Palladium-catalyzed oxidative aminocarbonylation by decarboxylative coupling: Synthesis of alkynyl amides

Article abstract of DOI:10.1002/ejoc.201403644

Alkynyl amides were synthesized from a palladium-catalyzed coupling reaction of alkynyl carboxylic acids and amines under carbon monoxide. The reaction was conducted with palladium(II) acetate (5 mol-%) and silver(I) oxide (1.0 equiv.) in acetonitrile at 80 °C for 1 h. This method provides good to moderate product yields and good functional group tolerance towards ketone, ester, and nitrile groups.

Full text of DOI:10.1002/ejoc.201403644

FULL PAPER
DOI: 10.1002/ejoc.201403644
Palladium-Catalyzed Oxidative Aminocarbonylation by Decarboxylative
Coupling: Synthesis of Alkynyl Amides
Jinil Hwang,[a] Jinseop Choi,[a] Kyungho Park,[a] Wonyoung Kim,[a] Kwang Ho Song,*[b] and
Sunwoo Lee*[a]
Keywords: Synthetic methods / Palladium / Carbonylation / Alkynes / Amides
Alkynyl amides were synthesized from a palladium-cata- (1.0 equiv.) in acetonitrile at 80 °C for 1 h. This method pro-
lyzed coupling reaction of alkynyl carboxylic acids and
amines under carbon monoxide. The reaction was conducted
with palladium(II) acetate (5 mol-%) and silver(I) oxide
vides good to moderate product yields and good functional
group tolerance towards ketone, ester, and nitrile groups.
been used [Scheme 1 (a)].[9] However, this method has some
drawbacks, as there are limited types of carbamoyl chlor-
ides commercially available and they are moisture sensitive.
A similar reaction type, the reaction of propiolic acid
derivatives with amines, has also been employed
[Scheme 1 (b)].[10] However, this process requires multiple
reaction steps to transform the acid into an active func-
tional group such as an ester and acid chloride. Recently,
Zhu and co-workers reported the copper-catalyzed direct
oxidative coupling of propiolic acid and formamide, but
only one example was described.[11] An alternative method,
the transition-metal-mediated or -catalyzed oxidative carb-
onylation of terminal alkynes and amines in the presence
of carbon monoxide has been reported, but there are few
published papers [Scheme 1 (c)]. Hoberg and co-workers re-
ported a noncatalytic system with a nickel complex for an
oxidative aminocarbonylation.[12] Gabriele and co-workers
first reported a PdI2-catalyzed oxidative aminocarbon-
ylation,[13] and the Yamamoto group employed PdCl2/PPh3
as a catalytic system in the synthesis of an alkynyl amide.[14]
Recently, Bhanage’s research group developed a hetero-
geneous reusable palladium catalytic system for an oxidat-
ive aminocarbonylation.[15] However, these methods employ
only four or five types of aryl alkynes in their coupling reac-
Introduction
Transition-metal-catalyzed carbonylations, which are
coupling reactions in the presence of carbon monoxide,
have been developed and widely used for the synthesis of a
number of carbonyl compounds such as ketones, aldehydes,
amides, and esters. These reactions with carbon monoxide
are valued because of their simplicity and atom economy.[1]
In addition, a variety of reactions such as Heck,[2] Suzuki,[3]
Stille,[4] and Sonogashira[5] coupling reactions have been
employed as carbonylative couplings to produce desired
ketones. We were first to report the palladium-catalyzed de-
carboxylative carbonylation for the synthesis of alkynyl
ketones from the coupling reactions of alkynyl carboxylic
acids and aryl halides in the presence of carbon mon-
oxide.[6] Although many kinds of decarboxylative coupling
reactions have been developed by our group and others,[7]
a decarboxylative oxidative carbonylation has never been
reported. Therefore, we have focused on developing the syn-
thesis of alkynyl amides by using a decarboxylative oxidat-
ive carbonylation.
In the pharmaceutical industry, the amide functionality
is one of the most important building blocks for the synthe-
sis of bioactive compounds.[8] Alkynyl amides are also im-
portant building blocks. Among the numerous methods to
prepare alkynyl amides, the coupling reaction between a
carbamoyl chloride and a terminal alkyne has most often
[a] Department of Chemistry and Institute of Basic Science,
Chonnam National University,
Gwangju 500-757, Republic of Korea
E-mail: sunwoo@chonnam.ac.kr
[b] Department of Chemical & Biological Engineering,
Korea University,
Seoul, 1360713, Republic of Korea
E-mail: khsong@korea.ac.kr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201403644.
Scheme 1. Synthesis of alkynyl amides.
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tions. This might be because a multistep process is required yields (Table 1, Entries 1 and 2). Copper oxidants did not
for the preparation of aryl alkynes. Compared with aryl alk- provide satisfactory results (Table 1, Entries 3 and 4).
ynes, aryl alkynyl carboxylic acids are more easily prepared Among the silver oxidants tested, Ag2O gave the best result
by employing one-pot coupling reactions between aryl hal- and afforded the amide product in 52% yield (Table 1, En-
ides and propiolic acid followed by a simple workup pro- try 7). In addition to Pd(OAc)2, other palladium sources
cess.[16] This factor and our previous success with regard to were also tested. PdI2, which has good activity in the
decarboxylative carbonylations encouraged us to develop aminocarbonylation of terminal alkynes, gave the product
the oxidative aminocarbonylation of aryl alkynyl carboxylic in 15% yield (Table 1, Entry 8). Reactions with PdCl2,
acids by using a palladium catalyst.
Pd(CH3CN)2Cl2, and Pd(PPh3)2Cl2 afforded the desired
product in 21, 10, and 47% yield, respectively (Table 1, En-
tries 9–11). The yields of the reactions that used 1,4-diox-
ane, toluene, DMSO, and DMF, respectively, as the solvent
Results and Discussion
To achieve our goal, phenylpropiolic acid and morph-
oline were chosen as the model substrates as shown in
Table 1. With regard to the coupling of two nucleophiles, it
is important to choose a suitable oxidant to obtain the de-
sired alkynyl amide in good yield. Hence, the first step of
our investigation was to screen a variety of oxidants.
