Synthesis of 5-Acetyloxazoles and 1,2-Diketones
FULL PAPER
was added. The phosphazene P2-base (2.0m in THF, 1.65 mL, 3.30 mmol)
was added dropwise to the solution at the same temperature and the mix-
ture was slowly warmed to RT overnight. Purification of the mixture di-
rectly on column chromatography (silica gel; hexane/ethyl acetate=20:1)
gave 38 (244 mg, 95%) as a colorless solid. M.p. 36–398C; 1H NMR
(CDCl3, 400 MHz): d=0.88–0.93 (m, 4H; cPr), 0.98–1.06 (m, 4H; cPr),
d=7.2, 8.1 (2ꢃt; cPr), 8.0, 9.0 (2ꢃd; cPr), 11.9 (q; C-2’), 112.9, 120.1,
129.3 (3ꢃd; Ph), 134.5 (s; C-4), 139.0 (s; C-5), 144.9 (s; C-1’), 163.3 ppm
À
À
(s; C-2); IR (ATR): n˜ =3200 (N-H), 3080–3025 (=C H), 2980–2860 (C
H), 1695–1635 cmÀ1 (C=C, C=N); HRMS (ESI-TOF): m/z calcd for
C11H19N3ONa: 304.1420 [M+Na]+; found: 304.1454.
Preparation of 2,4-dicyclopropyl-5-(1H-indol-2-yl)oxazole (45): A mix-
ture of 44 (700 mg, 0.533 mmol) and polyphosphoric acid (700 mg) was
heated at 808C for 1 h. Further polyphosphoric acid (700 mg) was added
and the mixture was heated for an additional 30 min. The mixture was
slowly diluted with ice water (10 mL) and extracted with CHCl3 (2ꢃ
10 mL). The combined organic phases were dried with Na2SO4 and con-
centrated to dryness. The residue was purified by column chromatogra-
phy on silica gel (hexane/ethyl acetate=4:1 to 1:1) to give 45 (75 mg,
53%) as a colorless solid. M.p. 115–1198C; 1H NMR (CDCl3, 400 MHz):
d=0.94–1.02 (m, 4H; cPr), 1.04 (mc, 2H; cPr), 1.11 (mc, 2H; cPr), 1.98–
2.11 (m, 2H; cPr), 6.76 (s, 1H; 3’-H), 7.13 (m, 1H; 8’-H), 7.20 (m, 1H; 7’-
H), 7.39 (d, J=8.1 Hz, 2H; 6’-H), 7.62 (d, J=7.8 Hz, 2H; 9’-H), 8.47 ppm
(br. s, 1H; NH); 13C NMR (CDCl3, 126 MHz): d=6.8, 8.2 (2ꢃt; cPr), 7.6,
9.0 (2ꢃd; cPr), 99.6 (d; C-3’), 110.7 (d; C-6’), 120.3 (d; C-9’), 120.4 (d; C-
7’), 122.4 (d; C-8’), 127.0 (s; C-4’), 128.8 (s; C-2’), 135.9 (s; C-5’), 137.5 (s;
ꢀ
1.85 (mc, 1H; cPr), 1.98 (mc, 1H; cPr), 3.70 ppm (s, 1H; C CH);
13C NMR (CDCl3, 101 MHz): d=7.0, 8.4 (2ꢃt; cPr), 7.6, 9.3 (2ꢃd; cPr),
ꢀ
71.6, 87.0 (s, d; C CH), 128.1 (s, C-4), 148.1 (s, C-5), 165.8 ppm (s, C-2);
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IR (ATR): n˜ =3190 ( C H), 2970–2865 (C H), 1570–1600 cm (C=N,
C=C); HRMS (ESI-TOF): m/z calcd for C11H12O: 174.0913 [M+H]+;
found: 174.0926.
