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Z.-L. Shen et al.
Paper
Synthesis
MS (EI, 70 eV): m/z (%) = 241 (33) [M+], 213 (21), 197 (16), 196 (100),
169 (17), 168 (58), 167 (34), 166 (13), 153 (14), 140 (15), 139 (23),
115 (41), 98 (19), 89 (16), 84 (43), 75 (19), 65 (24), 63 (21), 50 (21).
HRMS (EI): m/z [M+] calcd for C19H20O4: 312.1362; found: 312.1305.
[4-(1,3-Dioxan-2-yl)phenyl](4-tert-butylphenyl)methanone (4nb)
HRMS (EI): m/z [M+] calcd for C15H15NO2: 241.1103; found: 241.1072.
The arylzinc reagent 5n was prepared according to GP1 from 2-(4-
chlorophenyl)-1,3-dioxane (1n; 0.199 g, 1 mmol) at –95 °C for 5 min
in 65% yield. Palladium-catalyzed cross-coupling with 4-tert-butyl-
benzoyl chloride (3n; 0.118 g, 0.6 mmol, 0.6 equiv) was performed
according to GP3 using PEPPSI-IPr (27 mg, 4 mol%) at 60 °C for 12 h,
leading to the corresponding benzophenone 4nb (128 mg, 62%) as a
colorless oil.
1H NMR (400 MHz, CD3COCD3): δ = 7.77–7.73 (m, 4 H), 7.63–7.58 (m,
4 H), 5.63 (s, 1 H), 4.22 (ddt, J = 10.6, 5.1, 1.4 Hz, 2 H), 4.07–4.00 (m,
2 H), 2.17–2.08 (m, 1 H), 1.49 (dtt, J = 13.5, 2.6, 1.3 Hz, 1 H), 1.37 (s,
9 H).
3-(3-Chloro-4-methylphenyl)pyridine (4ma)
The arylzinc reagent 5m was prepared according to GP1 from 2-
chloro-4-iodo-1-methylbenzene (1m; 0.252 g, 1 mmol) at –95 °C for
5 min in 73% yield. Palladium-catalyzed cross-coupling with 3-bro-
mopyridine (3k; 0.111 g, 0.7 mmol, 0.7 equiv) was performed accord-
ing to GP3 using PEPPSI-IPr (27 mg, 4 mol%) at 60 °C for 12 h, leading
to the corresponding 3-arylated pyridine 4ma (99 mg, 70%) as a col-
orless oil.
1H NMR (300 MHz, CDCl3): δ = 8.82 (d, J = 2.5 Hz, 1 H), 8.60 (dd, J = 4.8,
1.5 Hz, 1 H), 7.84 (ddd, J = 7.9, 2.4, 1.7 Hz, 1 H), 7.57 (d, J = 1.4 Hz,
1 H), 7.40–7.32 (m, 3 H), 2.43 (s, 3 H).
13C NMR (100 MHz, CD3COCD3): δ = 195.9, 156.9, 144.3, 138.9, 135.9,
130.8, 130.3, 127.1, 126.3, 101.5, 68.0, 35.7, 31.5, 26.7.
13C NMR (75 MHz, CDCl3): δ = 148.7, 148.1, 137.0, 135.9, 135.2, 135.1,
134.1, 131.5, 127.5, 125.2, 123.5, 19.7.
MS (EI, 70 eV): m/z (%) = 205 (31), 204 (17), 203 (100) [M+], 202 (12),
169 (12), 168 (78), 167 (31), 166 (10), 139 (13).
MS (EI, 70 eV): m/z (%) = 325 (18), 324 (61) [M+], 323 (86), 309 (46),
267 (21), 266 (21), 265 (76), 252 (20), 251 (69), 223 (33), 222 (100),
207 (27), 195 (12), 167 (12), 161 (35), 133 (35), 118 (14), 111 (16),
105 (57), 104 (13), 91 (14), 87 (52), 77 (27), 57 (20), 41 (20).
HRMS (EI): m/z [M+] calcd for C21H24O3: 324.1725; found: 324.1711.
HRMS (EI): m/z [M+] calcd for C12H10ClN: 203.0502; found: 203.0482.
3-[4-(1,3-Dioxan-2-yl)phenyl]-2-methylcyclohex-2-enone (4nc)
(3-Chloro-4-methylphenyl)(4-methoxyphenyl)methanone (4mb)
The arylzinc reagent 5n was prepared according to GP1 from 2-(4-
chlorophenyl)-1,3-dioxane (1n; 0.199 g, 1 mmol) at –95 °C for 5 min
in 65% yield. Palladium-catalyzed cross-coupling with 3-iodo-2-
methylcyclohex-2-enone (3o; 0.142 g, 0.6 mmol, 0.6 equiv) was per-
formed according to GP3 using PEPPSI-IPr (27 mg, 4 mol%) at 60 °C for
12 h, leading to the corresponding 3-arylated enone 4nc (121 mg,
74%) as a colorless oil.
The arylzinc reagent 5m was prepared according to GP1 from
2-chloro-4-iodo-1-methylbenzene (1m; 0.252 g, 1 mmol) at –95 °C
for 5 min in 73% yield. Palladium-catalyzed cross-coupling with
4-methoxybenzoyl chloride (3h; 0.119 g, 0.7 mmol, 0.7 equiv) was
performed according to GP3 using PEPPSI-IPr (27 mg, 4 mol%) at 60 °C
for 12 h, leading to the corresponding benzophenone 4mb (103 mg,
56%) as a colorless oil.
