OAc)2 (5)/
Cu(OAc)2 (5)
Pd(OAc)2 (5)/
Cu(OAc)2 (5)
none
18 (–)
13
14
TsOH
TsOH
air
air
15
14
–
–
Cu(OAc)2 (5)
[a] Typical procedure: Benzamide (0.5 mmol, 1 equiv.), butyl acry-
late (0.55 mmol, 1.1 equiv.), additive (0.5 mmol, 1 equiv.), room
temperature, AcOH-toluene (3:1, 2 mL). [b] Determined by 1H
NMR spectroscopy. Product 1 was observed as a mixture of E/Z
isomers, the yield of 2 is provided in parenthesis. [c] 70 °C.
The yield of 1a is lower in the absence of CuII co-catalyst,
regardless of whether benzoquinone is present (entries 4–
The first task was to interrogate each component of the 6). After screening of some oxidants, air was found to be
catalytic system, to examine their effect on the reaction the most effective (entries 7–9). Attempts to replace
(Table 1). The isoindolinone derivative 2 appears to be a Cu(OAc)2 with CuCl (previously used as a co-catalyst,
secondary product of the reaction; its formation can be sup- Scheme 2), and TsOH with phosphoric and camphor sul-
pressed by conducting the reaction at ambient temperature, fonic acids, did not lead to any improvement (entries 10–
yielding 1a as the only product (Table 1, entries 1 and 2). 12). Last but not least, appropriate controls were per-
Notably, the presence of toluenesulfonic acid was found to formed, to rule out possible operation of Brønsted acid- or
be critical for catalytic activity (entry 3). In line with pre- copper-catalysis (entries 13 and 14).
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Oxidative Amidation of Activated Alkene
Having identified the key components necessary for the carboxamide gave a very low yield (entries 10 and 11).
reaction, further optimisation was achieved by judicious ad- Overall, product yields are similar to that obtained pre-
justment of stoichiometry, reaction medium and tempera- viously for the addition of acyclic amides to ethyl acrylate
ture, aided by parallel experimentation (Table 2). The first (53–85% using 5–10 mol-% catalyst loading).[7]
goal was to remove acetic acid from the solvent system,
Variable results were obtained with alkyl carbamates.[11]
which causes competitive side reactions to occur at 50 °C. An acceptable 70% yield was obtained for the addition of
Polar solvents were examined to ensure homogeneity. At methyl carbamate (entry 12), but benzyl carbamate was un-
room temperature, the reaction was sequestered by DMSO, reactive under these conditions (entry 13). The addition of
dioxane afforded an inferior yield, while THF, DMF and tert-butyl carbamate furnished a modest yield (entry 14).
diglyme afforded similar conversions (entries 3, 4, 5, 9 and At higher catalytic loading, competitive decomposition of
13). These results revealed an important solvent effect on product 4c led to not net gain in yield (entry 15).
selectivity: while reactions conducted in THF and diglyme
So far, our experiments showed that N–H nucleophile is
gave ca. 1:1 mixtures of isomers, DMF clearly favoured the important in these reactions. This was further verified by
E-isomer (10:1, entry 9), in contrast to the Z-selectivity ob- comparing results obtained with unsubstituted and N-sub-
tained by using AcOH-toluene (1:11, entry 1). Raising tem- stituted benzamides (entries 1 vs. 22) and acetamides (en-
perature to 50 °C improved reactions in DMF and diglyme, tries 6 vs. 23). No significant product formation was ob-
but a further increase induced competitive polymerisation tained with the secondary amides despite their higher nu-
(entries 6 vs. 7, 10 vs. 11, and 14 vs. 15). Finally, further cleophilicity, thus reactions are sensitive to the steric hin-
improvements were obtained by increasing the amount of drance at nitrogen.
alkene to 3 equivalents (entries 16 and 17), and by diluting
the reaction mixture (entry 18).
This being the case, cyclic amides, carbamates and ureas
are sterically less hindered and should give better yields.
Indeed, corresponding oxidative amidation reactions with
pyridinone, oxazolidine and imidazolidinone were much
more successful. Excellent yields of their corresponding en-
amide products were isolated exclusively as E-isomers (en-
tries 16–19). Expanding the ring size to piperidinone led to
a marked decrease in reaction yield, however, although the
selectivity was maintained (entries 20 and 21).
Table 2. Reaction optimisation.[a]
Entry Solvent
Alkene
T /°C t /h
Yield /%[b] E/Z
1
2
3
4
5
6
7
8
AcOH/toluene
1.05
1.05
1.05
1.05
1.05
1.05
1.05
3
1.05
1.05
1.05
3
1.05
1.05
1.05
3
3
3
r.t.
50
r.t.
r.t.
r.t.
50
70
50
r.t.
50
70
50
r.t.
50
70
50
50
50
15
15
15
14
15
15
16
16
15
15
16
16
15
15
16
16
65
16
25
–
–
12
1:11
–
[c]
DMSO
dioxane
THF
–
1:3[f]
1:1
26
In the earlier system reported by Murahashi,[5] the reac-
tion of 2-pyrrolidinone was found to be much slower than
2-oxazaolidinone, due to the presence of an inductive
period, which can be eliminated by the use of HMPA as
additive. In the present system, reactions of these cyclic sub-
strates were essentially complete within 48 h (entries 16 and
17). By monitoring the addition of 2-oxaziridine and pyr-
rolidinone to n-butyl acrylate over the course of the reac-
23
1:1.3
1:2.5
1:1.5
10:1
6:1
14[d]
33
9
DMF
21
10
11
12
13
14
15
16
17
18
42
32[d]
35
4.3:1
5:1
diglyme
22
1.2:1
1:1.2
1:1.5
1:1.3
1:1.3
1:1.3
49
53[d]
60
1
tion by H NMR spectroscopy (Figure 1), it is clear that
neither of these reactions exhibit induction periods, i.e.
competitive binding of the amide to the metal centre is not
significant. Furthermore, the reaction of 2-pyrrolidinone
appeared to be faster than 2-oxazolidinone. As the former
is more nucleophilic, this suggests that the nucleophilic at-
tack of the amide is likely to be turnover-limiting in this
particular system.
76
72[e]
[a] Typical procedure: Pd(OAc)2 (0.025 mmol, 5 mol-%), Cu-
(OAc)2 (0.025 mmol, 5 mol-%), benzamide (0.5 mmol, 1 equiv.),
butyl acrylate (1.05 or 3 equiv.), TsOH (0.5 mmol, 1 equiv.), solvent
(2 mL). [b] Determined by 1H NMR spectroscopy. [c] Predomi-
nantly polymerised product. [d] Competitive polymerisation de-
tected. [e] 5 mL of diglyme. [f] An unknown impurity was detected.
Oxidative amidation products can be subjected to hydro-
Other N–H substrates were also subjected to reactions genation, achieving a hydroamidation reaction formally in
with n-butyl acrylate (Table 3). Substituted benzamides two steps, avoiding harsh reaction conditions.[4] This is
were first examined: the oxidative amidation reaction of the demonstrated by the reduction of 1a using H2 catalysed by
electron-deficient 4-chlorobenzamide proceeded in low 10% Pd/C. Reaction was complete within 3 h, to give the
yield, even with double catalyst loading (entries 2 and 3). amido ester 6 in a quantitative yield (Scheme 5).
