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4-Methyl-4-phenyl-1-tosylazetidin-2-one (1g): White solid, 1.2 g
(61 % yield). M.p. 132–134 °C. H NMR (300 MHz, CDCl3): δ = 7.80–
4.30–4.10 (m, 1 H, major), 3.17 (dd, J = 16.9, 7.8 Hz,1 H, minor), 2.84
(dd, J = 16.4, 10.5 Hz, 1 H minor+2 H, major), 1.36 (t, J = 7.1 Hz, 3
H, minor), 1.25 (t, J = 7.1 Hz, 3 H, major) ppm. 13C NMR (75 MHz,
CDCl3): δ = 166.83, 166.51, 166.01, 165.44, 150.13, 149.70, 145.44,
1
7.59 (m, 2 H), 7.52–7.11 (m, 7 H), 3.27–3.03 (m, 2 H), 2.45 (s, 3 H),
2.11 (d, J = 1.5 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 164.03,
145.01, 140.15, 136.56, 129.66, 128.65, 128.19, 127.56, 125.46, 65.86, 144.36, 137.03, 136.40, 129.13, 128.87, 128.34, 127.49, 126.88,
53.57, 24.49, 21.68 ppm. IR: ν = 3090, 3052, 2983, 2952, 1783, 1589,
123.78, 82.09, 81.64, 63.87, 56.71, 55.78, 36.57, 32.30, 14.01 ppm. IR:
˜
˜
1496, 1440, 1357, 1199, 1147, 1085, 808, 770, 673 cm–1. HRMS (ESI, ν = 3118, 2983, 2900, 1780, 1749, 1534, 1347, 1171, 1081, 1050,
TOF): m/z calcd. for C14H18NO3S [M + H]+ 316.1007; found 316.1003. 856 cm–1. HRMS (ESI, TOF): m/z calcd. for C19H18N2O8NaS [M + Na]+
457.0682; found 457.0685.
(3,4-trans)-3-Methyl-4-phenyl-1-tosylazetidin-2-one (1n): White
solid, 0.42 g (29 % yield). M.p. 103–105 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.75–7.52 (m, 2 H), 7.49–7.08 (m, 7 H), 4.62 (d, J = 2.9 Hz,
1 H), 3.18 (dd, J = 7.4, 3.0 Hz, 1 H), 2.45 (s, 3 H), 1.37 (d, J = 7.4 Hz,
3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 167.66, 145.08, 136.10,
135.68, 129.76, 128.92, 128.83, 127.45, 126.60, 64.99, 54.68, 21.69,
Ethyl
3-[(4-Methyl)sulfonyl]-6-oxo-4-phenyl-1,3-oxazinane-2-
carboxylate (3b): White solid, 97 mg (80 % yield) 1H NMR
(200 MHz, CDCl3): δ = 7.63 (d, J = 8.3 Hz, 2 H, major), 7.38–6.98 (m,
10 H, major+minor), 6.61 (s, 1 H, major), 6.22 (s, 1 H, minor), 5.23
(dd, J = 7.6, 4.7 Hz, 1 H, minor), 5.00 (dd, J = 10.1, 7.7 Hz, 1 H,
major), 4.40 (q, J = 7.0 Hz, 2 H, minor), 4.27–3.99 (m, 2 H, major),
3.22 (dd, J = 16.8, 7.6 Hz, 1 H, minor), 3.04–2.67 (m, 2 H major+1 H
minor), 2.40 +2.34 (s+s', 3 H, major+minor), 1.40 (t, J = 7.1 Hz, 3 H,
minor), 1.26 (t, J = 7.2 Hz, 3 H, major) ppm. 13C NMR (75 MHz,
CD3CN): δ = 166.41, 166.31, 166.15, 164.71, 145.11, 144.66, 139.54,
134.01, 129.68, 129.28, 128.34, 128.20, 127.73, 127.65, 127.46,
125.91, 125.85, 81.73, 81.58, 63.17, 62.64, 55.24, 54.66, 36.41, 35.27,
12.55 ppm. IR: ν = 3066, 3032, 2969, 2928, 1787, 1593, 1489, 1451,
˜
1358, 1244, 1164, 1137, 1081, 798, 748, 659 cm–1. HRMS (ESI, TOF):
m/z calcd. for C17H17NO3NaS [M + Na]+ 338.0827; found 338.0424.
