O. J.-C. Nicaise et al. / Tetrahedron 59 (2003) 6433–6443
6441
(s). EI-MS: 320 (M, 6), 236 (100), 221 (31), 205 (6), 179 (3),
91 (3), 85 (2), 57 (5). EI-HRMS: calcd for C19H28O4 [Mþ]
320.1987, found 320.1989.
(15), 129 (100), 121 (2), 91 (2), 73 (27), 57 (4). EI-
HRMS: calcd for C22H36O4Si [Mþ] 392.2382, found
392.2376.
5.4. General procedure for the preparation of enol ester
derivatives (5 and 6)
5.5. General procedure for the preparation of
unprotected 1,2-amide esters (7a–c)
5.4.1. Preparation of the enol ester methyl carbonate
derivative (5). The crude, ketone-free (1H NMR analysis of
the isolated crude material) enol ester (4b) was first
prepared according to the procedure described in Section
5.3.2; from 2a (0.322 g, 0.96 mmol, 1.0 equiv.), dry Et2O
(52 mL), and a 2.78 M solution of EtMgBr in Et2O
(0.38 mL, 1.06 mmol, 1.10 equiv.). Dry CH2Cl2 (20 mL)
was added to the flask containing crude enol ester 4b, and
the resulting colorless solution was cooled to 08C, and
stirred for ca. 5 min. It was then treated (dropwise addition)
successively with methyl chloroformate (0.30 mL,
3.88 mmol, 4.04 equiv.) and Et3N (0.20 mL, 1.43 mmol,
1.49 equiv.), and the reaction mixture was allowed to warm
to RT and stir overnight. The reaction mixture was then
poured into H2O (10 mL), and was extracted with CH2Cl2
(2£50 mL). The extracts were combined, dried (MgSO4)
upon stirring, filtered, and concentrated in vacuo to afford a
thick, pale yellow oil. This material was purified by silica
gel column chromatography (hexane/ethyl acetate, 5:1) to
afford 0.329 g (91% yield) of 5 as a very thick, colorless oil.
Further purification was accomplished by bulb-to-bulb
5.5.1. Preparation of N-2,4,6-tri-tert-butylphenyl-substi-
tuted 1,2-amide ester (7a). A two-necked, 100 mL round-
bottom flask with a magnetic stir bar was charged with
2,4,6-tri-tert-butylaniline (1.491 g, 5.70 mmol, 1.0 equiv.),
and was fitted with a gas inlet adapter and a septum. The
flask was then purged with nitrogen, dry CH2Cl2 (35 mL)
was added, and the resulting solution was cooled to 08C, and
stirred for ca. 5 min. It was then treated successively with
Et3N (1.60 mL, 11.48 mmol, 2.01 equiv.), 4-(dimethyl-
amino)pyridine (DMAP; 0.144 g, 1.18 mmol, 0.21 equiv.),
and ethyl oxalyl chloride (dropwise addition; 1.30 mL,
11.64 mmol, 2.04 equiv.), and the yellow reaction mixture
was allowed to warm to RT and stir overnight. The reaction
mixture was then poured into H2O (50 mL), and was
extracted with CH2Cl2 (2£100 mL). The extracts were
combined, dried (MgSO4) upon stirring, filtered, and
concentrated in vacuo to afford a pale yellow solid. This
material was purified by silica gel column chromatography
(CH2Cl2) to afford 1.805 g (88% yield) of 7a as a white
solid: mp 229–2308C. 1H NMR (300 MHz, CDCl3): 8.51 (s,
1H, NH, br), 7.42 (s, 2H, Ph), 4.45 (q, J¼7.2 Hz, 2H,
CH2CH3), 1.44 (t, J¼7.2 Hz, 3H, CH2CH3), 1.38 (s, 18H,
2£C6H2-o-C(CH3)3), 1.32 (s, 9H, C6H2-p-C(CH3)3). 13C
NMR (126 MHz, CDCl3): 161.3, 157.0, 150.0, 147.8, 128.6,
123.2, 63.6, 36.1, 34.9, 31.9, 31.3, 13.9. IR (CH2Cl2): 3395
(m), 3053 (w), 2967 (s), 2873 (m), 1762 (m), 1711 (s), 1597
(w), 1507 (m), 1478 (m), 1395 (m), 1365 (m), 1295 (s), 1258
(m), 1180 (m), 1140 (w), 1016 (m). EI-MS: 361 (M, 3), 346
(2), 304 (100), 288 (3), 272 (8), 258 (14), 244 (3), 230 (12),
214 (4), 200 (3), 174 (3), 172 (3), 158 (3), 91 (1), 57 (5). EI-
HRMS: calcd for C22H35NO3 [Mþ] 361.2616, found
361.2620.
