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M. Cordaro et al.
LETTER
(3) Keni, M.; Tepe, J. J. J. Org. Chem. 2005, 70, 4211.
(4) Cordaro, M.; Di Donna, L.; Foti, F.; Grassi, G.; Napoli, A.;
Risitano, F.; Sindona, G. Synlett 2003, 1710.
anhydride in dichloroethane to afford the desidered cyclo-
dehydration to the corresponding oxazoles
9
(Scheme 4).11 The results are summarized in Table 1. All
new compounds showed spectral data fully consistent
with the assigned structure.12
(5) Typical Procedure
DBU (1.5 mmol) was added to a solution of 1,3-dicarbonyl
compound 6 (3 mmol) in anhyd MeCN (20 mL). After
stirring for 15 min at r.t., a solution of 2-phenyl-4-methyl-
(4H)-oxazol-5-one 7 (6 mmol) in anhyd MeCN was added,
and the reaction mixture was heated by MW irradiation at
85 °C for 1 h. The progress of the reaction was monitored by
TLC (CHCl3–EtOAc, 95:5). After the solvent was removed,
the crude product was purified by column chromatography
on SiO2 (CHCl3–EtOAc, 95:5) to afford 8.
Me
OH
N
DCE, TFAA
8
Ph
O
0 °C, 5 h
X
O
9
(6) Under conditions thus identified, compounds 8 were the only
isolated products.
(7) Selected Data for 8a–g
Scheme 4
Table 1 Reactions of 6 with 7 to Afford 8 and Subsequently 9
Compound 8a: white solid; mp 150–151 °C. IR (Nujol):
3312, 1653, 1636 cm–1. 1H NMR (300 MHz, CDCl3): d =
1.48 (d, J = 7.1 Hz, 3 H), 1.98–2.05 (m, 2 H), 2.50–2.56 (m,
2 H), 2.73 (t, J = 6.3 Hz, 2 H), 5.91 (dq, J = 7.1, 7.6 Hz, 1 H),
Entry Starting material, X
C-Acylation
Oxazole
product (yield, %)a (yield, %)a
6.91 (d, J = 7.6 Hz, NH), 7.41–7.82 (m, arom., 5 H). 13
C
NMR (75 MHz, CDCl3): d = 18.6, 19.0, 32.4, 38.4, 52.1,
111.6, 127.1, 128.4, 131.5, 134.1, 166.6, 191.0, 194.6,
204.0. MS (EI): m/z = 287.4.
1
2
3
6a
6b
6c
8a (75)
8b (68)
8c (77)
9a (83)
9b (88)
9c (81)
Compound 8b: white solid; mp 149–150 °C. IR (Nujol):
3310, 1650, 1631 cm–1. 1H NMR (300 MHz, CDCl3): d =
1.09 (s, J = 8.6 Hz, 6 H), 1.48 (d, J = 7.0 Hz, 3 H), 2.40 (d,
J = 7.4 Hz, 2 H), 2.59 (s, 2 H), 5.91 (dq, J = 7.0, 8.4 Hz,
1 H), 6.94 (d, J = 8.4 Hz, NH), 7.41–7.82 (m, arom., 5 H).
13C NMR (75 MHz, CDCl3): d = 18.6, 27.7, 28.4, 30.8, 45.9,
52.0, 52.2, 110.6, 127.0, 128.5, 131.5, 134.1, 166.5, 194.4,
196.6, 204.3. MS (EI): m/z = 314.6.
Compound 8c: white solid; mp 108–110 °C. IR (Nujol):
3257, 1658, 1629 cm–1. 1H NMR (300 MHz, CDCl3): d =
1.09 (d, J = 3.0 Hz, 3 H), 1.11 (d, J = 2.1 Hz, 3 H), 1.46 (d,
J = 3.0 Hz, 3 H), 1.48 (d, J = 3.0 Hz, 3 H), 2.18–2.78 (m,
5 H), 5.85 (m, 1 H), 6.92 (m, N H), 7.41–7.82 (m, arom.,
5 H). 13C NMR (75 MHz, CDCl3): d = 18.7, 20.8, 26.4, 40.2,
46.5, 52.0, 111.1, 127.0, 128.5, 131.5, 134.1, 166.5, 194.5,
197.2, 204.7. MS (EI): m/z = 302.0.