Organic oxidants such as benzoquinone and tert-butyl
hydroperoxide provided the desired amide product in low
Table 2. Aminocarbonylation of phenylpropiolic acid with a variety
of amines.[a]
Table 1. Optimization of aminocarbonylation of phenylpropiolic
acid (1a) with morpholine (2a).[a]
Entry Catalyst
Additive
Solvent
Yield [%][b]
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdI2
benzoquinone
TBHP[c]
Cu(OAc)2
Cu(OTf)2
Ag2CO3
AgOAc
Ag2O
Ag2O
Ag2O
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
dioxane
toluene
DMSO[c]
DMF[c]
CH3CN
CH3CN
CH3CN
trace
7
2
8
12
21
52
15
21
10
47
47
2
29
12
75
92
43
9
PdCl2
Pd(MeCN)2Cl2 Ag2O
10
11
12
13
14
15
16[d]
17[e]
18[f]
Pd(PPh3)2Cl2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
[a] Reagents and conditions: 1a (0.3 mmol), CO (8.0 bar), 2a
(0.6 mmol), Pd (0.015 mmol), and the additive (0.3 mmol) were
combined in the solvent (1.0 mL) at 80 °C for 1 h. [b] Yield was
determined by GC analysis with an internal standard. [c] TBHP =
tert-butyl hydroperoxide, DMSO = dimethyl sulfoxide, DMF =
N,N-dimethylformamide. [d] Morpholine (3 equiv.) was used.
[e] Morpholine (3.0 equiv.) was used under CO (5 bar). [f] Morph-
oline (3.0 equiv.) was used under CO (2 bar).
[a] Reagents and conditions: 1a (3.0 mmol), CO (5.0 bar),
(9.0 mmol), Pd(OAc)2 (0.15 mmol), and Ag2O (3.0 mmol) were
combined in CH3CN (5 mL) at 80 °C for 1 h. [b] Isolated yield.
2
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Palladium-Catalyzed Oxidative Aminocarbonylation
were lower than that of the reaction in CH3CN (Table 1,
Next, a variety of amines were treated with phenylpropi-
Entries 12–15). Increasing the amount of morpholine to olic acid to evaluate the optimized reaction conditions for
3 equiv. increased the yield of the product to 75% (Table 1, the oxidative aminocarbonylation. As shown in Table 2,
Entry 16). Decreasing the pressure of the carbon monoxide both cyclic and noncyclic secondary amines provided the
to 5 bar led to the formation of the product in 92% yield desired alkynyl amides. The reactions with morpholine (2a),
(Table 1, Entry 17). The reaction that was carried out under pyrrolidine (2b), piperidine (2c), and azepane (2d) afforded
2 bar of carbon monoxide gave only 43% yield of the prod- the corresponding alkynyl amides in 92, 57, 75, and 88%
uct (Table 1, Entry 18).
yield, respectively (Table 2, Entries 1–4). The reaction of
Table 3. Synthesis of a variety of aryl alkynyl amides.[a]
[a] Reagents and conditions: 1a (3.0 mmol), CO (5.0 bar), 2 (9.0 mmol), Pd(OAc)2 (0.15 mmol), and Ag2O (3.0 mmol) were combined in
the CH3CN (5 mL) at 80 °C for 1 h.
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FULL PAPER
1,2,3,4-tetrahydroisoquinoline and phenylpropiolic acid
with carbon monoxide produced the desired product 3ae in
72% yield (Table 2, Entry 5). N-Methylbenzylamine (2f)
gave the desired product in 62% yield (Table 2, Entry 6).
The reaction with acyclic amines such as diethylamine (2g),
dipropylamine (2h), and diallylamine (2i) afforded moder-
ate product yields (Table 2, Entries 7–9). When primary
amines such as aniline (2j) and cyclohexylamine (2k) were
allowed to react with phenylpropiolic acid and carbon mon-
oxide, we failed to obtain the desired amide products
(Table 2, Entries 10 and 11). The Bhanage group also re-
ported that their coupling reactions with a primary amine
had failed.[15]
To expand on this methodology, we employed a variety
of aryl alkynyl carboxylic acids, which are easily synthesized
from the coupling reaction of aryl halides and propiolic
acid. The results are summarized in Table 3. Methyl-substi-
tuted aryl propiolic acids such as o-, m-, and (p-tolyl)propi-
olic acids as well as (2,4-dimethylphenyl)propiolic acid were
treated with morpholine and carbon monoxide to give the
corresponding alkynyl amides in 74, 80, 77, and 71% yield,
respectively (Table 3, Entries 1–4). 2-Methoxy- and (3,4,5-
trimethoxy)phenylpropiolic acids gave the corresponding
products in 73 and 54% yield, respectively (Table 3, En-
tries 5 and 6).
(4-Fluorophenyl)propiolic acid underwent the reaction
with morpholine and carbon monoxide to give the product
in 68% yield (Table 3, Entry 7). 1-Naphthyl- and 4Ј-biphen-
ylpropiolic acid provided the desired products in 65 and
66% yield, respectively (Table 3, Entries 8 and 9). Aryl
proplioic acids that contain a ketone, ester, or nitrile group
afforded the corresponding alkynyl amides in 53, 45, and
47% yield, respectively (Table 3, Entries 10–12). When an
acyclic diamine such as dipropylamine was allowed to react
with substituted aryl propiolic acids, the desired products
were afforded in moderate to good yields. In this case, the
methyl-substituted aryl propiolic acids provided the corre-
sponding alkynyl amides in 69 and 62% yield, respectively
(Table 3, Entries 13 and 14). 4-(Fluorophenyl)propiolic acid
gave the corresponding product in 65% yield (Table 3, En-
try 15). Aryl propiolic acid 1l, which contained an ester
group, and (thiophenyl)propiolic acid (1n) gave the desired
products in 49 and 41% yield, respectively (Table 3, En-
tries 16 and 17).
As shown in Scheme 2, alkyl-substituted propiolic acids
such as 2-butynoic acid (1o), 2-pentynoic acid (1p), 2-hex-
ynonic acid (1q), and 2-octynoic acid (1r) were treated with
morpholine and carbon monoxide to give the correspond-
ing amides in 42, 38, 41, and 59% yield, respectively.
