I--catalyzed reaction of 5-methoxyoxazoles with organic iodides - An efficient synthesis of azalactones

Article abstract of DOI:10.1002/ejoc.200600637

An I^--catalyzed methoxy carbon-oxygen bond cleavage in 5-methoxyoxazoles leading to the synthesis of azalactones, precursors of quaternary amino acids, has been developed. A series of 4-substituted azalactones were obtained through the variatio

Full text of DOI:10.1002/ejoc.200600637

FULL PAPER
DOI: 10.1002/ejoc.200600637
I–-Catalyzed Reaction of 5-Methoxyoxazoles with Organic Iodides –
An Efficient Synthesis of Azalactones
Lianghua Lu,[a] Ping Lu,[a] and Shengming Ma*[a]
Keywords: Oxazoles / Organic iodides / Azalactones / Cleavage reactions / Heterocycles
An I–-catalyzed methoxy carbon–oxygen bond cleavage in
5-methoxyoxazoles leading to the synthesis of azalactones,
precursors of quaternary amino acids, has been developed.
A series of 4-substituted azalactones were obtained through
the variation of the alkyl iodides and differently substituted
5-methoxyoxazoles. Further study indicated that azalactone
3aa may be easily converted to benzoyl-protected quaternary
amino acid 4aa.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
Although the C–O bond cleavage of O-acylated oxazoles
in the Steglich reaction has been widely investigated [Equa-
tion (1), Scheme 1],[1a,1c,2] the methyl–oxygen bond cleavage
of 5-methoxyoxazole under the catalysis of mild and easily
available NaI has never been reported [Equation (2),
Scheme 1]. Recently, we have observed very mild cleavage
of the methyl–oxygen bond of 2-methoxyfurans under the
catalysis of I–, which was followed by the formation of a
new C–C bond with organic halides at the 5-position of the
furans to afford butenolides.[3] It is well known that substi-
tution at the α-carbon of α-amino acid derivatives intro-
duces conformational constraints that can probe the molec-
ular structure of receptor or enhance biological activity by
helping to preorganize peptides for binding.[4,5] Therefore,
chemists have been interested in the synthesis of α-alkylated
α-amino acids and have developed many powerful methods
for their preparation. Nitrogen-containing heterocycles
such as azalactones and oxazoles are efficiently used as
building blocks for the synthesis of α,α-disubstituted amino
acids[6,7] and numerous efforts have been devoted to this
area, such as α-allylation or α-arylation of azalactones,[8]
cycloaddition of oxazolones,[9] and rearrangement of ox-
azoles.[1] Thus, it is desirable to develop new methods for
the efficient synthesis of azalactones. Herein, we wish to
report our recent results on the I–-catalyzed methyl–oxygen
bond cleavage reaction in 5-methoxyoxazoles to afford 4-
disubstituted azalactones.
Scheme 1. Two routes for the synthesis of azalactones by C–O bond
cleavage.
Results and Discussion
Synthesis of Starting Materials
5-Methoxyoxazoles 1a–e used in this study were easily
prepared by the Rh2(OAc)4-catalyzed one-pot cyclopropan-
ation of the corresponding carbonitriles with α-diazo car-
boxylic acid esters followed by a rearrangement reaction
(Scheme 2).[10]
[a] State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, P. R. China
Fax: +8621-64167510
E-mail: masm@mail.sioc.ac.cn
Scheme 2. Synthesis of starting materials 1a–e.
676
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Eur. J. Org. Chem. 2007, 676–680

I–-Catalyzed Reaction of 5-Methoxyoxazoles with Organic Iodides
FULL PAPER
I–-catalyzed Methyl–Oxygen Bond Cleavage Reaction in 5-
Table 2. The reaction of 1 and 2 for the synthesis of azalactones.[a]
Methoxyoxazoles for the Synthesis of Azalactones
In our first attempt, the reaction of 2-phenyl-4-meth-
oxycarbonyl-5-methoxyoxazole (1a) with 2 equiv. of allyl io-
dide (2a) under the catalysis of sodium iodide in THF[8]
smoothly afforded product 3aa in 59% yield (Entry 1,
Table 1). It should be noted that C–C bond formation in
this case occurred at the 4-position, which was different
from the reaction of 2-methoxyfurans with alkyl iodides.
