Zinc Chloride Mediated Synthesis of 3H-Oxazol-2-one and Pyrrolo-oxazin-1-one from Ynamide

Article abstract of DOI:10.1002/ejoc.201900428

A simple zinc chloride mediated cyclization of ynamidyl N-carbamates or 2-ynamidyl-(hetero)arylcarboxylates is achieved under mild reaction conditions, leading to the synthesis of useful heterocyclic scaffolds, 3H-oxazol-2-ones and pyrrolo-oxazin-1-ones, with good yields.

Full text of DOI:10.1002/ejoc.201900428

A Journal of
Accepted Article
Title: Zinc chloride mediated synthesis of 3H-oxazol-2-one and pyrrolo-
oxazin-1-one from ynamide
Authors: Isabelle Gillaizeau, Loic HABERT, Romain SALLIO, Muriel
DURANDETTI, and corinne Gosmini
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900428
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10.1002/ejoc.201900428
European Journal of Organic Chemistry
COMMUNICATION
Zinc chloride mediated synthesis of 3H-oxazol-2-one and pyrrolo-
oxazin-1-one from ynamide
Loïc Habert,[a] Romain Sallio,[a] Muriel Durandetti,[c] Corinne Gosmini,[b] and Isabelle Gillaizeau*[a]
Abstract: A simple zinc chloride mediated cyclization of ynamidyl N-
carbamates or 2-ynamidyl-(hetero)arylcarboxylates is achieved under
mild reaction conditions, leading to the synthesis of useful heterocyclic
scaffolds, 3H-oxazol-2-ones and pyrrolo-oxazin-1-ones, with good
yields.
1-ones with TBAF in DMF. One should also mention the work of
Wei[9] describing the synthesis of pyrido- and pyrrolo[1,2-
c][1,3]oxazinon-1-ones through a nucleophilic addition-cyclization
process of N,O-acetal with ynamides. The pyrrolo[1,2-
a]pyrazinone core was also obtained by Kucher[10] during the
iodolactonization of methyl 7-allylpyrrolo[2,3-d]pyrimidine-6-
carboxylate. In general, intramolecular cycloisomerization
reactions that involve an ynamide functionality are achieved either
by electrophilic cyclization or by using expensive transition metal
catalysts, as previously described by some of us.[11] Oxygen-
containing internal nucleophiles have been used in this respect.
The literature survey clearly pointed out the lack of simple, cost-
effective and ecofriendly protocols for accessing useful
frameworks. Given that an acidic environment is necessary for the
successful cyclization of ynamidyl N-carbamates or 2-ynamidyl-
(hetero)arylcarboxylates, we were intrigued to explore the
opportunity of using cheap and non-toxic zinc salt to mediate the
synthesis. One of our current research interests deals with the
functionalization of ynamide to provide key intermediates for the
synthesis of small nitrogen-containing scaffolds.[11e,12] Pursuing
this objective, we describe herein the zinc chloride mediated
synthesis of 5-mono substituted oxazol-2-ones or 3-mono
substituted pyrrolo-oxazin-1-ones. The remaining free-alpha-
position to the nitrogen atom may afford the possibility of
performing further functionalization on this site. It is noteworthy
that the formation of ring systems using zinc halides is scarce;
only one example of zinc chloride-catalyzed cycloisomerization of
alkynes has been reported in the literature to date.[13]
Introduction
Significant efforts have been devoted toward developing methods
and technologies to synthesize original collections of small
molecules with useful therapeutic properties. Nowadays, the
sustainability of a chemical process is a major aspect that must
be considered, and the implementation of green methodologies is
of considerable importance. Oxazol-2-one occupies a unique
position in the design and synthesis of novel biologically active
agents that exhibit significant medicinal activities.[1] However,
most of the reported procedures to access these heterocycles
have drawbacks, such as the use of expensive catalysts,[2] the
need for complex starting materials,[3] and/or drastic conditions.[4]
Furthermore, pyrrole-containing heterocycles are widely
disseminated within a large number of natural products and
biologically active molecules. For instance, pyrrole-fused
oxazinone heterocycles are found in marine natural products,
such as Lukianol A or B but also in pyrazine analogues like the
alkaloid Peramine (Scheme 1).[5] Despite the widespread interest
in these structures, the pyrrolo-oxazinone core motif is underused
in the literature.[5d] Recently, Balci[6] reported a nucleophilic and
electrophilic cyclization of N-alkyne-substituted pyrrole
derivatives for the construction of similar pyrrolopyrazinone,
pyrrolotriazinone and pyrrolo-oxazinone moieties. Previously, the
same group[7] achieved access to 3,4-dihydropyrrolo-oxazin-1-
one derivatives via a gold(III)-catalyzed cyclization reaction from
N-propargyl-substituted
pyrrole.
