The Journal of Organic Chemistry
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The resulting reaction mixture was diluted with n-hexane (5 mL),
filtered through a thin pad of silica gel (AcOEt), and concentrated
under reduced pressure. The crude material obtained was purified by
flash chromatography on silica gel (n-hexane) to provide the title
(m, 3H), 7.01 (d, J = 2.0 Hz, 2H), 7.24 (t, J = 2.0 Hz, 1H); 13C NMR
(176.0 MHz, CDCl3) δ 19.4, 28.5, 34.9, 39.7, 47.5, 119.5, 120.5, 124.7,
125.8, 130.1, 131.3, 137.3, 137.6, 147.2, 149.7; MS (EI) m/z (%) 336
(M+, 3.1), 231 (100); HRMS (EI) found 336.2817, calcd for C25H36
336.2817.
1
compound (229.4 mg, 0.812 mmol, 84%) as a colorless oil. H NMR
(399.9 MHz, CDCl3) δ 1.06 (d, J = 6.8 Hz, 6H), 1.08 (d, J = 6.8 Hz,
6H), 1.20 (t, J = 6.8 Hz, 3H), 2.56 (sept, J = 6.8 Hz, 2H), 3.99 (q, J =
6.8 Hz, 2H), 6.92−7.00 (m, 2H), 7.03 (dd, J = 7.6 Hz, J = 2.0 Hz, 1H),
7.20 (d, J = 7.6 Hz, 2H), 7.30−7.36 (m, 2H); 13C NMR (100.6 MHz,
CDCl3) δ 14.6, 23.8, 24.2, 30.5, 62.9, 111.1, 119.9, 122.2, 127.6, 128.1,
129.3, 131.3, 135.9, 147.1, 156.3; MS (EI) m/z (%) 282 (M+, 78), 239
(70), 225 (49), 211 (34), 197 (100); HRMS (EI) found 282.1982,
calcd for C20H26O 282.1984.
1-Ethoxy-2-[2-methyl-2-(3,5-di-tert-butylphenyl)propyl]-
benzene (4eb) (Table 5, Entry 4). Following the general procedure,
a mixture of 2,4,6-tri-tert-butylbromobenzene (1e) (325.7 mg, 1.00
mmol), 2-ethylphenylboronic acid (2b) (225.4 mg, 1.50 mmol),
K3PO4·H2O (717.1 mg, 3.11 mmol), and a dioxane solution (480 μL,
1.11 mM, 0.53 μmol) of the precatalyst composed of Pd(dba)2, CyR-
Phos, and ethyl 4-bromobenzoate in a 1.0:5.0:23.3 ratio in dioxane (2
mL) was stirred at 100 °C for 8 h. The resulting reaction mixture was
diluted with n-hexane (5 mL), filtered through a thin pad of silica gel
(n-hexane), and concentrated under reduced pressure. The crude
material obtained was purified by flash chromatography on silica gel
(n-hexane) to provide the title compound (319.7 mg, 0.912 mmol,
2,6-Diisopropyl-2′-isopropoxybiphenyl (3cg) (Table 4, Entry
7). Following the general procedure, a mixture of 2,6-diisopropyl-
chlorobenzene (1c) (193.8 mg, 0.985 mmol), 2-isopropoxyphenylbor-
onic acid (2g) (278.0 mg, 1.54 mmol), K3PO4·H2O (716.6 mg, 3.11
mmol), and a dioxane solution (400 μL, 1.20 mM, 0.48 μmol) of the
precatalyst composed of Pd(dba)2, CyR-Phos, and ethyl 4-
bromobenzoate in a 1.0:4.1:25.8 ratio in dioxane (2 mL) was stirred
at 100 °C for 240 min. The resulting reaction mixture was diluted with
n-hexane (5 mL), filtered through a thin pad of silica gel (n-hexane),
and concentrated under reduced pressure. The crude material
obtained was purified by flash chromatography on silica gel (1:30
AcOEt/n-hexane) to provide the title compound (200.4 mg, 0.676
mmol, 69%) as a white solid, 2,2′-diisopropoxybiphenyl (26.0 mg,
0.096 mmol, 13%) as a colorless oil, and 1,3-diisopropylbenzene (8.0
1
91%) as a colorless oil. H NMR (399.9 MHz, CDCl3) δ 0.97 (t, J =
7.6 Hz, 3H), 1.26 (s, 18H), 1.40 (s, 6H), 2.09 (q, J = 7.6 Hz, 2H), 2.84
(s, 2H), 6.80 (dd, J = 7.6 Hz, J = 1.2 Hz, 1H), 6.96−7.05 (m, 2H),
7.01 (d, J = 2.0 Hz, 2H), 7.01 (td, J = 7.6 Hz, J = 1.2 Hz, 1H), 7.24 (t, J
= 2.0 Hz, 1H); 13C NMR (100.6 MHz, CDCl3) δ 15.1, 25.1, 28.5,
31.5, 34.9, 39.6, 46.7, 119.5, 120.5, 124.6, 126.1, 128.0, 131.4, 136.5,
143.5, 147.4, 149.7; MS (EI) m/z (%) 350 (M+, 1.8), 231 (100);
HRMS (EI) found 350.2973, calcd for C26H38 350.2974.
