N -heterocyclic carbene catalyzed domino cyclization of propargylic alcohols and benzoyl isocyanates

Article abstract of DOI:10.1021/jo202102y

N-Hetereocyclic carbenes (NHCs) were found to be efficient catalysts for the cyclization of propargylic alcohols and isocyanates. Domino cyclization reactions were carried out using isopropyl-substituted imidazolium salt as a precatalyst, and a wide range

Full text of DOI:10.1021/jo202102y

Note
pubs.acs.org/joc
N-Heterocyclic Carbene Catalyzed Domino Cyclization of Propargylic
Alcohols and Benzoyl Isocyanates
Kyoung A Jo,†,§ Muchchintala Maheswara,†,§ Eunyoung Yoon,† Yun Yeong Lee,† Hoseop Yun,‡
and Eun Joo Kang*,†
†Department of Applied Chemistry, Kyung Hee University, Yongin 446-701, Korea
‡Division of Energy Systems Research and Department of Chemistry, Ajou University, Suwon 443-749, Korea
S
* Supporting Information
ABSTRACT: N-Hetereocyclic carbenes (NHCs) were found to be efficient
catalysts for the cyclization of propargylic alcohols and isocyanates. Domino
cyclization reactions were carried out using isopropyl-substituted imidazolium
salt as a precatalyst, and a wide range of substituted oxazolidinones were
obtained in high yields.
N-Heterocyclic carbenes (NHCs) have come to be heavily
researched for the role of nucleophilic organocatalysts and
ligands, and the remarkable success of NHCs is innately caused
by their powerful capacity as two-electron donors.1 The most
attractive catalytic role of NHCs is to convert aldehydes into
acyl anion equivalents during transformations such as benzoin
and Stetter reactions. Although the development of these
reactions to trigger umpolungs has received significant
attention, different modes of reactivity for NHCs has received
considerably less attention. In this study, we have discovered
oxazolidinone heterocycles, having pre-existing issues of lower
reactivities of internal propargylic alcohols compared to
terminal ones7e and benzoyl isocyanates compared to phenyl
isocyanates (Table 1).6a N-Heterocyclic carbene catalysts have
previously been shown to activate CO2 in 1,3-dioxolan-2-ones
synthesis with internal propargylic alcohols,8 which led us to
investigate their use as potential catalysts. The use of 1,3-
diisopropylimidazolium chloride and DBU resulted in the
synthesis of benzylideneoxazolidinone with a 62% yield, which
was accompanied by an unreacted propargyl alcohol. An
increase in reaction temperature resulted in little improvement;
however, when KOtBu was used as a base, a remarkable
increase in reactivity and isolated yield was achieved even with a
reduced reaction time. Screening tests with other imidazolium,
triazolium, and thiazolium catalysts demonstrated that
precatalyst I was the most effective, and we hypothesized that
this higher reactivity was due to the lower steric hindrance in
isopropyl substituents. During solvent optimization studies,
other polar solvents, such as CH3CN and CH3NO2, were
shown to provide little benefit relative to DCE. On the basis of
these results, we performed a control experiment with only the
DBU base catalyst, which resulted in a 50% yield even with a
prolonged reaction time (12 h). Remarkably, this reaction
resulted in the exclusive formation of the (E)-configured
another Bronsted basic property2 of various NHCs in the
̈
benzylidene oxazolidinone synthesis.
Oxazolidinones and their derivatives are a very important
class of heterocyclic compounds in terms of bioactive and chiral
molecules. They exhibit a wide range of biological properties
including monoamine oxidase inhibitors, renin inhibitors, sigma
receptors, cytokine modulators and antibiotics,3 and also been
used as chiral synthons or auxiliaries, allowing high levels of
diastereoselectivity in the chirality transfer reactions and
asymmetric reactions.4 Due to the importance of their
structures, several methods for the synthesis of 1,3-oxazolidin-
2-ones have been developed. Classical methods for the
oxazolidinone formations involve condensation reactions with
amino alcohols and carbonyl precursors such as phosgene,
chloroformate, and dialkyl carbonates. An alternative approach
is the cyclization reaction of vinyl or propargyl carbamate
catalyzed by base5 or transition metal6 catalysts under mild
conditions. Although another method using CO2 as a carbonyl
source has been developed recently,7 these procedures were
mostly applied to the construction of 4-methylene-1,3-
oxazolidin-2-one, and only a few 4-arylidene compounds have
been reported. In this context, concise catalytic methods for the
direct synthesis of 4-arylideneoxazolidinones are presented as
an atom-economical and environmentally benign process using
propargylic alcohols and isocyanates.