On the basis of this interesting result, the solvent effects
were further investigated and some typical results are listed
in Table 1: it was concluded that acetone was the best sol-
vent for this reaction and Na2CO3 was not necessary. The
reaction did not occur in the absence of NaI (Entry 9,
Table 1).
Table 1. The optimization of the reaction conditions between 1a
and 2a.[a]
Entry
Na2CO3
[equiv.]
2a
[equiv.]
Solvent
Time
[h]
Yield of 3aa
[%]
1
2
3
4
5
6
7
0.5
0.2
0.2
0.2
0.2
0.2
0.2
–
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.2
1.2
THF
8
59
14
63
trace
49
72
78
76
NR
CH2Cl2
CH3CN
toluene[b]
dioxane[b]
DMF[b]
acetone
acetone
acetone
52
7.3
22.5
7
3
3.5
5
[a] The reactions were carried out with 1 (0.25–0.5 mmol) and 2
(1.2 equiv.) in 1–2 mL of acetone heated at reflux. [b] The reaction
was carried out in a sealed tube heated at 80 °C. [c] 2 equiv. of 2c
were used in the reaction.
8
9[c]
–
44
Because azalactones can be regarded as the precursor to
amino acids, we developed a tandem allylation/ring-open-
ing reaction of 1a with 2a to form benzoyl-protected qua-
ternary amino acid 4aa (Scheme 3). The structure of 4aa
was further confirmed by its X-ray diffraction analysis (Fig-
ure 1).[11]
[a] The reaction was carried out with 1a (0.25–0.5 mmol), Na2CO3
and 2a in solvent (1–2 mL) heated at reflux. [b] The reaction was
conducted at 80 °C. [c] The reaction was conducted in the absence
of NaI.
With the optimized reaction conditions in hand, we fur-
ther examined the scope of the reaction with a variety of
differently substituted compounds 1 and organic iodides
(Table 2). This reaction proceeded well with 2-aryl-, 2-ben-
zyl- or 2-alkyl-5-methoxyoxazoles 1, and provided desired
azalactones 3 in satisfactory yields (Entries 1–4, Table 2).
The reaction of phenylsulfonyl-substituted 1e with 2a ap-
peared to be facile and afforded 3ea in 91% yield (Entry 5,
Table 2). Different organic iodides were also tested in this
reaction (Entries 6–10, Table 2). Basically, sp3 C-centered
organic iodides could all participate in the reaction. How-
ever, methyl iodide showed a much lower reactivity (Entry
6, Table 2). It should be noted that 4-methylazolactone 3ab
was not formed in any of the other cases, though MeI
would be formed in situ after the methyl–oxygen bond
Scheme 3. Tandem allylation/ring-opening reaction of 1a with 2a
to form 4aa.
A plausible catalytic cycle for this reaction is depicted in
cleavage as proven in our previous research.[3] The reason Scheme 4.[8] The attack of I– at the methyl group led to the
may be that the in situ formed MeI evaporated from the cleavage of the methyl–oxygen bond in compound 1 with
reaction mixture due to its low b.p. (41–43 °C) under the the formation of MeI and intermediate 5, which reacts with
current reaction conditions.
organic iodide 2 to afford 3 and regenerate I–.