On the other hand, sluggish addition of 4-methoxybenza-
Reactions of oxazolidinone with different alkenes
mide can be improved by using 10 mol-% of the catalyst (methyl methacrylate, methyl crotonate, N,N-dimethylacryl-
(entries 4 and 5). A similar pattern of activity can be ob- amide and acrylonitrile) were examined. So far, product for-
served in the addition of acyclic aliphatic amides. While mation was only observed with unsubstituted alkenes (se-
acetamide and butyramide gave reasonable yields of en- lected examples are given in Table 4). We attribute this to
amides 3a and 3b, respectively (entries 6–8), trifluoroacet- the ability of alkenes to bind to palladium, which is gen-
amide did not afford any product (entry 9). Steric effect erally favoured by sterically unhindered, electron-poor alk-
also proved to be important, as the reaction of cyclohexyl enes. The addition of benzamide to tert-butyl acrylate is
Eur. J. Org. Chem. 2010, 5181–5189
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X. Liu, K. K. Hii
FULL PAPER
Table 3. Reactions of amides, carbamates and imides with n-butyl acrylate.[a]
[a] General reaction conditions: Amide substrate (1 mmol, 1 equiv.), butyl acrylate (3 mmol, 3 equiv.), Pd(OAc)2 (0.05 mmol, 5 mol-%),
Cu(OAc)2 (0.05 mmol, 5 mol-%), TsOH (1 mmol, 1 equiv.), diglyme (10 mL). [b] Isolated yield after column chromatography. E/Z ratio
given in parenthesis. [c] 10 mol-% Pd(OAc)2, 10 mol-% Cu(OAc)2. [d] Competitive polymerisation. [e] Ratio di-/mono-substituted product
= 1:2. [f] 6 equiv. of alkene, ratio of di-/mono-substituted product, 1:2.
Scheme 5. Hydrogenation of enamide 1a.
virtually identical to that obtained with n-butylacrylate
(Table 4, entry 1 vs. Table 2, entry 1); the size of the ester
substituent does not exert any effect. In contrast, reactions
with N,N-dimethylacrylamide and acrylonitrile gave disap-
pointingly low yields (entries 2–6). Nevertheless, it is inter-
esting to note that reactions of the acyclic N-nucleophiles
with N,N-dimethylacrylamide favours formation of the Z-
isomer (entries 2, 5 and 6), while the cyclic N-nucleophiles
Figure 1. Rate of conversion of the reaction between 2-oxazolid-
inone (᭛) and 2-pyrrolidinone (᭺) with n-butyl acrylate under con-
ditions described in footnote [a] of Table 3.
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Oxidative Amidation of Activated Alkene
still favour the E-isomer exclusively (entries 3 and 4). Thus,
the reaction appears to be highly substrate-dependent, thus
re-optimisation of each oxidative amidation reaction may
be necessary.
Experimental Section
General Experimental Procedure for the Pd-Catalysed Oxidative
Amidation of Butyl Acrylate: A thick-walled test tube was charged
with a magnetic stir bar, the requisite amide (1 mmol, 1 equiv.),
toluenesulfonic acid (190 mg, 1 mmol, 1 equiv.), Pd(OAc)2
(11.2 mg, 0.05 mmol, 5 mol-%), and Cu(OAc)2 (9.6 mg, 0.05 mmol,
5 mol-%). Diglyme (10 mL) was added to generate a homogeneous
solution. The reaction tube was positioned in an aluminium block
and stirred in opened air, while the temperature of the solution was
adjusted to 50 °C. n-Butyl acrylate (480 µL, 3 mmol, 3 equiv.) was
then added, and heating was continued at 50 °C for 48 h. After
cooling to room temperature, the mixture was dilute with EtOAc
(100 mL) and washed successively with aq. NaHCO3 (2ϫ15 mL),
brine (15 mL), dried (MgSO4) and concentrated in vacuo. The
crude product was purified by column chromatography.
Table 4. Oxidative amidation with different alkenes.[a]
(E)-Butyl 3-Benzamidoacrylate (E-1a): White solid; m.p. 80–81 °C;
R = 0.35, hexane/EtOAc (3:1). IR: ν
= 3310, 1701, 1673, 1630,
˜
f
max
1267, 1138 cm–1. H NMR (400 MHz, CDCl3, 22 °C): δ = 8.36 [d,
1
3J(H,H) = 11.5 Hz, 1 H, NH], 8.23 (dd, JH,H = 14.0, 11.5 Hz, 1
3
H, =CHN), 7.85 (m, 2 H, Ar), 7.62–7.55 (m, 1 H, Ar), 7.51–7.47
3
3
(m, 2 H, Ar), 5.63 (d, JH,H = 14.0 Hz, 1 H, =CH), 4.15 (t, JH,H
= 6.7 Hz, 2 H, OCH2), 1.71–1.60 (m, 2 H), 1.46–1.34 (m, 2 H),
0.94 (t, JH,H = 7.4 Hz, 3 H) ppm. 13C NMR: δ = 167.5, 165.0,
3
138.0, 132.8, 132.4, 128.9, 127.5, 102.6, 64.2, 30.8, 19.2, 13.7 ppm.
MS (EI): m/z (%) = 247 (20) [M+], 146 (27), 105 (100), 77 (50).
HRMS-ESI calcd. for C14H18NO3 [MH]+: 248.1287; found
248.1283. C14H17NO3 (247.13): calcd. C 68.00, H 6.93, N 5.66;
found C 68.08, H 7.02, N 5.64.
(Z)-Butyl 3-Benzamidoacrylate (Z-1a): White solid; m.p. 49–50 °C;
R = 0.65, hexane/EtOAc (3:1). IR: ν
= 3326, 1697, 1678, 1626,
˜
f
max
1199 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ = 11.52 (d, 3JH,H
3
= 11.1 Hz, 1 H, NH), 8.00–7.92 (m, 2 H, Ar), 7.74 (dd, JH,H
=
11.1, 8.8 Hz, 1 H, =CHN), 7.60–7.56 (m, 1 H, Ar), 7.51–7.47 (m,
3
3
2 H, Ar), 5.27 (d, JH,H = 8.8 Hz, 1 H, =CH), 4.18 (t, JH,H
=
6.7 Hz, 2 H, OCH2), 1.75–1.60 (m, 2 H, CH2), 1.48–1.37 (m, 2 H,
3
CH2), 0.94 (t, JH,H = 7.4 Hz, 3 H, CH3) ppm. 13C NMR: δ =
169.8, 164.5, 138.8, 132.9, 132.2, 128.9, 127.7, 97.2, 64.2, 30.7, 19.1,
13.7 ppm. MS (EI): m/z (%) = 247 (22) [M+], 146 (30), 105 (100),
77 (46). HRMS-ESI calcd. for C14H18NO3 [MH]+: 248.1287; found
248.1287. C14H17NO3 (247.13): calcd. C 68.00, H 6.93, N 5.66;
found C 68.05, H 6.96, N 5.70.
[a] Reactions conditions as described in previous Table. [b] E/Z
ratio indicated in parenthesis. [c] Isolated yield.
(E)-Butyl 3-(4-Chlorobenzamido)acrylate (E-1b): White solid; m.p.
