The Journal of Organic Chemistry
Article
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3022, 2916, 1680, 1583, 1259, 1205, 989, 817, 698, 557; H NMR
(400 MHz, CDCl3) δ 7.77 (d, J = 8.5 Hz, 2H), 7.56 (d, J = 8.5 Hz,
2H), 7.26−7.15 (m, 5H), 7.13 (d J = 7.1 Hz, 2H), 7.07 (d, J = 8.0 Hz,
2H), 4.75 (t, J = 7.4 Hz, 1H), 3.67 (d, J = 7.4 Hz, 2H), 2.26 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 197.1, 144.1, 140.9, 136.0, 135.8,
(ESI-Q-TOF) m/z calcd for C23H20O3[M + Na]+ 367.1310, found
367.1310.
(E)-5-(Benzo[d][1,3]dioxol-5-yl)-1,5-diphenylpent-1-en-3-one
(3r). 98 mg, yield 80%; gummy solid; mp 106−108 °C; IR (KBr,
cm−1) 3022, 2920, 1651, 1487, 1234, 1176, 1037, 690; 1H NMR (400
MHz, CDCl3) δ 7.53−7.49 (m, 3H), 7.37−7.36 (m, 3H), 7.29−7.21
(m, 4H), 7.18−7.15 (m, 1H), 6.74−6.67 (m, 4H), 5.89 (s, 2H), 4.65
(t, J = 7.4 Hz, 1H), 3.35 (d, J = 7.4 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 197.9, 147.7, 145.9, 144.1, 142.8, 137.9, 134.3, 130.5, 128.9,
128.5, 128.2, 127.8, 126.4, 126.1, 120.8, 108.3, 108.1, 100.8, 46.9, 45.7;
HRMS (ESI-Q-TOF) m/z calcd for C24H20O3[M + Na]+ 379.1310,
found 379.1311.
(E)-5-(4-Methoxyphenyl)-1,5-diphenylpent-1-en-3-one (3s). 71
mg, yield 61%; white solid; mp 124−126 °C; IR (KBr, cm−1) 3026,
2930, 1635, 1512, 1251, 1180, 1032, 692; 1H NMR (400 MHz,
CDCl3) δ 7.50 (d, J = 16.2 Hz, 1H), 7.50−7.49 (m, 2H), 7.38−7.36
(m, 3H), 7.31−7.23 (m, 5H), 7.17 (d, J = 8.3 Hz, 2H), 6.81 (m, 2H),
6.69 (d, J = 16.2 Hz, 1H), 4.67 (t, J = 7.6 Hz, 1H), 3.75 (s, 3H), 3.38
(d, J = 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 198.2, 158.1,
144.4, 142.8, 136.2, 134.5, 130.5, 128.9, 128.8, 128.6, 128.3, 127.7,
126.3, 126.3, 113.9, 55.2, 47.2, 45.4; HRMS (ESI-Q-TOF) m/z calcd
for C24H22O2[M + H]+ 343.1698, found 343.1700.
131.9, 129.6, 129.3, 128.6, 128.2, 127.7, 127.6, 126.4, 45.6, 44.7, 21.0;
HRMS (ESI-Q-TOF) m/z calcd for C22H19BrO[M + Na]+ 401.0517,
found 401.0517.
3-(Benzo[d][1,3]dioxol-5-yl)-1-(2,4-dichlorophenyl)-3-phenylpro-
pan-1-one (3l). 102 mg, yield 97%; light brown liquid; IR (neat,
cm−1) 3584, 2926, 1697, 1583, 1485, 1242, 933, 665; H NMR (400
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MHz, CDCl3) δ 7.38 (d, J = 1.9 Hz, 1H), 7.25−7.22 (m, 2H), 7.20−
7.16 (m, 4H), 7.08 (d, J = 8.5 Hz, 1H), 6.68−6.67 (m, 3H), 5.87 (s,
2H), 4.60 (t, J = 7.8 Hz, 1H), 3.64 (d, J = 7.8 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ 200.2, 147.7, 146.1, 143.4, 137.7, 137.3, 137.2, 131.7,
130.1, 128.6, 127.6, 127.2, 126.5, 120.6, 108.3, 108.1, 100.9, 49.1, 46.2;
HRMS (ESI-Q-TOF) m/z calcd for C22H16Cl2O3[M + Na]+ 421.0374,
found 421.0374.
3-(Benzo[d][1,3]dioxol-5-yl)-3-phenyl-1-(thiophen-2-yl)propan-1-
one (3m). 123 mg, yield 92%, cream colored solid; mp 134−136 °C;
IR (KBr, cm−1) 3084, 2872, 1639, 1487, 1415, 1244, 1039, 939, 729,
543; 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 3.5 Hz, 1H), 7.61 (d,
J = 4.8 Hz, 1H), 7.29−7.24 (m, 4H), 7.19−7.15 (m, 1H), 7.10 (d, J =
4.3 Hz, 1H), 6.74 (d, J = 9.4 Hz, 2H), 6.70 (d, J = 7.8 Hz, 1H), 5.89 (s,
2H), 4.73 (t, J = 7.6 Hz, 1H), 3.60 (d, J = 7.6 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ 190.8, 147.7, 146.0, 144.3, 143.9, 137.8, 133.7, 131.8,
128.6, 128.1, 127.6, 126.5, 120.7, 108.4, 108.2, 100.9, 45.8, 45.5;
HRMS (ESI-Q-TOF) m/z calcd for C20H16O3S[M + H]+ 337.0898,
found 337.0889.