We then attempted to employ the secondary amino ester
methyl pyrrolidine-2-carboxylate in this aminocarb-
onylation reaction, but the desired product was not ob-
tained. In addition, carrying out the reaction with N-meth-
oxy-N-methylamine did not provide any coupled product.
Scheme 2. Synthesis of alkyl alkynyl amides. Reagents and condi-
tions:
1 (3.0 mmol), CO (5.0 bar), 2a (9.0 mmol), Pd(OAc)2
(0.15 mmol), and Ag2O (3.0 mmol) were combined in the CH3CN
(5 mL) at 80 °C for 1 h.
of carbonylated product 3aa or aminated product 5
[Scheme 3 (a)]. This result supports the theory that the alk-
ynyl amide is formed from a carbonylation reaction not a
direct condensation between the acid and amine. In ad-
dition, carbon monoxide might inhibit the decarboxylative
homocoupling of phenylpropiolic acid. When the amino-
carbonylation was conducted with 1.0 equiv. of Pd(OAc)2
in the absence of Ag2O, a trace amount of product 3aa was
detected [Scheme 3 (b)]. This result implies that Ag2O
works as a base as well as an oxidant. When amido-palla-
dium complex 6[17] was allowed to react with phenylprop-
iolic acid in the presence of Ag2O, the desired coupled
product 3ag was formed in 67% yield [Scheme 3 (c)]. The
alkynyl-palladium complex 7[18] was allowed to react with
CO and morpholine in the presence of Ag2O to produce
the corresponding amide product in 71% yield
[Scheme 3 (d)]. We found that methyl phenylpropiolate (8)
did not provide amide 3aa under the reaction conditions
[Scheme 3 (e)]. In addition, when amide 3dh was treated
with morpholine, morpholine-substituted amide 3da was
not formed [Scheme 3 (f)]. This suggests that no amine sub-
stitution had occurred in the palladium catalytic cycle of
the reaction.
On the basis of these results, we proposed two reaction
pathways as shown in Scheme 4. In path A, the palladium
undergoes a reaction with phenylpropiolic acid to produce
a phenyl alkynyl palladium complex by a decarboxylative
reaction that is mediated by silver oxide. The insertion of
carbon monoxide into this palladium complex is followed
by a substitution reaction with the amine to produce the
resulting aminocarbonylated product. In path B, the palla-
dium first undergoes a reaction with the amine and carbon
monoxide to produce carbamoylpalladium complex, which
is then treated with the phenyl alkynyl carboxylic acid to
give the desired product.
Conclusions
In summary, we have developed a palladium-catalyzed
aminocarbonylation for the synthesis alkynyl amides from
We then studied the reaction pathway. When phenyl- the coupling reactions alkynyl carboxylic acids, amines, and
propiolic acid and morpholine were allowed to react in the carbon monoxide. Although atom economy is an issue with
absence of carbon monoxide, homocoupled product 1,4-di- the employment of alkynyl carboxylic acids, compared with
phenylbuta-1,3-diyne was obtained without the formation terminal alkynes, alkynyl carboxylic acids have several ad-
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Palladium-Catalyzed Oxidative Aminocarbonylation
Scheme 3. Studies to determine the reaction pathway.
vantages such as a simple preparation, easy handling, and
good stability. This is the first example of an oxidative
aminocarbonylation of alkynyl carboxylic acids. Cyclic and
acyclic amines afforded the desired alkynyl amides when
they were treated with a variety of aryl alkynyl carboxylic
acids under carbon monoxide. We found that Ag2O is the
key reagent and acts as both an oxidant and a base.
Experimental Section
General Procedure for the Synthesis of Alkynyl Amides: All coupling
reaction experiments were carried out in a 200 mL autoclave that
was equipped with magnetic stirring and automatic temperature
control. The aryl alkynyl carboxylic acid (3.0 mmol), secondary
amine (9.0 mmol), Pd(OAc)2 (33.7 mg, 0.15 mmol), Ag2O
(695.7 mg, 3.0 mmol), and CH3CN (5 mL) were mixed in the
20 mL vial. The reaction mixture was placed in an autoclave. After
the autoclave was closed, the reaction mixture was purged with
carbon monoxide (3ϫ), pressurized with CO (5 bar), and then
stirred at 80 °C for 1 h. The reaction mixture was poured into
Scheme 4. Proposed reaction pathways.
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J. Hwang, J. Choi, K. Park, W. Kim, K. H. Song, S. Lee
FULL PAPER
water, and the resulting mixture was extracted with ethyl acetate
(3ϫ 20 mL). The combined ethyl acetate extracts were dried with
MgSO4 and then was passed through Celite. The solvent was re-
moved under vacuum, and the resulting crude residue was purified
by flash chromatography on silica gel [ethyl acetate/hexane, 1:40
(for 3ac); ethyl acetate/hexane, 1:10 (for 3ah, 3ch, 3lh, and 3nh);
hydroisoquinoline (2e, 1.199 g, 9.0 mmol) afforded product 3ae
(0.564 g, 2.16 mmol, 72% yield) as a yellow oil. 1H NMR
(300 MHz, CDCl3): δ = 7.63–7.54 (m, 2 H), 7.44–7.35 (m, 3 H),
7.24–7.14 (m, 4 H), 4.98 (s, 1 H), 4.82 (s, 1 H), 4.10–4.06 (m, 1 H),
3.91 (t, 1 H), 2.95 (dt, J = 6.0 Hz, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 153.7, 153.4, 134.6, 133.8, 132.4, 132.3, 132.2, 130.1,
ethyl acetate/hexane, 1:4 (for 3ae, 3af, 3ag, 3ia, 3ja, and 3dh); ethyl 129.0, 128.6, 128.5, 127.0, 126.70, 126.67, 126.6, 126.5, 126.1,
acetate/hexane, 1:2 (for 3aa, 3ab, 3ad, 3ai, 3ba, 3ca, 3da, 3ea, 3fa,
3hh, and 3ra); and ethyl acetate/hexane, 1:1 (for 3ga, 3ha, 3ka, 3la,
3ma, 3oa, 3pa, and 3qa)].