Subsequently,
Kerwin[8]
described the cyclization of ynpyrroles into pyrrolo[2,1-c]oxazin-
[a]
Prof. I. Gillaizeau, Dr. L. Habert, Dr. R. Sallio
Institute of Organic and Analytical Chemistry, ICOA UMR 7311
CNRS, Université d’Orléans, rue de Chartres, 45100 Orléans,
France.
Scheme 1. Pyrrolo-oxazin-2-one containing structure and analogue.
E-mail: isabelle.gillaizeau@univ-orleans.fr
Homepage: http://www.icoa.fr/en/gillaizeau
Dr. C. Gosmini
Laboratoire de Chimie Moléculaire, CNRS, Ecole polytechnique,
IPParis,, 91128 Palaiseau, France
Dr. M. Durandetti
Normandie Univ, UNIROUEN, INSA Rouen, CNRS,
COBRA (UMR 6014& FR 3038)
Results and Discussion
[b]
[c]
As part of our effort to access molecular diversity and original
nitrogen-containing scaffolds, we began our investigation from the
ynamide 1a, selected as a model substrate, in order to determine
the best reaction conditions for the cyclization step. 1a was readily
prepared by the application of the Hsung copper-catalyzed N-
alkynylation reaction.[14] Finally, reaction of 1a with cheap and
readily accessible zinc salts led to good yields (Table 1). The
76000 Rouen, France
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201900428
European Journal of Organic Chemistry
COMMUNICATION
optimized conditions were found to be ZnCl2 (1,2 equiv.) and
CH2Cl2 as a solvent at 40°C for 4h. Accordingly, oxazolone 2a
was obtained in 97% isolated yield via a 5-endo-dig process. This
strategy is a significant achievement in the synthesis of 5-
substituted oxazol-2-ones with a free 4-position thanks to its
performance, simplicity, and low cost. A series of common
solvents were examined revealing that CH2Cl2 is best suited to
the reaction (entries 1-5). The cyclization was also efficiently
performed using ZnBr2 (entry 7), however a subsequent reduction
in the yield was observed when the amount of Lewis acid was
decreased (entry 6). No reaction occurred in the absence of metal
salt (entry 8). It is noticeable that a green solvent such as
dimethylcarbonate (entry 9) could also be advantageously used.
The use of ultrapure and ultra-dry ZnCl2 (entry 10) resulted in a
slightly lower yield of 2a. Different sources of inexpensive metal
salts were also tested and good yields were observed using
copper (I) bromide but only a 10% yield was obtained when
employing copper (II) bromide (entries 11-12).
ynamide or the ynamide having a trimethylsilyl (TMS) group on
the alkyne part was incompatible with the cyclization reaction; as
competing substrate decomposition was observed prior to the
complete consumption of the starting material.