Eur. J. Org. Chem. 2007, 676–680
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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677

L. Lu, P. Lu, S. Ma
FULL PAPER
5-Methoxy-4-(methoxycarbonyl)-2-(1Ј-naphthyl)oxazole (1b): The
reaction of dimethyl 2-diazomalonate (2.20 g, 15 mmol), 1-naph-
thonitrile (6.63 g, 50 mmol), and Rh2(OAc)4 (33 mg + 33 mg,
0.15 mmol) in CHCl3 (20 mL) afforded 3.01 g (71%) of 1b. Solid,
m.p. 141–144 °C (petroleum ether/ethyl acetate). 1H NMR
(300 MHz, CDCl3): δ = 9.19 (d, J = 8.7 Hz, 1 H), 8.03 (d, J =
7.2 Hz, 1 H), 7.90 (d, J = 15.4 Hz, 1 H), 7.87 (d, J = 15.4 Hz, 1
H), 7.63 (t, J = 7.5 Hz, 1 H), 7.57–7.44 (m, 2 H), 4.26 (s, 3 H), 3.93
(s, 3 H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 161.9, 161.6,
150.5, 133.7, 131.2, 129.7, 128.4, 127.7, 127.3, 126.3, 125.9, 124.6,
122.5, 107.2, 59.7, 51.7 ppm. MS: m/z (%) = 283 (40.83) [M]+, 155
(100). IR (KBr): ν = 1713, 1614, 1597, 1475, 1400, 1269, 1097 cm–1.
˜
C16H13NO4 (283.28): calcd. C 67.84, H 4.63, N 4.94; found C
67.97, H 4.59, N 4.85.
2-Benzyl-5-methoxy-4-(methoxycarbonyl)oxazole (1c): The reaction
of dimethyl 2-diazomalonate (2.37 g, 15 mmol), 2-phenylacetoni-
trile (3.52 g, 30 mmol), and Rh2(OAc)4 (44 mg, 0.1 mmol) in
CHCl3 (10 mL) afforded 1.98 g (54%) of 1c. Solid, m.p. 71–73 °C
Figure 1. ORTEP representation of compound 4aa.
1
(hexane/CH2Cl2). H NMR (300 MHz, CDCl3): δ = 7.40–7.20 (m,
5 H), 4.10 (s, 3 H), 4.02 (s, 2 H), 3.87 (s, 3 H) ppm. 13C NMR
(75.4 MHz, CDCl3): δ = 161.7, 161.5, 151.8, 134.4, 128.5, 128.4,
127.0, 105.6, 59.4, 51.4, 34.4 ppm. MS: m/z (%) = 247 (26.15)
[M]+, 91 (100). IR (KBr): ν = 1719, 1634, 1591, 1263, 1092 cm–1.
˜
C13H13NO4 (247.25): calcd. C 63.15, H 5.30, N 5.67; found C
63.11, H 5.28, N 5.56.
5-Methoxy-4-(methoxycarbonyl)-2-methyloxazole (1d):[9] The reac-
tion of dimethyl 2-diazomalonate (1.58 g, 10 mmol), acetonitrile
(0.83 g, 20 mmol), and Rh2(OAc)4 (22 mg + 22 mg, 0.1 mmol) in
CHCl3 (10 mL) afforded 1.09 g (63%) of 1d. Solid, m.p. 119–122 °C
(petroleum ether/ethyl acetate) (119–122 °C[10]). 1H NMR
(300 MHz, CDCl3): δ = 4.13 (s, 3 H), 3.85 (s, 3 H), 2.37 (s, 3 H)
ppm. 13C NMR (75.4 MHz, CDCl3): δ = 161.8, 161.6, 150.5, 105.7,
Scheme 4. A plausible mechanism for the reaction of 1 and 2.
Conclusions
In summary, we have developed a catalytic reaction of
readily available organic iodides and differently substituted
5-methoxyoxazoles for the synthesis of azalactones. In this
reaction, I–-catalyzed methoxy carbon–oxygen bond cleav-
age in 5-methoxyoxazoles and the new C–C bond formation
at the 4-position were observed, which is different from our
previous reported reaction of alkyl iodides with 2-meth-
oxyfurans forming butenolides. Furthermore, a tandem re-
action of 1a with 2a to afford amino acid derivative 4aa in
one-pot was realized. Further investigations are being pur-
sued in our laboratory.
59.6, 51.6, 13.8 ppm. MS: m/z (%)
=
171 (24.00)
[M]+, 43 (100). IR (KBr): ν = 1713, 1640, 1597, 1470, 1401, 1236,
˜
1093 cm–1.