90–91 °C; R = 0.35, hexane/EtOAc (3:1). IR: ν
= 3311, 1717,
˜
f
max
1679, 1628, 1203 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ =
8.34 (d, 3JH,H = 11.6 Hz, 1 H, NH), 8.20 (dd, 3JH,H = 14.1, 11.6 Hz,
1 H, =CHN), 7.83–7.77 (m, 2 H, Ar), 7.50–7.43 (m, 2 H, Ar), 5.64
Conclusions
We have discovered a new catalytic protocol for the oxi-
dative amidation of butyl acrylate under “chloride-free”
conditions, using a mixture of Pd(OAc)2/Cu(OAc)2 as cata-
lysts and air as terminal oxidant. Under optimised reaction
conditions, addition of cyclic or acyclic amides, carbamates,
pyridinone, oxazolidine and imidazolidinone can be
achieved with excellent yields, effectively replacing toxic
HMPA[5] with TsOH. Moderate yields were also obtained
with primary acyclic amides and carbamates, as long as ste-
ric hindrance is not an issue. Overall, reactions are sensitive
to the electronic and steric nature of the substrates, requir-
ing modification of reaction conditions to achieved optimal
yields and selectivity. Nevertheless, given the tools of paral-
lel synthesis available to a modern laboratory, this is not
longer an insurmountable problem.
3
3
(d, JH,H = 14.1 Hz, 1 H, =CH), 4.15 (t, JH,H = 6.7 Hz, 2 H,
OCH2), 1.70–1.60 (m, 2 H, CH2), 1.45–1.36 (m, 2 H, CH2), 0.94
3
(t, JH,H = 7.4 Hz, 3 H, CH3) ppm. 13C NMR: δ = 167.2, 163.8,
139.4, 137.6, 130.8, 129.3, 128.9, 103.0, 64.3, 30.8, 19.2, 13.7 ppm.
281 (M+, 14%), 180 (40), 139 (100), 111 (37). HRMS-ESI calcd.
for C14H17ClNO3 [MH]+: 282.0897; found: 282.0896.
C14H16ClNO3 (281.09): calcd. C 59.68, H 5.72, N 4.97; found C
59.73, H 5.74, N 4.93.
(Z)-Butyl 3-(4-Chlorobenzamido)acrylate (Z-1b): White solid; m.p.
46–47 °C; R = 0.65, hexane/EtOAc (3:1). IR: ν
= 3322, 1696,
˜
f
max
1677, 1623, 1194 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ =
3
11.53 (d, JH,H = 10.9 Hz, 1 H, NH), 7.92–7.86 (m, 2 H, Ar), 7.71
3
(dd, JH,H = 10.9, 8.8 Hz, 1 H, =CHN), 7.50–7.44 (m, 2 H, Ar),
3
3
5.28 (d, JH,H = 8.8 Hz, 1 H, =CH), 4.18 (t, JH,H = 6.7 Hz, 2 H,
OCH2), 1.71–1.64 (m, 2 H, CH2), 1.48–1.37 (m, 2 H, CH2), 0.96
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X. Liu, K. K. Hii
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(t, JH,H = 7.4 Hz, 3 H, CH3) ppm. 13C NMR: δ = 169.8, 163.5,
139.6, 138.6, 130.6, 129.2, 129.1, 97.6, 64.3, 30.7, 19.1, 13.7 ppm.
MS (EI): m/z (%) = 281 (22) [M+], 180 (40), 139 (100), 111 (39).
HRMS-ESI calcd. for C14H17ClNO3 [MH]+: 282.0897; found
9.0 Hz, 1 H, =CH), 4.13 (t, 3JH,H = 6.6 Hz, 2 H, OCH2), 2.14 (s, 3
H, Ac), 1.69–1.62 (m, 2 H, CH2), 1.46–1.37 (m, 2 H, CH2), 0.96
(t, 3JH,H = 7.4 Hz, 3 H, CH3) ppm. 13C NMR (100.6 MHz, CDCl3,
22 °C): δ = 169.3, 168.3, 138.0, 96.3, 64.1, 30.7, 23.6, 19.1,
3
282.0891. C14H16ClNO3 (281.09): calcd. C 59.68, H 5.72, N 4.97; 13.7 ppm. MS (EI): m/z (%) = 185 (18) [M+], 87 (75), 84 (100), 70
found C 59.73, H 5.75, N 4.96.
(66), 48 (83). HRMS-EI calcd. for C9H15NO3 [M]+: 185.1052;
found 185.1054. C9H15NO3 (185.10): calcd. C 58.36, H 8.16, N
7.56; found C 58.39, H 8.17, N 7.50.
(E)-Butyl 3-(4-Methoxybenzamido)acrylate (E-1c): White solid;
m.p. 114–115 °C; R = 0.15, hexane/EtOAc (3:1). IR: ν
= 3345,
˜
f
max
1705, 1684, 1605, 1258, 1140 cm–1. 1H NMR (400 MHz, CDCl3,
(E)-Butyl 3-Butyramidoacrylate (E-3b): Colourless solid; m.p. 56–
3
22 °C): δ = 11.45 (d, JH,H = 11.8 Hz, 1 H, NH), 8.26 (dd, 3JH,H
=
57 °C; R = 0.25, hexane/EtOAc (2:1). IR: νmax = 3295, 1716, 1683,
˜
f
14.1, 11.8 Hz, 1 H, =CHN), 7.85 (d, 3JH,H = 8.9 Hz, 2 H, Ar), 7.00
1627, 1136 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ = 8.47 (d,
3
(d, JH,H = 8.9 Hz, 2 H, Ar), 5.61 (d, 3JH,H = 14.1 Hz, 1 H, =CH),
3JH,H = 11.4 Hz, 1 H, NH), 8.01 (dd, JH,H = 11.4, 14.1 Hz, 1 H,
3
4.18 (t, 3JH,H = 6.7 Hz, 2 H, OCH2), 3.87 (s, 3 H, OMe), 1.74–1.62
3
3
=CHN), 5.42 (d, JH,H = 14.1 Hz, 1 H, =CH), 4.11 (t, JH,H
=
3
3
(m, 2 H, CH2), 1.48–1.39 (m, 2 H, CH2), 0.97 (t, JH,H = 7.3 Hz,
6.6 Hz, 2 H, OCH2), 2.29 (t, JH,H = 7.4 Hz, 2 H, CH2), 1.73–1.65
(m, 2 H), 1.64–1.58 (m, 2 H, CH2), 1.39–1.34 (m, 2 H, CH2), 0.94
3 H, CH3) ppm. 13C NMR: δ = 167.4, 164.1, 163.3, 138.1, 129.5,
124.6, 114.2, 101.9, 64.1, 55.5, 30.9, 19.2, 13.8 ppm. MS (EI): m/z
(%) = 277 (12) [M+], 143 (42), 91 (100), 68 (32). HRMS-ESI calcd.
for C15H20NO4 [MH]+: 278.1392; found 278.1392. C15H19NO4
(277.14): calcd. C 64.97, H 6.91, N 5.05; found C 64.95, H 6.97, N
5.11.
(t, J = 7.4 Hz, 3 H, CH3), 0.91 (t, J = 7.4 Hz, 3 H, CH3) ppm. 13
C
NMR (100.6 MHz, CDCl3, 22 °C): δ = 171.5, 167.8, 137.8, 101.1,
64.2, 38.4, 30.8, 19.2, 18.6, 13.7 ppm. MS (EI): m/z (%) = 213 (25)
[M+], 87 (100), 70 (70). HRMS-ESI calcd. for C11H20NO3 [MH]+:
214.1443; found 214.1438. C11H19NO3 (213.14): calcd. C 61.95, H
8.98, N 6.57; found C 61.99, H 9.02, N 6.53.