120.5, 91.1, 90.3, 81.4, 81.3, 48.6, 44.7, 44.0, 39.7, 29.7, 29.5,
28.3 ppm. MS: m/z (relative intensity) = 261 (8), 217 (25), 205 (55),
175 (30), 57 (100).
General Procedure for the Synthesis of Aryl Alkynyl Carboxylic
Acids: Propiolic acid (385.3 mg, 5.5 mmol) was diluted with DMSO
N-Benzyl-N-methyl-3-phenylpropiolamide (3af):[19] Phenylpropiolic
acid (1a, 0.439 g, 3.0 mmol) and N-methylbenzylamine (2f, 0.364 g,
(3.0 mL). The solution was added to a mixture of Pd(PPh3)4 9.0 mmol) afforded product 3af (0.464 g, 1.86 mmol, 62% yield) as
1
(288.9 mg, 0.25 mmol), the aryl iodide (5.0 mmol), 1,8-diazabi-
a yellow oil. H NMR (300 MHz, CDCl3): δ = 7.59–7.53 (m, 1 H),
cyclo[5.4.0]undec-7-ene (DBU, 1.67 g, 11.0 mmol), and DMSO 7.53–7.46 (m, 1 H), 7.44–7.26 (m, 8 H), 4.86, 4.67 (s, 2 H), 3.19,
(7.0 mL) in a small round-bottom flask. The resulting mixture was
stirred at 25 °C and poured into ethyl acetate (25.0 mL). The re-
2.94 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 154.8 (2 C),
136.2, 136.1, 132.4 (2 C), 130.0 (2 C), 128.8, 128.7, 128.5 (2 C),
sulting mixture was extracted with a saturated aqueous NaHCO3 128.2, 127.9, 127.6, 127.5, 120.5, 120.4, 90.7, 90.2, 81.6 (2 C), 55.0,
solution. The aqueous layer was separated and acidified to pH =
2.0 by the addition of cold HCl (1 n). The resulting mixture was
extracted with ethyl ether. The combined organic layers were dried
with MgSO4 and filtered, and the solvent was removed under re-
duced pressure. The resulting crude residue was purified by flash
chromatography on silica gel.
49.9, 35.8, 31.9 ppm. MS: m/z (relative intensity) = 249 (10), 248
(39), 220 (15), 144 (25), 129 (100).
N,N-Diethyl-3-phenylpropiolamide (3ag):[15] Phenylpropiolic acid
(1a, 0.439 g, 3.0 mmol) and diethylamine (2g, 0.658 g, 9.0 mmol)
afforded product 3ag (0.410 g, 2.04 mmol, 68% yield) as a yellow
oil 1H NMR (300 MHz, CDCl3): δ = 7.56–7.52 (m, 2 H), 7.44–7.33
1-Morpholino-3-phenylprop-2-yn-1-one (3aa):[19] Phenylpropiolic (m, 3 H), 3.67 (q, J = 7.1 Hz, 2 H), 3.48 (q, J = 7.2 Hz, 2 H), 1.28
acid (1a, 0.439 g, 3.0 mmol) and morpholine (2a, 0.784 g, (t, J = 7.2 Hz, 3 H), 1.18 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR
9.0 mmol) afforded product 3aa (0.594 g, 2.76 mmol, 92% yield) as
a yellow oil. H NMR (300 MHz, CDCl3): δ = 7.56–7.51 (m, 2 H), 43.6, 39.3, 14.4, 12.9 ppm. MS: m/z (relative intensity) = 201 (18),
(75 MHz, CDCl3): δ = 154.0, 132.3, 129.8, 128.5, 120.7, 89.0, 81.9,
1
7.44–7.34 (m, 3 H), 3.89–3.83 (m, 2 H), 3.77–3.73 (m, 2 H), 3.71
(s, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.2, 132.3, 130.2,
128.5, 120.2, 91.2, 80.7, 66.9, 66.5, 47.3, 41.9 ppm. MS: m/z (rela-
tive intensity) = 215 (10), 129 (100), 101 (10), 86 (28), 75 (20).
172 (5), 129 (100), 75 (10), 51 (7).
3-Phenyl-N,N-dipropylpropiolamide (3ah): Phenylpropiolic acid (1a,
0.439 g, 3.0 mmol) and dipropylamine (2h, 0.911 g, 9.0 mmol) af-
forded product 3ah (0.454 g, 1.98 mmol, 66% yield) as a yellow oil.
1H NMR (300 MHz, CDCl3): δ = 7.59–7.47 (m, 2 H), 7.43–7.32
(m, 3 H), 3.57 (m, 2 H), 3.37 (m, 2 H), 1.76–1.56 (m, 4 H), 1.00–
0.90 (m, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 154.5, 132.2,
3-Phenyl-1-(pyrrolidin-1-yl)prop-2-yn-1-one (3ab):[15] Phenylprop-
iolic acid (1a, 0.439 g, 3.0 mmol) and pyrrolidine (2b, 0.640 g,
9.0 mmol) afforded product 3ab (0.340 g, 1.71 mmol, 57% yield) as
1
a yellow oil. H NMR (300 MHz, CDCl3): δ = 7.59–7.50 (m, 2 H), 129.8, 128.5, 120.8, 89.2, 82.1, 50.8, 46.5, 22.2, 20.7, 11.34,
7.42–7.33 (m, 3 H), 3.76–3.71 (m, 2 H), 3.56–3.51 (m, 2 H), 2.00–
11.25 ppm. HRMS (ESI, TOF): calcd. for C15H20NO [M + H]+
1.93 (m, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 152.7, 132.4, 230.1545; found 230.1542.
129.9, 128.4, 120.6, 88.7, 82.6, 48.1, 45.3, 25.4, 24.7 ppm. MS: m/z
N,N-Diallyl-3-phenylpropiolamide (3ai): Phenylpropiolic acid (1a,
(relative intensity) = 199 (18), 184 (32), 171 (12), 129 (100), 101
(20).
0.439 g, 3.0 mmol) and diallylamine (2i, 0.874 g, 9.0 mmol) af-
forded product 3ai (0.412 g, 1.83 mmol, 61% yield) as a yellow oil.