5-Methoxy-2-phenyl-4-(phenylsulfonyl)oxazole (1e): The reaction of
2-(phenylsulfonyl)-2-diazoacetic acid methyl ester (2.40 g,
10 mmol), benzonitrile (2.58 g, 25 mmol), and Rh2(OAc)4 (22 mg,
0.05 mmol) in CHCl3 (10 mL) afforded 2.54 g (81%) of 1e. Solid,
m.p. 129–131 °C (hexane/CH2Cl2). 1H NMR (300 MHz, CDCl3): δ
= 8.10–8.00 (m, 2 H), 7.93–7.83 (m, 2 H), 7.65–7.47 (m, 3 H), 7.47–
7.35 (m, 3 H), 4.26 (s, 3 H) ppm. 13C NMR (75.4 MHz, CDCl3): δ
= 158.3, 151.1, 141.2, 133.2, 130.7, 129.0, 128.6, 127.3, 125.8, 125.7,
114.7, 60.3 ppm. MS: m/z (%) = 315 (1.36) [M]+, 105 (100). IR
(KBr): ν = 1622, 1586, 1321, 1158 cm–1. C H NO S (315.34):
˜
16 13
4
calcd. C 60.94, H 4.16, N 4.44; found C 60.76, H 4.11, N 4.43.
Experimental Section
5-Methoxy-4-(methoxycarbonyl)-2-phenyloxazole (1a).[10,12] Typical
Reaction of 5-Methoxyoxazole with Organic Iodides
Procedure:
A
solution of dimethyl 2-diazomalonate (4.9 g,
4-Allyl-4-(methoxycarbonyl)-2-phenyl-4H-oxazol-5-one (3aa). Typi-
cal Procedure: In a flame-dried argon-flushed flask, a solution of
31 mmol) in CHCl3 (8 mL) was added with a syringe to a solution
of benzonitrile (2.2 g, 21 mmol) and Rh2(OAc)4 (40 mg, 1a (117 mg, 0.5 mmol), allyl iodide 2a (103 mg, 0.6 mmol), and NaI
0.09 mmol) in CHCl3 (2 mL) heated under reflux. After the ad-
dition was over, the mixture was stirred for 2 h while heated at
reflux. After evaporation, the residue was purified by column
chromatography on silica gel (petroleum ether/diethyl ether, 4:1) to
afford 3.63 g (78%) of 1a. Solid, m.p. 91–93 °C (petroleum ether/
ethyl acetate) (98–99 °C[10]). 1H NMR (300 MHz, CDCl3): δ =
(8 mg, 0.05 mmol) in dry acetone (2 mL) (the solvent was refluxed
over anhydrous MgSO4 and distilled prior to use) was stirred for
5 h heated at reflux. After evaporation, the residue was purified by
column chromatography (petroleum ether/Et2O, 5:1) on silica gel
to afford (98 mg, 76%) of 3aa. Liquid. 1H NMR (300 MHz, C6D6):
δ = 8.00–7.93 (m, 2 H), 7.07–6.90 (m, 3 H), 5.72–5.53 (m, 1 H),
8.05–7.93 (m, 2 H), 7.50–7.40 (m, 3 H), 4.26 (s, 3 H), 3.91 (s, 3 H) 5.12 (d, J = 16.8 Hz, 1 H), 4.92 (d, J = 11.1 Hz, 1 H), 3.16 (dd, J
ppm. 13C NMR (75.4 MHz, CDCl3): δ = 161.9, 161.7, 150.8, 130.4, = 13.8, 6.6 Hz, 1 H), 2.99 (dd, J = 13.8, 7.8 Hz, 1 H), 3.09 (s, 3 H)
128.7, 126.2, 125.8, 107.3, 59.7, 51.8 ppm. MS: m/z (%) = 233
ppm. 13C NMR (75.4 MHz, C6D6): δ = 174.0, 166.1, 163.6, 133.2,
129.8, 129.0, 128.4, 125.7, 121.5, 77.0, 53.0, 38.3 ppm. MS: m/z
(13.55) [M]+, 105 (100). IR (KBr): ν = 1717, 1622, 1587, 1396,
˜
1208, 1106 cm–1.
