Reaction of Ynamides with Iminoiodinane-Derived Nitrenes: Formation of Oxazolones and Polyfunctionalized Oxazolidinones

Article abstract of DOI:10.1021/acs.joc.7b01623

This article describes the reaction of ynamides with metallanitrenes generated in the presence of an iodine(III) oxidant. N-(Boc)-Ynamides are converted to oxazolones via a cyclization reaction. The reaction is mediated by a catalytic dirhodium-bound nitrene species that first behaves as a Lewis acid. The oxazolones can be converted in a one pot manner to functionalized oxazolidinones following a regio- and stereoselective oxyamination reaction with the same nitrene reagent generated in stoichiometric amounts.

Full text of DOI:10.1021/acs.joc.7b01623

Note
pubs.acs.org/joc
Reaction of Ynamides with Iminoiodinane-Derived Nitrenes:
Formation of Oxazolones and Polyfunctionalized Oxazolidinones
Romain Rey-Rodriguez,† Gwendal Grelier,† Loïc Habert,‡ Pascal Retailleau,† Benjamin Darses,†
Isabelle Gillaizeau,*,‡ and Philippe Dauban*,†
†Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Universite
91198 Gif-sur-Yvette, France
́
Paris-Sud, Universite
́
Paris-Saclay, Avenue de la terrasse,
‡Institute of Organic and Analytical Chemistry, ICOA UMR 7311 CNRS, Universite
France
́
d’Orlea
́
ns, rue de Chartres, 45100 Orleans,
́
S
* Supporting Information
ABSTRACT: This article describes the reaction of ynamides
with metallanitrenes generated in the presence of an
iodine(III) oxidant. N-(Boc)-Ynamides are converted to
oxazolones via a cyclization reaction. The reaction is mediated
by a catalytic dirhodium-bound nitrene species that first
behaves as a Lewis acid. The oxazolones can be converted in a
one pot manner to functionalized oxazolidinones following a
regio- and stereoselective oxyamination reaction with the same nitrene reagent generated in stoichiometric amounts.
Scheme 1. Background for the Study
minoiodinanes PhINR are trivalent iodine reagents, which
Ihave been useful for the development of alkene azidination
and C(sp3)H amination reactions.1 Their ability to react with
a transition metal complex to generate a metallanitrene was first
reported by Breslow and Mansuy,2 and then developed by
Evans3 and Muller.4 However, their troublesome preparation5
̈
has long hampered their application in organic synthesis. This
limitation was overcome with the discovery of practical
methods for their in situ generation in the presence of
PhIO or PhI(OAc)2.6 The chemistry of iminoiodinanes has
considerably expanded since then. Catalytic C(sp3)H
amination and alkene aziridination reactions mediated by
these iodine(III) oxidants are now methods of choice for the
synthesis of nitrogen-containing compounds.1,7
Recent studies with iminoiodinane-derived nitrenes have
enabled to extend the scope of the synthetic nitrene chemistry.8
Several efficient alkene difunctionalization9 and cascade10
reactions have been reported in the presence of rhodium,
copper, or silver complexes. These synthetic methods generally
opening.13b Based on these results, we have decided to further
study the scope of the Lewis acidic property of Rh2(esp)2-
derived nitrenes. In this article, we wish to report that these
species mediate the one pot conversion of ynamides15,16 to
oxazolones and, then, to functionalized oxazolidinones
(Scheme 1b).
Ynamides are useful building blocks in organic synthesis that
allow to perform efficient and regioselective transformations.17
These stable compounds are easily prepared by application of
copper-catalyzed C−N couplings from alkynyl bromides.18 This
occur intra- or intermolecularly with excellent regio- and
stereocontrol from alkenes, alkynes, or allenes.
Our group has contributed to this area with the development
of rhodium(II)-catalyzed nitrene additions to indoles,11
enamides,12 and alkenes.13 The combination of trichloroethyl-
sulfamate (TcesNH2) with Rh2(esp)2 (esp = α,α,α′,α′-
tetramethyl-1,3-benzenedipropionic acid),14 in the presence of
PhI(OAc)2 and a nucleophile enabled us to develop efficient
regioslective oxyamination and diamination reactions (Scheme
1a). Importantly, we have demonstrated, through a combina-
tion of experimental and theoretical studies, that the
dirhodium-bound nitrene species not only acts as a nitrogen-
transfer intermediate, but also possesses a crucial Lewis acidity
enabling the aziridine activation toward the nucleophilic ring
Special Issue: Hypervalent Iodine Reagents
Received: June 30, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.7b01623
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a
protocol was used for the formation of 1-octyne-derived
ynamides that were chosen as model substrates in this study.