Table 2. Synthesis of 3H-oxazol-2-ones 2b-q from ynamides 1b-q.[a,b]
Table 1. Optimization studies.[a]
Entry
1
Lewis acid
ZnCl2
Solvent
CH3CN
CH3CN
EtOH
Time
12 h
12 h
12 h
12 h
4 h
T°C
Yields[b]
79
25°C
50°C
50°C
50°C
40°C
40°C
40°C
40°C
40°C
40°C
50°C
50°C
2
ZnCl2
97
3
ZnCl2
48
4
ZnCl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DMC
95
5
ZnCl2
97
[c]
6
ZnCl2
4 h
78
[a] The reactions were performed with 1 (0.2 mmol), ZnCl2 (1.2 equiv.) in CH2Cl2
(2 ml) at 40°C for 4h. [b] Isolated yields.
7
ZnBr2
-
4 h
94
8
4 h
0
To further explore the utility of this simple procedure, upon
modification of the core of the carboxylate moiety, ynpyrrole
carboxylate 3a-m gave satisfactory results leading to a range of
original 1H-pyrrolo[2,1-c][1,4]oxazin-1-one derivatives 4a-m
having a free 2-position (Table 3). The reaction proceeded
smoothly in the sole presence of ZnCl2 and with a range of readily
available ynpyrroles. We noticed in this case a slight increase in
the reaction time. No trace of pyrrolo[2,1-b]oxazole derivative
resulting from a 5-exo-dig cyclization was observed. Various
substituents borne by the ynamide were compatible. The
presence of an aryl group bearing either electron-donating (4b) or
–withdrawing groups (4c-e) gave satisfactory results. Hence,
given the prevalence of heterocycles in medicinal chemistry, we
were pleased to observe that electron-rich heterocycles such as
benzothiophene (4f) or furan (4g) are allowed, giving the
corresponding cyclization product in excellent yield. Moreover,
when the alkyne terminus bears an aryl group, a linear
substitution or a cyclic alkenyl group, 6-endo-dig cyclization
products were isolated in good yields. This mild method works
well with long alkyl chain (4h), a terminal OTBDMS (4i-j), a halide
(4k), or with unprotected hydroxyl (4l) group. 4h was also
successfully synthesized starting from the corresponding tert-
butyl ester (R=t-Bu). It is worth noting that the chloro compound
4k is the synthetic precursor of peramine (Scheme 1), a food
deterrent for insects.[15] This strategy should prove highly useful
9
ZnCl2
4 h
75
[d]
10
11
12
ZnCl2
CH2Cl2
CH3CN
CH3CN
4 h
88
CuBr
12 h
12 h
76
CuBr2
10
[a] General conditions: 1a (0.2 mmol), Lewis acid (1.2 equiv.), solvent (2 mL).
[b] Isolated yields. [c] 0.3 equiv. of ZnCl2 was used. [d] Ultrapure ZnCl2 (99.995%
based on trace metals, Sigma-Aldrich) was used. DMC: dimethylcarbonate.
With the optimized reaction conditions in hand, we set about
assessing the generality of this protocol and an array of ynamides
1 underwent the desired 3H-oxazol-2-ones 2 (Table 2). To extend
the scope of the reaction, different ynamides 1b-l bearing benzyl,
heteroarylmethyl or aryl protecting group on nitrogen were indeed
easily prepared by Hsung coupling.[14] Then, compounds 1b-l
were successfully subjected to the reaction with ZnCl2 for 4h at
40°C, in a similar manner as 1a. We then tested the possibility of
increasing the level of structural complexity by introducing various
chains on the alkyne terminus that could be used for further
functionalization (2m-q). Synthetically useful functional groups
such as alkyl, aryl, halide, alkoxy, alkene, and ketone were well
tolerated. Electron-rich hindered aryl groups on the alkyne
terminus gave good yields (2m). It is noteworthy that the terminal
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10.1002/ejoc.201900428
European Journal of Organic Chemistry
COMMUNICATION
for the synthesis of 3-substituted pyrrolo[2,1-c][1,4]oxazin-1-one
derivatives with a free 2-position because of the ease of
implementation, the smooth conditions and the good yields
observed.