1
isomer, and H NMR experiments did not show any trace of
the (Z)-isomer. The structure of the product was determined
by 1D NOE and subsequently confirmed by X-ray crystallog-
raphy.9 The (E)-conformer, which is accessed by the anti-
addition of amine nucleophile and proton, could provide a
mechanistic insight into this reaction, which will be discussed
later. For the reactivities of other isocyanates bearing various N-
substituents, no reaction occurred with n-butyl or benzyl
isocyanates, and phenyl isocyanate induced cyclization even in
the presence of the DBU catalyst.10 In addition, tosyl or
trichloromethyl isocyanate having an electron withdrawing
To examine the possibility of using internal propargyl
alcohols as potential substrates, phenyl-substituted propargyl
alcohol (1a) and benzoyl isocyanate were used to create
Received: October 13, 2011
Published: February 15, 2012
© 2012 American Chemical Society
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Note
a
Table 1. Optimization of Conditions for Benzylidene Oxazolidinone Synthesis
b
entry
catalyst
base
DBU
solvent
temp (°C)
yield (%)
c
1
I
DCE
rt
55
55
55
55
55
55
55
55
55
55
55
62
68
0
c
2
I
DBU
DCE
3
I
TEA
DCE
4
I
KOtBu
Cs2CO3
KHMDS
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
DCE
92
54
90
50
35
0
5
I
DCE
6
I
DCE
7
II
III
IV
I
DCE
8
DCE
9
DCE
10
11
CH3CN
CH3NO2
DCE
28
51
55
I
d
12
I
a
Reactions and conditions: propargylic alcohol (1a: 0.25 mmol), BzNCO (0.375 mmol), NHC catalyst (20 mol %), base (15 mol %), solvent (0.2
b
c
d
M) under N2, unless otherwise specified. Isolated yield after chromatographic purification. Reaction for 12 h. Reaction with 15 mol % of catalyst
and 12 mol % of base.
a
Table 2. Synthesis of Arylidene Oxazolidinones: Substrate Scope
b
entry
R1
R2
product
yield (%)
1
2
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
2a
2b
2c
2d
2e
2f
92
71
51
99
99
76
84
49
77
10
0
4-MeC6H4
4-MeOC6H4
4-FC6H4
3
4
5
4-ClC6H4
4-BrC6H4
2-ClC6H4
3-ClC6H4
4-Cl-2-F- C6H4
4-CN-C6H4
4-CH3CO-C6H4
4-NO2−C6H4
1-naphthyl
2-thienyl
6
7
2g
2h
2i
8
9
10
11
12
13
14
15
16
17
18
19
2j
2k
2l
0
2m
2n
2o
2p
2q
2r
2s
56
78
65
99
77
56
0
2-pyridyl
4-ClC6H4
Ph
iPr
H
nBu
Et
Me
a
Reactions and conditions: propargylic alcohol (1: 0.25 mmol), BzNCO (0.375 mmol), NHC catalyst (20 mol %), base (15 mol %), solvent (0.2 M)
b
under N2, unless otherwise specified. Isolated yield after chromatographic purification.
group could not produce the corresponding oxazolidinone,
whereas the tosyl-substituted carbamate was formed in good
yield within 1 h.
Encouraged by this initial result, we explored the generality
of this process (Table 2). Preparation of the required
propargylic alcohols was straightforward and was performed
either by Sonogasira coupling with aryl iodide and 2-methyl-3-
butyn-2-ol or alternatively via alkynylation with lithiated phenyl
acetylene to various ketones. The presence of the electron-
donating groups on the phenyl group led to slightly lower
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Note
yields of the oxazolidinone products (entries 2, 3). Propargylic
alcohols containing halogen groups on an aryl ring were
converted into the corresponding oxazolidinones 2d-i with
good to excellent yield, and the reaction of substrates 1d and
1e, which have p-fluorophenyl and p-chlorophenyl groups
resulted in the exclusive formation of oxazolidinones with 99%
yields. Substrates bearing electron-withdrawing substitutents on
an aryl group did not participate in the cyclization reactions,
even under harsh conditions (CH3NO2, 100 °C, 48 h).
Heterocycles such as thiophene and pyridine were able to
tolerate these reaction conditions (entries 14 and 15) and
substrates 1p and 1q, which have different dialkyl substituents
also afforded the expected product with excellent yield. On the
basis of the cyclization results for substrates 1r and 1s, it was
inferred that the substituents on the alkynyl group delicately
affected reactivity (entries 18 and 19). The reaction with
terminal propargylic alcohol 1r afforded 4-methylene-1,3-
oxazolidin-2-one; however, the reaction with n-butyl substituted
alkyne 1s did not produce any product.