HN
HN
4
6d
8d (70)
9d (85)
O
N
H
5
6
6e
6f
8e (91)
8f (88)
9e (92)
O
S
N
Me
–
Compound 8d: pink solid; mp 195–197 °C. IR (Nujol):
3306, 1751, 1681, 1640 cm–1. 1H NMR (300 MHz, DMSO-
d6): d = 1.41 (d, J = 7.0 Hz, 3 H), 5.79 (dq, J = 7.0 Hz, 1 H),
7.44–7.89 (m, arom., 5 H), 8.73 (m, NH). 13C NMR (75
MHz, DMSO-d6): d = 15.0, 46.8, 90.8, 125.3, 126.0, 129.2,
131.4, 146.8, 164.0, 197.0. MS (EI): m/z = 302.8.
7
6g
8g (70)
9g (72)
O
Compound 8e: white solid; mp 185–186 °C. IR (Nujol):
3303, 1721, 1681, 1642 cm–1. 1H NMR (300 MHz, CDCl3):
d = 1.58 (d, J = 5.3 Hz, 3 H), 3.38 (s, 6 H), 6.12 (dq, J = 5.3,
7.0 Hz, 1 H), 6.77 (d, J = 7.0 Hz, NH), 7.42–7.82 (m, arom.,
5 H). 13C NMR (75 MHz, CDCl3): d = 18.2, 27.9, 49.2, 93.9,
127.0, 128.5, 131.7, 133.6, 150.0, 160.1, 166.9, 170.1,
198.3. MS (EI): m/z = 330.8.
a Yield of pure isolated product.
In conclusion, a novel and efficient approach for the syn-
thesis of highly substituted and functionalized oxazoles
has been achieved. The procedure provides straightfor-
ward access to important cyclization precursors, contain-
ing an enolizable 1,3,3¢-tricarbonyl moiety, which
represent both valuable building blocks in organic synthe-
sis and an important structural motif in biologically signif-
icant compounds.
Compound 8f: brown solid; mp 49–50 °C. IR (neat): 3320,
1657 cm–1. 1H NMR (300 MHz, CDCl3): d = 1.52 (d, J = 7.0
Hz, 3 H), 3.32–3.69 (m, 4 H), 5.84 (dq, J = 7.0, 6.4 Hz, 1 H),
6.76 (d, J = 6.4 Hz, NH), 7.42–7.81 (m, arom., 5 H). 13
C
NMR (75 MHz, CDCl3): d = 18.3, 32.3, 36.5, 51.2, 110.7,
127.0, 128.3, 131.5, 134.5, 166.7, 188.8, 195.1, 204.0. MS
(EI): m/z = 305.8.
Compound 8g: white solid; mp 168–170 °C. IR (Nujol):
3372, 1716, 1646 cm–1. 1H NMR (300 MHz, CDCl3): d =
1.45–1.47 (m, 6 H), 2.75–3.04 (m, 4 H), 3.40–3.60 (m, 1 H),
5.89 (m, 1 H), 6.09 (m, 1 H), 6.31 (m, 1 H), 6.87 (d, J = 7.0
Hz, NH), 6.94 (d, J = 8.7 Hz, NH), 7.35 (m, 1 H), 7.42–7.82
(m, arom., 5 H). 13C NMR (75 MHz, CDCl3): d = 18.2, 30.4,
36.9, 42.8, 52.1, 105.3, 110.2, 111.4, 127.0, 128.5, 130.0,
References and Notes
(1) For a recent review see: Jin, Z. Nat. Prod. Rep. 2006, 23,
464; and references cited therein.
(2) Palmer, D. C. Oxazoles: Synthesis, Reactions, and
Spectroscopy, In Chemistry of Heterocyclic Compounds,
Vol. 60, Parts A and B; John Wiley and Sons: New York,
2004.
Synlett 2009, No. 1, 103–105 © Thieme Stuttgart · New York