(%) = 259 (7.48) [M]+, 105 (100). IR (neat): ν = 1827, 1756, 1653,
˜
678
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Eur. J. Org. Chem. 2007, 676–680

I–-Catalyzed Reaction of 5-Methoxyoxazoles with Organic Iodides
1245 cm–1. C14H13NO4 (259.26): calcd. C 64.86, H 5.05, N 5.40; 1630, 1328, 1149 cm–1. C18H15NO4S (341.38): C 63.33, H 4.43, N
FULL PAPER
found C 65.06, H 5.14, N 5.42.
4.10; found C 63.42, H 4.42, N 4.05.
Compound 3aa is unstable and will decompose to give compound
4aa when it is exposed to air for a long time. 4aa: Solid, m.p. 115–
118 °C (petroleum ether/ethyl acetate). 1H NMR (300 MHz,
CDCl3): δ = 7.83 (d, J = 7.5 Hz, 2 H), 7.80–7.60 (br. s, 1 H), 7.57
(t, J = 7.5 Hz, 1 H), 7.50–7.40 (m, 3 H), 5.78–5.60 (m, 1 H), 5.23–
5.15 (m, 2 H), 3.87 (s, 3 H), 3.24 (dd, J = 14.1, 7.5 Hz, 1 H), 3.13
(dd, J = 14.1, 7.5 Hz, 1 H) ppm. 13C NMR (75.4 MHz, CD3OD):
δ = 170.1, 169.8, 168.7, 134.7, 133.3, 132.8, 129.9, 128.3, 120.2,
67.7, 53.8, 38.3 ppm. MS: m/z (%) = 277 (0.72) [M]+, 105 (100). IR
4-(Methoxycarbonyl)-4-methyl-2-phenyl-4H-oxazol-5-one
(3ab):
The reaction of 1a (117 mg, 0.5 mmol), iodomethane (2b; 215 mg,
1.5 mmol), and NaI (8 mg, 0.05 mmol) in dry acetone (2 mL) in a
sealed tube afforded 71 mg (61%) of 3ab. Solid, m.p. 82–85 °C
1
(hexane/diethyl ether). H NMR (300 MHz, CDCl3): δ = 8.01 (d,
J = 7.2 Hz, 2 H), 7.59 (t, J = 7.5 Hz, 1 H), 7.48 (t, J = 7.8 Hz, 2
H), 3.77 (s, 3 H), 1.76 (s, 3 H) ppm. 13C NMR (75.4 MHz, CDCl3):
δ = 174.9, 166.3, 163.1, 133.3, 128.8, 128.2, 125.1, 72.6, 53.6, 20.5
ppm. MS: m/z (%) = 233 (9.71) [M]+, 105 (100). IR (KBr): ν =
˜
(KBr): ν = 3379, 1762, 1734, 1606, 1575, 1519, 1217 cm–1.
1833, 1758, 1646, 1257 cm–1. C12H11NO4 (233.22): C 61.80, H 4.75,
N 6.01; found C 61.83, H 4.85, N 5.90.
˜
C14H15NO5 (277.27): calcd. C 60.64, H 5.45, N 5.05; found C
60.79, H 5.48, N 5.02.