1H NMR (400 MHz, CD3COCD3): δ = 7.52–7.48 (m, 2 H), 7.28–7.25 (m,
2 H), 5.55 (s, 1 H), 4.19 (ddt, J = 10.5, 5.1, 1.4 Hz, 2 H), 4.03–3.97 (m,
2 H), 2.64 (tq, J = 6.0, 1.9 Hz, 2 H), 2.45–2.42 (m, 2 H), 2.14–2.02 (m,
3 H), 1.63 (t, J = 2.0 Hz, 3 H), 1.47 (dtt, J = 13.5, 2.6, 1.4 Hz, 1 H).
13C NMR (100 MHz, CD3COCD3): δ = 199.1, 156.7, 142.6, 140.1, 132.0,
127.7, 127.1, 101.8, 67.9, 38.3, 33.5, 26.7, 23.6, 13.1.
MS (EI, 70 eV): m/z (%) = 272 (49) [M+], 271 (85), 216 (24), 214 (20),
213 (44), 186 (12), 185 (56), 163 (17), 158 (12), 157 (10), 142 (12),
130 (12), 129 (26), 128 (26), 127 (11), 115 (27), 87 (100), 59 (12), 42
(12), 41 (14).
1H NMR (300 MHz, CDCl3): δ = 7.83–7.78 (m, 2 H), 7.76 (d, J = 1.7 Hz,
1 H), 7.56 (dd, J = 7.7, 1.7 Hz, 1 H), 7.33 (d, J = 7.7 Hz, 1 H), 7.00–6.95
(m, 2 H), 3.90 (s, 3 H), 2.46 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 193.8, 163.3, 140.4, 137.4, 134.4, 132.4,
130.7, 130.3, 129.8, 128.0, 113.6, 55.5, 20.2.
MS (EI, 70 eV): m/z (%) = 262 (13), 261 (7), 260 (43) [M+], 153 (8), 135
(100), 92 (8), 77 (8).
HRMS (EI): m/z [M+] calcd for C15H13ClO2: 260.0604; found: 260.0526.
Ethyl 4-[4-(1,3-dioxan-2-yl)phenyl]benzoate (4na)
HRMS (EI): m/z [M+] calcd for C17H20O3: 272.1412; found: 272.1463.
The arylzinc reagent 5n was prepared according to GP1 from 2-(4-
chlorophenyl)-1,3-dioxane (1n; 0.199 g, 1 mmol) at –95 °C for 5 min
in 65% yield. Palladium-catalyzed cross-coupling with ethyl 4-bromo-
benzoate (3m; 0.138 g, 0.6 mmol, 0.6 equiv) was performed according
to GP3 using PEPPSI-IPr (27 mg, 4 mol%) at 60 °C for 12 h, leading to
the corresponding biphenyl 4na (154 mg, 82%) as a colorless oil.
1H NMR (400 MHz, CD3COCD3): δ = 8.11–8.08 (m, 2 H), 7.81–7.78 (m,
2 H), 7.72–7.69 (m, 2 H), 7.59–7.56 (m, 2 H), 5.58 (s, 1 H), 4.37 (q, J =
7.1 Hz, 2 H), 4.21 (ddt, J = 10.4, 5.1, 1.4 Hz, 2 H), 4.05–3.98 (m, 2 H),
2.16–2.07 (m, 1 H), 1.47 (dtt, J = 13.4, 2.6, 1.3 Hz, 1 H), 1.38 (t, J =
7.1 Hz, 3 H).
13C NMR (100 MHz, CD3COCD3): δ = 166.6, 145.9, 140.7, 140.6, 130.8,
130.4, 127.9, 127.8, 127.6, 101.8, 67.9, 61.5, 26.7, 14.7.
MS (EI, 70 eV): m/z (%) = 312 (79) [M+], 311 (100), 267 (36), 254 (32),
253 (50), 239 (17), 226 (33), 225 (37), 210 (17), 209 (55), 198 (17),
181 (55), 163 (31), 153 (38), 152 (97), 151 (33), 144 (40), 129 (31),
104 (19), 87 (34), 76 (21), 57 (17), 44 (18), 42 (20).
4-(1,3-Dioxan-2-yl)benzaldehyde (4nd)
The aryllithium reagent 2n was prepared according to GP1 from 2-(4-
chlorophenyl)-1,3-dioxane (1n; 0.199 g, 1 mmol) at –95 °C for 5 min
in 65% yield. Reaction with DMF (0.044 g, 0.6 mmol, 0.6 equiv) was
performed according to GP2 from –95 °C to r.t. over 2 h, leading to the
corresponding aldehyde 4nd (100 mg, 87%) as a colorless oil.
1H NMR (400 MHz, CD3COCD3): δ = 10.05 (s, 1 H), 7.93–7.90 (m, 2 H),
7.68–7.65 (m, 2 H), 5.61 (s, 1 H), 4.23–4.19 (m, 2 H), 4.05–3.99 (m,
2 H), 2.16–2.06 (m, 1 H), 1.51–1.45 (m, 1 H).
13C NMR (100 MHz, CD3COCD3): δ = 192.8, 146.3, 137.7, 130.1, 127.8,
101.3, 68.0, 26.6.
MS (EI, 70 eV): m/z (%) = 192 (21) [M+], 191 (30), 149 (15), 134 (20),
133 (100), 105 (32), 87 (19), 77 (25), 51 (14), 42 (13).
HRMS (EI): m/z [M+] calcd for C11H12O3: 192.0786; found: 192.0787.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2617–2630