Preparation of 2,4-dicyclopropyl-5-(phenylethynyl)-1,3-oxazole (39): A
mixture of iodobenzene (196 mg, 0.960 mmol), 38 (200 mg, 1.15 mmol),
PdACHTUNGTRENNUNG(OAc)2 (15 mg, 0.067 mmol), PPh3 (63 mg, 0.240 mmol), and CuI
(9.1 mg, 0.050 mmol) in DMF (4.8 mL) and triethylamine (2.4 mL) was
heated to 608C for 3 h under an argon atmosphere. The mixture was al-
lowed to cool to RT, diluted with brine (10 mL), and extracted with di-
ethyl ether (3ꢃ10 mL). The combined organic phase was dried with
Na2SO4 and concentrated to dryness. The residue was purified by chro-
matography on silica gel (hexane/ethyl acetate=20:1) to give 39 (201 mg,
84%) as a colorless solid. M.p. 388C; 1H NMR (CDCl3, 400 MHz): d=
0.96–0.99 (m, 4H; cPr), 1.03–1.09 (m, 4H; cPr), 1.93 (mc, 1H; cPr), 2.02
(mc, 1H; cPr), 7.26–7.36, 7.49–7.52 ppm (2ꢃm, 3H, 2H; Ph); 13C NMR
(CDCl3, 101 MHz): d=7.1, 8.4 (2ꢃt; cPr), 7.9, 9.4 (2ꢃd; cPr), 76.7 (s; C-
1’), 98.4 (s; C-2’), 122.4, 128.4, 128.6, 131.1 (3ꢃd, s; Ph), 128.7 (s; C-4),
C-4), 139.1 (s; C-5), 163.8 ppm (s; C-2); IR (ATR): n˜ =3420 (NH), 3090,
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À
3050, 3005 (=CH), 2920, 2850 (C H), 1635, 1580 cm (C=C); HRMS
(ESI-TOF): m/z calcd for C17H17N2O: 265.1341 [M+H]+; found:
265.1342.
Preparation
oxazol-5-yl}ethanone (47): A mixture of 46 (91 mg, 0.170 mmol), PdCl2-
(PPh3)2 (5.0 mg, 0.007 mmol), and 7j (30 mg, 0.142 mmol) in [BMIm]-
AHCTUNTGREG[NNNU BF4] (0.5 mL) and diisopropylamine (90 mL) was heated to 608C for 3 h
of
1-{2-[(E)-2-(diisopropylamino)ethenyl]-4-phenyl-1,3-
À
147.0 (s; C-5), 165.7 ppm (s; C-2); IR (ATR): n˜ =3085–3010 (=C H),
AHCTUNGTRENNUNG
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2205 (C C), 1570 cm (C=C); UV/Vis (MeCN): l (log e) =302 nm
(4.36); Fluorescence (MeCN): l=376 nm; HRMS (ESI-TOF): m/z calcd
for C17H16NO: 250.1154 [M+H]+; found: 250.1219; elemental analysis
calcd (%) for C17H15NO (249.1): C 81.90, H 6.06, N 5.62; found: C 82.01,
H 5.86, N 5.67.
under an argon atmosphere. The mixture was allowed to cool to RT, di-
luted with brine (3 mL), and extracted with diethyl ether (3ꢃ3 mL). The
combined organic phases were dried with Na2SO4 and concentrated to
dryness. The residue was purified by column chromatography on silica
gel (hexane/ethyl acetate=10:1) to give 47 (22 mg, 50%) as a yellow oil.
