Cycloaddition of N-Metalated Azomethine Ylides
J . Org. Chem., Vol. 67, No. 3, 2002 987
Tol), 1.63 (s, 3H, CH3); 13C NMR δ 177.0, 168.0, 142.3, 137.3,
136.5, 133.3, 133.1, 129.4, 127.8, 127.8, 127.6, 126.5, 126.3,
126.0, 125.1, 125.0, 81.0, 67.0, 64.0, 52.7, 51.1, 34.2, 21.33; MS
(FAB) m/z 466 (MH+). Anal. Calcd for C26H27NO5S: C, 67.08;
H, 5.85; N, 3.01; S, 6.89. Found: C, 67.06; H, 6.13; N, 2.84; S,
7.37.
(d, 1H, J ) 2.4, CH-Nph), 4.31 (q, 2H, J ) 7.0, CH2-O), 3.68
(s, 3H, CO2Me), 1.59 (s, 3H, CH3), 1.33 (t, 3H, J ) 7.0,
CH3-CH2); 13C NMR δ 178.2, 169.5, 142.5, 141.2, 137.4, 134.3,
133.4, 128.5, 127.6, 127.1, 126.3, 125.7, 125.4 125.0, 65.8, 64.1,
61.7, 50.2, 29.6, 14.3; MS (EI) m/z 339.3 (M+). Anal. Calcd for
C
20H21NO4: C, 70.78; H, 6.24; N, 4.13. Found: C, 70.80; H,
2-Eth yl 4-Meth yl (-)-(2S,4S,5R,SS)-2-Meth yl-5-(2-n a p h -
6.20; N, 4.21.
th yl)-4-(p-tolylsu lfin yl)pyr r olidin e-2,4-dicar boxylate (4d):
Dim eth yl (-)-(2S,5S)-5-P h en yl-2,5-d ih yd r o-1H-p yr r ole-
yellow needles (ether-hexane), mp 127-129 °C; [R]20 -36 (c
2,4-d ica r boxyla te (7a ): yellow oil; [R]20D -15 (c 0.2, CHCl3);
D
0.2, CHCl3) (ee g 99%, HPLC); IR (CHCl3) 3440, 1730 cm-1
;
IR (CHCl3) 3350, 1730 cm-1 1H NMR δ 7.55-7.36 (m, 5 H,
;
1H NMR δ 8.06-7.44 (m, 7H, Nph), 7.40 and 7.25 (AA′BB′
system, 4H, Tol), 5.14 (s, 1H, CH-Nph), 4.24 (q, 2H, CH2-O,
J ) 7.0), 3.55 (d, 1H, J ) 14, CH), 3.20 (s, 3H, CO2Me), 2.66
(d, 1H, J ) 14, CH), 2.37 (s, 3H, CH3-Tol), 1.67 (s, 3H, CH3),
1.38 (t, 3H, CH3-CH2, J ) 7.0); 13C NMR δ 177.0, 168.0, 142.0,
137.1, 135.4, 133.3, 133.1, 129.5, 127.9, 127.6, 127.5, 126.4,
126.0, 125.9, 125.4, 125.3, 81.3, 67.0, 64.0, 61.6, 51.5, 34.1, 26.7,
Ph), 6.82 (dd, 1H, J ) 2.4, J ) 1.7, CHdC), 6.12 (dd, 1H, J )
5, J ) 1.7, CH-Ph), 5.57 (dd, 1H, CH, J ) 5, J ) 2.4), 3.68 (s,
3H, CO2Me), 3.58 (s, 3H, CO2Me); 13C NMR δ 179.1, 169.1,
137.2, 128.3, 128.1, 126.8, 128.5, 126.4, 124.2, 65.0, 63.6, 55.5;
MS (EI) m/z 261.1 (M+). Anal. Calcd for C14H15NO4: C, 64.36;
H, 5.79; N, 5.36. Found: C, 64.48; H, 5.65; N, 5.42.