Scheme 2. Further Synthetic Transformations of 4-
Benzylideneoxazolidinones
underwent the debenzoylation reactions with BuNH2 under
heating in EtOH, resulting in amine 6 with a yield of 64%.
In summary, we have developed an NHC-catalyzed
intermolecular domino cyclization of propargylic alcohol and
BzNCO to afford a range of arylidene oxazolidinones in a mild
one-step synthesis. In particular, the first use of the NHC
catalyst to activate isonitriles has a significant advantage in
regard to oxazolidinone formation relative to previously
reported conditions. Enantioselective hydrogenation of oxazo-
lidinone products could be used to build a wide range of chiral
synthons in asymmetric organic transformations.15 The NHC
catalyzed cyclization reactions using various accumulated
double bond systems are currently being investigated.
On the basis of the results shown in Tables 1 and 2, it is very
clear that N-heterocyclic carbene plays a vital role in reducing
the reaction time and improving the yield of oxazolidinone
formation, rendering a plausible pathway proposed in Scheme
1. Base promoted reaction, with the N-heterocyclic carbene
Scheme 1. Mechanistic Investigation of 4-
Benzylideneoxazolidinone Formation
EXPERIMENTAL SECTION
■
General Procedure for Preparation of 4-Benzylideneoxazo-
lidinones. Propargylic alcohol (0.25 mmol) in DCE (0.2 M) was
treated with benzoyl isocyanate (55.2 mg, 0.375 mmol), 1,3-
diisopropylimidazolium chloride (9.4 mg, 0.05 mmol), and KOtBu
(4.2 mg, 0.0375 mmol) at 55 °C under N2 atmosphere. After stirring
for 5 h, the reaction mixture was concentrated and purified by silica
column chromatography.
(Z)-3-Benzoyl-4-benzylidene-5,5-dimethyloxazolidin-2-one
(2a): 1H NMR (300 MHz, CDCl3) δ 7.74 (d, 2H, J = 8.4 Hz), 7.57 (t,
1H, J = 7.5 Hz), 7.41 (t, 2H, J = 7.7 Hz), 7.11−7.08 (m, 3H), 7.03−
7.00 (m, 2H), 5.92 (s, 1H), 1.74 (s, 6H) ppm; 13C NMR (75 MHz,
CDCl3) δ 166.8, 152.8, 139.0, 134.6, 133.7, 132.5, 130.2, 130.1, 128.2,
128.2, 127.6, 127.2, 107.2, 84.1, 27.8 ppm; MS m/z (EI, relative
intensity) 307 (M+, 12), 248 (2), 122 (6), 105 (100), 77 (28); HRMS
(EI) calcd for C19H17NO3 (M+) 307.1208, found 307.1206.
(Z)-3-Benzoyl-5,5-dimethyl-4-(4-methylbenzylidene)-
oxazolidin-2-one (2b): 1H NMR (300 MHz, CDCl3) δ 7.74 (d, 2H,
J = 8.6 Hz), 7.56 (t, 1H, J = 7.5 Hz), 7.41 (t, 2H, J = 7.6 Hz), 6.89 (s,
4H), 5.88 (s, 1H), 2.19 (s, 3H) 1.71 (s, 6H) ppm; 13C NMR (75
MHz, CDCl3): δ 166.9, 152.9, 138.1, 136.9, 133.6, 132.6, 131.6, 130.2,
128.9, 128.2, 127.4, 107.4, 84.1, 27.7, 21.1 ppm; MS m/z (EI, relative
intensity) 321 (M+, 48), 159 (44), 143 (42), 119 (49), 105 (100), 77
(61); HRMS (EI) calcd for C20H19NO3 (M+) 321.1365, found
321.1363.
