Thomson et al.
) 6.3) and 1.22 (3H, d, J ) 6.3); δC (100 MHz; CDCl3) 175.5,
165.73, 163.6, 162.8, 130.2, 117.6, 114.3, 72.9, 71.0, 55.5, 21.4
and 20.4; m/z (CI) 292.1 (45, M + H+); HRMS (CI) C15H18NO5
requires 292.1185, found 292.1183 (-0.7 ppm).
undergoes efficient conversion to (()-67 using this procedure,
indicating that functionalized heteroatom containing substituents
are also tolerated in this reaction protocol.
Methyl 4-iso-Butyl-2-(4-methoxyphenyl)-5-oxo-4,5-dihydroox-
azole-4-carboxylate (()-59. Following general procedure A,
KHMDS (0.040 mL, 0.020 mmol, 1.5 mol %), triazolium salt 18
(0.007 g, 0.027 mmol, 2 mol %), THF (2 mL) and a solution of
carbonate 52 (0.407 g, 1.333 mmol) in THF (2 mL) gave after 5
min and chromatography (petrol/Et2O 80:20) ester (()-59 (0.323
g, 79%) as a colorless oil. νmax (KBr disc)/cm-1 2959 (C-H), 1755
(CdO), 1649 (CdO), 1513 (CdN) and 1262 (C-O); δH (300 MHz;
CDCl3) 8.01-7.96 (2H, m), 7.01-6.96 (2H, m), 3.88 (3H, s), 3.78
(3H, s), 2.37 (1H, ABX, JA,B 14.2, JA,X 5.8), 2.05 (1H, ABX, JB,A
14.2, JB,X 7.2), 1.70 (1H, sept, J ) 6.7) and 0.94-0.88 (6H, m);
δC (75 MHz; CDCl3) 175.1, 166.8, 164.7, 162.4, 130.2, 117.5,
114.3, 76.2, 55.6, 53.6, 42.9, 24.6, 23.7 and 23.0; m/z (CI) 306.1
(100, M + H+); HRMS (CI) C16H20NO5 requires 306.1341, found
306.1341 (-0.2 ppm).
Conclusion
In conclusion, we have shown that the NHC 28 derived from
triazolium salt 18 is a highly efficient and versatile catalyst for
the rearrangement of oxazolyl carbonates, with variation within
the carbonate functionality and C(4)-substitution readily toler-
ated. A simplified experimental procedure allowing a one-pot
protocol to be employed has been investigated. Current studies
are focused upon developing an efficient enantioselective version
of this NHC-catalyzed reaction process and understanding fully
the mechanism of this transformation. Further applications of
NHCs in asymmetric catalysis are ongoing.
Experimental Section
Methyl 2-(4-Methoxyphenyl)-4-iso-propyl-5-oxo-4,5-dihy-
drooxazole-4-carboxylate (()-63. Following general procedure A,
KHMDS (0.080 mL, 0.040 mmol, 4 mol %), triazolium salt 18
(0.014 g, 0.051 mmol, 5 mol %), THF (2 mL) and a solution of
carbonate 56 in THF (2 mL) gave after 5 min and chromatography
(petrol/Et2O 85:15) ester (()-63 (0.200 g, 67%) as a colorless oil
that solidified on standing. νmax (KBr disc)/cm-1 2958 (C-H), 1736
(CdO), 1647 (CdO), 1513 (CdN) and 1261 (C-O); mp 68-
70 °C; δH (300 MHz; CDCl3) 8.02-7.97 (2H, m), 7.00-6.95 (2H,
m), 3.88 (3H, s), 3.81 (3H, s), 2.78 (1H, sept, J ) 6.8), 1.06 (3H,
d, J ) 6.8) and 0.97 (3H, d, J ) 6.8); δC (75 MHz; CDCl3) 173.7,
166.4, 163.6, 162.5, 130.3, 117.4, 114.3, 80.3, 55.5, 53.5, 34.8,
17.2 and 16.3; m/z (CI) 292.1 (100, M + H+); HRMS (CI)
C19H17N5Na requires 292.1185, found 292.1188 (+1.1 ppm).
