9352
F.D. King, S. Caddick / Tetrahedron 68 (2012) 9350e9354
and the THF removed by rotary evaporation. The product was
extracted into DCM (3ꢁ50 mL), dried (MgSO4) and concentrated.
Purification by column chromatography on SiO2, initially eluting
with 1:1 petroleum ether/DCM to remove the excess benzyl bro-
mide, then DCM to 1% MeOH/DCM to give the product.
14.7 Hz), 3.73 (1H, d, J¼15.0 Hz), 4.36e4.39 (1H, m), 4.80 (1H, d,
J¼15.0 Hz), 7.12e7.20 (6H, m), 7.24e7.33 (3H, m); 13C NMRþDEPT
(125 MHz)
d¼21.3 (CH3), 44.6 (CH2), 46.9 (CH2), 53.4 (CH), 126.6
(CH), 127.7 (CH), 128.6 (CH), 128.8 (CH), 129.7 (CH), 134.9 (C), 135.8
(C), 138.4 (C), 167.4 (C); nmax (liquid film) 1743, 1387, 1352, 940, 822,
726, 715, 703 cmꢂ1; LRMS (EI) 251, 208, 119, 118; HRMS (EI): Mþ,
found 251.1307. C17H17NO requires 251.1305.
4.2.1. N-Benzyl-4-phenyl-azetidin-2-one (1a). Colourless oil (93%
yield); spectroscopically consistent with the literature data.9 Rf
(Et2O) 0.5; 1H NMR (500 MHz)
d
¼2.87 (1H, dd, J¼2.2, 14.7 Hz), 3.34
4.2.7. N-Benzyl-4-(3-methylphenyl)-azetidin-2-one (1g). Colourless
oil (92% yield); Rf (DCM) 0.3; 1H NMR (500 MHz)
d
¼2.30 (3H, s),
(1H, dd, J¼5.1, 14.7 Hz), 3.76 (1H, d, J¼15.0 Hz), 4.40 (1H, dd, J¼2.2,
2.87 (1H, dm, J¼14.6 Hz), 3.35 (1H, dd, J¼5.2, 14.6 Hz), 3.72 (1H, d,
J¼14.9 Hz), 4.39e4.42 (1H, m), 4.80 (1H, d, J¼14.9 Hz), 6.91e6.97
(2H, m), 7.08 (1H, d, J¼7.6 Hz), 7.18 (1H, t, J¼7.5 Hz), 7.24e7.27 (2H,
5.1 Hz), 4.80 (1H, d, J¼15.0 Hz), 7.14 (2H, d, J¼7.2 Hz), 7.20e7.40 (8H,
m); 13C NMRþDEPT (125 MHz)
¼44.8 (CH2), 47.0 (CH2), 53.6 (CH),
d
126.6 (CH), 127.8 (CH), 128.6 (CH), 128.8 (CH), 129.1 (CH), 135.6 (C),
138.0 (C), 167.3 (C).
m), 7.30e7.39 (3H, m); 13C NMRþDEPT (125 MHz)
¼21.4 (CH3),
d
44.7 (CH2), 47.0 (CH2), 53.6 (CH), 125.6 (CH), 126.6 (CH), 128.5 (CH),
128.6 (CH), 128.7 (CH), 129.0 (CH), 129.3 (CH), 135.5 (C), 138.1 (C),
138.5 (C), 167.3 (C); nmax (liquid film) 1743, 1456, 1387, 1360, 939,
766, 739, 696 cmꢂ1; LRMS (EI) 251; HRMS (EI): Mþ, found 251.1306.
C17H17NO requires 251.1305.
4.2.2. N-(4-Methylbenzyl)-4-phenyl-azetidin-2-one (1b). Colourless
oil (85% yield); Rf (Et2O) 0.5; 1H NMR (500 MHz)
d
¼2.33 (3H, s), 2.86
(1H, ddd, J¼0.8, 2.3, 14.7 Hz), 3.32 (1H, dd, J¼5.2, 14.7 Hz), 3.71 (1H,
d, J¼14.9 Hz), 4.39 (1H, dd, J¼2.3, 5.2 Hz), 4.78 (1H, d, J¼14.9 Hz),
7.03 (2H, d, J¼8.0 Hz), 7.10 (2H, d, J¼8.0 Hz), 7.23e7.27 (2H, m),
7.30e7.40 (3H, m); 13C NMRþDEPT (125 MHz)
¼21.2 (CH3), 44.5
d
4. 2. 8 . N-(Benzyl) -4-(4-bromophenyl)-azetidin-2-one
(1h). Colourless oil (89% yield); Rf (DCM) 0.3; 1H NMR (500 MHz)
(CH2), 46.9 (CH2), 53.4 (CH), 126.6 (CH), 128.5 (CH), 128.6 (CH), 129.0
(CH), 129.5 (CH), 132.6 (C), 137.5 (C), 138.1 (C), 167.2 (C); nmax (liquid
film) 1743, 1455, 1387, 1359, 770, 750, 698 cmꢂ1; LRMS (EI) 251, 105,
104; HRMS (EI): Mþ, found 251.1300. C17H17NO requires 251.1305.