(Z)-Butyl 3-(4-Methoxybenzamido)acrylate (Z-1c): White solid;
m.p. 50–51 °C; R = 0.25, hexane/EtOAc (3:1). IR: ν
= 3330,
˜
f
max
(Z)-Butyl 3-Butyramidoacrylate (Z-3b): Colourless oil; Rf = 0.65,
1678, 1621, 1605, 1196, 1173 cm–1. 1H NMR (400 MHz, CDCl3,
hexane/EtOAc (2:1). IR: ν
= 3345, 1718, 1684, 1630 cm–1. 1H
˜
max
3
3
3
22 °C): δ = 11.45 (d, JH,H = 11.0 Hz, 1 H, NH), 7.93 (d, JH,H
=
NMR (400 MHz, CDCl3, 22 °C): δ = 10.45 (d, JH,H = 11.3 Hz, 1
8.9 Hz, 2 H, Ar), 7.74 (dd, 3JH,H = 11.0, 8.8 Hz, 1 H, =CHN), 6.98
3
H, NH), 7.49 (dd, JH,H = 8.9, 11.3 Hz, 1 H, =CHN), 5.12 (d,
3
3
3JH,H = 8.9 Hz, 1 H, =CH), 4.15 (t, JH,H = 6.7 Hz, 2 H, OCH2),
3
(d, JH,H = 8.9 Hz, 2 H, Ar), 5.23 (d, JH,H = 8.8 Hz, 1 H, =CH),
4.17 (t, 3JH,H = 6.7 Hz, 2 H, OCH2), 3.88 (s, 3 H, OMe), 1.71–1.64
2.35 (t, 3JH,H = 7.4 Hz, 2 H, CH2), 1.78–1.67 (m, 2 H, CH2), 1.67–
1.59 (m, 2 H, CH2), 1.45–1.34 (m, 2 H, CH2), 0.98 (t, J = 7.4 Hz,
3 H, CH3), 0.94 (t, J = 7.4 Hz, 3 H, CH3) ppm. 13C NMR
(100.6 MHz, CDCl3, 22 °C): δ = 171.3, 169.4, 138.1, 96.2, 64.1,
38.7, 30.7, 19.1, 18.5, 13.7 ppm. MS (EI): m/z (%) = 213 (55) [M+],
87 (100), 70 (92), 43 (88). HRMS-ESI calcd. for C11H20NO3 [MH]
+: 214.1443; found 214.1444. C11H19NO3 (213.14): calcd. C 61.95,
H 8.98, N 6.57; found C 62.02, H 9.04, N 6.52.
3
(m, 2 H, CH2), 1.47–1.38 (m, 2 H, CH2), 0.96 (t, JH,H = 7.4 Hz,
3 H, CH3) ppm. 13C NMR: δ = 169.9, 164.0, 163.4, 139.1, 129.8,
124.5, 114.1, 96.5, 64.2, 55.5, 30.7, 19.1, 13.7 ppm. MS (EI): m/z
(%) = 277 (20) [M+], 135 (100). HRMS-EI calcd. for C15H19NO4
[M]+: 277.1314; found 277.1316. C15H19NO4 (277.13): calcd. C
64.97, H 6.91, N 5.05; found C 65.03, H 6.94, N 5.06.
Butyl [3-Oxo-2,3-dihydroisoindol-(1Z)-ylidene]acetate (2): White so-
lid; m.p. 100–101 °C; R = 0.5, hexane/EtOAc (3:1). IR: ν
=
˜
f
max
(E)-Butyl 3-(Cyclohexanecarboxamido)acrylate (E-3d): Pale yellow
3311, 1712, 1688, 1650, 1181 cm–1. 1H NMR (400 MHz, CDCl3,
22 °C): δ = 9.63 (s, 1 H, NH), 7.89–7.87 (m, 1 H, Ar), 7.71–7.68
(m, 1 H, Ar), 7.67–7.59 (m, 2 H, Ar), 5.78 (s, 1 H, =CH), 4.22 (t,
3JH,H = 6.7 Hz, 2 H, OCH2), 1.75–1.63 (m, 2 H, CH2), 1.50–1.36
(m, 2 H, CH2), 0.97 (t, 3JH,H = 7.4 Hz, 3 H, CH3) ppm. 13C NMR:
δ = 168.1, 167.7, 147.4, 136.5, 132.8, 131.6, 129.6, 124.1, 121.0,
91.8, 64.6, 30.7, 19.2, 13.8 ppm. MS (EI): m/z (%) = 245 (39) [M+],
189 (79), 172 (100), 145 (78), 130 (38). HRMS-ESI calcd. for
C14H16NO3 [MH]+: 246.1130; found 246.1127. C14H15NO3
(245.11): calcd. C 68.56, H 6.16, N 5.71; found C 68.60, H 6.15, N
5.75.
solid; m.p. 77–78 °C; R = 0.4, hexane/EtOAc (3:1). IR: ν
=
˜
f
max
3294, 1717, 1684, 1630, 1199, 1140 cm–1. 1H NMR (400 MHz,
CDCl3, 22 °C): δ = 8.03 (dd, J = 11.3, 14.1 Hz, 1 H, =CHN), 7.75
3
3
(d, JH,H = 11.3 Hz, 1 H, NH), 5.44 (d, JH,H = 14.1 Hz, 1 H,
=CH), 4.18–4.03 (m, 2 H, OCH2), 2.22–2.16 (m, 1 H, CH), 1.95–
1.73 (m, 4 H, CH2), 1.69–1.66 (m, 1 H, CH2), 1.64–1.59 (m, 2 H,
CH2), 1.51–1.44 (m, 2 H, CH2), 1.41–1.35 (m, 2 H, CH2), 1.30–
1.20 (m, 3 H, CH2), 0.93 (t, J = 7.4 Hz, 3 H) ppm. 13C NMR
(100.6 MHz, CDCl3, 22 °C): δ = 174.0, 167.5, 137.6, 101.4, 64.1,
45.4, 30.7, 29.2, 25.6, 25.5, 19.2, 13.7 ppm. MS (EI): m/z (%) = 253
(36) [M+], 110 (38), 86 (53), 84 (100), 55 (50). HRMS-ESI calcd.
for C14H24NO3 [MH]+: 254.1756; found 254.1751. C14H23NO3
(253.17): calcd. C 66.37, H 9.15, N 5.13; found C 66.42, H 9.05, N
5.49.
(E)-Butyl 3-Acetamidoacrylate (E-3a): Colourless solid; m.p. 71–
72 °C; R = 0.15, hexane/EtOAc (1:1). IR: νmax = 3290, 1741, 1686,
˜
f
1630, 1256, 1136 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ =
8.91 (d, 3JH,H = 11.2 Hz, 1 H, NH), 8.01 (dd, 3JH,H = 14.1, 11.2 Hz,
1 H, =CHN), 5.47 (t, JH,H = 14.1 Hz, 1 H, =CH), 4.13 (t, JH,H
= 6.7 Hz, 2 H, OCH2), 2.14 (s, 3 H, Ac), 1.70–1.55 (m, 2 H, CH2),
(Z)-Butyl 3-(Cyclohexanecarboxamido)acrylate (Z-3d): Pale yellow
3
3
oil; R = 0.75, hexane/EtOAc (3:1). IR: ν
= 3299, 1738, 1681,
˜
f
max
1625 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ = 10.55 (d, 3JH,H
3
1.45–1.31 (m, 2 H, CH2), 0.93 (t, JH,H = 7.4 Hz, 3 H, CH3) ppm.