Further, to demonstrate the usefulness of this strategy, the
pyrrolo-oxazinones 4a and 4c were diversified (scheme 3). We
sought first to explore the reactivity of 4 in a halogenation reaction.
A chemoselective bromination was carried out from 4c in the
presence of NBS, leading with good yields to the -bromo pyrrole
derivative 5[16] whereas in the presence of Selectfluor, the
oxyfluorination of the oxazinone ring of 4a took place, giving the
selective formation of the -fluoroacetal 6. Compound 6 was
isolated as a single diastereoisomer (d.r.>98:2); however, the
diastereoselectivity of this oxyfluorination reaction could not be
determined.[17] More importantly, the reaction proceeded with a
complete regioselectivity[18] with the introduction of the fluorine
alpha to the nitrogen atom which is opposite to that observed with
enamides.[19] This switch in regioselectivity might be attributed to
the presence of a phenyl substituent at the C-3 position of the
oxazinone intermediate that may favor the building of a transient
positive charge. In addition, to include diverse functionalities,
Sonogashira and Suzuki-Miyaura cross-coupling reactions were
applied to 4c leading respectively to 7a-b or 8 with good yields.
These kinds of scaffolds are found in many natural products
and/or pharmacologically relevant therapeutic agents.
Table 3. Synthesis of 1H-pyrrolo[2,1-c][1,4]oxazin-1-one derivatives 4a-m from
ynamides 3a-m.[a,b]
Scheme 3. Functionalization of the pyrrolo-oxazin-1-one 4a or 4c.
[a] The reactions were performed with 3 (0.2 mmol), ZnCl2 (1.2 equiv.) in CH2Cl2
(2 ml) at 40°C for 4-8h. [b] Isolated yields.
Based on the literature precedence, a plausible mechanism is
proposed here for the zinc-mediated cyclization of ynamide to
oxazolone, and is outlined in Scheme 2. First, an interaction of
zinc chloride with the alkyne moiety of 1 promotes a regioselective
5-endo-dig intramolecular nucleophilic attack of carbonyl oxygen.
The generating intermediate I forms a resonance-stabilized cation
intermediate II that loses benzyl halide, evidenced by 1H NMR of
the crude mixture, to give the vinylzinc intermediate III. Finally, the
vinylzinc intermediate III is then spontaneously quenched in situ
leading to the observed oxazolone derivative 2. A similar
approach is envisaged from 3 via a regioselective 6-endo-dig
process leading to the 1H-pyrrolo[2,1-c][1,4]oxazin-1-one 4.
Scheme 2. Plausible mechanism.
Conclusions
In summary, we have developed an original and simple zinc-
chloride mediated synthesis of 3H-oxazol-2-ones and 1H-
pyrrolo[2,1-c][1,4]oxazin-1-ones from ynamides, which exhibited
good substrate scope and functional group compatibility. A variety
of derivatives was obtained under mild reaction conditions and
using a cheap, abundant and low-toxic metal such as zinc salts
which provide a good handle for further elaboration. This result
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6-bromo-3-(4(bromophenyl)pyrrolo[2,1-c][1,4]oxazin-1-one
(5). To a solution of 3-(4-bromophenyl)pyrrolo[2,1-c][1,4]oxazin-
1-one 4c (72 mg, 0.25 mmol, 1 equiv.) in DMF (2 mL) was added
NBS (48 mg, 0.27 mmol, 1.1 equiv) at 25°C. After 2h, the reaction
mixture was quenched with water (2 mL). The organic phase was
extracted with EtOAc (3x10 mL), dried over MgSO4 and
concentrated under reduced pressure. The product was purified
by flash chromatography on silica gel with petroleum ether/ethyl
acetate (80/20) as eluent to give compound 5 as a white gum (72
mg, 79 %). 1H NMR (400 MHz, CDCl3): δ 7.63-6.56 (m, 4H), 7.52
(s, 1H), 7.28 (d, J = 4.2 Hz, 1H), 6.63 (d, J = 4.2 Hz, 1H). 13C NMR
(100 MHz, CDCl3): 13C NMR (100 MHz, CDCl3): δ 153.5, 142.0,
132.1, 129.2, 126.0, 123.9, 117.7, 116.6, 116.2, 104.2, 102.3.