d
¼2.82 (1H, dm, J¼14.7 Hz), 3.34 (1H, dd, J¼5.2, 14.7 Hz), 3.76 (1H,
d, J¼14.9 Hz), 4,35 (1H, dd, J¼2.3, 5.2 Hz), 4.77 (1H, d, J¼14.9 Hz),
7.09e7.13 (4H, m), 7.25e7.32 (3H, m), 7.48 (2H, d, J¼8.4 Hz); 13C
NMRþDEPT (125 MHz) ¼44.9 (CH2), 47.0 (CH2), 53.0 (CH), 122.5
d
(C), 127.9 (CH), 128.3 (CH), 128.7 (CH), 129.1 (CH), 132.1 (CH), 135.4
(C), 142.6 (C), 167.0 (C); nmax (liquid film) 1744, 1487, 1385, 1072,
1009, 938, 825, 717, 708, 695 cmꢂ1; LRMS (EI) 317, 315, 184, 182, 86;
HRMS (EI): Mþ, found 315.0255. C16H1479BrNO requires 315.0253.
4.2.3. N-(3-Methylbenzyl)-4-phenyl-azetidin-2-one (1c). Colourless
oil (93% yield); Rf (Et2O) 0.5; 1H NMR (500 MHz)
d
¼2.30 (3H, s), 2.87
(1H, dm, J¼14.6 Hz), 3.35 (1H, dd, J¼5.2, 14.6 Hz), 3.72 (1H, d,
J¼14.9 Hz), 4.39e4.42 (1H, m), 4.80 (1H, d, J¼14.9 Hz), 6.91e6.97
(2H, m), 7.08 (1H, d, J¼7.6 Hz), 7.18 (1H, t, J¼7.5 Hz), 7.24e7.27 (2H,
4. 2. 9. N -(Benzyl) -4-(2-chlorophenyl)-azetidin-2-one
m), 7.30e7.39 (3H, m); 13C NMRþDEPT (125 MHz)
¼21.4 (CH3),
d
(1i). Colourless oil (95% yield); Rf (DCM) 0.3; 1H NMR (500 MHz)
44.7 (CH2), 47.0 (CH2), 53.6 (CH), 125.6 (CH), 126.6 (CH), 128.5 (CH),
128.6 (CH), 128.7 (CH), 129.0 (CH), 129.3 (CH), 135.5 (C), 138.1 (C),
138.5 (C), 167.3 (C); nmax (liquid film) 1743, 1386, 1349, 777,
699 cmꢂ1; LRMS (EI) 251, 105, 104; HRMS (EI): Mþ, found 251.1300.
C17H17NO requires 251.1305.
d
¼2.79 (1H, dd, J¼2.2, 14.7 Hz), 3.42 (1H, dd, J¼5.4, 14.7 Hz), 3.92
(1H, d, J¼14.9 Hz), 4.84 (1H, d, J¼14.9 Hz), 4.87 (1H, dd, J¼2.2,
5.4 Hz), 7.18 (2H, d, J¼7.2 Hz), 7.22e7.37 (7H, m); 13C NMRþDEPT
(125 MHz)
d¼45.5 (CH2), 46.3 (CH2), 50.4 (CH), 126.6 (CH), 127.5
(CH),127.9 (CH), 128.6 (CH), 128.9 (CH), 129.3 (CH), 130.0 (CH), 133.3
(C), 135.4 (C), 136.0 (C), 167.4 (C); nmax (liquid film) 1746, 1443, 1385,
1348, 1035, 754, 709, 696 cmꢂ1; LRMS (EI) 273, 271, 140, 138; HRMS
(EI): Mþ, found 271.0753. C16H14ClNO requires 271.0758.