(3,4-cis)-3-Methyl-4-phenyl-1-tosylazetidin-2-one (1m): White
solid, 0.42 g (29 % yield). M.p. 131–134 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.82 (d, J = 8.2 Hz, 2 H), 7.33 (dd, J = 6.9, 4.7 Hz, 5 H),
7.15 (dd, J = 6.3, 2.7 Hz, 2 H), 5.24 (d, J = 6.7 Hz, 1 H), 3.61 (p, J =
7.4 Hz, 1 H), 2.47 (s, 3 H), 0.83 (d, J = 7.6 Hz, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 167.78, 145.32, 135.70, 133.78, 129.91, 128.54,
20.28, 20.24, 12.95, 12.85 ppm. IR: ν = 3066, 3007, 2952, 1766, 1756,
˜
1597, 1455, 1365, 1209, 1168, 1078, 1019, 818 cm–1. HRMS (ESI,
TOF): m/z calcd. for C20H21NO6NaS [M + Na]+ 426.0987; found
426.0993.
128.48, 127.66, 127.08, 61.04, 50.16, 21.73, 9.56 ppm. IR: ν = 3066,
˜
3032, 2969, 2928, 1787, 1593, 1489, 1451, 1358, 1244, 1164, 1137,
1081, 798, 748, 659 cm–1
C
.
HRMS (ESI, TOF): m/z calcd. for
Ethyl 3-(Methylsulfonyl)-6-oxo-4-phenyl-1,3-oxazinane-2-carb-
oxylate (3c): White solid, 83 mg (84 % yield). 1H NMR (200 MHz,
CDCl3): δ = 7.54–7.30 (m, 5 H), 6.45 (s, 1 H, major), 6.12 (s, 1 H,
minor), 5.32 (dd, J = 7.9, 4.1 Hz, 1 H, minor), 5.19 (t, J = 9.3 Hz, 1 H,
major), 4.37 (q, J = 7.1 Hz, 2 H, minor+major), 3.30 (dd, J = 16.8,
7.8 Hz, 1 H, minor), 3.01 (d, J = 9.3 Hz, 2 H, major), 2.88 (dd, J =
16.8, 4.0 Hz, 1 H, minor), 2.72 (s, 3 H, major), 2.61 (s, 3 H, minor),
1.38 (dd, J = 9.2, 5.1 Hz, 3 H, major+minor) ppm. 13C NMR (75 MHz,
CD3CN): δ = 166.69, 166.57, 139.81, 139.58, 128.69, 128.43, 128.12,
127.91, 125.99, 125.80, 81.55, 81.49, 63.29, 62.79, 55.36, 54.94, 40.94,
17H17NO3NaS [M + Na]+ 338.0827; found 338.0424.
4-Phenyl-1-tosylazetidine-2-thione (1h): Brown solid, 0.24 g
(15 % yield). M.p. 122–125 °C. 1H NMR (200 MHz, CDCl3): δ = 7.65
(d, J = 8.3 Hz, 2 H), 7.48–7.03 (m, 7 H), 5.56 (dd, J = 5.7, 2.7 Hz, 1
H), 3.38 (dd, J = 16.6, 5.7 Hz, 1 H), 2.95 (dd, J = 16.6, 2.7 Hz, 1 H),
2.43 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 203.02, 145.94,
136.22, 133.70, 129.31, 128.76, 128.43, 127.78, 126.61, 64.27, 48.73,
20.41 ppm. IR: ν = 3062, 3026, 1785, 1712, 1592, 1492, 1450, 1411,
˜
1366, 1310, 1291, 1277, 1165, 1129, 1109, 1087, 805, 758 cm–1
.
39.11, 37.12, 35.77, 12.89 ppm. IR: ν = 3017, 2994, 1780, 1731, 1462,
˜
HRMS (ESI, TOF): m/z calcd. for C16H15NO2S2 [M + H]+ 318.0622;
1361, 1207, 1184, 1161, 1088, 1039, 1007, 762 cm–1. HRMS (ESI,
found 318.0608.
TOF): m/z calcd. for C14H18NO6S [M + H]+ 328.0855; found 328.0847.