HRMS (ESI+): calcd for C13H8NBr2O2 [M+H]+ : 389.8735, found
389.8735.
showcases the potential application of this method to the late
stage diversification of pharmaceutically active compounds.
Experimental Section
General Information. All reagents and solvents were purchased
from commercial sources and used as received. All manipulations
were conducted under argon. The reactions were monitored by
thin-layer chromatography (TLC) using silica gel (60 F254) plates.
Compounds were visualized using a UV lamp (254 nm) and/or by
potassium permanganate stain. Flash column chromatography
was carried out on silica gel 60 (230-400 mesh, 0.040-0.063 mm).
Melting points (mp [°C]) were taken on samples in open capillary
tubes and are uncorrected. The infrared spectra of compounds
1
were recorded on a Thermo Scientific Nicolet iS10. H, 13C and
4-fluoro-3-methoxy-3-phenyl-3,4-dihydro-1H-pyrrolo[5,1-
c][1,4]oxazin-1-one (6). To a solution of 3-phenylpyrrolo[2,1-
c][1,4]oxazin-1-one 4a (42.2 mg, 0.2 mmol) and Selectfluor®
(70.4 mg, 0.2 mmol) in CH3CN (2 mL) at 0 °C was added CH3OH
(24 μL, 0.59 mmol). The reaction was then stirred at the same
temperature for 1.5 h. The reaction was quenched with H2O, and
the organic phase was extracted with EtOAc. The combined
extracts were washed with brine, dried over MgSO4 and
concentrated under reduced pressure. The product was purified
by flash chromatography on silica gel with petroleum ether/ethyl
acetate (9/1) as eluent to give 6 as a white gum (24 mg, 47 %).
1H NMR (400 MHz, CDCl3): δ 7.72-7.68 (m, 3H), 7.57-7.48 (m,
2H), 7.30 (dd, J = 3.7, 1.7 Hz, 1H), 7.15 (dd, J = 2.8, 1.5 Hz, 1H),
6.48 (dd, J = 3.9, 2.8 Hz, 1H), 6.02 (d, J = 54.8 Hz, 1H), 3.25 (s,
3H). 13C NMR (100 MHz, CDCl3): 13C NMR (100 MHz, CDCl3): δ
155.8, 133.0, 130.0, 128.9, 127.0, 126.0, 119.8, 117.8, 112.7,
103.8, 90.2 (J = 210 Hz), 51.2. 19F NMR (376 MHz, CDCl3):  -
135.4 (J = 54.8 Hz). HRMS (ESI+): calcd for C14H13NFO3 [M+H]+ :
262.0873 found 262.0872.
19F NMR spectra were recorded on a spectrometer at 250 MHz
(13C, 62.9 MHz) or 400 MHz (13C, 100 MHz; 19F: 376 MHz CPD).
Chemical shifts are given in parts per million from
tetramethylsilane (TMS) as internal standard. The following
abbreviations are used for the proton spectra multiplicities: s:
singlet, d: doublet, t: triplet, q: quartet, qt: quintuplet, m: multiplet,
br.: broad, dd: double doublet, dt: double triplet. High-resolution
accurate mass measurements (HRAM) were recorded with a
Maxis Bruker 4G instrument and were performed in positive mode
with an ESI source on a Q-TOF mass spectrometer with an
accuracy tolerance of 2 ppm by the “Fédération de Recherche”
ICOA/CBM (FR2708) platform.