serving as an active Bronsted base,2 starts by an initial
̈
nucleophilic addition of the anionic oxygen of propargylic
alcohol to the electrophilic carbon of isocyanate. The
consecutive intramolecular cyclization of carbamate intermedi-
ate affords the arylidene oxazolidinone synthesis. Although the
alternative route of zwitterionic NHC-NCO adduct generation
could not be exclusively ruled out,11 formation of carbamate 3
as an intermediate confirmed by isolating in the middle of the
reaction, also the verification test of base-catalyzed cyclization
of carbamate 3 was conducted. Comparison between two
reactions, N-heterocyclic carbene or DBU catalyzed cycliza-
tion,12 led us to theorize that NHC as a more active Bronsted
̈
base is indispensable for cyclization of the benzoyl substituted
carbamate 3, whereas the phenyl substituted carbamates
provided satisfactory results in the DBU-catalyzed reaction
between propargylic alcohols and PhNCO.10
(Z)-3-Benzoyl-4-(4-methoxybenzylidene)-5,5-dimethyloxa-
1
zolidin-2-one (2c): H NMR (300 MHz, CDCl3) δ 7.76 (d, 2H, J =
7.3 Hz), 7.58 (t, 1H, J = 7.4 Hz), 7.43 (t, 2H, J = 7.6 Hz), 6.95 (d, 2H,
J = 8.6 Hz), 6.63 (d, 2H, J = 8.6 Hz), 5.87 (s, 1H), 3.70 (s, 3H) 1.72
(s, 6H) ppm; 13C NMR (75 MHz, CDCl3): δ 166.8, 158.4, 137.4,
133.6, 130.2, 128.9, 128.2, 127.0, 113.6, 107.2, 84.1, 55.1, 27.7 ppm;
MS m/z (EI, relative intensity) 337 (M+, 21), 105 (100), 77 (57);
HRMS (EI) calcd for C20H19NO4 (M+) 337.1314, found 337.1316.
(Z)-3-Benzoyl-4-(4-fluorobenzylidene)-5,5-dimethyloxazoli-
din-2-one (2d): 1H NMR (300 MHz, CDCl3) δ 7.68 (d, 2H, J = 8.4
Hz), 7.53 (t, 1H, J = 7.3 Hz), 7.37 (t, 2H, J = 7.6 Hz), 6.91 (dd, 2H, J
= 8.2, 5.3 Hz), 6.73 (t, 1H, J = 8.6 Hz), 5.81 (s, 1H), 1.67 (s, 6H)
The synthesized 4-benzylidene oxazolidinones would act as
synthetic precursors in the further transformation reactions
(Scheme 2). Hydrogenation of 2a in MeOH provided the
reduced product 4,13 which was accompanied by the
unexpected debenzoylated one 5,14 while the change of solvent
to EtOAc afforded the formation of only 4 with a yield of 83%.
We also examined the alkylamine mediated hydrolysis to form
debenzoylated oxazolidinone, which could be applied in the
synthesis of the chiral auxiliary. Benzylidene oxazolidinone 2a
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Note
ppm; 13C NMR (75 MHz, CDCl3) δ 166.8, 161.4 (d, J = 245.4 Hz),
152.7, 139.1, 133.9, 132.3, 130.7, 130.6, 130.1, 129.2, 129.1, 128.3,
115.3 (d, J = 21.6 Hz), 106.1, 84.1, 27.8 ppm; MS m/z (EI, relative
intensity) 325 (M+, 8), 105 (100), 77 (24); HRMS (EI) calcd for
C19H16FNO3 (M+) 325.1114, found 325.1118.
167.0, 152.6, 138.0, 136.4, 133.8, 132.7, 130.6, 128.2, 127.2, 126.9,
125.9, 101.7, 84.3, 27.5 ppm; MS m/z (EI, relative intensity) 313 (M+,
23), 105 (100), 77 (39); HRMS (EI) calcd for C17H15NO3S (M+)
313.0772, found 313.0770.
(Z)-3-Benzoyl-5,5-dimethyl-4-(pyridin-2-ylmethylene)-
oxazolidin-2-one (2o): 1H NMR (300 MHz, CDCl3) δ 7.96 (d, 1H,
J = 7.5 Hz), 7.63 (d, 1H, J = 4.2 Hz), 7.55 (t, 1H, J = 7.2 Hz), 7.47−
7.41 (m, 2H), 7.01 (d, 1H, J = 7.9 Hz), 6.79 (t, 1H, J = 6.0 Hz), 5.77
(s, 1H), 1.68 (s, 6H) ppm; 13C NMR (75 MHz, CDCl3) δ 167.8,
152.0, 146.9, 142.9, 136.3, 133.6, 133.3, 130.7, 128.9, 128.2, 127.9,
123.1, 121.1, 102.9, 84.4, 27.7 ppm; MS m/z (EI, relative intensity)
308 (M+, 31), 204(47), 105 (100), 77 (68); HRMS (EI) calcd for
C18H16N2O3 (M+) 308.1161, found 308.1162.