1H NMR (300 MHz, CDCl3): δ = 7.54 (m, 2 H), 7.45–7.33 (m, 3
H), 5.91–5.71 (m, 2 H), 5.28–5.16 (m, 4 H), 4.23 (dt, J = 5.7,
1.4 Hz, 2 H), 4.07 (dt, J = 6.0, 1.4 Hz, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 154.5, 132.7, 132.4, 132.1, 130.0, 128.5,
120.5, 118.1, 118.0, 89.9, 81.5, 50.8, 46.4 ppm. HRMS (ESI, TOF):
3-Phenyl-1-(piperidin-1-yl)prop-2-yn-1-one (3ac):[15] Phenylpropiolic
acid (1a, 0.439 g, 3.0 mmol) and piperidine (2c, 0.766 g, 9.0 mmol)
afforded product 3ac (0.480 g, 2.25 mmol, 75% yield) as a yellow
1
solid; m.p. 80–81 °C. H NMR (300 MHz, CDCl3): δ = 7.63–7.47
(m, 2 H), 7.46–7.30 (m, 3 H), 3.92–3.68 (m, 2 H), 3.67–3.51 (m, 2
H), 1.68–1.57 (m, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = calcd. for C15H16NO [M + H]+ 226.1232; found 226.1231.
152.9, 132.3, 129.8, 128.4, 120.7, 90.2, 81.4, 48.2, 42.4, 26.4, 25.4,
1-Morpholino-3-o-tolylprop-2-yn-1-one (3ba): 3-o-Tolylpropiolic
24.5 ppm. MS: m/z (relative intensity) = 213 (64), 184 (25), 143
acid (1b, 0.481 g, 3.0 mmol) and morpholine (2a, 0.784 g,
(10), 129 (100), 75 (13).
9.0 mmol) afforded product 3ba (0.509 g, 2.22 mmol, 74% yield) as
1
1-(Azepan-1-yl)-3-phenylprop-2-yn-1-one (3ad): Phenylpropiolic
acid (1a, 0.439 g, 3.0 mmol) and azepane (2d, 0.893 g, 9.0 mmol)
afforded product 3ad (0.600 g, 2.64 mmol, 88% yield) as a yellow
oil. 1H NMR (300 MHz, CDCl3): δ = 7.57–7.51 (m, 2 H), 7.42–
a yellow oil. H NMR (300 MHz, CDCl3): δ = 7.52 (dd, J = 7.6,
1.3 Hz, 1 H), 7.32 (td, J = 7.5, 1.3 Hz, 1 H), 7.26–7.14 (m, 2 H),
3.94–3.82 (m, 2 H), 3.80–3.73 (m, 2 H), 3.71 (s, 4 H), 2.47 (s, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.3, 141.2, 132.9,
7.32 (m, 3 H), 3.78 (m, 2 H), 3.60 (m, 2 H), 1.85–1.73 (m, 4 H), 130.1, 129.7, 125.8, 120.1, 90.2, 84.5, 66.8, 66.4, 47.3, 41.9,
1.62–1.58 (m, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 154.5, 20.7 ppm. HRMS (ESI, TOF): calcd. for C14H16NO2 [M + H]+
132.3, 129.8, 128.4, 120.8, 89.6, 81.9, 49.1, 45.3, 29.2, 27.2, 27.1,
27.0 ppm. HRMS (ESI, TOF): calcd. for C15H18NO [M + H]+
228.1388; found 228.1387.
230.1181; found 230.1181.
1-Morpholino-3-m-tolylprop-2-yn-1-one (3ca): 3-m-Tolylpropiolic
acid (1c, 0.481 g, 3.0 mmol) and morpholine (2a, 0.784 g,
1-[3,4-Dihydroisoquinolin-2(1H)-yl]-3-phenylprop-2-yn-1-one (3ae):[15] 9.0 mmol) afforded product 3ca (0.550 g, 2.40 mmol, 80% yield) as
Phenylpropiolic acid (1a, 0.439 g, 3.0 mmol) and 1,2,3,4-tetra-
1
a yellow oil. H NMR (300 MHz, CDCl3): δ = 7.37–7.34 (m, 2 H),
2240
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 2235–2243

Palladium-Catalyzed Oxidative Aminocarbonylation
7.28–7.18 (m, 2 H), 3.86–3.80 (m, 2 H), 3.77–3.73 (m, 2 H), 3.70
7.2 Hz, 1 H), 4.00–3.90 (m, 2 H), 3.82–3.77 (m, 2 H), 3.77–3.50 (m,
(s, 4 H), 2.35 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.3, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.2, 133.2, 133.0,
138.3, 132.8, 131.1, 129.5, 128.4, 120.0, 91.4, 80.4, 66.9, 66.5, 47.3,
41.9, 21.1 ppm. HRMS (ESI, TOF): calcd. for C14H16NO2 [M +
H]+ 230.1181; found 230.1182.
132.1, 130.7, 128.5, 127.5, 126.8, 125.6, 125.1, 117.8, 89.6, 85.3,
66.9, 66.5, 47.4, 42.0 ppm. HRMS (ESI, TOF): calcd. for
C17H16NO2 [M + H]+ 266.1181; found 266.1178.
3-(Biphenyl-4-yl)-1-morpholinoprop-2-yn-1-one (3ja): 3-(Biphenyl-4-
yl)propiolic acid (1j, 0.667 g, 3.0 mmol) and morpholine (2a,
0.784 g, 9.0 mmol) afforded product 3ja (0.576 g, 1.98 mmol, 66%
1-Morpholino-3-p-tolylprop-2-yn-1-one (3da): 3-p-Tolylpropiolic
acid (1d, 0.481 g, 3.0 mmol) and morpholine (2a, 0.784 g,
9.0 mmol) afforded product 3da (0.529 g, 2.31 mmol, 77% yield) as
1
1
yield) as a yellow solid; m.p. 129.0–130.0 °C. H NMR (300 MHz,
a yellow solid; m.p. 88.0–89.0 °C. H NMR (300 MHz, CDCl3): δ
CDCl3): δ = 7.65–7.56 (m, 6 H), 7.50–7.42 (m, 2 H), 7.42–7.34 (m,
1 H), 3.93–3.83 (m, 2 H), 3.81–3.75 (m, 2 H), 3.72 (s, 4 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 153.2, 143.0, 139.8, 132.8, 128.9,
128.1, 127.2, 127.1, 119.0, 91.2, 81.3, 66.9, 66.5, 47.3, 42.0 ppm.