= 10.1 Hz, 1 H, NH), 7.51 (dd, 3JH,H = 11.2, 8.9 Hz, 1 H, =CHN),
13C NMR: δ = 168.8, 168.0, 137.8, 101.3, 64.3, 30.7, 23.6, 19.2,
13.7 ppm. MS (EI): m/z (%) = 185 (35) [M+], 112 (47), 87 (100), 70
(99), 43 (92). HRMS-EI calcd. for C9H15NO3 [M]+: 185.1052;
found 185.1053. C9H15NO3 (185.10): calcd. C 58.36, H 8.16, N
7.56; found C 58.41, H 8.22, N 7.49.
3
3
5.12 (d, JH,H = 8.9 Hz, 1 H, =CH), 4.13 (t, JH,H = 6.7 Hz, 2 H,
OCH2), 2.29–2.22 (m, 1 H, CH), 2.01–1.89 (m, 2 H, CH2), 1.86–
1.74 (m, 2 H, CH2), 1.70–1.68 (m, 1 H, CH2), 1.67–1.53 (m, 2 H,
CH2), 1.48–1.45 (m, 2 H, CH2), 1.42–1.36 (m, 2 H, CH2), 1.32–
1.21 (m, 3 H, CH2), 0.95 (t, J = 7.4 Hz, 3 H, CH3) ppm. 13C NMR
(100.6 MHz, CDCl3, 22 °C): δ = 174.3, 169.6, 138.4, 96.2, 64.1,
(Z)-Butyl 3-Acetamidoacrylate (Z-3a): Colourless oil; Rf = 0.65,
hexane/EtOAc (1:1). IR: νmax = 3322, 1718, 1682, 1627, 1186 cm–1. 45.4, 30.7, 29.2, 25.6, 25.5, 19.2, 13.7 ppm. MS (EI): m/z (%) = 253
˜
1H NMR (400 MHz, CDCl3, 22 °C): δ = 10.46 (br. s, 1 H, NH),
(36) [M+], 110 (38), 86 (53), 83 (100), 49 (58). HRMS-ESI calcd.
for C14H24NO3 [MH]+: 254.1756; found 254.1752. C14H23NO3
3
3
7.49 (dd, JH,H = 11.3, 9.0 Hz, 1 H, =CHN), 5.14 (d, JH,H
=
5186
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5181–5189

Oxidative Amidation of Activated Alkene
(253.17): calcd. C 66.37, H 9.15, N 5.13; found C 66.42, H 9.14, N
5.46.
212.1293. C11H17NO3 (211.13): calcd. C 62.54, H 8.11, N 6.63;
found C 62.61, H 8.08, N 6.62.
(E)-Butyl 3-(Methoxycarbonylamino)acrylate (E-4a): White solid;
(E)-Butyl 3-(2-Oxooxazolidin-3-yl)acrylate (E-5b): White solid;
m.p. 105–106 °C; R = 0.1, hexane/EtOAc (4:1). IR: ν
= 3265,
m.p. 61–62 °C; R = 0.35, hexane/EtOAc (1:2). IR: ν
= 1769,
˜
˜
f
max
f
max
1739, 1707, 1641 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ =
1702, 1633, 1197, 1161 cm–1. H NMR (400 MHz, CDCl3, 22 °C):
1
3
3
3
3
7.80 (dd, JH,H = 6.9, 14.0 Hz, 1 H, =CHN), 7.13 (d, JH,H
=
δ = 7.94 (d, JH,H = 14.1 Hz, 1 H, =CHN), 5.15 (d, JH,H =
3
3
6.9 Hz, 1 H, NH), 5.38 (d, JH,H = 14.0 Hz, 1 H, =CH), 4.12 (t, 14.1 Hz, 1 H, =CH), 4.53 (t, JH,H = 7.9 Hz, 2 H, CH2O), 4.15 (t,
3JH,H = 6.7 Hz, 2 H, OCH2), 3.80 (s, 3 H, OMe), 1.67–1.57 (m, 2
3JH,H = 6.7 Hz, 2 H, OCH2), 3.85–3.71 (t, JH,H = 7.9 Hz, 2 H,
3
3
H, CH2), 1.43–1.32 (m, 2 H, CH2), 0.93 (t, JH,H = 7.4 Hz, 3 H, CH2N), 1.68–1.61 (m, 2 H, CH2), 1.44–1.35 (m, 2 H, CH2), 0.94
CH3) ppm. 13C NMR (100.6 MHz, CDCl3, 22 °C): δ = 167.4,
153.4, 139.3, 100.1, 64.1, 53.3, 30.7, 19.2, 13.8 ppm. MS (EI): m/z
(%) = 201 (18) [M+], 145 (98), 128 (100), 96 (97). HRMS-ESI calcd.
for C9H16NO4 [MH]+: 202.1079; found 202.1078. C9H15NO4
(201.11): calcd. C 53.72, H 7.51, N 6.96; found C 53.71, H 7.52, N
6.98.
(t, 3JH,H = 7.4 Hz, 3 H, CH3) ppm. 13C NMR (100.6 MHz, CDCl3,
22 °C): δ = 166.6, 154.6, 138.0, 100.6, 64.2, 64.5, 42.2, 30.7, 19.2,
13.7 ppm. MS (EI): m/z (%) = 213 (36) [M+], 140 (100), 113 (47),
95 (56). HRMS-ESI calcd. for C10H16NO4 [MH]+: 214.1079; found
214.1076. C10H15NO4 (213.11): calcd. C 56.33, H 7.09, N 6.57;
found C 56.33, H 7.16, N 6.62.
(Z)-Butyl 3-(Methoxycarbonylamino)acrylate (Z-4a): Colourless li-
(E)-Butyl 3-(2-Oxoimidazolidin-1-yl)acrylate (E-5c, monosubstitu-
tion product): White solid; m.p. 80–82 °C; Rf = 0.3, hexane/EtOAc
quid; R = 0.4, hexane/EtOAc (4:1). IR: ν
= 3331, 1747, 1683,
˜
f
max
1627, 1181 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ = 9.78 (br. (1:5). IR: νmax = 3241, 1729, 1699, 1619, 1265, 1169 cm–1. 1H NMR
˜
3
3
s, 1 H), 7.23–7.28 (m, 1 H, obscured by CHCl3), 5.05 (d, JH,H
=
(400 MHz, CDCl3, 22 °C): δ = 8.01 (d, JH,H = 14.0 Hz, 1 H,
=CHN), 6.20 (br. s, 1 H, NH), 4.96 (d, JH,H = 14.0 Hz, 1 H,
3
3
8.8 Hz, 1 H, =CH), 4.11 (t, JH,H = 6.7 Hz, 2 H, OCH2), 3.79 (s, 3
3
H, OMe), 1.67–1.59 (m, 2 H, CH2) 1.43–1.36 (m, 2 H, CH2), 0.94 =CH), 4.11 (t, JH,H = 6.7 Hz, 2 H, OCH2), 3.76–3.50 (m, 4 H,
(t, J = 7.4 Hz, 3 H) ppm. 13C NMR (100.6 MHz, CDCl3, 22 °C): CH2), 1.67–1.59 (m, 2 H, CH2), 1.45–1.35 (m, 2 H, CH2), 0.97 (t,
δ = 169.0, 154.0, 140.0, 95.1, 64.0, 53.0, 30.7, 19.1, 13.7 ppm. MS 3JH,H = 7.4 Hz, 3 H, CH3) ppm. 13C NMR (100.6 MHz, CDCl3,
(EI): m/z (%) = 201 (32) [M+], 145 (100), 128 (78), 96 (80). HRMS-
ESI calcd. for C9H16NO4 [MH]+: 202.1079; found 202.1073.