1-Isopropyl-2-[2-methyl-2-(3,5-di-tert-butylphenyl)propyl]-
benzene (4ec) (Table 5, Entry 5). Following the general procedure,
a mixture of 2,4,6-tri-tert-butylbromobenzene (1e) (326.0 mg, 1.00
mmol), 2-isopropylphenylboronic acid (2c) (246.7 mg, 1.50 mmol),
K3PO4·H2O (689.8 mg, 3.00 mmol), and a dioxane solution (460 μL,
1.11 mM, 0.51 μmol) of the precatalyst composed of Pd(dba)2, CyR-
Phos, and ethyl 4-bromobenzoate in a 1.0:4.6:22.3 ratio in dioxane (2
mL) was stirred at 100 °C for 8 h. The resulting reaction mixture was
diluted with n-hexane (5 mL), filtered through a thin pad of silica gel
(n-hexane), and concentrated under reduced pressure. The crude
material obtained was purified by flash chromatography on silica gel
(n-hexane) to provide the title compound (299.5 mg, 0.821 mmol,
1
mg, 0. 049 mmol, 5%). The title compound: mp = 61.1−65.9 °C; H
NMR (399.9 MHz, CDCl3) δ 1.04 (d, J = 6.8 Hz, 6H), 1.09 (d, J = 6.8
Hz, 6H), 1.15 (d, J = 6.0 Hz, 6H), 2.56 (sept, J = 6.8 Hz, 2H), 4.46
(sept, J = 6.0 Hz, 1H), 6.90−6.98 (m, 2H), 7.02 (dd, J = 7.2 Hz, J =
1.6 Hz, 1H), 7.18 (d, J = 8.0 Hz, 2H), 7.28−7.38 (m, 2H); 13C NMR
(100.6 MHz, CDCl3) δ 21.9, 23.8, 24.4, 30.4, 68.8, 112.5, 119.8, 122.1,
127.4, 128.0, 130.0, 131.6, 136.1, 147.1, 155.2; MS (EI) m/z (%) 296
(M+, 46), 254 (71), 239 (26), 211 (97), 197 (100), 169 (47); HRMS
(EI) found 296.2140, calcd for C21H28O 296.2140.
1-Methoxy-4-[2-methyl-2-(3,5-di-tert-butylphenyl)propyl]-
benzene (4eh) (Table 5, Entry 2). Following the general procedure,
a mixture of 2,4,6-tri-tert-butylbromobenzene (1e) (325.4 mg, 1.00
mmol), 4-methoxyphenylboronic acid (2h) (230.4 mg, 1.52 mmol),
K3PO4·H2O (693.3 mg, 3.01 mmol), and a dioxane solution (200 μL,
1.30 mM, 0.26 μmol) of the precatalyst composed of Pd(dba)2, CyR-
Phos, and ethyl 4-bromobenzoate in a 1.0:3.8:22.7 ratio in dioxane (2
mL) was stirred at 100 °C for 9 h. The resulting reaction mixture was
diluted with n-hexane (5 mL), filtered through a thin pad of silica gel
(1:5 to 1:0 AcOEt/n-hexane), and concentrated under reduced
pressure. The crude material obtained was purified by flash
chromatography on silica gel (1:2 CHCl3/n-hexane) to provide the
title compound (331.6 mg, 0.940 mmol, 94%) as a white solid: mp =
1
82%) as a colorless oil. H NMR (399.9 MHz, CDCl3) δ 0.94 (d, J =
6.8 Hz, 3H), 1.26 (s, 18H), 1.40 (s, 6H), 2.79 (sept, J = 6.8 Hz, 1H),
2.91 (s, 2H), 6.81 (d, J = 7.2 Hz, 1H), 6.95−7.00 (m, 1H), 7.05 (d, J =
2.0 Hz, 2H), 7.10−7.15 (m, 2H), 7.23 (t, J = 2.0 Hz, 1H); 13C NMR
(100.6 MHz, CDCl3) δ 23.7, 28.7, 28.8, 31.9, 34.9, 39.5, 46.1, 119.6,
120.6, 124.4, 124.7, 126.2, 131.4, 135.7, 147.5, 147.8, 149.6; MS (EI)
m/z (%) 364 (M+, 1.2), 231 (100); HRMS (EI) found 364.3131, calcd
for C27H40 364.3130.