(Z)-3-Benzoyl-4-(4-chlorobenzylidene)-5-ethyl-5-methyloxa-
zolidin-2-one (2p): 1H NMR (300 MHz, CDCl3) δ 7.74 (d, 2H, J =
7.3 Hz), 7.59 (t, 1H, J = 7.4 Hz), 7.43 (t, 2H, J = 7.7 Hz), 7.05 (d, 2H,
J = 8.2 Hz), 6.92 (d, 2H, J = 8.3 Hz), 5.78 (s, 1H), 2.05−1.86 (m, 2H),
1.69 (s, 3H), 1.06 (t, 3H, J = 7.3 Hz) ppm; 13C NMR (75 MHz,
CDCl3) δ 166.8, 153.1, 138.2, 134.0, 133.2, 132.7, 132.4, 130.2, 128.8,
128.4, 105.9, 86.7, 34.0, 26.3, 7.6 ppm; MS m/z (EI, relative intensity)
355 (M+, 11), 139(66), 105 (100), 77 (60); HRMS (EI) calcd for
C20H18ClNO3 (M+) 355.0975, found 355.0980.
(Z)-3-Benzoyl-4-benzylidene-5-isopropyl-5-methyloxazoli-
din-2-one (2q): 1H NMR (300 MHz, CDCl3) δ 7.70 (d, 2H, J = 8.2
Hz), 7.52 (t, 1H, J = 7.3 Hz), 7.37 (t, 2H, J = 7.6 Hz), 7.03−6.95 (m,
5H), 5.81 (s, 1H), 2.02 (m, 1H), 1.64 (s, 3H), 1.06 (t, 6H, J = 6.6 Hz)
ppm; 13C NMR (75 MHz, CDCl3) δ 166.8, 153.5, 138.0, 134.9, 133.7,
132.7, 130.3, 128.3, 128.2, 127.5, 127.1, 107.5, 88.6, 38.0, 24.4, 16.5,
16.5 ppm; MS m/z (EI, relative intensity) 335 (M+, 14), 105 (100), 77
(22); HRMS (EI) calcd for C21H21NO3 (M+) 335.1521, found
335.1519.
(Z)-3-Benzoyl-4-(4-chlorobenzylidene)-5,5-dimethyloxazoli-
1
din-2-one (2e): H NMR (300 MHz, CDCl3) δ 7.68 (d, 2H, J = 7.5
Hz), 7.53 (t, 1H, J = 7.3 Hz), 7.38 (t, 2H, J = 7.6 Hz), 7.00 (d, 2H, J =
8.5 Hz), 6.87 (d, 2H, J = 8.2 Hz), 5.79 (s, 1H), 1.66 (s, 6H) ppm; 13C
NMR (75 MHz, CDCl3) δ 166.8, 152.6, 139.5, 134.0, 133.1, 132.8,
132.3, 130.2, 128.8, 128.4, 128.4, 106.0, 84.1, 27.8 ppm; MS m/z (EI,
relative intensity) 341 (M+, 8), 297 (6), 282 (5), 105 (100), 77 (27);
HRMS (EI) calcd for C19H16ClNO3 (M+) 341.0819, found 341.0821.
(Z)-3-Benzoyl-4-(4-bromobenzylidene)-5,5-dimethyloxazoli-
1
din-2-one (2f): H NMR (300 MHz, CDCl3) δ 7.78 (d, 2H, J = 8.4
Hz), 7.64 (t, 1H, J = 7.3 Hz), 7.48 (t, 2H, J = 7.6 Hz), 7.28 (d, 2H, J =
7.5 Hz), 6.91 (d, 2H, J = 8.4 Hz), 5.87 (s, 1H), 1.76 (s, 6H) ppm; 13C
NMR (75 MHz, CDCl3) δ 166.8, 152.6, 139.5, 134.0, 133.5, 132.2,
131.3, 130.2, 129.1, 128.3, 121.0, 106.0, 84.1, 27.7 ppm; MS m/z (EI,
relative intensity) 387 (M++2, 6), 385 (M+, 6), 105 (100), 77 (24);
HRMS (EI) calcd for C19H16BrNO3 (M+) 385.0313, found 385.0314.
(Z)-3-Benzoyl-4-(2-chlorobenzylidene)-5,5-dimethyloxazoli-
din-2-one (2g): 1H NMR (300 MHz, CDCl3) δ 7.59 (d, 2H, J = 8.4
Hz), 7.50 (t, 2H, J = 7.5 Hz), 7.34 (t, 2H, J = 7.7 Hz), 7.14 (d, 2H, J =
7.5 Hz), 7.05−6.95 (m, 3H), 5.86 (s, 1H), 1.76 (s, 6H) ppm; 13C
NMR (75 MHz, CDCl3) δ 166.5, 152.5, 141.2, 133.6, 133.3, 133.0,
132.2, 129.7, 129.7, 129.3, 129.2, 128.6, 128.2, 128.2, 126.3, 103.4,
83.8, 28.0 ppm; MS m/z (EI, relative intensity) 341 (M+, 13), 105
(100), 77 (40); HRMS (EI) calcd for C19H16ClNO3 (M+) 341.0819,
found 341.0816.