C9H15NO4 (201.11): calcd. C 53.72, H 7.51, N 6.96; found C 53.70,
H 7.56, N 6.95.
22 °C): δ = 167.7, 157.5, 138.7, 96.4, 63.9, 42.1, 37.5, 30.9, 19.2,
13.8 ppm. MS (EI): m/z (%) = 212 (41) [M+], 156 (60), 139 (100).
HRMS-ESI calcd. for C10H18N2O3 [MH]+: 213.1239; found
213.1233. C10H17N2O3 (212.12): calcd. C 56.59, H 7.60, N 13.20;
found C 56.59, H 7.75, N 13.02.
(E)-Butyl 3-(tert-Butoxycarbonylamino)acrylate (E-4c): Pale yellow
oil; R = 0.2, hexane/EtOAc (7:1). IR: ν
= 3341, 1739, 1683,
(2E,2ЈE)-Dibutyl 3,3Ј-(2-Oxoimidazolidine-1,3-diyl)diacrylate (E,E-
5cЈ, disubstitution product): Colourless solid; m.p. 140–142 °C; Rf =
˜
f
max
1629, 1140 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ = 7.79 (dd,
J = 11.7, 14.1 Hz, 1 H, =CHN), 6.65 (br. s, 1 H, NH), 5.30 (d, 0.75, hexane/EtOAc (1:5). IR: νmax = 1734, 1698, 1629, 1221, 1158,
˜
3
3JH,H = 14.1 Hz, 1 H, =CH), 4.13 (t, JH,H = 6.7 Hz, 2 H, OCH2),
907, 729 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ = 8.03 (d,
3
1.70–1.61 (m, 2 H, CH2), 1.49 (s, 9 H, tBu), 1.44–1.35 (m, 2 H,
3JH,H = 14.1 Hz, 2 H, =CHN), 5.13 (d, JH,H = 14.1 Hz, 2 H,
CH2), 0.96 (t, JH,H = 7.4 Hz, 3 H, CH3) ppm. 13C NMR =CH), 4.13 (t, JH,H = 6.7 Hz, 4 H, OCH2), 3.74 (s, 4 H, CH2),
3
3
3
(100.6 MHz, CDCl3, 22 °C): δ = 169.3, 152.1, 140.3, 94.0, 81.8,
63.8, 30.7, 28.1, 19.2, 13.7 ppm. MS (EI): m/z (%) = 243 (17) [M+],
87 (39), 57 (100), 43 (83). HRMS-EI calcd. for C12H21NO4 [M]+:
1.66–1.59 (m, 4 H, CH2), 1.48–1.20 (m, 4 H, CH2), 0.92 (t, JH,H
= 7.4 Hz, 6 H, CH3) ppm. 13C NMR (100.6 MHz, CDCl3, 22 °C):
δ = 166.8, 151.9, 137.7, 99.4, 64.2, 39.7, 30.4, 19.2, 13.7 ppm. MS
243.1471; found 243.1469. C12H21NO4 (242.15): calcd. C 59.24, H (EI): m/z (%) = 338 (41) [M+], 256 (100), 226 (48), 206 (51). HRMS-
8.70, N 5.76; found C 59.19, H 8.68, N 5.81.
ESI calcd. for C17H27N2O5 [MH]+: 339.1920; found 339.1917.
C17H26N2O5 (338.19): calcd. C 60.34, H 7.74, N 8.28; found C
60.44, H 7.63, N 8.25.
(Z)-Butyl 3-(tert-Butoxycarbonylamino)acrylate (Z-4c): Pale yellow
oil; R = 0.5, hexane/EtOAc (7:1). IR: ν
= 3345, 1739, 1683,
˜
f
max
1629, 1141 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ = 9.61 (br. (E)-Butyl 3-(2-Oxopiperidin-1-yl)acrylate (E-5d): Yellow oil; Rf =
3
s, 1 H, NH), 7.23 (dd, JHH = 9.0, 11.1 Hz, 1 H, =CHN), 4.99 (d, 0.2, hexane/EtOAc (2:1). IR: ν
= 1707, 1682, 1619, 1250, 1146
˜
max
3JH,H = 9.0 Hz, 1 H, =CH), 4.11 (t, JH,H = 6.7 Hz, 2 H, OCH2),
cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ = 8.61 (d, JH,H
=
3
3
3
1.67–1.58 (m, 2 H, CH2), 1.49 (s, 9 H, tBu), 1.44–1.37 (m, 2 H,
14.5 Hz, 1 H, =CHN), 5.27 (d, JH,H = 14.5 Hz, 1 H, =CH), 4.15
CH2), 0.94 (t, JH,H = 7.4 Hz, 3 H, CH3) ppm. 13C NMR (t, 3JH,H = 6.7 Hz, 2 H, OCH2), 3.44 (t, 3JH,H = 6.2 Hz, 2 H, CH2),
3
3
(100.6 MHz, CDCl3, 22 °C): δ = 169.3, 152.3, 140.3, 94.0, 81.8,
64.0, 30.7, 28.1, 19.2, 13.7 ppm. MS (EI): m/z (%) = 243 (15) [M+],
87 (53), 84 (62), 57 (100), 43 (89). HRMS-EI calcd. for C12H21NO4
[M]+: 243.1471; found 243.1470. C12H21NO4 (243.15): calcd. C
59.24, H 8.70, N 5.76; found C 59.27, H 8.74, N 5.79.
2.57 (t, JH,H = 6.6 Hz, 2 H, CH2), 1.96–1.92 (m, 2 H, CH2) 1.87–
1.82 (m, 2 H, CH2), 1.68–1.61 (m, 2 H, CH2), 1.44–1.35 (m, 2 H,
CH2), 0.92 (t, JH,H = 7.4 Hz, 3 H, CH3) ppm. 13C NMR
3
(100.6 MHz, CDCl3, 22 °C): δ = 169.3, 167.5, 140.7, 100.0, 64.0,
45.6, 33.1, 30.8, 22.4, 22.2, 19.2, 13.7 ppm. MS (EI): m/z (%) = 225
(6) [M+], 152 (20), 124 (100). HRMS-ESI calcd. for C12H20NO3
[MH]+: 226.1443; found 226.1447. C12H19NO3 (225.14): calcd. C
63.98, H 8.50, N 6.22; found C 63.99, H 8.49, N 6.15.