Phenyl 2-(4-Methoxyphenyl)-5-oxo-4-iso-propyl-4,5-dihy-
drooxazole-4-carboxylate (()-64. Following general procedure A,
KHMDS (0.030 mL, 0.015 mmol, 1.5 mol %), triazolium salt 18
(0.006 g, 0.020 mmol, 2 mol %), THF (2 mL) and a solution of
carbonate 57 (0.353 g, 1.000 mmol) in THF (2 mL) gave after 5
min and chromatography (petrol/Et2O 85:15) ester (()-64 (0.279
g, 0.790 mmol, 79%) as a colorless oil. νmax (thin film)/cm-1 2971
(C-H), 1818 (CdO), 1764 (CdO), 1651 (CdC), 1513 (CdN) and
1262 (C-O); δH (300 MHz; CDCl3) 8.02-7.97 (2H, m), 7.37-
7.05 (5H, m), 6.97-6.92 (2H, m), 3.83 (3H, s), 2.87 (1H, sept, J
) 6.8), 1.13 (3H, d, J ) 6.8) and 0.97 (3H, d, J ) 6.8); δC (75
MHz; CDCl3) 173.5, 164.6, 163.7, 162.9, 150.3, 130.4, 129.5, 126.4,
121.2, 117.4, 114.3, 80.4, 55.6, 34.8, 17.2 and 16.4; m/z (CI) 354.1
(65, M + H+); HRMS (CI) C20H20NO5 requires 354.1341, found
354.1344 (+0.7 ppm).
Phenyl 4-tert-Butyl-2-(4-methoxyphenyl)-5-oxo-4,5-dihydroox-
azole-4-carboxylate (()-65. Following general procedure A,
KHMDS (0.142 mL, 0.071 mmol, 9 mol %), triazolium salt 18
(0.022 g, 0.079 mmol, 10 mol %), THF (4 mL) and a solution of
carbonate 58 (0.290 g, 0.790 mmol) in THF (4 mL) gave after 1 h
and chromatography (petrol/Et2O 85:15) ester (()-65 (0.207 g,
0.563 mmol, 71%) as an oil which solidified on standing to give
an off-white solid. νmax (KBr disc)/cm-1 2963 (C-H), 1817 (Cd
O), 1647 (CdO), 1608 (CdN), 1514 (CdC), 1261 (C-O) and 1185
(C-O); mp 106-108 °C; δH (300 MHz; CDCl3) 8.08-8.03 (2H,
m), 7.40-7.33 (2H, m), 7.26-7.21 (1H, m), 7.13-7.08 (2H, m),
7.03-6.98 (2H, m), 3.89 (3H, s) and 1.29 (9H, s); δC (75 MHz;
CDCl3) 173.3, 163.8, 163.7, 162.4, 150.2, 130.3, 129.5, 126.4,
121.3, 117.5, 114.3, 81.6, 55.6, 39.5 and 25.1; m/z (ESI+) 390.2
(100, M + Na+); HRMS (ESI+) C21H21NO5Na requires 390.1318,
found 390.1318 (+0.1 ppm).
For general experimental details see Supporting Information.
General Procedure A. Rearrangement of Oxazolyl Carbon-
ates. KHMDS (0.5 M in toluene) was added to a solution of azolium
salt in THF and stirred at room temperature for 30 min. The desired
oxazolyl carbonate was added, either as a solution in THF or as a
solid, and stirred for the specified time before concentration in
vacuo. Chromatographic purification (silica) gave the desired
product.
General Procedure B. One-Pot NHC-Catalyzed Rearrange-
ments. KHMDS (0.5 M in toluene) was added to a mixture of
azolium salt and oxazolyl carbonate in THF and stirred at room
temperature for 5 min before concentration in vacuo. Chromato-
graphic purification (silica) gave the desired product.