General procedure GP1 : Synthesis of ynamides (1b-1q). In a
reaction vial flushed with argon and equipped with a stirring bar,
were added bromoalkyne (1.1 equiv.), the protected secondary
amine (1.0 equiv.), CuSO4•5H2O (10 mol%), 1,10-phenantroline
(20 mol%), K3PO4 (2.0 equiv.) and toluene (0.33 M). The reaction
mixture was capped and heated at 80 °C until completion (TLC
monitoring). The mixture was then allowed to cool down to room
temperature and concentrated. The crude compounds were
purified by silica gel flash-column chromatography with a
petroleum ether/AcOEt elution system. Ynamides 1a,[12a]
1h,[19],1i[2c] were synthesized according to reported literature
procedures.
General Procedure GP4: Synthesis of 7a-7b via
a
Sonogashira coupling. To a mixture of the arylbromide 4c (0.30
mmol, 1 equiv) and alkyne (0.33 mmol, 1.1 equiv) in toluene (1.0
mL) were added PPh3 (0.03 mmol, 0.1 equiv), Et3N (60 µl), and
CuI (0.015 mmol, 5 mol%). The reaction mixture was degassed
under argon, PdCl2(PPh3)2 (4 mg, 0.006 mmol, 2 mol%) was
added and was heated at reflux for 18 h. After cooling down to
room temperature, water (25 mL) was added. The reaction
mixture was extracted with ethyl acetate (3 x 30 mL). The organic
extracts were combined, washed with water (2 x 25 mL) and brine
(50 mL), and dried over MgSO4. The solvent was evaporated
under reduced pressure and the residue was purified by silica gel
flash column chromatography with a petroleum ether/AcOEt
elution system.
General Procedure GP2: Synthesis of 2b-2q and 4a-4m. To a
mixture of ynamide 1 or 3 (see GP3) (0.2 mmol) in CH2Cl2 (2 mL)
in a reaction vial was added ZnCl2 (1.2 equiv.). The reaction
mixture was capped and heated in an oil bath at 40°C for 2-8 h
while being monitored by TLC analysis. Upon completion, the
reaction mixture was cooled to rt. The crude products were
purified by silica gel flash column chromatography with a
petroleum ether/AcOEt elution system. Oxazolones 2a,[11] 2h,[2]
2i[14] were synthesized according to the literature procedures.
3-[4-(2-trimethylsilylethynyl)phenyl]pyrrolo[2,1-
c][1,4]oxazin-1-one (7a): Flash-column chromatography on
silica gel with petroleum ether/ethyl acetate (90:10) as eluent
gave 7a as a colourless oil (51 mg, 65 %) according to GP4. 1H
NMR (400 MHz, CDCl3): δ 7.69-7.66 (m, 2H), 7.56-7.54 (m, 2H),
7.50 (s, 1H), 7.32-7.30 (m, 1H), 7.21-7.19 (m, 1H), 6.63-6.62 (m,
1H), 0.29 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 154.5, 141.5,
132.4, 130.3, 125.8, 123.9, 121.5, 116.8, 116.0, 113.8, 104.9,
104.3, 96.4, -0.10. HRMS (ESI+): calcd for C18H18NO2Si [M+H]+ :
308.1101 found 308.1105.
General Procedure GP3: Synthesis of ynamides (3a-3m). To
a mixture of pyrrole-2-carboxylate (1.0 equiv.), K3PO4 (2.0 equiv.),
CuSO4.5H2O (0.10 equiv.), and 1,10-phenanthroline (0.20 equiv.)
in a reaction vial was added a solution of 1- bromoalkyne (1.3
equiv., 1.0 M) in toluene. The reaction mixture was capped and
heated in an oil bath at 80°C for 48 h while being monitored by
TLC analysis. Upon completion, the reaction mixture was cooled
to room temperature, diluted with EtOAc, filtered through CeliteTM
,
and the filtrate was concentrated in vacuo. The crude products
were purified by silica gel flash column chromatography with a
petroleum ether/AcOEt elution system.
