Reaction of Aziridines with Nitriles and Carbonyls
1
10.7 Hz, 1H), 2.46 (s, 3H), 1.62 (d, J ) 5.4 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) δ 144.3, 136.8, 134.8, 129.9, 128.6, 128.5,
127.7, 126.0, 88.8, 78.7, 53.3, 22.7, 21.6. Anal. Calcd for C17H19-
NO3S: C, 64.33; H, 6.03; N, 4.41. Found: C, 64.54; H, 6.12; N,
4.34.
+51.72 (c 1.5, CHCl3); H NMR (CDCl3, 400 MHz) (NMR for
major diastereomer) δ 7.35 (m, 5H), 5.20 (d, J ) 5.4 Hz, 1H),
4.08 (m, 1H), 3.03 (s, 3H), 2.24 (m, 3H), 1.97 (m, 1H), 1.89 (m,
1H), 1.76 (m, 1H), 1.64 (m, 3H), 1.25 (m, 1H), 0.90 (d, J ) 6.6
Hz, 3H). Anal. Calcd for C16H23NO3S: C, 62.11; H, 7.49; N, 4.53.
Found: C, 62.30; H, 7.36; N, 4.58.
5-(4-Chlorophenyl)-2,2-dimethyl-3-(toluene-4-sulfonyl)oxazo-
lidine (26h): yield 40%; mp 89-91 °C; Rf 0.57 (20% EtOAc in
(2S,3R)-4-Benzenesulfonyl-3-methyl-2-phenyl-1-oxa-4-azaspiro-
[4.5]decane: diastereomeric ratio (27e/28e) 93:7; total yield 97%;
petroleum ether); FT IR (KBr) 1343, 1216, 1155, 1092, 1014 cm-1
;
1H NMR (CDCl3, 400 MHz) δ 7.74 (d, J ) 8.3 Hz, 2H), 7.27 (m,
6H), 5.07 (dd, J ) 9.3, 5.6 Hz, 1H), 3.85 (dd, J ) 8.8, 5.8 Hz,
1H), 3.09 (t, J ) 9.0 Hz, 1H), 2.40 (s, 3H), 1.73 (s, 3H), 1.67 (s,
3H); 13C NMR (CDCl3, 100 MHz) δ 143.5, 137.0, 135.9, 134.3,
129.6 , 128.8 , 127.5, 127.3, 97.4, 75.5, 53.9, 27.5, 26.9, 21.5. Anal.
Calcd for C18H20ClNO3S: C, 59.09; H, 5.51; N, 3.83. Found: C,
59.32; H, 5.55; N, 3.88.
viscous liquid; Rf 0.57 (20% EtOAc in petroleum ether); [R]25
)
D
-1.00 (c 1.5, CHCl3); 1H NMR (CDCl3, 400 MHz) (NMR for major
diastereomer) δ 7.95 (m, 2H), 7.54 (m, 3H), 7.30 (m, 5H), 4.97 (d,
J ) 5.1 Hz, 1H), 4.05 (m, 1H), 2.30 (m, 3H), 1.61 (m, 7H), 0.80
(d, J ) 6.6 Hz, 3H). Anal. Calcd for C21H25NO3S: C, 67.89; H,
6.78; N, 3.77. Found: C, 67.72; H, 6.80; N, 3.75.
General Procedure for the Cleavage of N-Tosyl Bond in
Oxazolidines. For 30a, 30b, 32a, and 32b, the same procedure, as
described above for the detosylation of imidazolines (Scheme 5),
was followed up to the formation of crude detosylated product. To
the crude detosylated product were added a saturated solution of
NaHCO3 (4 mL) and toluene (4 mL). This was followed by the
addition of substituted chloroformate (1.5 mmol), and the reaction
mixture was subsequently stirred for 1 h. The organic layer was
then separated and the aqueous layer extracted with ethyl acetate.
The combined organic layers were then washed with water and
brine, dried over anhydrous Na2SO4, and concentrated to give the
crude product. Purification by column chromatography gave the
desired product.
2-(4-Chlorophenyl)-4-(toluene-4-sulfonyl)-1-oxa-4-azaspiro-
[4.5]decane (26i): yield 75%; mp 132-134 °C; Rf 0.60 (20%
EtOAc in petroleum ether); FT IR (KBr) 1331, 1221, 1152, 1096,
1
1005 cm-1; H NMR (CDCl3, 400 MHz) δ 7.73 (d, J ) 8.3 Hz,
2H), 7.28 (m, 6H), 5.03 (dd, J ) 9.5, 5.9 Hz, 1H), 3.88 (dd, J )
8.8, 5.6 Hz, 1H), 3.07 (t, J ) 9.0 Hz, 1H), 2.42 (s, 3H), 2.33 (td,
J ) 12.2, 4.2 Hz, 1H), 2.22 (td, J ) 13.4, 4.7 Hz, 1H), 1.95 (m,
1H), 1.62 (m, 6H), 1.29 (m, 1H); 13C NMR (CDCl3, 100 MHz) δ
143.3, 137.7, 136.4, 134.1, 129.6, 128.7, 127.5, 127.3, 99.2, 75.2,
53.9, 36.2, 35.4, 24.6, 23.6, 23.4, 21.5; MS (ES+) 429 (M+
+
Na+). Anal. Calcd for C21H24ClNO3S: C, 62.13; H, 5.96; N, 3.45.