Methyl 2-(4-Methoxyphenyl)-4-methyl-5-oxo-4,5-dihydroox-
azole-4-carboxylate (()-11. Following general procedure A,
KHMDS (0.040 mL, 0.020 mmol, 0.9 mol %), triazolium salt 18
(0.006 g, 0.022 mmol, 1 mol %), THF (5 mL) and carbonate 10
(0.585 g, 2.222 mmol) gave after 5 min and chromatography (petrol/
Et2O 70:30) (()-11 (0.497 g, 1.888 mmol, 84%) as a colorless solid.
νmax (KBr disc)/cm-1 2954 (C-H), 1751 (CdO), 1645 (CdO),
1497 (CdN) and 1262 (C-O); mp 58-60 °C; δH (300 MHz;
CDCl3) 8.00-7.95 (2H, m), 7.01-6.96 (2H, m), 3.89 (3H, s), 3.79
(3H, s) and 1.77 (3H, s); δC (75 MHz; CDCl3) 175.2, 166.8, 163.7,
162.9, 130.3, 117.4, 114.3, 72.7, 55.6, 53.7 and 20.7; m/z (ESI+)
264.1 (100, M + H+) and 286.1 (35, M + Na+); HRMS (ESI+)
C13H14NO5 requires 264.0872, found 264.0874 (+0.9 ppm).
Methyl 4-Benzyl-2-(4-methoxyphenyl)-5-oxo-4,5-dihydroox-
azole-4-carboxylate (()-22. Following general procedure A,
KHMDS (0.030 mL, 0.015 mmol, 0.9 mol %), triazolium salt 18
(0.005 g, 0.016 mmol, 1 mol %), THF (4 mL) and carbonate 19
(0.565 g, 1.665 mmol) gave after 5 min and chromatography (petrol/
Et2O 80:20) ester (()-22 (0.465 g, 82%) as a colorless oil. νmax
(thin film)/cm-1 2956 (C-H), 1753 (CdO), 1648 (CdO), 1513
(CdN) and 1261 (C-O); δH (300 MHz; CDCl3) 7.85-7.80 (2H,
m), 7.20-7.14 (5H, m, PhH), 6.94-6.89 (2H, m), 3.85 (3H, s),
3.83 (3H, s), 3.62 (1H, ABq, J ) 13.7) and 3.49 (1H, ABq, J )
13.7); δC (75 MHz; CDCl3) 173.8, 166.4, 163.6, 162.7, 132.9, 130.4,
130.1, 128.2, 127.6, 117.2, 114.2, 55.5, 53.7, 40.3; m/z (ESI+) 362.1
(100, M + Na+) and 394.1 (95, M + MeOH + Na+); HRMS (CI)
C19H18NO5 requires 340.1185, found 340.1185 (+0.0 ppm).
iso-Propyl 2-(4-Methoxyphenyl)-4-methyl-5-oxo-4,5-dihy-
drooxazole-4-carboxylate (()-34. Following general procedure A,
KHMDS (0.155 mL, 0.077 mmol, 9 mol %), triazolium salt 18
(0.023 g, 0.086 mmol, 10 mol %), THF (3 mL) and carbonate 30
(0.250 g, 0.859 mmol) gave after 5 min and chromatography (petrol/
Et2O 65:35) ester (()-34 (0.180 g, 0.618 mmol, 72%) as a colorless
solid. νmax (KBr disc)/cm-1 2983 (C-H), 1737 (CdO), 1608 (Ar
CdC), 1496 (CdN), 1295 (C-O) and 1260 (C-O); mp 48-50 °C;
δH (400 MHz; CDCl3) 7.98-7.94 (2H, m), 6.99-6.96 (2H, m),
5.05 (1H, sept, J ) 6.3), 3.87 (3H, s), 1.73 (3H, s), 1.25 (3H, d, J
Phenyl 2-(4-Methoxyphenyl)-4-(2-(methylthio)ethyl)-5-oxo-
4,5-dihydrooxazole-4-phenyl carboxylate (()-67. Following gen-
eral procedure B, KHMDS (0.010 mL, 0.005 mmol, 0.9 mol %),
triazolium salt 18 (0.0014 g, 0.005 mmol, 1 mol %), carbonate 58
(0.200 g, 0.519 mmol) and THF (2 mL) gave after chromatography
2790 J. Org. Chem., Vol. 73, No. 7, 2008