Application of the previous conditions (1.2 equiv TcesNH2, 1.4
equiv PhI(OAc)2, 3 mol% Rh2(esp)2, 12 equiv MeOH,
benzene, rt)12,13 to the benzyl carbamate 1 led to the formation
of the oxazolone 3a (Scheme 2). A rapid screening of the
Table 1. Scope of the Cyclization Reaction
Scheme 2. Formation of Oxazolone 2
conditions allowed us to find that the simultaneous presence of
the sulfamate, the iodine(III) oxidant, and the rhodium
complex was required for the reaction to proceed,19 thereby
demonstrating that the Lewis acidic rhodium-bound nitrene
species is involved in the cyclization of the ynamide through the
activation of the alkyne.20 This hypothesis was confirmed by
the fact that the reaction can be performed in the presence of
only a catalytic amount of the metallanitrene generated by
using 3 mol% of Rh2(esp)2, 10 mol% of TcesNH2 and 10 mol%
of PhI(OAc)2. Under these conditions, compound 3a was
isolated in 60% yield. More interestingly, application of these
conditions to the Boc-ynamide 2a allows for isolation of the
same oxazolone 3a in quantitative yield. The reaction is highly
chemoselective as no product arising from the possible
C(sp3)H amination at the propargylic position is observed.21
This excellent conversion prompted us to study the scope of
the cyclization reaction mediated by the rhodium-bound
nitrene species. The cyclization was found to proceed efficiently
in 2 h at room temperature to afford the expected oxazolones 3
with yields in the 63−99% range (Table 1). The reaction can be
applied to Boc-ynamides 2 bearing either an aryl or a benzyl
group on the nitrogen, as illustrated by compounds 3a−d.
More interestingly, the cyclization tolerates the presence of
various functional groups, such as a nonprotected hydroxyl
group as in the case of products 3e−g, or a secondary amide
(3i).22 This functional group compatibility that has not been
reported in previous cyclization reactions catalyzed by gold or
palladium complexes,20 has already been noticed in previous
reactions involving iminoiodinane-derived nitrenes.1,7 The
oxazolone 3j is also a relevant example as it results from a
chemoselective reaction of the alkyne in the presence of an
alkene. Finally, the conditions nicely apply to an α,ω-bis-
ynamide affording the bis-oxazolone product 3k in quantitative
yield.
a
Reactions conditions: (Boc)-ynamide 2 (0.2−0.3 mmol), Rh2(esp)2
(3 mol%), TcesNH2 (10 mol%), PhI(OAc)2 (10 mol%), benzene (c =
0.1 M), rt, 2 h.
Table 2. Scope of the Tandem Cyclization−Oxyamination
Reaction
a
The rhodium-bound nitrene-mediated cyclization of yna-
mides appeared to us appropriate to design a one-pot protocol
with the possible application of the catalytic oxyamidation
reaction,12 to oxazolones 3. Thus, after complete conversion of
the ynamide to 3a, the addition of 1.1 equiv of TcesNH2, 1.3
equiv of PhI(OAc)2, and 12 equiv of methanol led us to isolate
the oxyaminated product 4aa in 30% yield. Running the
reaction at 80 °C for 1 h, then, allowed for a slight
improvement of the yield, the compound 4aa being obtained
in 37% yield (Table 2). Despite the screening of the reaction
conditions, this result could not be improved as the product
4aa was shown to decompose in the presence of PhI(OAc)2.23
Nevertheless, we have decided to study the scope of direct
conversion of ynamides to the complex oxazolidinones 4 as the
a
Reactions conditions: (Boc)-ynamide 2 (0.2−0.3 mmol), Rh2(esp)2
(3 mol%), TcesNH2 (10 mol%), PhI(OAc)2 (10 mol%), benzene (c =
0.1 M), rt, 2 h, then TcesNH2 (1.1 equiv), PhI(OAc)2 (1.3 equiv),
MeOH (12 equiv), 80 °C, 1 h.
latter are stereodefined products that would not be so easily
accessible by application of other strategies.
The tandem of cyclization-intermolecular oxyamination
reactions proceeds with yields in the 37−44% range using
alcohols as nucleophiles. The corresponding highly oxidized
products 4aa, 4ab, 4ca, 4da, and 4ja were obtained as single
B
DOI: 10.1021/acs.joc.7b01623
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Note
regioisomers resulting from the formation of a ketal α- to an
N,N-aminal. The compatibility of the cyclization reaction with
alcohols and amides, then, gave the opportunity to combine
this transformation with an intramolecular oxyamination or
diamination. Starting from oxazolones 3e, 3g, and 3i, this led us
to isolate the sole spiro compounds 4ea, 4ga, and 4ia.
The regio- and stereochemistry of the oxyamination reaction
were determined by the X-ray structure obtained for the
compound 4ga, and NOESY experiments performed from the
products 4ab and 4da (see Supporting Information). Thus,
these led us to conclude that the oxyamination occurs with a
trans stereoselectively, and a regiochemistry that is opposite to
that observed with nonsubstituted enamides and benzoxa-
zines.12 This switch in regioselectivity, previously observed with
C3-substituted indoles,11 might be attributed to the presence of
a substituent at the C-4 position of the oxazolone intermediate
that would favor the building of a transient positive charge
during the nucleophilic ring opening of a putative aziridine
intermediate.
tandem reaction confirms the possibility to design new
reactions in which a metallanitrene can behave as a Lewis
acid, thereby extending the scope of reactions involving
nitrenes generated in the presence of iodine(III) oxidants.