1H NMR (CDCl3, 500 MHz): d=2.41 (s, 3H; 2’-H), 1.26 (d, J=6.8 Hz,
12H; iPr), 3.68–3.78 (hept, J=6.8 Hz, 2H; iPr), 5.20 (d, J=13.3 Hz, 1H;
=CH), 7.37–7.44, 8.06–8.09 (2 m, 3H, 2H; Ph), 7.64 ppm (d, J=13.3 Hz,
1H; =CH); 13C NMR (CDCl3, 126 MHz): d=21.6, 48.2 (q, d; iPr), 27.9
(q; C-2’), 80.5 (d; =CH), 128.0, 129.3, 129.5, 131.6 (3ꢃd, s; Ph), 143.4 (d;
Preparation 7-tert-butyl-2-(2’,4’-dicyclopropyl-1,3-oxazol-5’-yl)-5-
of
(trifluoromethyl)furoACHTUNGTRENNUNG[2,3-c]pyridine (42): Pyridine 41 (329 mg,
0.671 mmol) was dissolved in a 1:5 mixture of trifluoroacetic acid and
CH2Cl2 (4 mL). After stirring for 2 h at RT, the reaction mixture was
quenched with H2O (5 mL) and extracted with CH2Cl2 (3ꢃ5 mL). The
combined organic phases were dried with Na2SO4 and concentrated to
dryness. The resulting crude product was dissolved in DMF (3.5 mL) and
K2CO3 (278 mg, 0.671 mmol) was added. After heating for 3 h at 808C,
the mixture was quenched at RT with H2O (10 mL) and extracted with
Et2O (3ꢃ10 mL). The combined organic phases were dried with Na2SO4
and concentrated to dryness. Column chromatography on silica gel
(hexane/ethyl acetate=20:1) afforded 42 (165 mg, 63%) as a colorless
solid. M.p. 117–1198C; 1H NMR (CDCl3, 400 MHz): d=1.01–1.16 (m,
8H; cPr), 1.56 (s, 9H; tBu), 2.08 (tt, J=8.2, 5.2 Hz, 1H; 1’’-H), 2.39 (tt,
J=8.1, 5.3 Hz, 1H; 1’’’-H), 6.82 (s, 1H; 3-H), 7.74 ppm (s, 1H; 4-H);
13C NMR (CDCl3, 101 MHz): d=7.6, 8.8 (2ꢃt; cPr), 7.8, 9.1 (2ꢃd; C-1’’,
=CH), 142.0, 148.3, 166.5 (3ꢃs; C-4, C-5, C-2), 185.4 ppm (s; C-1’); IR
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(neat): n˜ =3070–3030 (=C H), 2975–2870 (C H), 1670–1580 cm (C=O,
C=C); UV/Vis (MeCN): l (log e)=292 (4.35), 378 nm (4.19); fluores-
cence (MeCN): l=482 nm; HRMS (ESI-TOF): m/z calcd for
C19H25N2O2: 313.1911 [M+H]+; found: 313.1918.
Preparation of star-shaped compound 50: 1,3,5-Tribromobenzene 49
(75 mg, 0.250 mmol) and alkyne 38 (216 mg, 1.25 mmol) were dissolved
in Et3N (4 mL) and [PdCl2ACHTNUTRGNEUNG(PPh3)2] (44 mg, 0.0625 mmol) was added.
After stirring for 5 min, CuI (6 mg, 0.0312 mmol) was added and the mix-
ture was heated at 508C overnight. The solution was filtered and concen-
trated in vacuo. The residue was taken up in diethyl ether (15 mL) and
washed with water (5 mL). The organic layer was dried with MgSO4, fil-
tered, and concentrated. Column chromatography (silica gel; hexane/
ethyl acetate=10:1, 4:1 to 1:1) provided 52 (12 mg, 3%) as a yellow oil,
51 (51 mg, 41%) and 50 (35 mg, 24%) both as pale-yellow solids.