General Procedure for α-Alkylation of Unactivated Ketones
with Cinnamyl Alcohols. To a solution of unactivated ketone (0.3
mmol (4a−f) or 0.224 mmol (4g−n), 1 equiv) and 1,3-diarylprop-2-
en-1-ols (1.2 equiv) in CCl4 (3 mL), trimethyl orthoformate (1 equiv)
and triflic acid (1 equiv) were added. The reaction mixture was stirred
at room temperature. After complete consumption of the ketone as
revealed by TLC, solvent was evaporated, and the crude product was
directly loaded on a silica gel column and eluted with ethyl acetate/
hexanes to get the pure alkylated product.
1-(4-Chlorophenyl)-2-(9H-xanthen-9-yl)ethanone (3n). 78 mg,
yield 72%; yellow colored solid; mp 92−94 °C; IR (KBr, cm−1)
3038, 1682, 1477, 1456, 1257, 829, 760; 1H NMR (400 MHz, CDCl3)
δ 7.71 (d, J = 8.5 Hz, 2H), 7.32 (d, J = 8.5 Hz, 2H), 7.30−7.25 (m,
2H), 7.22−7.18 (m, 2H), 7.10 (d, J = 8.4 Hz, 2H), 7.03−6.99 (m, 2H)
4.81 (t, J = 6.6 Hz, 1H), 3.29 (d, J = 6.6 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ 196.9, 152.4, 139.7, 135.4, 129.6, 128.8, 128.8, 128.0,
125.4, 123.6, 116.7, 49.6, 35.0; HRMS (ESI-Q-TOF) m/z calcd for
C21H15ClO2[M + Na]+ 357.0658, found 357.0659.
(E)-1,3,5-Triphenylpent-4-en-1-one (4a).27 84 mg, yield 90%; H
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NMR (400 MHz, CDCl3) δ 7.93 (d, J = 7.2 Hz, 2H), 7.53 (t, J = 7.6
Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H), 7.32−7.18 (m, 10H), 6.40−6.39 (m,
2H), 4.33−4.28 (m, 1H), 3.54−3.47(m, 2H); 13C NMR (100 MHz,
CDCl3) δ 198.3, 143.4, 137.3, 137.2, 133.2, 132.7, 130.2, 128.8, 128.7,
128.6, 128.2, 127.9, 127.4, 126.7, 126.4, 44.6, 44.1.
(E)-3,5-Diphenyl-1-(p-tolyl)pent-4-en-1-one (4b). 90 mg, yield
92%; yellow gummy liquid; IR (neat, cm−1) 3028, 1682, 1493, 1450,
3-Ferrocenyl-1,3-diphenylpropan-1-one (3o).26e 90 mg, yield
55%; 1H NMR (400 MHz, CDCl3) δ 7.88−7.90 (m, 2H), 7.53−
7.51 (m, 1H), 7.42 (t, J = 7.6 Hz, 2H), 7.27−7.21 (m, 4H), 7.16−7.14
(m, 1H), 4.54 (dd, J = 8.0, 5.6 Hz 1H), 4.18 (s, 1H), 4.11 (s, 1H), 4.06
(s, 6H), 4.0 (s, 1H), 3.66−3.63 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 198.6, 144.9, 137.4, 133.1, 128.7, 128.4, 128.2, 127.9, 126.5,
93.5, 68.8, 68.1, 67.8, 67.4, 67.1, 46.4, 41.0.
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1180, 966, 698; H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.4 Hz,
2H), 7.30−7.26 (m, 6H), 7.24−7.17 (m, 5H), 7.16−7.14 (m, 1H),
6.44−6.35 (m, 2H), 4.32−4.27 (m, 1H), 3.51−3.40 (m, 2H), 2.38 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 197.8, 143.9, 143.5, 137.3,
134.7, 132.8, 130.1, 129.4, 128.8, 128.5, 128.3, 127.9, 127.3, 126.7,
126.3, 44.4, 44.1, 21.7; HRMS (ESI-Q-TOF) calcd for C24H22O [M +
H]+ 327.1749, found 327.1749.
(E)-1-(4-Chlorophenyl)-3,5-diphenylpent-4-en-1-one (4c). 86 mg,
83%; yellow colored gummy liquid; IR (neat, cm−1) 3026, 1685, 1493,
1452, 1240, 1091, 696; 1H NMR (400 MHz, CDCl3) δ 7.88−7.86 (m,
2H), 7.42−7.40 (m, 2H), 7.32−7.29 (m, 6H), 7.26−7.24 (m, 3H),
7.23−7.18 (m, 1H), 6.39−6.38 (m, 2H), 4.30−4.25 (m, 1H), 3.51−
3.40 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 197.1,143.2, 139.6,
137.2, 135.5, 132.4, 130.3, 129.6, 129.1, 128.8, 128.6, 127.8, 127.4,
126.8, 126.4, 44.6, 44.1; HRMS (ESI-Q-TOF) calcd for C23H19OCl
[M + Na]+ 369.1022, found 369.1022.