(E)-Butyl 3-(2-Oxopyrrolidin-1-yl)acrylate (E-5a): Pale yellow oil;
R = 0.2, hexane/EtOAc (1:1). IR: ν
= 1726, 1698, 1623, 1203,
˜
f
max
1147 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ = 8.09 (d, JH,H
3
= 14.2 Hz, 1 H, =CHN), 5.20 (d, 3JH,H = 14.2 Hz, 1 H, =CH), 4.14
Experimental Procedure for the Hydrogenation of 1a: A two-neck
10 mL round bottomed flask was charged with a magnetic stir bar,
Pd/C (5% on carbon, 0.025 mmol, 0.1 equiv.), a mixture of E- and
Z-enamide 1a (1:1, 1 mmol, 1 equiv.) and EtOH (2.5 mL). The
flask was then purged and filled with H2, and left to stir under the
H2 atmosphere for 3 h. The reaction mixture was filtered through
a short silica gel pad, and evaporated to afford analytically pure 7
3
3
(t, JH,H = 6.7 Hz, 2 H, OCH2), 3.54 (t, JHH = 8.0 Hz, 2 H,
CH2N), 2.53 (t, JH,H = 8.0 Hz, 2 H, CH2CO), 2.20–2.13 (m, 2 H,
3
CH2), 1.65–1.58 (m, 2 H, CH2), 1.49–1.29 (m, 2 H, CH2), 0.94 (t,
3JH,H = 7.4 Hz, 3 H, CH3) ppm. 13C NMR (100.6 MHz, CDCl3,
22 °C): δ = 174.2, 167.2, 137.1, 100.6, 64.0, 44.9, 30.9, 30.8, 19.1,
17.4, 13.7 ppm. MS (EI): m/z (%) = 211 (30) [M+], 155 (56), 138
(100), 110 (71). HRMS-ESI C10H18NO3 [MH]+: 212.1287; found quantitatively.
Eur. J. Org. Chem. 2010, 5181–5189
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5187

X. Liu, K. K. Hii
FULL PAPER
Butyl 3-(Benzamido)propanoate (7):[5] Colourless oil. IR: ν
=
δ = 153.7, 141.9, 117.0, 77.9, 62.5, 41.7 ppm. MS (EI): m/z (%) =
˜
max
3328, 1732, 1640, 1536, 1181 cm–1. 1H NMR (400 MHz, CDCl3, 138 (87) [M+], 83 (52), 79 (100), 52 (76), 42 (52). HRMS-EI calcd.
22 °C): δ = 7.80–7.71 (m, 2 H, Ar), 7.52–7.45 (m, 1 H, Ar), 7.44– for C6H6N2O2 [M]+: 138.0429; found 138.0429. C6H6N2O2
3
7.41 (m, 2 H, Ar), 6.89 (br. s, 1 H, NH), 4.11 (t, JH,H = 6.7 Hz, 2
(138.04): calcd. C 52.17, H 4.38, N 20.28; found C 52.33, H 4.29,
H, OCH2), 3.72 (dd, 3JH,H = 6.0, 11.8 Hz, 2 H, CH2), 2.64 (t, 3JH,H N 20.37.
= 6.0 Hz, 2 H, CH2), 1.66–1.55 (m, 2 H, CH2), 1.42–1.30 (m, 2 H,
(Z)-Methyl 3-(Dimethylamino)-3-oxoprop-1-enylcarbamate (Z-10):
Off white solid; m.p. 91–92 °C (lit.[12] 93–94 °C); Rf = 0.5, hexane/
3
CH2), 0.92 (t, JH,H = 7.4 Hz, 3 H, CH3) ppm. 13C NMR
(100.6 MHz, CDCl3, 22 °C): δ = 173.1, 167.3, 131.6, 128.6, 126.9,
64.8, 35.3, 33.9, 30.6, 19.2, 13.7 ppm. MS (EI): m/z (%) = 249 (25)
[M+], 144 (56), 105 (100), 77 (43).
EtOAc (1:2). IR: ν
= 3233, 1741, 1641, 1589, 1472, 1387, 1366,
˜
max
1272, 1206, 1047, 795 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ
3
= 10.73 (br. s, 1 H, NH), 7.14 (dd, JH,H = 9.9, 8.9 Hz, 1 H,
3
=CHN), 5.28 (d, JH,H = 8.9 Hz, 1 H, =CH), 3.73 (s, 3 H, OMe),
(E)-tert-Butyl 3-(Benzamido)acrylate (E-8a): White solid; m.p. 133–
3.01 (s, 3 H, NMe), 2.94 (s, 3 H, NMe) ppm. 13C NMR
(100.6 MHz, CDCl3, 22 °C): δ = 168.8, 154.5, 137.9, 93.4, 52.8,
37.4, 35.1 ppm. MS (EI): m/z (%) = 172 (56) [M+], 128 (50), 96
(100), 44 (56).
134 °C; R = 0.1, hexane/EtOAc (5:1). IR: νmax = 3307, 1672, 1632,
˜
f
1277, 1134, 704 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ = 8.63
(br. d, 3JH,H = 11.6 Hz, 1 H, NH), 8.12 (dd, 3JH,H = 11.6, 14.1 Hz,
1 H, =CHN), 7.85–7.83 (m, 2 H, Ar), 7.57–7.54 (m, 1 H, Ar), 7.47–
3
7.43 (m, 2 H, Ar), 5.55 (d, JH,H = 14.1 Hz, 1 H, =CH), 1.48 (s, 9
(Z)-3-(2-Oxooxazolidin-3-yl)acrylonitrile (Z-11): Yellow oil; Rf
=
H, tBu) ppm. 13C NMR (100.6 MHz, CDCl3, 22 °C): δ = 166.8,
165.1, 137.2, 132.8, 132.5, 128.9, 127.5, 104.5, 80.4, 28.3 ppm. MS
(EI): m/z (%) = 247 (7) [M+], 191 (39), 105 (100), 77 (42). HRMS-
EI calcd. for C14H17NO3 [M]+: 247.1208; found 247.1208.
C14H17NO3 (247.12): calcd. C 68.00, H 6.93, N 5.66; found C
68.002, H 6.95, N 5.69.
0.4, hexane/EtOAc (1:2). IR: ν = 3264, 1699, 1637, 1596, 1390,
˜
max
1148, 789 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ = 11.44 (br.
3
3
s, 1 H, NH), 7.40 (t, JH,H = 9.1 Hz, 1 H, =CHN), 5.35 (d, JH,H
= 9.1 Hz, 1 H, =CH), 3.04 (s, 3 H, NMe), 2.97 (s, 3 H, NMe), 2.29
3
(t, JH,H = 7.5 Hz, 2 H, CH2), 1.73–1.64 (m, 2 H, CH2), 0.94 (t,
3JH,H = 7.4 Hz, 3 H, CH3) ppm. 13C NMR (100.6 MHz, CDCl3,
22 °C): δ = 171.6, 169.0, 136.0, 94.6, 38.8, 37.5, 35.2, 18.6,
13.7 ppm. MS (EI): m/z (%) = 184 (53) [M+], 131 (39), 70 (100),
43 (39). HRMS-EI calcd. for C9H16N2O2 [M]+: 184.1212; found
184.1210. C9H16N2O2 (184.12): calcd. C 58.67, H 8.75, N 15.21;
found C 58.71, H 8.77, N 15.23.
(Z)-tert-Butyl 3-Benzamidoacrylate (Z-8a): White solid; m.p. 66–
67 °C; R = 0.35, hexane/EtOAc (5:1). IR: νmax = 3331, 1694, 1671,
˜
f
1522, 1367, 1224, 1148, 694 cm–1. 1H NMR (400 MHz, CDCl3,
3
22 °C): δ = 11.51 (br. d, JH,H = 10.9 Hz, 1 H, NH), 7.96–7.94 (m,
2 H, Ar), 7.67 (dd, JH,H = 10.9, 8.9 Hz, 1 H, =CHN), 7.60–7.56
(m, 1 H, Ar), 7.52–7.49 (m, 2 H, Ar), 5.17 (d, JH,H = 10.9 Hz, 1
3
3
Supporting Information (see also the footnote on the first page of
H, =CH), 1.52 (s, 9 H, tBu) ppm. 13C NMR (100.6 MHz, CDCl3,
22 °C): δ = 169.1, 164.6, 137.8, 132.7, 132.4, 128.9, 127.7, 99.17,
80.9, 28.3 ppm. MS (EI): m/z (%) = 247 (14) [M+], 191 (45), 105
(100), 77 (36). HRMS-EI calcd. for C14H17NO3 [M]+: 247.1208;
found 247.1209. C14H17NO3 (247.12): calcd. C 68.00, H 6.93, N
5.66; found C 68.09, H 6.90, N 5.71.
