The Journal of Organic Chemistry
Note
NMR analyses were recorded using CDCl3 as the solvent and TMS as
the internal standard. Chemical shifts are reported in parts per million
with reference to TMS (δ 0.00). Data are presented as follows:
chemical shift, multiplicity (br, broad; s, singlet; d, doublet; t, triplet; q,
quartet; m, multiplet), coupling constant (hertz), and integration. 13C
NMR spectra were recorded on 100 MHz spectrometers with
reference to CDCl3 (δ 77.0). Masses were recorded on a LC/MS
system. High-resolution mass spectra (HRMS) were recorded on a
Time-of-Flight (TOF, ESI mode) LC/HRMS system.
General Procedure A for the Phosphonium Salt-Activated,
Pd-Catalyzed Suzuki−Miyaura Cross-Coupling Reaction. Prep-
aration of 3-Phenylcyclopent-2-en-1-one (2a).1a In a two-neck flask
were placed cyclopentane-1,3-dione (196 mg, 2 mmol) and PyBroP
(1118 mg, 2.4 mmol). The air was removed and the flask refilled with
N2 (twice). Then, 1,4-dioxane (4 mL) and Et3N (0.56 mL, 4 mmol)
were added. The mixture was stirred at rt for 1.5 h. A mixture of
phenylboronic acid (366 mg, 3 mmol), PdCl2(PPh3)2 (70 mg, 0.1
mmol), and K2CO3 (829 mg, 6 mmol) was added under N2, and then
H2O (2 mL) was added. The mixture was stirred at 95 °C for 1 h. The
mixture was poured into an EtOAc/H2O solvent (10 mL/10 mL), and
the aqueous layer was extracted with EtOAc (2 × 5 mL). The
combined organic layer was dried (Na2SO4) and then filtered. After
removal of solvent, the product was purified by silica gel
chromatography (24g column) using a 0 to 30% EtOAc/heptane
gradient as the eluent to give 234 mg of 3-phenylcyclopent-2-en-1-one
(2a, 74%): 1H NMR (400 MHz, CDCl3) δ 7.67 (dd, J = 7.3, 2.3 Hz, 2
H), 7.40−7.54 (m, 3 H), 6.59 (s, 1 H), 3.06 (dd, J = 4.8, 2.8 Hz, 2 H),
2.52−2.66 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 209.5, 174.0,
134.1, 131.3, 128.9, 127.5, 126.8, 35.3, 28.7; MS m/z (M + H)+ 159
(100%).
H)+ 273 (100%); HRMS (ESI/TOF) calcd for C17H21O3 [M + H]+
273.1485, found 273.1499.
5,5-Dimethyl-3-(4-trifluoromethylphenyl)cyclohex-2-en-1-one
(3b). According to general procedure A described above, compound
3b was prepared from 5,5-dimethylcyclohexane-1,3-dione (280 mg, 2
mmol) and 4-trifluoromethylphenylboronic acid (570 mg, 3 mmol) in
1
82% yield (441 mg): H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.6
Hz, 2 H), 7.63 (d, J = 8.6 Hz, 2 H), 6.43 (s, 1 H), 2.65 (s, 2 H), 2.37
(s, 2 H), 1.15 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ 199.8, 156.0,
2
3
142.7, 131.6 (q, JC−F = 32.6 Hz), 126.5, 125.9, 125.7 (q, JC−F = 3.6
Hz), 123.8 (q, 1JC−F = 270.6 Hz), 50.9, 42.4, 33.9, 28.4; MS m/z (M +
H)+ 269 (100%); HRMS (ESI/TOF) calcd for C15H16F3O [M + H]+
269.1148, found 269.1157.
5,5-Dimethyl-3-(4-methoxyphenyl)cyclohex-2-en-1-one (3c).1a
According to general procedure A described above, compound 3c
was prepared from 5,5-dimethylcyclohexane-1,3-dione (280 mg, 2
mmol) and 4-methoxyphenylboronic acid (456 mg, 3 mmol) in 95%
yield (438 mg): 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 9.1 Hz, 2
H), 6.93 (d, J = 8.6 Hz, 2 H), 6.40 (s, 1 H), 3.85 (s, 3 H), 2.63 (s, 2
H), 2.33 (s, 2 H), 1.13 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ
200.2, 161.2, 157.0, 131.1, 127.7, 122.7, 114.2, 55.5, 50.9, 42.1, 33.7,
28.5; MS m/z (M + H)+ 231 (100%).