1
distillation: bp 210–2158C (0.1 mm Hg, ABT). H NMR
(300 MHz, CDCl3): 6.94 (q, J¼7.1 Hz, 1H, HCvC), 6.86
(s, 2H, Ph), 3.86 (s, 3H, (CvO)OCH3), 3.79 (s, 3H, C6H2-p-
OCH3), 1.93 (d, J¼7.1 Hz, 3H, H3CCvC), 1.31 (s, 18H,
2£C(CH3)3). 13C NMR (75.5 MHz, CDCl3): 161.8, 156.6,
152.9, 143.8, 141.1, 140.2, 129.6, 111.7, 55.5, 55.2, 35.5,
31.3, 11.7. IR (CCl4): 2960 (m), 1773 (s), 1748 (m), 1673
(w), 1590 (w), 1442 (m), 1418 (w), 1366 (w), 1270 (s), 1249
(s), 1175 (m), 1128 (m), 1067 (m), 1031 (m). EI-MS: 378
(M, 18), 236 (76), 221 (33), 205 (22), 193 (4), 177 (10), 164
(7), 149 (5), 135 (7), 129 (5), 119 (7), 105 (7), 99 (46), 91
(9), 77 (4), 59 (17), 57 (6). EI-HRMS: calcd for C21H30O6
[Mþ] 378.2042, found 378.2036.
5.5.2. Preparation of N-2,6-di-iso-propylphenyl-substi-
tuted 1,2-amide ester (7b). From 2,6-di-iso-propylaniline
(3.104 g, 17.51 mmol, 1.0 equiv.), dry CH2Cl2 (100 mL),
Et3N (4.90 mL, 35.16 mmol, 2.01 equiv.), 4-(dimethyl-
amino)pyridine (DMAP; 0.439 g, 3.59 mmol, 0.21 equiv.),
and ethyl oxalyl chloride (2.40 mL, 21.48 mmol,
1.23 equiv.). The crude material was purified by silica gel
column chromatography (hexane/ethyl acetate, 5:1) to
afford 3.686 g (76% yield) of 7b as a white solid: mp
131–1338C. 1H NMR (300 MHz, CDCl3): 8.40 (s, 1H, NH,
br), 7.37–7.31 (m, 1H, p-Ph), 7.22–7.19 (m, 2H, m-Ph),
4.44 (q, J¼7.2 Hz, 2H, CH2CH3), 3.01 (sept, J¼6.9 Hz, 2H,
CH(CH3)2), 1.45 (t, J¼7.2 Hz, 3H, CH2CH3), 1.20 (d,
J¼6.9 Hz, 12H, 2£CH(CH3)2). 13C NMR (126 MHz,
CDCl3): 160.8, 155.7, 145.6, 129.2, 128.7, 123.5, 63.4,
28.6, 23.4, 13.7. IR (CCl4): 3393 (m), 3069 (w), 2965 (s),
2930 (m), 2870 (m), 1719 (s), 1501 (s), 1474 (m), 1446 (w),
1370 (m), 1293 (s), 1205 (m), 1160 (m). EI-MS: 278 (Mþ1,
13), 277 (M, 7), 248 (7), 230 (3), 204 (100), 189 (16), 186
(24), 176 (12), 170 (8), 160 (19), 146 (38), 144 (28), 130
(21), 128 (18), 117 (18), 115 (17), 106 (11), 91 (17), 77 (7),
65 (2). EI-HRMS: calcd for C16H23NO3 [Mþ] 277.1677,
found 277.1680.
5.4.2. Preparation of the enol ester trimethylsilyl ether
derivative (6). From 2a (0.313 g, 0.93 mmol, 1.0 equiv.),
dry Et2O (47 mL), and a 2.78 M solution of EtMgBr in Et2O
(0.40 mL, 1.11 mmol, 1.19 equiv.); the crude, ketone-free
(1H NMR analysis of the isolated crude material) enol ester
(4b) was obtained in quantitative yield. From crude enol
ester 4b, dry CH2Cl2 (10 mL), trimethylsilyl chloride
(dropwise addition; 0.60 mL, 4.73 mmol, 5.09 equiv.), and
Et3N (0.20 mL, 1.43 mmol, 1.54 equiv.). The crude
material was purified by silica gel column chromatography
(hexane/ethyl acetate, 5:1) to afford 0.246 g (67% yield) of
6 as a white solid: mp 90–928C. 1H NMR (300 MHz,
CDCl3): 6.86 (s, 2H, Ph), 6.39 (q, J¼7.1 Hz, 1H, HCvC),
3.78 (s, 3H, OCH3), 1.85 (d, J¼7.1 Hz, 3H, H3CCvC),
1.31 (s, 18H, 2£C(CH3)3), 0.22 (s, 9H, Si(CH3)3). 13C
NMR (75.5 MHz, CDCl3): 164.9, 156.4, 143.7, 142.7,
141.5, 119.5, 111.7, 55.1, 35.5, 31.4, 11.6, 0.8. IR (CCl4):
2963 (s), 2913 (m), 2874 (m), 2834 (w), 1739 (s), 1646
(m), 1590 (m), 1419 (m), 1391 (m), 1344 (m), 1253 (s),
1224 (m), 1184 (s), 1131 (s), 1067 (s). EI-MS: 392 (M,
27), 377 (13), 236 (31), 221 (12), 205 (4), 181 (2), 157