EXPERIMENTAL SECTION
■
Melting points were measured in capillary tubes and were uncorrected.
Infrared spectra were recorded on a FT-IR spectrometer. Proton (1H)
and carbon (13C) NMR spectra were recorded on 300 and 500 MHz
spectrometers (13C, 31P, 19F - probe or Dual 13C probe). Chemical
shifts (δ) are reported in parts per million (ppm) with reference to
CDCl3 (1H: 7.26; 13C: 77.13). The following abbreviations are used
for the proton spectra multiplicities: s: singlet, d: doublet, t: triplet, q:
quartet, quint: quintuplet, sept: septuplet, m: multiplet, br: broad.
Coupling constants (J) are reported in Hertz (Hz). The multiplicity of
carbons was given using 2D spectra (HMQC and HMBC). The
HRMS data were measured on MALDI-TOF type of instrument for
the high resolution mass spectra (HRMS). Thin-layer chromatography
were performed on silica gel 60 F254 on aluminum plates and visualized
under a UVP Mineralight UVLS-28 lamp (254 nm). Flash
chromatography was performed on silica gel 60 (230−400 mesh).
All reagents were obtained from commercial suppliers and were used
as received.
Based on the experimental results and the previously
reported studies,9,11−13 a proposed mechanism for the tandem
cyclization−oxyamidation reactions from ynamides is shown in
Scheme 3. A catalytic amount of the Lewis acidic species I,
General Procedure A for the Cyclization Reaction. In a
sealable tube flushed with argon was introduced the ynamide (1.0
equiv), TcesNH2 (10 mol%), Rh2(esp)2 (3 mol%), and benzene (c =
0.1 M). PhI(OAc)2 (10 mol%) was added in one portion and the
reaction mixture was stirred at room temperature for 2 h. The mixture
was then concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel.
Scheme 3. Proposed Mechanism for the Formation of
Oxazolidinones
General Procedure B for the Tandem Cyclization−Inter-
molecular Oxyamidation Reaction. In a sealable tube flushed with
argon was introduced the ynamide (1.0 equiv), TcesNH2 (10 mol%),
Rh2(esp)2 (3 mol%), and benzene (c = 0.1 M). PhI(OAc)2 (10 mol%)
was added in one portion and the reaction mixture was stirred at room
temperature for 2 h. TcesNH2 (1.0 equiv), external nucleophile (12.0
equiv), and PhI(OAc)2 (1.0 equiv) were sequentially added to the tube
before it was heated at 80 °C for 2 h. The reaction mixture was
allowed to cool down to room temperature before it was concentrated
under reduced pressure. The residue was purified by column
chromatography on silica gel.
3-Benzyl-5-hexyloxazol-2(3H)-one (3a).16 Prepared according to
the general procedure A. Purification on a column of silica gel with
ethyl acetate in petroleum ether (10/90) as eluent gave the desired
product (62 mg, 99%) as a white gum. 1H NMR (500 MHz, CDCl3):
δ 7.40−7.25 (m, 5H), 6.21 (s, 1H), 4.59 (s, 2H), 2.35 (t, J = 8.9 Hz,
2H), 1.45−1.15 (m, 8H), 0.92 (t, J = 7.3 Hz, 3H).
generated by the combination of Rh2(esp)2, TcesNH2, and
PhI(OAc)2, will activate the triple bond of ynamide 1. This
would promote its cyclization accompanied by the release of
isobutene, leading to the formation of the oxazolone 3. The
latter, then, would undergo a rhodium-catalyzed nitrene
addition to provide an aziridine intermediate II. Following its
activation by I,13b the aziridine undergoes a ring opening at the
more substituted position, with different nucleophiles, in an
inter- or intramolecular manner to afford the oxazolidinone 4.
In conclusion, ynamides can be converted in a simple one-
pot three-step procedure to functionalized oxazolidinones by
reaction with iminoiodinane-derived rhodium-bound nitrenes.
The overall transformation relies on a tandem process in which
the metallanitrene species plays a dual role. It first acts as a
Lewis acid to catalyze the cyclization of ynamides to
oxazolones. The reaction takes place with yields of up to 99%
and displays very good functional group tolerance. Then, the
rhodium-bound nitrene can add to the oxazolone in a one pot
manner to afford products resulting from a regio- and
stereocontrolled alkene difunctionalization reaction. This
3-Benzyl-5-phenyloxazol-2(3H)-one (3b).20b Prepared according
to the general procedure A. Purification on a column of silica gel with
ethyl acetate in petroleum ether (10/90) as eluent gave the desired
product (70 mg, 82%) as a white solid. 1H NMR (500 MHz, CDCl3):
δ 7.54−7.20 (m, 10H), 6.61 (s, 1H), 4.77 (s, 2H).