(Z)-3-Benzoyl-4-(3-chlorobenzylidene)-5,5-dimethyloxazoli-
1
din-2-one (2h): H NMR (300 MHz, CDCl3) δ 7.73 (d, 2H, J = 8.2
3-Benzoyl-5-ethyl-5-methyl-4-methyleneoxazolidin-2-one
(2r): 1H NMR (300 MHz, CDCl3) δ 7.60 (d, 2H, J = 7.1 Hz), 7.52 (t,
1H, J = 7.4 Hz), 7.39 (t, 2H, J = 7.5 Hz), 5.53 (d, 1H, J = 2.5 Hz), 4.49
(d, 1H, J = 2.4 Hz), 1.93−1.84 (m, 1H), 1.79−1.71 (m, 1H), 1.55 (s,
3H), 0.97 (t, 3H, J = 7.3 Hz) ppm; 13C NMR (75 MHz, CDCl3) δ
169.1, 152.5, 144.6, 133.5, 133.0, 129.03, 129.00, 128.21, 128.17, 91.2,
85.6, 33.9, 26.7, 7.5 ppm; MS m/z (EI, relative intensity) 245 (M+,
10), 201(7), 105 (100), 77 (49); HRMS (EI) calcd for C14H15NO3
(M+) 245.1052, found 245.1056.
Hz), 7.58 (t, 1H, J = 7.5 Hz), 7.42 (t, 2H, J = 7.6 Hz), 7.01−6.89 (m,
4H), 5.82 (s, 1H), 1.72 (s, 6H) ppm; 13C NMR (75 MHz, CDCl3): δ
166.9, 152.6, 140.4, 136.4, 134.2, 134.0, 132.1, 130.2, 129.5, 128.4,
127.5, 127.2, 125.6, 105.5, 84.0, 27.7 ppm; MS m/z (EI, relative
intensity) 341 (M+, 24), 105 (100), 77 (64); HRMS (EI) calcd for
C19H16ClNO3 (M+) 341.0819, found 341.0821.
(Z)-3-Benzoyl-4-(4-chloro-2-fluorobenzylidene)-5,5-dime-
1
thyloxazolidin-2-one (2i): H NMR (300 MHz, CDCl3) δ 7.73 (d,
2H, J = 7.5 Hz), 7.57 (t, 1H, J = 7.5 Hz), 7.42 (t, 2H, J = 7.2 Hz),
7.03−6.98 (m, 2H), 6.83 (d, 2H, J = 10.1 Hz), 5.74 (s, 1H), 1.73 (s,
6H) ppm; 13C NMR (75 MHz, CDCl3) δ 166.4, 158.8 (d, J = 249.1
Hz), 152.3, 141.1, 133.8, 133.7, 133.6, 132.4, 130.1, 129.9, 129.9,
128.1, 125.0, 124.2, 121.5 (d, J = 15.5 Hz), 116.0 (d, J = 25.3 Hz),
99.2, 83.9, 28.1 ppm; MS m/z (EI, relative intensity) 359 (M+, 10),
105 (100), 77 (24); HRMS (EI) calcd for C19H15FClNO3 (M+)
359.0724, found 359.0722.
2-Methyl-4-phenylbut-3-yn-2-yl benzoylcarbamate (3): 1H
NMR (300 MHz, CDCl3) δ 7.92 (s, 1H), 7.75 (d, 2H, J = 8.4 Hz),
7.51 (t, 1H, J = 7.3 Hz), 7.43−7.37 (m, 4H), 7.24−7.20 (m, 3H), 1.79
(s, 6H) ppm; 13C NMR (75 MHz, CDCl3) δ 164.9, 148.6, 133.1,
132.9, 131.9, 128.8, 128.5, 128.2, 127.5, 122.2, 89.1, 84.8, 75.1, 29.0
ppm; MS m/z (EI, relative intensity) 307 (M+, 11), 160 (28), 143
(40), 105 (100), 77 (55); HRMS (EI) calcd for C19H17NO3 (M+)
307.1208, found 307.1207.