5,5-Dimethyl-3-(3-methoxyphenyl)cyclohex-2-en-1-one (3d).1a
According to general procedure A described above, compound 3d
was prepared from 5,5-dimethylcyclohexane-1,3-dione (280 mg, 2
mmol) and 3-methoxyphenylboronic acid (456 mg, 3 mmol) in 95%
yield (439 mg): 1H NMR (400 MHz, CDCl3) δ 7.32 (t, J = 8.0 Hz, 1
H), 7.12 (dd, J = 7.7, 1.7 Hz, 1 H), 7.01−7.06 (m, 1 H), 6.95 (dd, J =
8.2, 2.6 Hz, 1 H), 6.40 (t, J = 1.5 Hz, 1 H), 3.84 (s, 3 H), 2.63 (d, J =
1.5 Hz, 2 H), 2.34 (s, 2 H), 1.13 (s, 6 H); 13C NMR (100 MHz,
CDCl3) δ 200.1, 159.8, 157.5, 140.5, 129.7, 124.5, 118.6, 115.3, 111.8,
55.3, 51.0, 42.4, 33.7, 28.4; MS m/z (M + H)+ 231 (100%); HRMS
(ESI/TOF) calcd for C15H19O2 [M + H]+ 231.1380, found 231.1397.
5,5-Dimethyl-3-(2-methoxyphenyl)cyclohex-2-en-1-one (3e).1a
According to general procedure A described above, compound 3e
was prepared from 5,5-dimethylcyclohexane-1,3-dione (280 mg, 2
mmol) and 2-methoxyphenylboronic acid (456 mg, 3 mmol) in 84%
3-Phenylcyclohex-2-en-1-one (2b).8a According to general proce-
dure A described above, compound 2b was prepared from cyclo-
hexane-1,3-dione (224 mg, 2 mmol) and phenylboronic acid (366 mg,
3 mmol) in 85% yield (292 mg): 1H NMR (400 MHz, CDCl3) δ 7.54
(dd, J = 6.6, 3.0 Hz, 2 H), 7.33−7.48 (m, 3 H), 6.43 (s, 1 H), 2.78 (t, J
= 5.3 Hz, 2 H), 2.44−2.57 (m, 2 H), 2.06−2.23 (m, 2 H); 13C NMR
(100 MHz, CDCl3) δ 200.0, 159.8, 138.8, 130.0, 128.8, 126.1, 125.4,
37.3, 28.1, 22.8; MS m/z (M + H)+ 173 (100%).
1
yield (386 mg): H NMR (400 MHz, CDCl3) δ 7.33 (td, J = 7.4, 1.8
5,5-Dimethyl-3-phenylcyclohex-2-en-1-one (2c).1a According to
general procedure A described above, compound 2c was prepared
from 5,5-dimethylcyclohexane-1,3-dione (280 mg, 2 mmol) and
Hz, 1 H), 7.14−7.20 (m, 1 H), 6.97 (t, J = 7.5 Hz, 1 H), 6.92 (d, J =
8.3 Hz, 1 H), 6.17 (t, J = 1.3 Hz, 1 H), 3.83 (s, 3 H), 2.62 (d, J = 1.5
Hz, 2 H), 2.33 (s, 2 H), 1.11 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ
200.2, 159.7, 156.6, 130.2, 129.9, 128.6, 127.1, 120.7, 111.1, 55.4, 51.2,
44.0, 34.2, 28.2; MS m/z (M + H)+ 231 (100%).
1
phenylboronic acid (366 mg, 3 mmol) in 90% yield (360 mg): H
NMR (400 MHz, CDCl3) δ 7.54 (dd, J = 6.6, 3.0 Hz, 2 H), 7.35−7.48
(m, 3 H), 6.42 (s, 1 H), 2.66 (s, 2 H), 2.35 (s, 2 H), 1.14 (s, 6 H); 13C
NMR (100 MHz, CDCl3) δ 200.2, 157.7, 139.1, 130.0, 128.8, 126.2,
124.4, 51.0, 42.4, 33.8, 28.5; MS m/z (M + H)+ 201 (100%).