3,5-Diphenyloxazol-2(3H)-one (3c).16 Prepared according to the
general procedure A. Purification on a column of silica gel with ethyl
acetate in petroleum ether (10/90) as eluent gave the desired product
(85 mg, 99%) as a white solid. 1H NMR (500 MHz, CDCl3): δ 7.60−
7.15 (m, 10H), 6.80 (s, 1H).
3-(3,5-Dimethoxyphenyl)-5-hexyloxazol-2(3H)-one (3d). Prepared
according to the general procedure A. Purification on a column of
silica gel with ethyl acetate in petroleum ether (10/90) as eluent gave
1
the desired product (78 mg, 99%) as a white gum; H NMR (400
MHz, CDCl3): δ 6.76−6.74 (m, 2H), 6.54 (s, 1H), 6.34 (s, 1H), 3.81
(s, 6H), 2.45 (t, J = 8.2 Hz, 2H), 1.65−1.57 (m, 2H), 1.41−1.26 (m,
6H), 0.90 (t, J = 6.7 Hz, 3H). 13C{1H} NMR (75 MHz, CDCl3): δ
161.3, 153, 141.9, 137.5, 108.9, 99.0, 98.0, 55.5, 31.4, 28.6, 26.4, 25.9,
22.5, 14.0; IR (Neat): ν = 2958, 2934, 1758, 1596, 1478, 1458, 1205,
1186, 1209, 1150, 1132, 1110 cm−1; HRMS (ESI): m/z calculated for
C17H24NO4 [M+H]+: 306.1699 found: 306.1700.
C
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3-Benzyl-5-(3-hydroxypropyl)oxazol-2(3H)-one (3e). Prepared
according to the general procedure A. Purification on a column of
silica gel with ethyl acetate in petroleum ether (50/50) as eluent gave
7.57−7.53 (m, 4H), 7.47−7.41 (m, 4H), 7.30−7.24 (m, 2H), 6.66 (s,
2H), 2.60 (td, J = 7.3, 1.3 Hz, 4H), 1.99 (p, J = 7.4 Hz, 2H). 13C{1H}
NMR (75 MHz, CDCl3): δ 155.9, 140.5, 134.2, 129.4, 126.3, 120.7,
109.8, 25.1, 23.9; IR (neat): ν = 3139, 3049, 2957, 1731, 1674, 1600,
1504, 1397, 1211, 1126, 898 cm−1; HRMS (ESI): m/z calcd for
C21H19N2O4 [M+H]+: 363.1340; found: 363.1326.
1
the desired product (34 mg, 99%) as a white gum. H NMR (300
MHz, CDCl3) δ 7.40−7.28 (m, 5H), 6.06 (t, J = 1.3 Hz, 1H), 4.68 (s,
2H), 3.67 (t, J = 6.2 Hz, 2H), 2.52−2.45 (m, 2H), 1.84−1.75 (m, 2H).
13C{1H} NMR (75 MHz, CDCl3): δ 140.3, 135.5, 129.0, 128.3, 127.9,
109.6, 61.5, 47.6, 29.5, 22.4; IR (neat): ν = 3414, 3138, 2929, 1726,
1667, 1443, 1402, 1160, 1056 cm−1; HRMS (ESI): m/z calcd for
C13H16NO3 [M+H]+: 234.1125; found: 234.1143.
5-(3-Hydroxypropyl)-3-phenyloxazol-2(3H)-one (3f). Prepared
according to the general procedure A. Purification on a column of
silica gel with ethyl acetate in petroleum ether (60/40) as eluent gave
the desired product (38 mg, 88%) as a white solid. mp 89.7−90.6 °C;
1H NMR (300 MHz, CDCl3) δ 7.58−7.54 (m, 2H), 7.53−7.41 (m,
2H), 7.30−7.25 (m, 1H), 6.64 (t, J = 1.2 Hz, 1H), 3.75 (t, J = 6.1 Hz,
2H), 2.65−2.60 (m, 2H), 1.95−1.83 (m, 2H). 13C{1H} NMR (75
MHz, CDCl3): δ 141.2, 135.7, 129.4, 126.2, 120.7, 109.4, 61.4, 29.5,
22.4; IR (neat): ν = 3394, 3147, 2936, 1727, 1679, 1601, 1505, 1393,
1210, 1140, 1050, 900 cm−1; HRMS (ESI): m/z calcd for C12H14NO3
[M+H]+: 220.0968; found: 220.0964.