General Procedure for Hydrogenation Reactions of 2a. A
solution of 2a (1 mmol) in anhydrous methanol or ethyl acetate (3
mL) was treated with palladium (10 wt % on charcoal) under a
hydrogen atmosphere (H2 balloon). The reaction mixture was stirred
for 2 h at room temperature. The progress of the reaction was
followed by TLC. After completion, the reaction was filtered through
Celite and the residue washed with solvent used. The filtrate was
concentrated under reduced pressure and purified by column
chromatography (EtOAc/hexane).
(Z)-4-((3-Benzoyl-5,5-dimethyl-2-oxooxazolidin-4-ylidene)-
1
methyl)benzonitrile (2j): H NMR (300 MHz, CDCl3) δ 7.74 (d,
2H, J = 7.3 Hz), 7.61 (t, 1H, J = 7.5 Hz), 7.44 (t, 1H, J = 7.6 Hz), 7.36
(d, 2H, J = 8.2 Hz), 7.08 (d, 2H, J = 8.0 Hz), 5.88 (s, 1H), 1.73 (s,
6H) ppm; 13C NMR (75 MHz, CDCl3) δ 166.8, 152.4, 141.6, 139.6,
134.3, 132.0, 131.9, 130.3, 128.5, 128.1, 118.6, 110.4, 105.0, 84.1, 27.8
ppm; MS m/z (EI, relative intensity) 332 (M+, 10), 288 (2), 228 (4),
105 (100), 77 (61); HRMS (EI) calcd for C20H16N2O3 (M+)
332.1161, found 332.1164.
(Z)-3-Benzoyl-5,5-dimethyl-4-(naphthalen-1-ylmethylene)-
3-Benzoyl-4-benzyl-5,5-dimethyloxazolidin-2-one (4): 1H
NMR (300 MHz, CDCl3) δ 7.60 (d, 2H, J = 7.1 Hz), 7.47 (t, 1H, J
= 7.3 Hz), 7.36 (t, 2H, J = 7.5 Hz), 7.25−7.21 (m, 3H), 7.18−7.12 (m,
2H), 4.59 (dd, 1H, J = 9.7, 4.2 Hz), 3.41 (dd, 1H, J = 14.1, 4.2 Hz),
2.82 (dd, 1H, J = 14.0, 9.8 Hz) 1.43 (s, 3H), 1.21 (s, 3H) ppm; 13C
NMR (75 MHz, CDCl3): δ 170.4, 152.6, 136.4, 133.4, 132.6, 129.2,
129.2, 129.1, 128.7, 128.4, 127.9, 127.0, 82.3, 64.5, 34.4, 28.1, 22.6
ppm; MS m/z (EI, relative intensity) 309 (M+, 15), 176 (34), 149, (9),
105, (100), 77 (25); HRMS (EI) calcd for C19H19NO3 (M+)
309.1365, found 309.1364.
1
oxazolidin-2-one (2m): H NMR (300 MHz, CDCl3) δ 7.66−7.63
(m, 2H), 7.57 (d, 1H, J = 7.0 Hz), 7.36−7.32 (m, 4H), 7.20−7.12 (m,
3H), 7.03 (t, 2H, J = 7.4 Hz), 6.17 (s, 1H), 1.85 (s, 6H) ppm; 13C
NMR (75 MHz, CDCl3) δ 166.6, 152.5, 142.1, 133.3, 132.9, 131.9,
131.6, 130.5, 129.0, 128.3, 128.1, 127.8, 125.95, 125.86, 125.79, 124.9,
124.2, 103.5, 83.6, 28.1 ppm; MS m/z (EI, relative intensity) 357 (M+,
28), 105 (100), 77 (22); HRMS (EI) calcd for C23H19NO3 (M+)
357.1365, found 357.1360.
(Z)-3-Benzoyl-5,5-dimethyl-4-(thiophene-2-ylmethylene)-
oxazolidin-2-one (2n): 1H NMR (300 MHz, CDCl3) δ 7.84 (d, 1H,
J = 8.4 Hz), 7.60 (t, 1H, J = 7.4 Hz), 7.45 (t, 2H, J = 7.6 Hz), 7.10 (d,
1H, J = 5.1 Hz), 6.82 (dd, 1H, J = 5.0, 3.7 Hz), 6.74 (d, 1H, J = 3.5
Hz), 6.07 (s, 1H), 1.70 (s, 6H) ppm; 13C NMR (75 MHz, CDCl3) δ
4-Benzyl-5,5-dimethyloxazolidin-2-one (5): 1H NMR (300
MHz, CDCl3) δ 7.36−7.23 (m, 3H), 7.16−7.15 (m, 2H), 4.81 (s, 1H),
3.66 (dd, 1H, J = 10.8, 3.7 Hz), 2.82 (dd, 1H, J = 13.3, 3.6 Hz), 2.64
2927
dx.doi.org/10.1021/jo202102y | J. Org. Chem. 2012, 77, 2924−2928

The Journal of Organic Chemistry
Note
(dd, 1H, J = 13.2, 11.0 Hz), 1.47 (s, 3H), 1.44 (s, 3H) ppm; 13C NMR
(75 MHz, CDCl3) δ 157.8, 136.8, 129.1, 128.8, 127.2, 83.2, 63.0, 37.0,
27.5, 21.9 ppm; MS m/z (EI, relative intensity) 205 (M+, 5), 114
(100), 91 (46), 71 (91); HRMS (EI) calcd for C12H15NO2 (M+)
205.1103, found 205.1105.