4-(Methoxycarbonyl)-4-(2Ј-methoxycarbonyl-2Ј-propenyl)-2-phenyl-
4-Allyl-4-(methoxycarbonyl)-2-(1Ј-naphthyl)-4H-oxazol-5-one (3ba): 4H-oxa-zol-5-one (3ac): The reaction of 1a (117 mg, 0.5 mmol), 2-
The reaction of 1b (142 mg, 0.5 mmol), allyl iodide (2a; 101 mg,
0.6 mmol), and NaI (8 mg, 0.05 mmol) in dry acetone (2 mL) af-
forded 123 mg (80%) of 3ba. Liquid. 1H NMR (300 MHz, CDCl3):
methoxycarbonyl allyl iodide (2c; 224 mg, 1.0 mmol), and NaI
(8 mg, 0.05 mmol) in dry acetone (2 mL) afforded 87 mg (57%) of
1
3ac. Oil. H NMR (300 MHz, CDCl3): δ = 7.97 (d, J = 7.5 Hz, 2
δ = 9.23 (d, J = 8.7 Hz, 1 H), 8.19 (d, J = 7.5 Hz, 1 H), 8.08 (d, J H), 7.59 (t, J = 7.5 Hz, 1 H), 7.48 (t, J = 7.5 Hz, 2 H), 6.23 (s, 1
= 8.1 Hz, 1 H), 7.93 (d, J = 7.8 Hz, 1 H), 7.75–7.50 (m, 3 H), 5.80–
5.64 (m, 1 H), 5.28 (d, J = 17.1 Hz, 1 H), 5.24 (d, J = 10.2 Hz, 1
H), 5.76 (s, 1 H), 3.78 (s, 3 H), 3.64 (s, 3 H), 3.52 (d, J = 14.0 Hz,
1 H), 3.20 (d, J = 14.0 Hz, 1 H) ppm. 13C NMR (75.4 MHz,
H), 3.84 (s, 3 H), 3.20 (dd, J = 13.8, 6.9 Hz, 1 H), 3.03 (dd, J = CDCl3): δ = 173.5, 166.7, 165.6, 163.4, 133.6, 133.3, 130.0, 128.7,
13.8, 7.8 Hz, 1 H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 173.4, 128.1, 124.8, 76.0, 53.7, 51.9, 35.5 ppm. MS: m/z (%) = 317 (2.25)
165.9, 163.0, 134.1, 133.7, 130.8, 130.6, 129.2, 128.8, 128.4, 126.6,
[M]+, 105 (100). IR (KBr): ν = 1826, 1755, 1726, 1650, 1243 cm–1.
˜
+
125.9, 124.6, 121.8, 120.9, 77.1, 53.7, 38.3 ppm. MS: m/z (%) = 309
HRMS (MALDI/DHB): calcd. for C16H16NO6 [M + H]+
(14.36) [M]+, 155 (100). IR (neat): ν = 1822, 1756, 1642, 1255 cm–1.
318.0972; found 318.0973.
˜
+
HRMS (MALDI/DHB): calcd. for C18H16NO4 [M
310.1074; found 310.1066.
+
H]+
4-(Ethoxycarbonylmethyl)-4-(methoxycarbonyl)-2-phenyl-4H-
oxazol-5-one (3ad): The reaction of 1a (117 mg, 0.5 mmol), ethyl 2-
iodoacetate (2d; 123 mg, 0.6 mmol), and NaI (8 mg, 0.05 mmol) in
dry acetone (2 mL) afforded 90 mg (59%) of 3ad. Liquid. 1H NMR
(300 MHz, CDCl3): δ = 7.96–7.87 (m, 2 H), 7.52–7.43 (m, 1 H),
7.37 (t, J = 7.5 Hz, 2 H), 4.02–3.87 (m, 2 H), 3.67 (s, 3 H), 3.29 (s,
4-Allyl-2-benzyl-4-(methoxycarbonyl)-4H-oxazol-5-one (3ca): The
reaction of 1c (124 mg, 0.5 mmol), allyl iodide (2a; 103 mg,
0.6 mmol), and NaI (8 mg, 0.05 mmol) in dry acetone (2 mL) af-
1
forded 85 mg (62%) of 3ca. Liquid. H NMR (300 MHz, CDCl3):
δ = 7.40–7.20 (m, 5 H), 5.58–5.40 (m, 1 H), 5.15 (d, J = 16.8 Hz, 2 H), 1.04 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (75.4 MHz, CDCl3):
1 H), 5.10 (d, J = 10.2 Hz, 1 H), 3.83 (s, 2 H), 3.75 (s, 3 H), 2.93
δ = 173.8, 168.4, 165.3, 165.1, 133.4, 128.8, 128.4, 125.1, 73.5, 61.4,
(dd, J = 13.8, 6.9 Hz, 1 H), 2.80 (dd, J = 13.8, 7.5 Hz, 1 H) ppm. 53.9, 38.1, 13.8 ppm. MS: m/z (%) = 305 (0.56) [M]+, 105 (100). IR
13C NMR (75.4 MHz, CDCl3): δ = 173.4, 166.2, 165.5, 132.4, (KBr): ν = 1830, 1754, 1736, 1649, 1222 cm–1. HRMS (MALDI/
˜
128.9, 128.8, 128.7, 127.6, 121.7, 75.8, 53.5, 37.8, 35.6 ppm. MS:
DHB): calcd. for C15H16NO6+ [M + H]+ 306.0972; found 306.0969.