Dim eth yl (-)-(2S,5S)-5-(2-Na p h th yl)-2,5-d ih yd r o-1H-
p yr r ole-2,4-d ica r boxyla te (7b): yellow oil; [R]20D -12 (c 0.2,
CHCl3); IR (CHCl3) 3540, 1740 cm-1; 1H NMR δ 7.55-7.36 (m,
11 H, Nph), 6.79 (dd, 1H, J ) 2.4, J ) 1.7, CHdC), 6.15 (dd,
1H, J ) 5, J ) 1.7, CH-Nph), 5.63 (dd, 1H, J ) 5, J ) 2.4,
CH), 3.68 (s, 3H, CO2Me), 3.58 (s, 3H, CO2Me); 13C NMR δ
178.1, 169.0, 135.2, 133.2, 131.2, 131.1, 128.2, 127.3, 127.1,
126.5, 125.7, 124.3, 129.5, 125.3, 65.6, 63.8, 61.2; MS (EI) m/z
311.2 (M+). Anal. Calcd for C18H17NO4: C, 69.44; H, 5.50; N,
4.50. Found: C, 69.58; H, 5.75; N, 4.45.
Dim eth yl (-)-(2S,5S)-2-Meth yl-5-(2-n a p h th yl)-2,5-d ih y-
d r o-1H -p yr r ole-2,4-d ica r b oxyla t e (7c): yellow needles
(ether-hexane), mp 102-104 °C; [R]20D -34 (c 0.2, CHCl3) (ee
g 99%, HPLC); IR (CHCl3) 3448, 1730 cm-1; 1H NMR δ 7.85-
7.36 (m, 11 H, Nph), 6.96 (d, 1H, J ) 2.43, CHdC), 5.41 (d,
1H, J ) 2.43, CH-Nph), 3.78 (s, 3H, CO2Me), 3.58 (s, 3H, CO2-
Me), 1.53 (s, 3H, CH3); 13C NMR δ 180.0, 169.0, 137.2, 136.5,
133.3, 129.3,128.5, 127.6, 125.9, 124.7, 123.0, 123.5, 66.0, 64.2,
60.4, 49.8, 29.6, 14.3; MS (EI) m/z 325.3 (M+). Anal. Calcd for
21.3, 14.3; MS (FAB) m/z 480.2 (MH+). Anal. Calcd for C27H29
-
NO5S: C, 67.62; H, 6.09; N, 2.92; S, 6.69. Found: C, 67.65; H,
5.93; N, 3.04; S, 6.51.
2-Eth yl 4-Meth yl (-)-(2S,4R,5S,SS)-2-Meth yl-5-(2-n a p h -
th yl)-4-(p-tolylsu lfin yl)pyr r olidin e-2,4-dicar boxylate (5d):
yellow needles (ether-hexane), mp 115-116 °C; [R]20 -47 (c
D
0.2, CHCl3); IR (CHCl3) 3438, 1742 cm-1
;
1H NMR δ 8.06-
7.44 (m, 7H, Nph), 7.40 and 7.25 (AA′BB′ system, 4H, Tol),
5.10 (s, 1H, CH-Nph), 4.30 (q, 2H, CH2-O, J ) 7.0), 3.20 (s,
3H, CO2Me), 2.72 (d, 1H, J ) 14, CH), 2.46 (d, 1H, J ) 14,
CH), 2.37 (s, 3H, CH3-Tol), 1.67 (s, 3H, CH3), 1.42 (t, 3H,
CH3-CH2, J ) 7.0 Hz); 13C NMR δ 177.6, 168.5, 142.5, 137.5,
136.8, 133.9, 133.4, 130.4, 128.2, 127.5, 127.2, 126.4, 126.1,
125.9, 125.2, 125.0, 81.5, 68.7, 63.8, 61.9, 51.6, 36.1, 30.12, 21.3,
14.1; MS (FAB) m/z 480.2 (MH+). Anal. Calcd for C27H29
-
NO5S: C, 67.62; H, 6.09; N, 2.92; S, 6.69. Found: C, 67.58; H,
6.12; N, 3.11; S, 6.80.