HRMS (ESI, TOF): calcd. for C19H18NO2 [M + H]+ 292.1338;
found 292.1336.
= 7.51–7.38 (m, 2 H), 7.21–7.13 (m, 2 H), 3.84 (ddd, J = 4.6, 2.9,
1.1 Hz, 2 H), 3.75 (ddd, J = 4.5, 2.8, 1.1 Hz, 2 H), 3.70 (s, 4 H),
2.38 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.3, 140.7,
132.3, 129.3, 117.1, 91.5, 80.3, 66.8, 66.4, 47.2, 41.9, 21.6 ppm.
HRMS (ESI, TOF): calcd. for C14H16NO2 [M + H]+ 230.1181;
found 230.1179.
3-(4-Acetylphenyl)-1-morpholinoprop-2-yn-1-one (3ka): 3-(4-Acet-
ylphenyl)propiolic acid (1k, 0.565 g, 3.0 mmol) and morpholine
(2a, 0.784 g, 9.0 mmol) afforded product 3ka (0.409 g, 1.59 mmol,
53% yield) as a yellow solid; m.p. 128.0–129.0 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.99–7.88 (m, 2 H), 7.69–7.57 (m, 2 H),
3.84 (ddd, J = 6.8, 5.1, 2.9 Hz, 2 H), 3.77 (ddd, J = 4.6, 2.5, 0.9 Hz,
2 H), 3.72 (s, 4 H), 2.62 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 197.0, 152.7, 137.7, 132.5, 128.3, 124.9, 89.8, 83.1, 66.9, 66.4,
47.3, 42.0, 26.7 ppm. HRMS (ESI, TOF): calcd. for C15H16NO3
[M + H]+ 258.1130; found 258.1127.
3-(2,4-Dimethylphenyl)-1-morpholinoprop-2-yn-1-one (3ea): 3-(2,4-
Dimethylphenyl)propiolic acid (1e, 0.523 g, 3.0 mmol) and morph-
oline (2a, 0.784 g, 9.0 mmol) afforded product 3ea (0.518 g,
2.13 mmol, 71% yield) as a yellow oil. 1H NMR (300 MHz,
CDCl3): δ = 7.41 (d, J = 7.8 Hz, 1 H), 7.05 (s, 1 H), 6.99 (d, J =
8.8 Hz, 1 H), 3.91–3.81 (m, 2 H), 3.75 (dt, J = 6.4, 4.3 Hz, 2 H),
3.71 (s, 4 H), 2.43 (s, 3 H), 2.34 (s, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 153.4, 141.1, 140.6, 132.8, 130.5, 126.6, 117.0, 90.7,
84.0, 66.8, 66.4, 47.2, 41.9, 21.5, 20.6 ppm. HRMS (ESI, TOF):
calcd. for C15H18NO2 [M + H]+ 244.1338; found 244.1337.
Methyl 4-(3-Morpholino-3-oxoprop-1-ynyl)benzoate (3la): 3-[4-
(Methoxycarbonyl)phenyl]propiolic acid (1l, 0.613 g, 3.0 mmol)
and morpholine (2a, 0.784 g, 9.0 mmol) afforded product 3la
(0.369 g, 1.35 mmol, 45% yield) as a yellow solid; m.p. 125.0–
126.0 °C. 1H NMR (300 MHz, CDCl3): δ = 8.14–7.95 (m, 2 H),
7.80–7.33 (m, 2 H), 3.94 (s, 3 H), 3.90–3.81 (m, 2 H), 3.81–3.74 (m,
2 H), 3.71 (s, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 166.1,
152.7, 132.2, 131.3, 129.6, 124.7, 89.8, 82.8, 66.8, 66.4, 52.4, 47.3,
42.0 ppm. HRMS (ESI, TOF): calcd. for C15H16NO4 [M + H]+
274.1079; found 274.1078.
3-(2-Methoxyphenyl)-1-morpholinoprop-2-yn-1-one (3fa): 3-(2-
Methoxyphenyl)propiolic acid (1f, 0.529 g, 3.0 mmol) and morph-
oline (2a, 0.784 g, 9.0 mmol) afforded product 3fa (0.537 g,
2.19 mmol, 73% yield) as a yellow solid; m.p. 91.0–92.0 °C. 1H
NMR (300 MHz, CDCl3): δ = 7.61–7.47 (m, 1 H), 7.39 (ddd, J =
8.4, 7.5, 1.8 Hz, 1 H), 7.06–6.77 (m, 2 H), 3.99–3.91 (m, 2 H), 3.88
(s, 3 H), 3.80–3.73 (m, 2 H), 3.70 (s, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 161.1, 153.4, 134.2, 131.8, 120.5, 110.6, 109.5, 87.8,
84.9, 66.9, 66.5, 55.7, 47.2, 41.9 ppm. HRMS (ESI, TOF): calcd.
for C14H16NO3 [M + H]+ 246.1130; found 246.1130.
4-(3-Morpholino-3-oxoprop-1-ynyl)benzonitrile (3ma): 3-(4-Cyano-
phenyl)propiolic acid (1m, 0.514 g, 3.0 mmol) and morpholine (2a,
0.784 g, 9.0 mmol) afforded product 3ma (0.339 g, 1.41 mmol, 47%
1-Morpholino-3-(3,4,5-trimethoxyphenyl)prop-2-yn-1-one (3ga): 3-
(3,4,5-Trimethoxyphenyl)propiolic acid (1g, 0.709 g, 3.0 mmol) and
morpholine (2a, 0.784 g, 9.0 mmol) afforded product 3ga (0.494 g,
1.62 mmol, 54% yield) as a yellow solid; m.p. 145.0–146.0 °C. 1H
NMR (300 MHz, CDCl3): δ = 6.79 (s, 2 H), 3.87 (d, J = 3.8 Hz, 9
H), 3.85–3.81 (m, 2 H), 3.77 (dd, J = 5.5, 3.6 Hz, 2 H), 3.70 (s, 4
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.02, 152.99, 140.3,
114.8, 109.6, 91.3, 79.8, 66.7, 66.3, 60.8, 56.1, 47.1, 41.8 ppm.