1
this article): H and 13C NMR spectra of isolated products.
Acknowledgments
We thank Imperial College London for studentship support (to
X. Z. L.), and Johnson Matthey plc for a loan of Pd salts.
N-[NЈ,NЈ-Dimethylamino-(Z)-propenoyl]benzamide (Z-8b): White
solid; m.p. 49–50 °C (lit.[7] 55–57 °C); Rf = 0.15, hexane/EtOAc
[1] a) V. Kotov, C. C. Scarborough, S. S. Stahl, Inorg. Chem. 2007,
46, 1910–1923; b) Y. Yamamoto, U. Radhakrishnan, Chem.
Soc. Rev. 1999, 28, 199–207.
[2] K. L. Li, P. N. Horton, M. B. Hursthouse, K. K. Hii, J. Or-
ganomet. Chem. 2003, 665, 250–257.
[3] J. J. Bozell, L. S. Hegedus, J. Org. Chem. 1981, 46, 2561–2563.
[4] a) K. Takasu, N. Nishida, M. Ihara, Synlett 2004, 1844–1846;
b) Y.-D. Lin, J.-Q. Kao, C.-T. Chen, Org. Lett. 2007, 9, 5195–
5198; c) S. Azad, T. Kobayashi, K. Nakano, Y. Ichikawa, H.
Kotsuki, Tetrahedron Lett. 2009, 50, 48–50.
[5] A. Hasaninejad, A. Parhami, A. R. M. Zare, A. Khalafi-
Nezhad, Pol. J. Chem. 2008, 82, 1059–1066.
(2:1). IR: ν
= 3208, 1682, 1632, 1595, 1452, 1382, 1255, 1140,
˜
max
785 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ = 12.59 (d, JH,H
3
3
= 10.2 Hz, 1 H, NH), 7.98–7.96 (m, 2 H, Ar), 7.66 (dd, JH,H
=
10.2, 8.9 Hz, 1 H, =CHN), 7.57–7.53 (m, 1 H, Ar), 7.49–7.45 (m,
2 H, Ar), 5.51 (d, 3JH,H = 8.9 Hz, 1 H, =CH), 3.07 (s, 6 H, NMe2)
ppm. 13C NMR (100.6 MHz, CDCl3, 22 °C): δ = 169.2, 164.7,
136.7, 132.6, 128.7, 127.8, 95.6, 37.6, 35.4 ppm. MS (EI): m/z (%)
= 218 (37) [M+], 174 (35), 105 (100), 77 (62).
(E)-N,N-Dimethyl-3-(2-oxooxazolidin-3-yl)acrylamide
(E-9a):
White solid; m.p. 231–232 °C; Rf = 0.35, hexane/EtOAc/MeOH
(2:2:1). IR: ν
= 1751, 1659, 1594, 1402, 1218, 753 cm–1. 1H
˜
[6] T. Hosokawa, M. Takano, Y. Kuroki, S. I. Murahashi, Tetrahe-
dron Lett. 1992, 33, 6643–6646.
max
3
NMR (400 MHz, CDCl3, 22 °C): δ = 7.92 (d, JH,H = 13.5 Hz, 1
H, =CHN), 5.58 (d, JH,H = 13.5 Hz, 1 H, =CH), 4.50 (t, JH,H
3
3
[7] J. M. Lee, D. S. Ahn, D. Y. Jung, J. Lee, Y. Do, S. K. Kim, S. K.
Chang, J. Am. Chem. Soc. 2006, 128, 12954–12962.
[8] a) L. Jiang, G. E. Job, A. Klapars, S. L. Buchwald, Org. Lett.
2003, 5, 3667–3669; b) P. Y. S. Lam, G. Vincent, D. Bonne,
C. G. Clark, Tetrahedron Lett. 2003, 44, 4927–4931; c) J. Bar-
luenga, M. A. Fernandez, F. Aznar, C. Valdes, Chem. Eur. J.
2004, 10, 494–507; d) X. H. Pan, Q. Cai, D. W. Ma, Org. Lett.
2004, 6, 1809–12; e) Y. Bolshan, R. A. Batey, Angew. Chem.
Int. Ed. 2008, 47, 2109–2112.
=
8.0 Hz, 2 H, CH2O), 3.79 (t, 3JH,H = 8.0 Hz, 2 H, CH2N), 3.03 (br.
s, 6 H, NMe2) ppm. 13C NMR (100.6 MHz, CDCl3, 22 °C): δ =
166.1, 154.7, 136.7, 99.8, 62.3, 42.6, 37.3, 35.7 ppm. MS (EI): m/z
(%) = 184 (20) [M+], 140 (100), 96 (56), 43 (58). HRMS-EI calcd.
for C8H12N2O3 [M]+: 184.0848; found 184.0851. C8H12N2O3
(184.08): calcd. C 52.17, H 6.57, N 15.21; found C 52.23, H 6.64,
N 15.19.
[9] a) M. D. K. Boele, G. P. F. van Strijdonck, A. H. M. de Vries,
P. C. J. Kamer, J. G. de Vries, P. W. N. M. van Leeuwen, J. Am.
Chem. Soc. 2002, 124, 1586–1587; b) W. Rauf, A. L. Thomp-
son, J. M. Brown, Chem. Commun. 2009, 3874–3876.
[10] C. E. Houlden, C. D. Bailey, J. G. Ford, M. R. Gagne, G. C.
Lloyd-Jones, K. I. Booker-Milburn, J. Am. Chem. Soc. 2008,
130, 10066–10067.
(E)-3-(2-Oxooxazolidin-3-yl)acrylonitrile (E-9b): White solid; m.p.
177–179 °C; R = 0.15, CH Cl /EtOAc (1:1). IR: νmax = 2215, 1761,
˜
f
2
2
1637, 1413, 1217, 750 cm–1. 1H NMR (400 MHz, CDCl3, 22 °C): δ
= 7.61 (d, 3JH,H = 14.6 Hz, 1 H, =CHN), 4.57 (d, 3JH,H = 14.6 Hz,
3
3
1 H, =CH), 4.56 (t, JH,H = 8.0 Hz, 2 H, CH2O), 3.77 (t, JH,H
=
8.0 Hz, 2 H, CH2N) ppm. 13C NMR (100.6 MHz, CDCl3, 22 °C):
5188
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Eur. J. Org. Chem. 2010, 5181–5189

Oxidative Amidation of Activated Alkene
[11] There was only one example of the reaction of ethyl carbamate
with ethyl acrylate, which gave a 1:2.1 mixture of E/Z-isomers,
from which the Z-enamide was isolated in 48% yield (see
ref.[6]).
[12] J. Farkas, J. Hapala, O. Jindrova, J. Skoda, Collect. Czech.
Chem. Commun. 1982, 47, 2932–2945.
Received: March 20, 2010
Published Online: August 3, 2010
Eur. J. Org. Chem. 2010, 5181–5189
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5189