Desu lfin yla tion of P r od u cts 4 or 5 (6 or 7). A solution
of 4 or 5 in toluene was refluxed for the time indicated in Table
2. The solvent was evaporated in vacuo, and the residue was
purified by column chromatography (ethyl acetate-hexane,
1:5) to give 6 or 7.
C
19H19NO4: C, 70.40; H, 5.89; N, 4.31. Found: C, 70.51; H,
5.82; N, 4.51.
2-Eth yl 4-Meth yl (-)-(2S,5S)-2-Meth yl-5-(2-n a p h th yl)-
2,5-d ih yd r o-1H-p yr r ole-2,4-d ica r boxyla te (7d ): yellow oil;
Dim eth yl (-)-(2S,5R)-5-P h en yl-2,5-dih ydr o-1H-pyr r ole-
[R]20 -25 (c 0.2, CHCl3) (ee g 99%, HPLC); IR (CHCl3) 3451,
D
2,4-d ica r boxyla te (6a ): yellow oil; [R]20D -12 (c 0.2, CHCl3);
1762 cm-1; 1H NMR δ 7.82-7.36 (m, 11 H, Nph), 6.96 (d, 1H,
J ) 2.4, CHdC), 5.43 (d, 1H, J ) 2.4, CH-Nph), 4.26 (q, 2H,
J ) 7.0, CH2-O), 3.67 (s, 3H, CO2Me), 1.58 (s, 3H, CH3), 1.33
(t, 3H, J ) 7.0, CH3-CH2); 13C NMR δ 180.0, 169.0, 142.7,
140.2, 137.7, 133.3, 133.1, 128.1, 127.6, 127.4, 126.5, 125.9,
125.6 125.3, 65.0, 63.6, 61.5, 49.8, 29.6, 14.3; MS (EI) m/z 339.3
(M+). Anal. Calcd for C20H21NO4: C, 70.78; H, 6.24; N, 4.13.
Found: C, 70.81; H, 6.26; N, 4.22.
IR (CHCl3) 3482, 1751 cm-1 1H NMR δ 7.58-7.34 (m, 5 H,
;
Ph), 6.78 (dd, 1H, J ) 2.2, J ) 1.7, CHdC), 6.05 (dd, 1H, J )
5, J ) 1.7, CH-Ph), 5.5 (dd, 1H, CH, J ) 5, J ) 2.2), 3.67 (s,
3H, CO2Me), 3.56 (s, 3H, CO2Me); 13C NMR δ 177.3, 165.2,
137.2, 128.3, 128.1, 126.8, 125.2, 124.5, 65.0, 63.6, 55.5; MS
(EI) m/z 261.1 (M+). Anal. Calcd for C14H15NO4: C, 64.36; H,
5.79; N, 5.36. Found: C, 64.29; H, 5.85; N, 5.34.
Dim eth yl (-)-(2S,5R)-5-(2-Na p h th yl)-2,5-d ih yd r o-1H-
p yr r ole-2,4-d ica r boxyla te (6b): yellow oil; [R]20D -10 (c 0.2,
CHCl3); IR (CHCl3) 3550, 1742 cm-1; 1H NMR δ 7.55-7.36 (m,
11 H, Nph), 6.75 (dd, 1H, J ) 2.2, J ) 1.7, CHdC), 6.09 (dd,
1H, J ) 5.0, J ) 1.7, CH-Nph), 5.60 (dd, 1H, CH, J ) 5, J )