Data for compound 50: M.p. 120–1228C; 1H NMR (CDCl3, 400 MHz):
d=0.90–1.10 (m, 24H; cPr), 1.90 (tt, J=5.4, 7.9 Hz, 3H; cPr), 2.01 (tt,
J=5.1, 8.4 Hz, 3H; cPr), 7.55 ppm (s, 3H; Ar); 13C NMR (CDCl3,
101 MHz): d=7.3, 8.5 (2ꢃt; cPr), 8.0, 9.4 (2ꢃd; cPr), 78.4, 96.7 (2ꢃs;
C-1’’’), 28.8, 37.4 (q, s; tBu), 100.1 (d; C-3), 111.4 (dq, 3J
(C,F)=3.0 Hz;
1
C-4), 122.2 (q, J=275 Hz; CF3), 128.9 (s; C-3a), 135.8 (s; C-4’), 136.3 (s;
C-5’), 140.4 (q, 2J
ACHTUNGTRENNUNG(C,F)=33.9 Hz; C-5), 143.1 (s; C-7a), 149.9 (s; C-2),
153.2 (s; C-7), 166.6 ppm (s; C-2’); 19F NMR (CDCl3, 470 MHz): d=
À
À
À66.5 ppm (s; CF3); IR (ATR): n˜ =3105–3040 (=C H), 2960–2870 (C
H), 1645–1575 (C=N, C=C), 1150–1130 cmÀ1 (C-F); UV/Vis (MeCN): l
(log e)=328 nm (4.48); fluorescence (MeCN): l=385 nm; HRMS (ESI-
TOF): m/z calcd for C21H22N2O2: 391.1633 [M+H]+; found: 391.1637.
Preparation of 1-(2,4-dicyclopropyl-1,3-oxazol-5-yl)ethanone phenylhy-
drazone (44): Phenylhydrazine (158 mg, 1.45 mmol) dissolved in EtOH
(2.5 mL) and acetic acid (43 mL, 0.75 mmol) were successively added to a
solution of oxazole 7e (287 mg, 1.50 mmol) dissolved in EtOH (2.5 mL).
After stirring for 30 min at 508C, the mixture was quenched with water
(1 mL) and the volume of the mixture was reduced to half. After storing
the solution for 6 d at 48C, the resulting precipitate was recrystallized
(EtOH/water=5:1). Drying in vacuo provided 44 (384 mg, 91%) as a
light-yellow solid. M.p. 81–848C; 1H NMR (CDCl3, 400 MHz): d=0.93–
1.04 (m, 8H; cPr), 2.00 (tt, J=5.2, 8.2 Hz, 1H; cPr), 2.18 (s, 3H; 2’-H),
2.55 (tt, J=5.5, 8.0 Hz, 1H; cPr), 6.86 (mc, 1H; Ph), 7.07 (mc, 2 H; Ph),
7.27 (mc, 2 H; Ph), 7.29 ppm (s, 1H; NH); 13C NMR (CDCl3, 101 MHz):
ꢀ
C C), 123.5, 128.3, 132.8, 148.2, 166.2 ppm (2ꢃs, d, 2ꢃs; oxazole, Ar);
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IR (ATR): n˜ =3090–2850 (=C H, C H), 2205 cm (C C); HRMS (ESI-
TOF): m/z calcd for C39H34N3O3: 592.2600 [M+H]+; found: 592.2606.
Data for compound 51: M.p. 118–1208C; 1H NMR (CDCl3, 400 MHz):
d=0.95–1.10 (m, 16H; cPr), 1.86–1.94 (m, 2H; cPr), 1.96–2.05 (m, 2H;
cPr), 7.52 (t, J=1.4 Hz, 1H; Ar), 7.57 ppm (d, J=1.4 Hz, 2H; Ar);
13C NMR (CDCl3, 101 MHz): d=7.4, 8.6 (2ꢃt; cPr), 8.0, 9.4 (2ꢃd; cPr),
ꢀ
79.0, 96.3 (2ꢃs; C C), 122.1, 124.6, 128.2, 131.7, 133.3, 148.5, 166.3 ppm
À
À
(3ꢃs, 2ꢃd, 2ꢃs; oxazole, Ar); IR (ATR): n˜ =3090–2850 (=C H, C H),
2200 cmÀ1 (C C); HRMS (ESI-TOF): m/z calcd for C28H24BrN2O2:
ꢀ
499.0943 [M+H]+; found: 499.1035.
Chem. Eur. J. 2011, 17, 7480 – 7491
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7489