2,2,2-Trichloroethyl (3-Benzyl-5-hexyl-5-methoxy-2-oxooxazoli-
din-4-yl)sulfamate (4aa). Prepared according to the general
procedure B. Purification on a column of silica gel with ethyl acetate
in petroleum ether (10/90) as eluent gave the desired product (33 mg,
1
37%) as a colorless gum. H NMR (300 MHz, CDCl3) δ 7.45−7.31
(m, 5H), 5.22−5.12 (m, 1H), 4.95 (s, 1H), 4.85 (d, J = 15.5 Hz, 1H),
4.78 (d, J = 12.0 Hz, 1H), 4.72−4.69 (m, 1H), 4.37 (d, J = 15.5 Hz,
1H), 3.26 (s, 3H), 2.12−2.04 (m, 1H), 1.98−1.91 (m, 1H), 1.40−1.23
(m, 7H), 0.92−0.85 (m, 4H). 13C{1H} NMR (75 MHz, CDCl3): δ
156.4, 134.8, 128.9, 128.2, 128.1, 107.4, 93.3, 78.7, 72.5, 50.2, 44.8,
31.5, 30.7, 29.3, 22.5, 22.1, 14.0; IR (neat): ν = 3287, 2927, 1741,
1450, 1372, 1187, 1085, 1012, 854 cm−1; HRMS (ESI): m/z calculated
for C19H28Cl3N2O6S [M+H]+: 517.0728, found 517.0727.
2,2,2-Trichloroethyl (3-Benzyl-5-ethoxy-5-hexyl-2-oxooxazolidin-
4-yl)sulfamate (4ab). Prepared according to the general procedure B.
Purification on a column of silica gel with ethyl acetate in petroleum
ether (10/90) as eluent gave the desired product (28 mg, 39%) as a
3-Benzyl-5-(4-hydroxybutyl)oxazol-2(3H)-one (3g). Prepared ac-
cording to the general procedure A. Purification on a column of silica
gel with ethyl acetate in petroleum ether (80/20) as eluent gave the
desired product (27 mg, 63%) as a yellow solid. mp 36.8−37.2 °C; 1H
NMR (300 MHz, CDCl3) δ 7.38−7.26 (m, 5H), 6.05 (t, J = 1.2 Hz,
1H), 4.67 (s, 2H), 3.63 (t, J = 5.8 Hz, 2H), 2.40 (t, J = 6.8 Hz, 2H),
1.64−1.55 (m, 4H). 13C{1H} NMR (75 MHz, CDCl3): δ 155.9, 140.9,
135.7, 129.1, 128.4, 128.1, 109.5, 62.5, 47.6, 31.9, 25.8, 23.0; IR (neat):
ν = 3385, 3130, 3059, 2932, 1723, 1669, 1604, 1495, 1450, 1438, 1407,
1360, 1302, 1182, 1168, 1085, 1052, 1038, 965 cm−1; HRMS (ESI):
m/z calcd for C14H18NO3 [M+H]+: 248.1281; found: 248.1268.
5-(3-Chloropropyl)-3-phenyloxazol-2(3H)-one (3h). Prepared ac-
cording to the general procedure A. Purification on a column of silica
gel with ethyl acetate in petroleum ether (10/90) as eluent gave the
1
white solid. mp 87.5−91.8 °C; H NMR (300 MHz, CDCl3) δ 7.30−
7.23 (m, 5H), 6.96 (d, J = 9.8 Hz, 1H), 4.83 (d, J = 9.8 Hz, 1H), 4.77
(d, J = 15.5 Hz, 1H), 4.69 (d, J = 11.0 Hz, 1H), 4.62 (d, J = 11.0 Hz,
1H), 4.28 (d, J = 15.5 Hz, 1H), 3.38−3.36 (m, 2H), 2.00−1.94 (m,
1H), 1.88−1.82 (m, 1H), 1.45−1.39 (m, 1H), 1.30−1.15 (m, 7H),
1.03 (t, J = 6.9 Hz, 3H), 0.79 (t, J = 6.8 Hz, 3H). 13C{1H} NMR (75
MHz, CDCl3): δ 156.7, 135, 129, 128.3, 128.1, 107.4, 93.5, 78.8, 72.8,
58.5, 44.9, 31.6, 31, 29.4, 22.7, 22.3, 15.3, 14.2; IR (neat): ν = 3150,
2929, 1746, 1450, 1422, 1392, 1320, 1221, 1186, 1085, 1006, 958, 855
cm−1; HRMS (ESI): m/z calcd for C20H30Cl3N2O6S [M+H]+:
531.0885; found: 531.0917.
2,2,2-Trichloroethyl (5-Methoxy-2-oxo-3,5-diphenyloxazolidin-4-
yl)sulfamate (4ca). Prepared according to the general procedure B.
Purification on a column of silica gel with ethyl acetate in petroleum
ether (10/90) as eluent gave the desired product (21 mg, 42%) as a
brownish solid with remaining traces of NH2Tces. mp 168−169.4 °C;
1H NMR (300 MHz, CDCl3) δ 7.63−7.60 (m, 2H), 7.56−7.51 (m,
5H), 7.44 (t, J = 7.7 Hz, 2H), 7.32 (t, J = 7.6 Hz, 1H), 5.82−5.80 (m,
1H), 5.09−5.07 (m, 1H), 4.69−4.68 (m, 1H), 3.80−3.73 (m, 2H),
3.34 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3): δ 153.2, 134.5, 131.6,
130.6, 129.6, 129.4, 127.5, 124.4, 107, 92.8, 77.9, 76.4, 52.1; IR (neat):
ν = 3169, 2989, 2947, 1758, 1742, 1599, 1505, 1452, 1418, 1390, 1368,
1230, 1168, 1116, 1083, 998, 943 cm−1; HRMS (ESI): m/z calculated
for C18H18Cl3N2O6S [M+H]+: 494.9945, found 494.9943.