Procedure for Side Reaction Study, Product 10: To a stirred solu-
tion of β-lactam (1a; 45.8 mg, 0.152 mmol) in CD3CN (0.5 mL), was
added a solution of PPY in CDCl3 (30 μL, 0.505 M, 10 mol-%). Conver-
General Procedure 3, Condition B: To a stirred solution of β-
lactams (0.303 mmol), ethyl glyoxalate (50 % in toluene, Alfa Aesar;
180 μL, 0.909 mmol, 3 equiv.) in CD3CN (1 mL), and mesitylene as
an internal reference (42 μL, 0.302 mmol, 1 equiv.) was added to a
sion rate to form product was monitored by NMR spectroscopy after
1
1 d. Product (10). H NMR (300 MHz, CD3CN): δ = 7.95–7.03 (m, H
solution of PPY in CDCl3 (60 μL, 0.505
M, 10 mol-%). After 1 d at
arom.), 6.80–6.49 (m, 2 H), 4.60 (t, J = 7.1 Hz, 1 H), 2.74 (dd, J = 15.4,
7.2 Hz, 1 H), 2.60 (dd, J = 15.4, 7.0 Hz, 1 H), 2.42 (s, 3 H), 2.33 (s, 3
H) ppm. HRMS (ESI, TOF): m/z calcd. for C32H30N2O6S2Na [M + Na]+
625.1437; found 625.1451.
40 °C, NMR spectroscopic analysis was performed and yields were
determined by using 1,3,5-mesitylene. The solvent was removed
under reduced pressure and the residue purified by silica-gel (60–
120 mesh) column chromatography.
General Procedures for Oxazinanones Synthesis. General Proce-
Ethyl 6-Oxo-4-propyl-3-tosyl-1,3-oxazinane-2-carboxylate (3e):
Yield 90 % as a mixture of isomers (50:50). 1H NMR (300 MHz,
CD3CN): δ = 7.84–7.79 (m, 2 H, major+minor), 7.45–7.41 (m, 2 H,
major+minor), 6.43 (s, 1 H, major), 5.85 (s, 1 H, minor), 4.47–4.20 (m,
2 H, major), 4.08–3.78 (m, 2 H, minor), 2.75–2.59 (m, 1 H minor+ 2
H major), 2.45 (s, 3 H, major+minor), 2.43–2.33 (m, 1 H, minor), 1.81–
1.45 (m, 2 H, major+minor), 1.42–1.11 (m, 6 H, major+minor), 0.87
(m, 6 H, major+minor) ppm. 13C NMR (75 MHz, CD3CN): δ = 166.72,
166.37, 163.90, 144.97, 135.42, 134.40, 129.73, 129.54, 127.94,
127.62, 81.15, 80.47, 63.02, 62.24, 52.26, 51.59, 38.54, 36.47, 34.47,
32.39, 20.29, 20.27, 17.68, 17.55, 12.97, 12.89, 12.58, 12.50 ppm. IR:
dure 2, Condition A: To
a stirred solution of β-lactams
(0.303 mmol), ethyl glyoxalate (50 % in toluene, Alfa Aesar; 60 μL,
0.303 mmol, 1 equiv.) in CD3CN (1 mL), was added a solution of
PPY in CDCl3 (60 μL, 0.505 M, 10 mol-%). After 3 h at room tempera-
ture, the solvent was removed under reduced pressure and the resi-
due purified by silica-gel (60–120 mesh) column chromatography
(EtOAc, Rf = 1) to afford the resulting oxazinone product.
Ethyl
3-[(4-Nitrophenyl)sulfonyl]-6-oxo-4-phenyl-1,3-oxazin-
1
ane-2-carboxylate (3a): White solid, 120 mg (91 % yield). H NMR
(300 MHz, CDCl3): δ = 8.05 (d, J = 8.7 Hz, 2 H, major), 7.95 (d, J =
8.5 Hz, 2 H, minor), 7.64 (d, J = 8.6 Hz, 2 H, major), 7.42 (d, J =
8.6 Hz, 2 H, minor), 7.23–6.87 (m, 5 H, major+minor), 6.61 (s, 1 H,
major), 6.29 (s, 1 H, minor), 5.21 (dd, J = 7.5, 3.8 Hz, 1 H, minor),
5.06 (t, J = 9.2 Hz, 1 H, major), 4.37 (dd, J = 7.0, 3.2 Hz, 2 H, minor),
ν = 2959, 2876, 1748, 1361, 1191, 1167, 1039 cm–1. HRMS (ESI, TOF):
˜
m/z calcd. for C17H23NO6NaS [M + Na]+ 392.1144; found 392.1146.
Ethyl 4-(Iodomethyl)-6-oxo-3-tosyl-1,3-oxazinane-2-carboxyl-
ate (3f): Yield 84 % as a mixture of isomers (60:40). 1H NMR
Eur. J. Org. Chem. 2016, 549–555
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