4.2.4. N-(4-Chlorobenzyl)-4-phenyl-azetidin-2-one (1d). Colourless
oil (87% yield); Rf (Et2O) 0.5; 1H NMR (500 MHz)
d¼2.89 (1H, ddd,
J¼0.7, 2.3, 14.7 Hz), 3.35 (1H, dd, J¼5.2, 14.7 Hz), 3.77 (1H, d,
J¼15.1 Hz), 4.39 (1H, dd, J¼2.3, 5.2 Hz), 4.75 (1H, d, J¼15.1 Hz), 7.07
(2H, d, J¼8.4 Hz), 7.20e7.27 (4H, m), 7.31e7.39 (3H, m); 13C
4.2.10. N-(Benzyl)-4-(2-naphthyl)-azetidin-2-one (1j). White solid
(88% yield), mp 85e87 ꢀC (Et2O/petroleum ether); Rf (Et2O) 0.5; 1H
NMRþDEPT (125 MHz) ¼44.2 (CH2), 47.0 (CH2), 53.8 (CH), 126.6
d
NMR (500 MHz)
d
¼2.97 (1H, dd, J¼2.2, 14.7 Hz), 3.42 (1H, dd, J¼5.2,
(CH), 126.7 (CH), 129.0 (CH), 129.1 (CH), 130.0 (CH), 133.7 (C), 134.2
(C), 137.8 (C), 167.2 (C); nmax (liquid film) 1742, 1491, 1386, 1090,
1015, 804, 768, 753, 698 cmꢂ1; LRMS (EI) 273, 271, 192, 86; HRMS
(EI): Mþ, found 271.0753. C16H1435ClNO requires 271.0758; spec-
troscopically consistent with the literature material.10
14.7 Hz), 3.81 (1H, d, J¼15.0 Hz), 4.58 (1H, dd, J¼2.2, 5.2 Hz), 4.85
(1H, d, J¼15.0 Hz), 7.16e7.19 (2H, m), 7.22e7.27 (3H, m), 7.38 (1H, dd,
J¼1.7, 8.5 Hz), 7.44e7.47 (2H, m), 7.69 (1H, s), 7.81 (1H, dd, J¼3.4,
8.5 Hz), 7.81e7.85 (2H, m); 13C NMRþDEPT (125 MHz)
¼44.9 (CH2),
d
47.0 (CH2), 53.8 (CH), 123.5 (CH), 126.3 (CH), 126.5 (CH), 126.7 (CH),
127.8 (CH), 127.9 (CH), 127.9 (CH), 128.6 (CH), 128.9 (CH), 129.2 (CH),
133.4 (C), 133.5 (C), 135.4 (C), 135.7 (C), 167.3 (C); nmax (solid) 1740,
1380,1307, 863, 829, 789, 751, 722, 703 cmꢂ1; LRMS (EI) 287,154, 91;
HRMS (EI): Mþ, found 287.1301. C20H17NO requires 287.1305.
4.2.5. N-(4-Fluorobenzyl)-4-phenyl-azetidin-2-one (1e). Colourless
oil (88% yield); Rf (Et2O) 0.5; 1H NMR (500 MHz)
d
¼2.87 (1H, ddd,
J¼0.6, 2.3 14.7 Hz), 3.33 (1H, dd, J¼5.2, 14.7 Hz), 3.78 (1H, d,
J¼15.0 Hz), 4.38 (1H, dd, J¼2.3, 5.2 Hz), 4.68 (1H, d, J¼15.0 Hz), 6.95
(2H, J¼8.7 Hz), 7.10 (2H, dd, J¼5.4, 8.6 Hz), 7.20e7.25 (2H, m),
4.3. N-Benzyl-cinnamamide 2a from 1a
7.30e7.38 (3H, m); 13C NMRþDEPT (125 MHz)
¼44.1 (CH2), 47.0
d
(CH2), 53.7 (CH), 115.6 (CH, d, J¼21.4 Hz), 126.6 (CH), 128.6 (CH),
129.1 (CH), 130.3 (CH, d, J¼8.3 Hz), 131.5 (C, d, J¼3.4 Hz), 137.9 (C),
A stirred mixture of triflic acid (0.50 mL, 5 mmol) and 1a (0.24 g,
1 mmol) in CHCl3 (10 mL) was heated under gentle reflux for
30 min. The reaction mixture was cooled to room temperature,
water (10 mL) was added and the mixture basified with an excess of
solid K2CO3. The product was extracted into DCM (2ꢁ50 mL), dried
(MgSO4), concentrated in vacuo and the product purified by column
chromatography on SiO2, eluting with DCMd1% MeOH/DCM to
give 2a (0.21 g, 85% yield), mp 106e108 ꢀC (EtOAc/petroleum ether)
(lit. 108e110 ꢀC11) identical to material prepared from cinnamoyl
chloride and benzylamine by the literature procedure.12 Rf (Et2O)
162.3 (C, d, J¼246 Hz), 167.2 (C); 19F NMR (282 MHz)
¼114.9 (tt,
d
J¼8.5, 5.6 Hz); nmax (liquid film) 1742, 1509, 1389, 1220, 1157, 840,
826, 753, 699 cmꢂ1; LRMS (EI) 255, 212; HRMS (EI): Mþ, found
251.1056. C16H14FNO requires 255.1054.
4. 2. 6. N-(Benzyl)-4-(4-methylphenyl)-azetidin-2-one
(1f). Colourless oil (90% yield); Rf (DCM) 0.3; 1H NMR (500 MHz)
d¼2.36 (3H, s), 2.85 (1H, dm, J¼14.7 Hz), 3.32 (1H, dd, J¼5.2,