2.2), 3.71 (s, 3H, CO2Me), 3.57 (s, 3H, CO2Me); 13C NMR δ
179.2, 170.4, 135.1, 133.4, 131.7, 131.5, 127.9, 127.4, 127.0,
126.1, 125.5, 124.2, 129.9, 125.1, 64.9, 63.4, 61.1; MS (EI) m/z
311.2 (M+). Anal. Calcd for C18H17NO4: C, 69.44; H, 5.50; N,
4.50. Found: C, 69.50; H, 5.59; N, 4.53.
Dim et h yl 5-(2-P h en yl)-1H -p yr r ole-2,4-d ica r b oxyla t e
(8a ): yellow oil; IR (CHCl3) 3512, 1721 cm-1; 1H NMR δ 9.35
(s, 1H, NH), 8.10 (s, 1H, CH-Ar), 7.92-7.40 (m, 5H, Ph), 3.90
(s, 3H, CO2Me), 3.78 (s, 3H, CO2Me); 13C NMR δ 171.3, 159.9,
135.5, 129, 128.5, 127.2, 123, 122, 115, 110, 61.2, 55; MS (EI)
m/z 259.3 (M+). Anal. Calcd for C14H13NO4: C, 64.86; H, 5.05;
N, 5.40. Found: C, 64.52; H, 4.87; N, 5.28.
Dim eth yl 5-(2-Na p h th yl)-1H-p yr r ole-2,4-d ica r boxyla te
(8b): yellow oil; IR (CHCl3) 3542, 1734 cm-1; 1H NMR δ 9.54
(s, 1H, NH), 8.36 (s, 1H, CH-Ar), 8.14-7.20 (m, 7H, Nph),
3.84 (s, 3H, CO2Me), 3.77 (s, 3H, CO2Me); 13C NMR δ 178.3,
157.2, 134.1, 133.9, 133.6, 128.5, 128.0, 126.5, 125.9, 124.4,
125.0, 123.4, 116.4, 112.1, 61.3, 57.2; MS (EI) m/z 309.3 (M+).
Anal. Calcd for C18H15NO4: C, 69.89; H, 4.89; N, 4.53. Found:
C, 70.15; H, 4.75; N, 4.59.
Dim et h yl (-)-(2S,5R)-2-Met h yl-5-(2-n a p h t h yl)-2,5-d i-
h yd r o-1H-p yr r ole-2,4-d ica r boxyla te (6c): yellow needles
(ether-hexane), mp 120-122 °C; [R]20D -31 (c 0.2, CHCl3); IR
(CHCl3) 3462, 1742 cm-1; 1H NMR δ 7.85-7.36 (m, 11 H, Nph),
6.85 (d, 1H, J ) 2.4, CHdC), 5.54 (d, 1H, J ) 2.4, CH-Nph),
3.79 (s, 3H, CO2Me), 3.57 (s, 3H, CO2Me), 1.68 (s, 3H, CH3);
13C NMR δ 179.5, 163.5, 142.3, 140.0, 137.6, 133.3, 133.0,
128.3, 127.9, 127.6, 126.7, 125.9, 125.8, 125.3,129.3, 72.0, 68.0,
Ack n ow led gm en t. We thank the Direccio´n General
de Investigacio´n Cient´ıfica y Te´cnica (DGICYT) for
financial support (Grant No. BQU2000-0246).
52.8, 51.6, 26.7; MS (EI) m/z 325.2 (M+). Anal. Calcd for C19H19
-
NO4: C, 70.40; H, 5.89; N, 4.31. Found: C, 70.48; H, 5.85; N,
4.45.
2-Eth yl 4-Meth yl (-)-(2S,5R)-2-Meth yl-5-(2-n a p h th yl)-
2,5-d ih yd r o-1H-p yr r ole-2,4-d ica r boxyla te (6d ): yellow oil;
[R]20D -21 (c 0.2, CHCl3); IR (CHCl3) 3452, 1734 cm-1; 1H NMR
δ 7.82-7.36 (m, 11 H, Nph), 6.84 (d, 1H, J ) 2.4, CHdC), 5.53
Su p p or tin g In for m a tion Ava ila ble: X-ray diagrams and
tables of data for compounds 4d and 5c. This material is
J O010797S