HRMS (ESI, TOF): calcd. for C16H20NO5 [M + H]+ 306.1341;
found 306.1340.
1
yield) as a yellow solid; m.p. 198.0–199.0 °C. H NMR (300 MHz,
CDCl3): δ = 7.71–7.66 (m, 2 H), 7.66–7.60 (m, 2 H), 3.85–3.79 (m,
2 H), 3.79–3.74 (m, 2 H), 3.72 (s, 4 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 152.3, 132.7, 132.2, 125.0, 117.9, 113.6, 88.6, 83.9,
66.8, 66.4, 47.3, 42.0 ppm. HRMS (ESI, TOF): calcd. for
C14H13N2O2 [M + H]+ 241.0977; found 241.0979.
N,N-Dipropyl-3-m-tolylpropiolamide (3ch): 3-m-Tolylpropiolic acid
(1c, 0.481 g, 3.0 mmol) and dipropylamine (2h, 0.911 g, 9.0 mmol)
afforded product 3ch (0.504 g, 2.07 mmol, 69% yield) as a yellow
oil. 1H NMR (300 MHz, CDCl3): δ = 7.35–7.28 (m, 2 H), 7.25–
7.19 (m, 2 H), 3.60–3.55 (m, 2 H), 3.39–3.35 (m, 2 H), 2.35 (s, 3 H),
1.76–1.55 (m, 4 H), 1.02–0.90 (m, 6 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 154.6, 138.2, 132.7, 130.7, 129.4, 128.4, 120.6, 89.5,
81.8, 50.8, 46.5, 22.2, 21.2, 20.7, 11.4, 11.3 ppm. HRMS (ESI,
TOF): calcd. for C16H22NO [M + H]+ 244.1701; found 244.1699.
3-(4-Fluorophenyl)-1-morpholinoprop-2-yn-1-one (3ha): 3-(4-Fluoro-
phenyl)propiolic acid (1h, 0.492 g, 3.0 mmol) and morpholine (2a,
0.784 g, 9.0 mmol) afforded product 3ha (0.476 g, 2.04 mmol, 68%
yield) as a yellow solid; m.p. 94.0–95.0 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.64–7.44 (m, 2 H), 7.16–7.00 (m, 2 H), 3.88–3.80 (m,
2 H), 3.80–3.73 (m, 2 H), 3.71 (s, 4 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 165.6 (d, J = 251.3 Hz), 153.0, 134.5 (d, J = 8.7 Hz),
116.3 (d, J = 3.5 Hz), 116.0 (d, J = 22.1 Hz), 90.1, 80.6, 66.8, 66.4,
47.3, 41.9 ppm. HRMS (ESI, TOF): calcd. for C13H13NO2F [M +
H]+ 234.0930; found 234.0932.
N,N-Dipropyl-3-p-tolylpropiolamide (3dh): 3-p-Tolylpropiolic acid
(1d, 0.481 g, 3.0 mmol) and dipropylamine (2h, 0.911 g, 9.0 mmol)
afforded product 3dh (0.452 g, 1.86 mmol, 62% yield) as a yellow
oil. 1H NMR (300 MHz, CDCl3): δ = 7.49–7.35 (m, 2 H), 7.17 (dd,
J = 8.4, 0.6 Hz, 2 H), 3.66–3.50 (m, 2 H), 3.43–3.30 (m, 2 H), 2.37
(s, 3 H), 1.73–1.58 (m, 4 H), 0.95 (dt, J = 14.6, 7.4 Hz, 6 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 154.7, 140.3, 132.2, 129.2, 117.7,
1-Morpholino-3-(naphthalen-1-yl)prop-2-yn-1-one (3ia): 3-(Naphth-
alen-1-yl)propiolic acid (1i, 0.589 g, 3.0 mmol) and morpholine (2a,
0.784 g, 9.0 mmol) afforded product 3ia (0.517 g, 1.95 mmol, 65%
1
yield) as a yellow oil. H NMR (300 MHz, CDCl3): δ = 8.27 (dd,
J = 8.2, 0.8 Hz, 1 H), 7.96–7.85 (m, 2 H), 7.80 (dd, J = 7.2, 1.2 Hz, 89.6, 81.7, 50.8, 46.5, 22.2, 21.6, 20.7, 11.4, 11.3 ppm. HRMS (ESI,
1 H), 7.65–7.58 (m, 1 H), 7.58–7.51 (m, 1 H), 7.46 (dd, J = 8.3, TOF): calcd. for C16H22NO [M + H]+ 244.1701; found 244.1700.
Eur. J. Org. Chem. 2015, 2235–2243
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2241

J. Hwang, J. Choi, K. Park, W. Kim, K. H. Song, S. Lee
FULL PAPER
3-(4-Fluorophenyl)-N,N-dipropylpropiolamide (3hh): 3-(4-Fluoro- 22.0, 18.8, 13.8 ppm. HRMS (ESI, TOF): calcd. for C12H20NO2
phenyl)propiolic acid (1h, 0.492 g, 3.0 mmol) and dipropylamine
(2h, 0.911 g, 9.0 mmol) afforded product 3hh (0.482 g, 1.95 mmol,
65% yield) as a yellow oil. 1H NMR (300 MHz, CDCl3): δ = 7.70–
7.33 (m, 2 H), 7.19–6.96 (m, 2 H), 3.78–3.48 (m, 2 H), 3.47–3.15
(m, 2 H), 1.75–1.56 (m, 4 H), 1.15–0.78 (m, 6 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 163.4 (d, J = 250.5 Hz), 154.4, 134.4 (d, J
= 8.7 Hz), 116.9 (d, J = 3.5 Hz), 115.9 (d, J = 22.5 Hz), 88.2, 82.0,
50.8, 46.5, 22.2, 20.7, 11.33, 11.26 ppm. HRMS (ESI, TOF): calcd.
for C15H19NOF [M + H]+ 248.1451; found 248.1451.
[M + H]+ 210.1494; found 210.1492.