m/z (%) = 273 (9.02) [M]+, 91 (100). IR (neat): ν = 1829, 1756,
˜
4-(Methoxycarbonyl)-4-(2Ј-octynyl)-2-phenyl-4H-oxazol-5-one
(3ae): The reaction of 1a (117 mg, 0.5 mmol), 1-iodooct-2-yne (2e;
142 mg, 0.6 mmol), and NaI (8 mg, 0.05 mmol) in dry acetone
(2 mL) afforded 111 mg (68%) of 3ae. Liquid. 1H NMR (300 MHz,
CDCl3): δ = 8.07 (d, J = 7.5 Hz, 2 H), 7.63 (t, J = 7.5 Hz, 1 H),
7.52 (t, J = 7.5 Hz, 2 H), 3.80 (s, 3 H), 3.15 (t, J = 2.1 Hz, 2 H),
1671, 1263, 1246 cm–1. HRMS (MALDI/DHB): calcd. for
C15H16NO4 [M + H]+ 274.1074; found 274.1076.
+
4-Allyl-4-(methoxycarbonyl)-2-methyl-4H-oxazol-5-one (3da): The
reaction of 1d (86 mg, 0.5 mmol), allyl iodide (2a; 101 mg,
0.6 mmol), and NaI (8 mg, 0.05 mmol) in dry acetone (2 mL) af-
forded 49 mg (50%) of 3da. Oil. 1H NMR (300 MHz, CDCl3): δ = 2.02–1.95 (m, 2 H), 1.30–1.17 (m, 2 H), 1–17–1.00 (m, 4 H), 0.72
5.63–5.48 (m, 1 H), 5.23–5.14 (m, 2 H), 3.76 (s, 3 H), 2.90 (dd, J
= 13.8, 6.6 Hz, 1 H), 2.76 (dd, J = 13.8, 7.5 Hz, 1 H), 2.24 (s, 3 H)
(t, J = 7.2 Hz, 3 H) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 173.4,
165.4, 164.0, 133.4, 128.8, 128.3, 125.0, 85.0, 76.1, 71.6, 53.8, 30.6,
ppm. 13C NMR (75.4 MHz, CDCl3): δ = 173.6, 165.6, 164.8, 129.0, 28.1, 25.3, 22.0, 18.4, 13.8 ppm. MS: m/z (%) = 327 (0.56) [M]+,
121.7, 75.8, 53.5, 38.0, 15.1 ppm. MS: m/z (%) = 198 (1.10) [M +
105 (100). IR (neat): ν = 1828, 1757, 1651, 1259 cm–1. HRMS
˜
1]+, 127 (100). IR (neat): ν = 1831, 1753, 1679, 1259 cm–1. HRMS
(MALDI/DHB): calcd. for C19H22NO4+ [M + H]+ 328.1543; found
328.1543.
˜
+
(MALDI/DHB): calcd. for C9H12NO4 [M + H]+ 198.0761; found
198.0758.