3-Phenylcyclohept-2-en-1-one (2d).8a According to general
procedure A described above, compound 2d was prepared from
cycloheptane-1,3-dione (252 mg, 2 mmol) and phenylboronic acid
5,5-Dimethyl-3-(2-hydroxymethylphenyl)cyclohex-2-en-1-one
(3f). According to general procedure A described above, compound 3f
was prepared from 5,5-dimethylcyclohexane-1,3-dione (280 mg, 2
mmol) and 2-hydroxymethylphenylboronic acid (456 mg, 3 mmol) in
1
72% yield (330 mg): H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 7.1
Hz, 1 H), 7.29−7.44 (m, 2 H), 7.14 (d, J = 7.1 Hz, 1 H), 6.02 (s, 1 H),
4.68 (d, J = 5.6 Hz, 2 H), 2.53 (s, 2 H), 2.36 (s, 2 H), 1.88 (t, J = 5.6
Hz, 1 H), 1.15 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ 199.8, 160.1,
140.0, 136.9, 128.72, 128.69, 127.9, 127.7, 127.1, 62.8, 50.9, 45.8, 34.2,
28.3; MS m/z (M + H)+ 231 (100%); HRMS (ESI/TOF) calcd for
C15H19O2 [M + H]+ 231.1380, found 231.1386.
1
(366 mg, 3 mmol) in ∼15% yield (65 mg, ∼85% purity): H NMR
(400 MHz, CDCl3) δ 7.30−7.50 (m, 5 H), 6.31 (s, 1 H), 2.80−2.96
(m, 2 H), 2.61−2.78 (m, 2 H), 1.80−2.05 (m, 4 H); MS m/z (M +
H)+ 187 (100%).
2-Methyl-3-phenylcyclohex-2-en-1-one (2e).3 According to gen-
eral procedure A described above, compound 2e was prepared from 2-
methylcyclohexane-1,3-dione (252 mg, 2 mmol) and phenylboronic
5,5-Dimethyl-3-(2,6-dimethylphenyl)cyclohex-2-en-1-one (3g).
According to general procedure A described above, compound 3g
was prepared from 5,5-dimethylcyclohexane-1,3-dione (280 mg, 2
mmol) and 2,6-dimethylphenylboronic acid (450 mg, 3 mmol) in 85%
1
acid (366 mg, 3 mmol) in 63% yield (234 mg): H NMR (400 MHz,
CDCl3) δ 7.29−7.47 (m, 3 H), 7.20 (d, J = 7.1 Hz, 2 H), 2.58−2.71
(m, 2 H), 2.45−2.58 (m, 2 H), 2.00−2.18 (m, 2 H), 1.72 (s, 3 H); 13C
NMR (100 MHz, CDCl3) δ 200.1, 156.6, 141.3, 131.9, 128.4, 127.9,
127.1, 37.8, 33.0, 22.8, 12.9; MS m/z (M + H)+ 187 (100%).
3-(4-Ethoxycarbonylphenyl)-5,5-dimethylcyclohex-2-en-1-one
(3a). According to general procedure A described above, compound
3a was prepared from 5,5-dimethylcyclohexane-1,3-dione (280 mg, 2
mmol) and 4-ethoxycarbonylphenylboronic acid (582 mg, 3 mmol) in
69% yield (378 mg): 1H NMR (400 MHz, CDCl3) δ 8.08 (m, J = 8.6
Hz, 2 H), 7.58 (d, J = 8.6 Hz, 2 H), 6.45 (s, 1 H), 4.40 (q, J = 7.1 Hz, 2
H), 2.66 (s, 2 H), 2.37 (s, 2 H), 1.41 (t, J = 7.3 Hz, 3 H), 1.15 (s, 6
H); 13C NMR (100 MHz, CDCl3) δ 199.9, 166.0, 156.3, 143.3, 131.5,
129.9, 126.1, 125.7, 61.2, 50.9, 42.3, 33.8, 28.4, 14.3; MS m/z (M +
1
yield (292 mg): H NMR (400 MHz, CDCl3) δ 7.09−7.19 (m, 1 H),
7.01−7.09 (m, 2 H), 5.94 (s, 1 H), 2.30−2.44 (m, 4 H), 2.22 (s, 6 H),
1.17 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ 198.1, 159.7, 138.0,
131.8, 126.1, 125.9, 125.8, 49.3, 42.6, 32.1, 26.8, 17.9; MS m/z (M +
H)+ 229 (100%); HRMS (ESI/TOF) calcd for C16H21O [M + H]+
229.1587, found 229.1599.
5,5-Dimethyl-3-(1-methylpyrazol-4-yl)cyclohex-2-en-1-one (3h).
According to general procedure A described above, compound 3h
was prepared from 5,5-dimethylcyclohexane-1,3-dione (280 mg, 2
mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
1H-pyrazole (624 mg, 3 mmol) in 69% yield (280 mg): 1H NMR (400
MHz, CDCl3) δ 7.73 (s, 1 H), 7.61 (s, 1 H), 6.28 (s, 1 H), 3.94 (s, 3
D
J. Org. Chem. XXXX, XXX, XXX−XXX