Acknowledgments
This research was financially supported by the National Research
Foundation of Korea (NRF), Ministry of Education, Science and
Technology, ICT and Future Planning [Nano Material Technology
Development Program (2012M3A7B4049655) and Basic Science
Research Program (2014R1A2A1A11050018)]. Spectra data were
obtained from the Korea Basic Science Institute, Gwangju branch.
Methyl 4-[3-(Dipropylamino)-3-oxoprop-1-ynyl]benzoate (3lh): 3-[4-
(Methoxycarbonyl)phenyl]propiolic acid (1l, 0.613 g, 3.0 mmol)
and dipropylamine (2h, 0.911 g, 9.0 mmol) afforded product 3lh
(0.422 g, 1.47 mmol, 49% yield) as a yellow oil. 1H NMR
(300 MHz, CDCl3): δ = 8.03 (d, J = 8.4 Hz, 2 H), 7.59 (d, J =
8.4 Hz, 2 H), 3.93 (s, 3 H), 3.70–3.47 (m, 2 H), 3.47–3.23 (m, 2 H),
1.77–1.55 (m, 4 H), 1.01–0.91 (m, 6 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 166.1, 154.1, 132.1, 130.9, 129.5, 125.3, 88.0, 84.3,
52.3, 50.8, 46.5, 22.2, 20.6, 11.3, 11.2 ppm. HRMS (ESI, TOF):
calcd. for C17H22NO3 [M + H]+ 288.1600; found 288.1596.
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Ed. 2009, 48, 4114–4133; Angew. Chem. 2009, 121, 4176; b)
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yl)propiolic acid (1n, 0.457 g, 3.0 mmol) and dipropylamine (2h,
0.911 g, 9.0 mmol) afforded product 3nh (0.289 g, 1.23 mmol, 41%
1
yield) as a yellow oil. H NMR (300 MHz, CDCl3): δ = 7.41–7.38
(m, 2 H), 7.05–7.02 (m, 1 H), 3.63–3.45 (m, 2 H), 3.43–3.32 (m, 2
H), 1.75–1.54 (m, 4 H), 1.00–0.90 (m, 6 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 154.3, 134.7, 129.7, 127.3, 120.5, 86.1, 83.0,
50.8, 46.5, 22.2, 20.7, 11.3, 11.2 ppm. HRMS (ESI, TOF): calcd.
for C13H18NOS [M + H]+ 236.1109; found 236.1107.
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1-Morpholinobut-2-yn-1-one (3oa): 2-Butynoic acid (1o, 0.252 g,
3.0 mmol) (1o) and morpholine (2a, 0.784 g, 9.0 mmol) afforded
product 3oa (0.193 g, 1.26 mmol, 42% yield) as a yellow oil. 1H
NMR (300 MHz, CDCl3): δ = 3.77–3.74 (m, 2 H), 3.73–3.69 (m, 2
H), 3.69–3.56 (m, 4 H), 2.02 (s, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 153.2, 90.0, 72.6, 66.9, 66.4, 47.2, 41.8, 29.7 ppm.
HRMS (ESI, TOF): calcd. for C8H12NO2 [M + H]+ 154.0868;
found 154.0867.
1-Morpholinopent-2-yn-1-one (3pa): 2-Pentynoic acid (1p, 0.294 g,
3.0 mmol) and morpholine (2a, 0.784 g, 9.0 mmol) afforded prod-
1
uct 3pa (0.191 g, 1.14 mmol, 38% yield) as a yellow oil. H NMR
(300 MHz, CDCl3): δ = 3.77–3.74 (m, 2 H), 3.71–3.69 (m, 2 H),
3.68–3.62 (m, 4 H), 2.38 (q, J = 7.5 Hz, 2 H), 1.22 (t, J = 7.5 Hz,
3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.3, 95.2, 72.6, 66.8,
66.4, 47.2, 41.8, 12.8, 12.6 ppm. HRMS (ESI, TOF): calcd. for
C9H14NO2 [M + H]+ 168.1025; found 168.1025.
1-Morpholinohex-2-yn-1-one (3qa): 2-Hexynoic acid (1q, 0.336 g,
3.0 mmol) and morpholine (2a, 0.784 g, 9.0 mmol) afforded prod-
1
uct 3qa (0.223 g, 1.23 mmol, 41% yield) as a yellow oil. H NMR
(300 MHz, CDCl3): δ = 3.77–3.74 (m, 2 H), 3.72–3.69 (m, 2 H),
3.69–3.62 (m, 4 H), 2.35 (t, J = 7.1 Hz, 2 H), 1.69–1.54 (m, 2 H),
1.02 (t, J = 7.4 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
153.3, 94.0, 73.3, 66.8, 66.4, 47.2, 41.8, 21.3, 20.8, 13.5 ppm.
HRMS (ESI, TOF): calcd. for C10H16NO2 [M + H]+ 182.1181;
found 182.1181.
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135–142; b) H. Hoberg, H. J. Riegel, J. Organomet. Chem.
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2004, 77, 2033–2045.
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Synth. Catal. 2012, 354, 2049–2056.
1-Morpholinooct-2-yn-1-one (3ra): 2-Octynoic acid (1r, 0.421 g,
3.0 mmol) and morpholine (2a, 0.784 g, 9.0 mmol) afforded prod-
1
uct 3ra (0.370 g, 1.77 mmol, 59% yield) as a yellow oil. H NMR
(300 MHz, CDCl3): δ = 3.75–3.71 (m, 2 H), 3.69–3.66 (m, 2 H),
3.66–3.59 (m, 4 H), 2.33 (t, J = 7.1 Hz, 2 H), 1.61–1.52 (m, 2 H),
1.41–1.23 (m, 4 H), 0.90–0.85 (m, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 153.3, 94.2, 73.2, 66.8, 66.4, 47.1, 41.7, 31.0, 27.4,
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 2235–2243

Palladium-Catalyzed Oxidative Aminocarbonylation
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Guzei, J. Am. Chem. Soc. 1998, 120, 9205–9219.
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Received: December 18, 2014
Akio, Bull. Chem. Soc. Jpn. 2004, 77, 2237–2250.
Published Online: February 16, 2015
Eur. J. Org. Chem. 2015, 2235–2243
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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