1
desired product (55 mg, 88%) as a white gum; H NMR (400 MHz,
CDCl3) δ 7.55 (d, J = 8.0 Hz, 2H), 7.43 (t, J = 7.8 Hz, 2H), 7.26 (t, J =
7.4 Hz, 1H), 6.67 (s, 1H), 3.61 (t, J = 6.1 Hz, 2H), 2.68 (t, J = 7.2 Hz,
2H), 2.13−2.07 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3): δ 153.1,
139.9, 135.6, 129.4, 126.3, 120.7, 110.1, 43.6, 29.3, 23.1; IR (neat): ν =
3145, 2916, 1735, 1675, 1601, 1506, 1400, 1260, 1209, 1135, 975, 757
cm−1; HRMS (ESI): m/z calcd for C12H13NO2Cl [M+H]+: 238.0629
found: 238.0628.
N-(3-(3-Benzyl-2-oxo-2,3-dihydrooxazol-5-yl)propyl)-4-methyl-
benzenesulfonamide (3i). Prepared according to the general
procedure A. Purification on a column of silica gel with ethyl acetate
in petroleum ether (60/40) as eluent gave the desired product (22 mg,
85%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 7.73−7.69 (m,
2H), 7.40−7.25 (m, 7H), 6.09 (t, J = 1.2 Hz, 1H), 4.84 (t, J = 6.4 Hz,
1H), 4.67 (s, 2H), 2.94 (d, J = 6.6 Hz, 2H), 2.45−2.39 (m, 5H), 1.76−
1.67 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3): δ 155.6, 143.5,
139.3, 136.8, 135.5, 129.8, 128.9, 128.3, 127.9, 127.0, 110.3, 47.6, 41.9,
26.8, 22.8, 21.5; IR (neat): ν = 3254, 2929, 1731, 1668, 1496, 1441,
1402, 1322, 1304, 1152, 1090, 958 cm−1; HRMS (ESI): m/z calcd for
C20H23N2O4S [M+H]+: 387.1373; found: 387.1390.
2,2,2-Trichloroethyl (3-(3,5-Dimethoxyphenyl)-5-hexyl-5-me-
thoxy-2-oxooxazolidin-4-yl)sulfamate (4da). Prepared according to
the general procedure B. Purification on a column of silica gel with
ethyl acetate in petroleum ether (20/80) as eluent gave the desired
product (33 mg, 38%) as a brown oil contamiated with remaining
1
traces of NH2Tces. H NMR (300 MHz, CDCl3) δ 6.69−6.68 (m,
2H), 6.37−6.35 (m, 2H), 5.52 (d, J = 9.8 Hz, 1H), 4.26 (d, J = 11.0
Hz, 1H), 4.06 (d, J = 11.0 Hz, 1H), 3.78 (s, 6H), 3.44 (s, 3H), 2.18−
2.08 (m, 1H), 1.95−1.88 (m, 1H), 1.39−1.15 (m, 7H), 0.95−0.85 (m,
4H). 13C{1H} NMR (75 MHz, CDCl3): δ 161.4, 153.8, 136.2, 106.8,
102.2, 99.4, 93.0, 78.5, 74.8, 55.5, 50.5, 31.5, 30.1, 29.3, 22.5, 22.0,
14.0; IR (neat): ν = 3285, 2955, 1749, 1598, 1451, 1368, 1182, 1086,
1012, 926 cm−1.; HRMS (ESI): m/z calculated for C20H30Cl3N2O8S
[M+H]+: 563.0782, found 563.0783.
3-Benzyl-5-(cyclohex-1-en-1-yl)oxazol-2(3H)-one (3j). Prepared
according to the general procedure A. Purification on a column of
silica gel with ethyl acetate in petroleum ether (15/85) as eluent gave
the desired product (70 mg, 85%) as a white solid. mp 128.6−129.6
1
°C; H NMR (300 MHz, CDCl3) δ 7.38−7.27 (m, 5H), 6.17−6.15
(m, 1H), 6.10 (s, 1H), 4.71 (s, 2H), 2.17−2.15 (m, 2H), 2.00−1.98
(m, 2H), 1.67−1.60 (m, 4H). 13C{1H} NMR (75 MHz, CDCl3): δ
135.5, 129.3, 129.0, 128.8, 128.3, 127.9, 124.0, 107.3, 47.7, 25.0, 23.3,
22.0, 21.8; IR (neat): ν = 3134, 3034, 2944, 1738, 1441, 1394, 1352,
1175, 1088, 1010, 845 cm−1; HRMS (ESI): m/z calcd for C16H18NO2
[M+H]+: 256.1332; found: 256.1344.