General Procedure for Debenzoylation Reactions of 2a. A
stirred solution of 2a (1 mmol) in ethanol (3 mL) was treated with
butylamine (1.5 mmol) at room temperature. The resulting mixture
was heated to 70 °C for 12 h. The progress of the reaction was
monitored by TLC. After completion, the reaction mixture was cooled
to room temperature and extracted with EtOAc (2 × 5 mL). The
combined organic portions were washed with water and brine, dried
over anhydrous MgSO4, and concentrated under reduced pressure.
The residue was purified by column chromatography over silica gel
(EtOAc/hexane) to give the desired product 6.
C. Tetrahedron Lett. 2000, 41, 4301. (g) Mukhtar, T. A.; Wright, G. D.
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(9) The X-ray crystal structure of 2a is available in the Supporting
Information.
(Z)-4-Benzylidene-5,5-dimethyloxazolidin-2-one (6): 1H
NMR (300 MHz, CDCl3) δ 7.81 (s, 1H), 7.40 (t, 2H, J = 7.6 Hz),
7.29−7.22 (m, 3H), 5.39 (s, 1H), 1.66 (s, 6H) ppm. 13C NMR (75
MHz, CDCl3): δ 155.8, 141.7, 135.2, 129.4, 129.0, 129.0, 128.6,
126.99, 126.97, 126.6, 97.4, 85.2, 27.9 ppm; MS m/z (EI, relative
intensity) 203 (M+, 100), 188 (8), 158 (23), 144 (59), 132 (84), 117
(60), 105 (48), 77 (21); HRMS (EI) calcd for C12H13NO2 (M+)
203.0946, found 203.0947.
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of 1H NMR and 13C NMR spectra for all products and
X-ray crystallographic information for 2a including an ORTEP
diagram and CIF. This material is available free of charge via
the Internet at http://pubs.acs.org.
(10) Kim, W. S.; Yoon, E.; Jo, K. A.; Kang, E. J. Bull. Korean Chem.
Soc. 2011, 32, 3158.
AUTHOR INFORMATION
Corresponding Author
*E-mail: ejkang24@khu.ac.kr.
(11) Naidu, K. C.; Babu, G. R.; Gangaiah, L.; Mukkanti, K.;
Madhusudhan, G. Tetrahedron Lett. 2010, 51, 1226.
■
(12) DBU-H+ as a π-activator toward the alkyne moiety: (a) Kundu,
N. G.; Pal, M.; Nandi, B. J. Chem. Soc., Perkin Trans. 1 1998, 561.
(b) Kanazawa, C.; Terada, M. Tetrahedron Lett. 2007, 48, 933.
(c) Park, J. H.; Bhilare, S. V.; Youn, S. W. Org. Lett. 2011, 13, 2228.
(13) Davies, S. G.; Nicholson, R. L.; Smith, A. D. Org. Biomol. Chem.
2004, 2, 3385.
Author Contributions
§These authors contributed equally to this work.
Notes
The authors declare no competing financial interest.
(14) (a) Davies, S. G.; Sanganee, H. J.; Szolcsanyl, P. Tetrahedron
1999, 55, 3337. (b) Sakaguchi, H.; Tokuyama, H.; Fukuyama, T. Org.
Lett. 2007, 9, 1635.
ACKNOWLEDGMENTS
■
This study was supported by the National Research Foundation
Grant funded by the Ministry of Education, Science and
Technology (2010-0015432).
(15) (a) Easton, N. R.; Cassady, D. R.; Dillard, R. D. J. Org. Chem.
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Bruneau, C.; Dixneuf, P. H. J. Org. Chem. 1998, 63, 1806. (d) Shen, Z.;
Lu, X.; Lei, A. Tetrahedron 2006, 62, 9237.
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