2-((4-Methoxyphenyl)(phenyl)methyl)cyclohexanone (3p). 114
mg, 76%; Mixture of diastereomers; liquid; IR (neat, cm−1) 2935,
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1711, 1512, 1249, 1033, 700; H NMR (400 MHz, CDCl3) δ 7.26−
7.17 (m, 10H), 7.15−7.08 (m, 4H), 6.79−6.76 (m, 4H), 4.27 (d, J =
10.8 Hz, 2H), 3.71 (s, 3H), 3.70 (s, 2H), 3.29 (m, 2H), 2.43−2.29 (m,
4H), 2.03−1.96 (m, 2H), 1.84−1.70 (m, 6H), 1.67−1.58 (m, 2H),
1.44−1.34 (m, 2H); 13C NMR(100 MHz, CDCl3) δ 212.5, 212.4,
157.9, 157.7, 144.1, 143.2, 135.8, 135.0, 129.1, 128.5, 128.4, 128.3,
128.1, 127.4, 126.1, 125.9, 113.8, 113.7, 55.0, 55.0, 54.9, 50.0, 50.0,
42.3, 42.2, 33.3, 33.2, 29.1, 24.4, 24.2; HRMS (ESI-Q-TOF) m/z calcd
for C20H22O2[M + Na]+ 317.1517, found 317.1526.
(E)-1-(4-Iodophenyl)-3,5-diphenylpent-4-en-1-one (4d). 116 mg,
88%; pale yellow colored solid; mp 101−104 °C; IR (KBr, cm−1)
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3-(Benzo[d][1,3]dioxol-5-yl)-2-methyl-1,3-diphenylpropan-1-one
(3q). 103 mg, yield 80%; mixture of diastereomers; white solid; mp
108−110 °C; IR (KBr, cm−1) 2874, 1674, 1502, 1487, 1440, 1232,
1037, 700; 1H NMR (400 MHz, CDCl3) δ 7.93 (t, J = 8.5 Hz, 3.3H),
7.56−7.52 (m, 2H), 7.46−7.41 (m, 3.5 H), 7.34−7.29 (m, 2.9H), 7.21
(d, J = 7.1 Hz, 2.8H), 7.11 (t, J = 7.1 Hz, 2.2H), 7.04−7.00 (m, 1H),
6.83−6.81 (m, 2H), 6.74 (d, J = 7.8 Hz, 1H), 6.73−6.69 (m, 1.3H),
6.55 (dd, J = 7.8 Hz, 1H), 5.90 (d, J = 7.3 Hz, 2H), 5.77 (d, J = 4.9 Hz,
1.3H), 4.38−4.29 (m, 3.3H), 1.14 (d, J = 6.2 Hz, 3H), 1.10 (d, J = 6.2
Hz, 1.9H); 13C NMR (100 MHz, CDCl3) δ 203.3, 203.2, 147.8, 147.5,
146.1, 145.8, 143.6, 143.0, 137.6, 137.0, 136.7, 132.9, 128.6, 128.4,
128.3, 128.1, 128.1, 127.4, 126.5, 126.2, 121.6, 120.3, 108.5, 108.4,
108.2, 108.1, 100.9, 100.7, 53.9, 53.9, 44.9, 44.8, 18.0, 17.9; HRMS
3026, 1687, 1493, 1450, 1392, 698; H NMR (400 MHz, CDCl3) δ
7.89−7.72 (m, 2H), 7.62−7.57 (m, 2H), 7.34−7.15 (m, 10H), 6.43−
6.33 (m, 2H), 4.27−4.25 (m, 1H), 3.44−3.41 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 197.5, 143.2, 138.0, 137.2, 136.4, 132.4, 130.3,
129.6, 128.8, 128.6, 127.8, 127.4, 126.8, 126.3, 101.2, 44.5, 44.1;
HRMS (ESI-Q-TOF) calcd for C23H19IO [M + H]+ 439.0559, found
439.0559.
(E)-1-(4-Nitrophenyl)-3,5-diphenylpent-4-en-1-one (4e). 82 mg,
76%; yellow colored solid; mp 97−100 °C; IR (KBr, cm−1) 3024,
1680, 1493, 1448, 744, 694; 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J
= 8.8 Hz, 2H), 8.03 (d, J = 8.8 Hz, 2H), 7.36−7.29 (m, 6H), 7.25−
7.19 (m, 3H), 7.18−7.16 (m, 1H), 6.40−6.35 (m, 2H), 4.30−4.25 (m,
1H), 3.53−3.52 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 196.9,
G
dx.doi.org/10.1021/jo500759a | J. Org. Chem. XXXX, XXX, XXX−XXX