1-Phenyl-2-[2-methyl-2-(3,5-di-tert-butylphenyl)propyl]-
benzene (4ed)10a (Table 5, Entry 6). Following the general
procedure, a mixture of 2,4,6-tri-tert-butylbromobenzene (1e) (324.8
mg, 1.00 mmol), 2-phenylphenylboronic acid (2d) (295.8 mg, 1.49
mmol), K3PO4·H2O (697.1 mg, 3.03 mmol), and a dioxane solution
(480 μL, 1.11 mM, 0.53 μmol) of the precatalyst composed of
Pd(dba)2, CyR-Phos, and ethyl 4-bromobenzoate in a 1.0:4.7:22.3
ratio in dioxane (2 mL) was stirred at 100 °C for 12 h. The resulting
reaction mixture was diluted with n-hexane (5 mL), filtered through a
thin pad of silica gel (n-hexane), and concentrated under reduced
pressure. The crude material obtained was purified by flash
chromatography on silica gel (n-hexane) to provide the title
compound (379.6 mg, 0.952 mmol, 95%) as a white solid: mp =
1
81−82 °C; H NMR (699.8 MHz, CDCl3) δ 1.30 (s, 18H), 1.31 (s,
6H), 2.76 (s, 2H), 3.74 (s, 3H), 6.67 (s, 4H), 7.10 (d, J = 1.4 Hz, 2H),
7.25 (t, J = 1.8 Hz, 1H); 13C NMR (100.6 MHz, CDCl3) δ 28.1, 31.6,
34.9, 39.1, 50.7, 55.0, 112.8, 119.3, 120.5, 131.1, 131.2, 147.7, 149.7,
157.8; MS (EI) m/z (%) 352 (M+, 4), 231 (100); HRMS (EI) found
352.2765, calcd for C25H36O 352.2766.
1-Methoxy-2-[2-methyl-2-(3,5-di-tert-butylphenyl)propyl]-
benzene (4ea)10a (Table 5, Entry 3). Following the general
procedure, a mixture of 2,4,6-tri-tert-butylbromobenzene (1e) (325.3
mg, 1.00 mmol), 2-methylphenylboronic acid (2a) (202.9 mg, 1.49
mmol), K3PO4·H2O (689.2 mg, 2.99 mmol), and a dioxane solution
(460 μL, 1.11 mM, 0.51 μmol) of the precatalyst composed of
Pd(dba)2, CyR-Phos, and ethyl 4-bromobenzoate in a 1.0:4.6:22.3
ratio in dioxane (2 mL) was stirred at 100 °C for 8 h. The resulting
reaction mixture was diluted with n-hexane (5 mL), filtered through a
thin pad of silica gel (n-hexane), and concentrated under reduced
pressure. The crude material obtained was purified by flash
chromatography on silica gel (n-hexane) to provide the title
compound (336.1 mg, 0.999 mmol, 100%) as a colorless oil. 1H
NMR (399.9 MHz, CDCl3) δ 1.25 (s, 18H), 1.41 (s, 6H), 1.73 (s,
3H), 2.82 (s, 2H), 6.82 (dd, J = 7.2 Hz, J = 1.2 Hz, 1H), 6.95−7.07
1
55−56 °C; H NMR (699.8 MHz, CDCl3) δ 1.07 (s, 6H), 1.26 (s,
18H), 2.99 (s, 2H), 6.79 (dd, J = 7.7 Hz, J = 0.7 Hz, 1H), 6.95 (d, J =
1.4 Hz, 2H), 7.11 (td, J = 7.7 Hz, J = 2.1 Hz 1H), 7.16−7.22 (m, 4H),
7.23 (t, J = 1.4 Hz, 1H), 7.31 (t, J = 7.7 Hz, 1H), 7.37 (t, J = 7.7 Hz,
2H); 13C NMR (100.6 MHz, CDCl3) δ 28.0, 31.5, 34.9, 40.0, 46.4,
119.4, 120.4, 125.8, 126.3, 126.4, 127.9, 129.9, 130.1, 131.1, 136.5,
142.7, 143.3, 148.3, 149.7; MS (EI) m/z (%) 398 (M+, 1.6), 231
(100); HRMS (EI) found 398.2974, calcd for C30H38 398.2974.
1-Methoxy-2-[2-methyl-2-(3,5-di-tert-butylphenyl)propyl]-
benzene (4ee) (Table 5, Entry 7). Following the general procedure,
a mixture of 2,4,6-tri-tert-butylbromobenzene (1e) (324.5 mg, 1.00
mmol), 2-methoxyphenylboronic acid (2e) (228.7 mg, 1.51 mmol),
11521
dx.doi.org/10.1021/jo402089r | J. Org. Chem. 2013, 78, 11513−11524