3-[4-[2-[4-
(trifluoromethyl)phenyl]ethynyl]phenyl]pyrrolo[2,1-
c][1,4]oxazin-1-one (7b): Flash-column chromatography on
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10.1002/ejoc.201900428
European Journal of Organic Chemistry
COMMUNICATION
silica gel with petroleum ether/ethyl acetate (90:10) as eluent
gave 7b as a colourless oil (67 mg, 68 %) according to GP4. 1H
NMR (400 MHz, CDCl3): δ 7.76-7.74 (m, 2H), 7.68-7.62 (m, 6H),
7.54 (s, 1H), 7.33-7.32 (m, 1H), 7.23-7.22 (m, 1H), 6.65-6.63 (m,
1H). 13C NMR (100 MHz, CDCl3): δ 154.5, 141.4, 132.2, 131.8,
130.6, 125.4, 124.1, 123.5, 121.6, 116.8, 116.1, 113.9, 105.0,
91.10, 89.7. 19F NMR (376 MHz , CDCl3):  -62.8. HRMS (ESI+):
calcd for C22H13NO2F3 [M+H]+ : 380.0892 found 380.0897.
Reddy, P. W. Daviesa, Adv. Synth. Catal. 2016, 358, 226-
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3-[4-(3,5-dimethoxyphenyl)phenyl]pyrrolo[2,1-c][1,4]oxazin-
1-one (8): To a mixture of the 3-(4-bromophenyl)pyrrolo[2,1-
c][1,4]oxazin-1-one 4c (0.20 mmol, 1 equiv) and the arylboronic
acid (0.40 mmol, 2 equiv) in toluene (1.0 mL) was added a
solution of aqueous Na2CO3 (0.30 mL, 2M). The reaction mixture
was degassed under argon, Pd(PPh3)4 (0.01 mmol, 5 mol %) was
added and it was heated at reflux for 6 h. After cooling down to
room temperature, water (25 mL) was added. The reaction
mixture was extracted with ethyl acetate (3 x 30 mL). The organic
extracts were combined and washed with water (2 x 25 mL) and
brine (50 mL), and dried over MgSO4. The solvent was
evaporated
under
reduced
pressure.
Flash-column
chromatography on silica gel with petroleum ether/ethyl acetate
1
(90:10) as eluent gave 8 as a colourless oil (68 mg, 76 %). H
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NMR (400 MHz, CDCl3): δ 7.79-7.76 (m, 2H), 7.66-7.62 (m, 2H),
7.50 (s, 1H), 7.30 -7.29 (m, 1H), 7.21-7.19 (m, 1H), 6.76-6.74 (m,
2H), 6.61-6.59 (m, 1H), 6.50-6.48 (m, 1H), 3.86 (s, 6H). 13C NMR
(100 MHz, CDCl3): δ 161.2, 154.7, 142.2, 142.1, 142.0, 129.6,
127.6, 124.6, 121.5, 116.9, 115.8, 113.7, 105.4, 104.3, 99.7, 55.5.
HRMS (ESI+): calcd for C21H18NO4 [M+H]+ : 348.1230 found
348.1233.
Acknowledgments
The authors thank the LABEX SynOrg (ANR-11-LABX-0029)
for financial support.
Keywords: ynamide • oxazolone • pyrrolo-oxazinone • zinc
chloride • cyclization
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This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900428
European Journal of Organic Chemistry
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
COMMUNICATION
A simple zinc chloride mediated
cyclization of ynamidyl N-carbamates
or 2-ynamidyl-(hetero)arylcarboxylates
is smoothly achieved, leading to the
synthesis of useful heterocyclic
scaffolds, 3H-oxazol-2-ones and
pyrrolo-oxazin-1-ones, with good
yields.
Oxazol-2-one and pyrrolo-oxazin-1-
one
Loïc Habert, Romain Sallio, Muriel
Durandetti Corinne Gosmini, and
Isabelle Gillaizeau*
Page No. – Page No.
Zinc chloride mediated synthesis of
3H-oxazol-2-one and pyrrolo-oxazin-
1-one from ynamide
This article is protected by copyright. All rights reserved.