2,2,2-Trichloroethyl (3-Benzyl-5-(cyclohex-1-en-1-yl)-5-methoxy-
2-oxooxazolidin-4-yl)sulfamate (4ja). Prepared according to the
general procedure B. Purification on a column of silica gel with ethyl
acetate in petroleum ether (15/85) as eluent gave the desired product
1
(69 mg, 44%) as a colorless gum. H NMR (300 MHz, CDCl3) δ
7.39−7.30 (m, 5H), 6.34−6.30 (m, 1H), 5.55 (d, J = 9.5 Hz, 1H),
4.96−4.88 (m, 2H), 4.65−4.63 (m, 2H), 4.35 (d, J = 15.7 Hz, 1H),
3.27 (s, 3H), 2.14−2.21 (m, 2H), 2.09−2.00 (m, 1H), 1.91−1.84 (m,
1H), 1.70−1.56 (m, 4H). 13C{1H} NMR (75 MHz, CDCl3): δ 155.3,
5,5′-(Propane-1,3-diyl)bis(3-benzyloxazol-2(3H)-one) (3k). Pre-
pared according to the general procedure A. Recrystallization of the
crude product in ethyl acetate gave the desired product (76 mg, 99%)
as a white solid. mp 163.3−164.5 °C; 1H NMR (300 MHz, CDCl3) δ
D
DOI: 10.1021/acs.joc.7b01623
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
135.1, 131.8, 129.7, 128.8, 128.0, 127.9, 107.1, 93.2, 78.5, 72.2, 51.1,
45.0, 25.0, 24.0, 22.1, 21.7; IR (neat): ν = 2937, 1745, 1456, 1429,
1384, 1187, 1088, 1007, 981, 858 cm−1; HRMS (ESI): m/z calcd for
C19H24Cl3N2O6S [M+H]+: 513.0415; found: 513.0439.
2,2,2-Trichloroethyl (3-Benzyl-2-oxo-1,6-dioxa-3-azaspiro[4.4]-
nonan-4-yl)sulfamate (4ea). Prepared according to the general
procedure B. Purification on a column of silica gel with ethyl acetate in
petroleum ether (30/70) as eluent gave the desired product (25 mg,
35%) as a yellow gum. 1H NMR (300 MHz, CDCl3) δ 7.38−7.30 (m,
5H), 7.23 (d, J = 9.8 Hz, 1H), 5.03 (d, J = 9.8 Hz, 1H), 4.82 (d, J =
16.1 Hz, 1H), 4.69 (d, J = 11.2 Hz, 1H), 4.63 (d, J = 11.2 Hz, 1H),
4.30 (d, J = 16.1 Hz, 1H), 4.21−4.17 (m, 1H), 4.05 (q, J = 7.9 Hz,
1H), 2.42−2.34 (m, 2H), 2.22−2.14 (m, 1H), 2.12−2.04 (m, 1H).
13C{1H} NMR (75 MHz, CDCl3): δ 155.5, 134.9, 129.1, 128.3, 128.1,
ACKNOWLEDGMENTS
■
We wish to thank the French National Research Agency
(program n° ANR-11-IDEX-0003-02, CHARMMMAT ANR-
11-LABX-0039, program n° ANR-15-CE29-0014-01; fellowship
to R.R.-R.), the Ministere de l′Enseignement Superieur et de la
̀ ́
Recherche (fellowship to G.G.), the Region Centre Val de
Loire (fellowship to L.H.), and the Institut de Chimie des
Substances Naturelles for their support.
REFERENCES
■
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2903, 1737, 1443, 1418, 1365, 1331, 1263, 1228, 1211, 1171, 1070,
1015, 949, 847 cm−1; HRMS (ESI): m/z calcd for C15H18Cl3N2O6S
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2,2,2-Trichloroethyl (3-Benzyl-2-oxo-1,6-dioxa-3-azaspiro[4.5]-
decan-4-yl)sulfamate (4ga). Prepared according to the general
procedure B. Purification on a column of silica gel with ethyl acetate
in petroleum ether (15/85) as eluent gave the desired product (35 mg,
1
23%) as a white solid. Mp 158.1−161.9 °C; H NMR (300 MHz,
CDCl3) δ 7.37−7.30 (m, 5H), 6.86−6.79 (m, 1H), 4.84−4.77 (m,
2H), 4.69 (d, J = 11.0 Hz, 1H), 4.61 (d, J = 11 Hz, 1H), 4.32 (d, J =
15.6 Hz, 1H), 4.04−3.95 (m, 1H), 3.83−3.79 (m, 1H), 2.10−2.04 (m,
1H), 1.96−1.89 (m, 3H), 1.69−1.64 (m, 2H). 13C{1H} NMR (75
MHz, CDCl3): δ 156.3, 134.8, 128.9, 128.1, 127.9, 104.0, 93.3, 78.5,
74.0, 63.9, 44.8, 28.7, 24.1, 18.7; IR (neat): ν = 3134, 1741, 1483,
1434, 1365, 1245, 1183, 1081, 1012, 976, 939, 871, 850 cm−1; HRMS
(ESI): m/z calcd for C16H20Cl3N2O6S [M+H]+: 473.0102; found:
473.0100.