4-(Benzoylmethyl)-4-(methoxycarbonyl)-2-phenyl-4H-oxazol-5-one
(3af): The reaction of 1a (117 mg, 0.5 mmol), 2-iodo-1-phenyle-
thanone (2f; 150 mg, 0.6 mmol), and NaI (8 mg, 0.05 mmol) in dry
acetone (2 mL) afforded 110 mg (65%) of 3af (eluent: petroleum
ether/diethyl ether/methanol, 10:1:0.15). Solid, m.p. 178–181 °C
4-Allyl-2-phenyl-4-(phenylsulfonyl)-4H-oxazol-5-one (3ea): The re-
action of 1e (158 mg, 0.5 mmol), allyl iodide (2a; 102 mg,
0.6 mmol), and NaI (8 mg, 0.05 mmol) in dry acetone (2 mL) af-
forded 141 mg (91%) of 3ea. Solid, m.p. 108–110 °C(petroleum
ether/ethyl acetate). 1H NMR (300 MHz, CDCl3): δ = 8.00–7.87
(m, 4 H), 7.70–7.57 (m, 2 H), 7.57–7.40 (m, 4 H), 5.60–5.40 (m, 1
1
(acetone). H NMR (300 MHz, CDCl3): δ = 8.01 (d, J = 7.5 Hz, 2
H), 7.88 (d, J = 7.5 Hz, 2 H), 7.60–7.50 (m, 2 H), 7.50–7.33 (m, 4
H), 5.23 (d, J = 16.5 Hz, 1 H), 5.18 (d, J = 9.9 Hz, 1 H), 3.21 (dd, H), 4.25 (d, J = 18.3 Hz, 1 H), 3.93 (d, J = 18.3 Hz, 1 H), 3.77 (s,
J = 13.2, 8.1 Hz, 1 H), 3.10 (dd, J = 13.2, 6.0 Hz, 1 H) ppm. 13C 3 H) ppm. 13C NMR (75.4 MHz, CD3Cl3): δ = 194.6, 174.3, 165.9,
NMR (75.4 MHz, CDCl3): δ = 169.9, 165.1, 135.1, 134.0, 133.8, 165.3, 135.2, 134.0, 133.2, 128.74, 128.71, 128.4, 128.2, 125.4, 73.3,
130.5, 129.0, 128.9, 128.4, 127.7, 124.1, 122.7, 90.7, 34.8 ppm. MS:
54.0, 42.9 ppm. MS: m/z (%) = 337 (0.29) [M]+, 309 (12.04) [M –
m/z (%) = 200 (28.15) [M – SO Ph]+, 105 (100). IR (KBr): ν = 1825,
CO]+, 105 (100). IR (KBr): ν = 1824, 1755, 1683, 1647, 1240 cm–1.
˜
˜
2
Eur. J. Org. Chem. 2007, 676–680
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
679

L. Lu, P. Lu, S. Ma
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FULL PAPER
C19H15NO5 (337.33): calcd. C 67.65, H 4.48, N 4.15; found C
67.52, H 4.56, N 3.98.
Procedure for the Synthesis of 2-(Benzamido)-2-(methoxycarbonyl)-
pent-4-enoic Acid (4aa): In a flame-dried argon-flushed 50 mL
flask, a solution of 1a (1.68 g, 5 mmol), 2a (1.01 g, 6 mmol), and
NaI (76 mg, 0.5 mmol) in dry acetone (10 mL) was stirred for 8 h
heated at reflux. After the starting material was completely con-
sumed on the basis of the monitoring with TLC, aqueous solution
of HCl (6 , 10 mL) was added in the reaction. The resulting solu-
tion was stirred at room temp. for 0.5 h as monitored by TLC,
extracted by CH2Cl2, and dried with anhydrous MgSO4. After
evaporation, the residue was purified by column chromatography
(CH2Cl2/MeOH, 15:1) on silica gel to afford the product, which
was further purified by recrystallization to afford 1.23 g (88%) of
4aa.
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noclinic, Space group P21/n, Mo-Kα, final R indices [IϾ2σ(I)],
Acknowledgments
Financial support from the National Natural Science Foundation
of China (Grant No. 20121202, 20332060 and 20423001) and the
Major State Basic Research Development Program (Grant No.
2006CB806105) was greatly appreciated.
R1
= 0.0621, wR2 = 0.1707, a = 10.4507(12) Å, b =
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11.8193(13) Å, c = 11.3355(13) Å, α = 90°, β = 92.007(2)°, γ =
90° V = 1399.3(3) Å3, T = 293(2) K, Z = 4, reflections col-
lected/unique: 8315/3249 (Rint = 0.0665), parameters 220.
CCDC-610577 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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Received: July 22, 2006
Published Online: November 29, 2006
680
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Eur. J. Org. Chem. 2007, 676–680