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diazaspiro[4.4]nonan-4-yl)sulfamate (4ia). Prepared according to
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361.
(6) (a) Yu, X.-Q.; Huang, J.-S.; Zhou, X.-G.; Che, C.-M. Org. Lett.
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1
product (19 mg, 19%) as a brown solid. Mp 80.5−80.7 °C; H NMR
(300 MHz, CDCl3) δ 7.66−7.64 (m, 2H), 7.53−7.50 (m, 2H), 7.38−
7.29 (m, 5H), 6.00−5.92 (m, 1H), 5.83−5.75 (m, 1H), 4.67 (d, J =
15.2 Hz, 1H), 4.63−4.54 (m, 2H), 4.53 (d, J = 15.2 Hz, 1H), 3.51−
3.38 (m, 2H), 2.62−2.51 (m, 1H), 2.42 (s, 3H), 2.08−2.15 (m, 1H),
1.94−1.83 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3): δ 154.9, 144.5,
135.6, 130.0, 129.9, 129.2, 129.0, 128.4, 128.1, 100.1, 99.6, 78.4, 75.0,
50.0, 47.3, 36.5, 21.9, 21.7; R (neat): ν = 2923, 1747, 1597, 1443,
1348, 1250, 1186, 1158, 1082, 1054, 1001, 966, 851 cm−1; HRMS
(ESI): m/z calcd for C22H25Cl3N3O7S2 [M+H]+: 612. 0121; found:
611.0121.
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ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.7b01623.
X-ray crystallographic data of compound 4ga (CIF)
1
General notes and general procedures and H and 13C
NMR spectra of compounds 2a, 2d−k, 3d−k, and 4
(PDF)
AUTHOR INFORMATION
Corresponding Authors
*isabelle.gillaizeau@univ-orleans.fr
*philippe.dauban@cnrs.fr
■
ORCID
(12) Gigant, N.; Dequirez, G.; Retailleau, P.; Gillaizeau, I.; Dauban,
P. Chem. - Eur. J. 2012, 18, 90.
(13) (a) Dequirez, G.; Ciesielski, J.; Retailleau, P.; Dauban, P. Chem. -
Eur. J. 2014, 20, 8929. (b) Ciesielski, J.; Dequirez, G.; Retailleau, P.;
Gandon, V.; Dauban, P. Chem. - Eur. J. 2016, 22, 9338.
Isabelle Gillaizeau: 0000-0002-7726-3592
Philippe Dauban: 0000-0002-1048-5529
Notes
The authors declare no competing financial interest.
E
DOI: 10.1021/acs.joc.7b01623
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The Journal of Organic Chemistry
Note
(14) (a) Guthikonda, K.; Du Bois, J. J. Am. Chem. Soc. 2002, 124,
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(16) For recent studies on ynamides from one of us, see: Sallio, R.;
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Org. Chem. 2017, 82, 1254.
(17) (a) Zificsak, C. A.; Mulder, J. A.; Hsung, R. P.; Rameshkumar,
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(19) We have performed several test experiments using only
Rh2(esp)2, or only PhI(OAc)2, or involving a combination of
PhI(OAc)2 and Rh2(esp)2, or of TcesNH2 and Rh2(esp)2. In each
case, we did not observe the formation of the oxazolone. These results
support the hypothesis that the dirhodium-nitrene complex promotes
the cyclization reaction. AcOH could also potentially mediate the
reaction as it is released from PhI(OAc)2 during the formation of the
iminoiodinane. However, we have also checked that the cyclization
does not proceed in the presence of AcOH.
(20) For previous reports on the catalytic cycloisomerization of
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́
2007, 1763. (b) Istrate, F. M.; Buzas, A. K.; Jurberg, I. D.; Odabachian,
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W.; Xia, S.; Bai, Y.; Luo, F.; Zhu, G. J. Org. Chem. 2012, 77, 9871.
(e) Huang, H.; Zhu, X.; He, G.; Liu, Q.; Fan, J.; Zhu, H. Org. Lett.
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(22) Screening of the solvents (CH2Cl2, (CHCl2)2, CF3CH2OH) and
the iodine oxidant (PhI(OPiv)2) has been made with ynamide 3e to
improve the yields albeit without success.
(23) The direct reaction of ynamide 3a in the presence of 3 mol% of
Rh2(esp)2, 1.2 equiv of TcesNH2, 1.4 equiv of PhI(OAc)2, and 12
equiv of methanol, was also performed but compound 4aa was isolated
with a lower yield because of its extensive decomposition. For a
previous example of the decomposition of oxazolone under oxidative
conditions, see: Sheehan, J. C.; Guziec, F. S., Jr. J. Am. Chem. Soc.
1972, 94, 6561.
F
DOI: 10.1021/acs.joc.7b01623
J. Org. Chem. XXXX, XXX, XXX−XXX