Found: C, 62.31; H, 5.86; N, 3.37.
2-(2-Bromophenyl)-4-(toluene-4-sulfonyl)-1-oxa-4-azaspiro-
[4.5]decane (26j): yield 32%; mp 133-135 °C; Rf 0.64 (20%
EtOAc in petroleum ether); FT IR (KBr) 1336, 1208, 1161, 1096,
2-Phenyl-1-oxa-4-azaspiro[4.5]decane-4-carboxylic acid ben-
zyl ester (30a): yield 38%; yellow liquid; Rf 0.35 (5% EtOAc in
petroleum ether); FT IR (neat) 1705, 1409, 1209, 1133, 1070 cm-1
;
1001 cm-1; H NMR (CDCl3, 400 MHz) δ 7.73 (d, J ) 8.1 Hz,
1H NMR (CDCl3, 400 MHz) δ 7.34 (m, 10H), 5.13 (m, 2H), 5.02
(dd, J ) 9.8, 5.8 Hz, 1H), 4.02 (dd, J ) 9.3, 6.1 Hz, 1H), 3.29 (t,
J ) 9.8 Hz, 1H), 2.55 (m, 1H), 2.29 (m, 1H), 1.67 (m, 7H), 1.28
(m, 1H); 13C NMR (CDCl3, 100 MHz) δ 152.0, 138.3, 136.6, 128.5,
128.4, 128.2, 127.9, 127.8, 126.2, 95.5, 75.5, 66.4, 52.8, 34.4, 31.7,
24.6, 23.2 (2C); MS (FAB) 352 (M+ + 1). Anal. Calcd for C22H25-
NO3: C, 75.19; H, 7.17; N, 3.99. Found: C, 75.36; H, 7.12; N,
3.91.
1
2H), 7.52 (t, J ) 8.7 Hz, 2H), 7.31 (m, 3H), 7.16 (td, J ) 7.8, 1.7
Hz, 1H), 5.31 (dd, J ) 9.0, 5.9 Hz, 1H), 4.22 (dd, J ) 8.8, 5.9 Hz,
1H), 2.98 (t, J ) 8.8 Hz, 1H), 2.41 (s, 3H), 2.35 (m, 1H), 2.20 (td,
J ) 13.4, 4.4 Hz, 1H), 1.97 (m, 1H), 1.62 (m, 6H), 1.28 (m, 1H);
13C NMR (CDCl3, 100 MHz) δ 143.2, 137.8, 132.6 (2C), 129.5,
127.7 (2C), 127.2 (2C), 121.6, 100.5, 98.7, 75.0, 52.4, 36.2, 35.3,
24.6, 23.6, 23.6, 21.5. Anal. Calcd for C21H24BrNO3S: C, 56.00;
H, 5.37; N, 3.11. Found: C, 56.22; H, 5.30; N, 3.04.
2-Phenyl-1-oxa-4-azaspiro[4.5]decane-4-carboxylic acid ethyl
ester (30b): yield 30%; yellow liquid; Rf 0.33 (5% EtOAc in
(2S,3R)-3-Methyl-2-phenyl-4-(toluene-4-sulfonyl)-1-oxa-4-
azaspiro[4.5]decane: diastereomeric ratio (27a/28a) 94:6; total
petroleum ether); FT IR (neat) 1707, 1413, 1210, 1127, 1068 cm-1
;
yield 97%; dense liquid; Rf 0.57 (20% EtOAc in petroleum ether);
1H NMR (CDCl3, 400 MHz) δ 7.30 (m, 5H), 5.03 (dd, J ) 9.8,
5.8 Hz, 1H), 4.12 (br, 2H), 3.27 (br, 1H), 3.32 (m, 1H), 2.52 (m,
1H), 2.29 (m, 1H), 1.72 (m, 8H), 1.28 (br, 3H); 13C NMR (CDCl3,
100 MHz) δ 152.4, 138.5, 128.5, 128.2, 126.2, 95.3, 75.5, 60.6,
52.8, 34.4, 31.8, 24.7, 23.2 (2C), 14.6; MS (ES+) 290 (M+ + 1).
Anal. Calcd for C17H23NO3: C, 70.56; H, 8.01; N, 4.84. Found:
C, 70.78; H, 7.95; N, 4.91.
1
[R]25 ) -11.00 (c 1.5, CHCl3); H NMR (CDCl3, 400 MHz)
D
(NMR for major diastereomer) δ 7.82 (d, J ) 8.0 Hz, 2H), 7.28
(m, 7H), 4.96 (d, J ) 5.4 Hz, 1H), 4.04 (m, 1H), 2.43 (s, 3H), 2.33
(m, 2H), 1.75 (m, 6H), 1.32 (m, 2H), 0.80 (d, J ) 6.6 Hz, 3H).
Anal. Calcd for C22H27NO3S: C, 68.54; H, 7.06; N, 3.63. Found:
C, 68.72; H, 6.90; N, 3.69.
(2S,3R)-4-(4-Bromobenzenesulfonyl)-3-methyl-2-phenyl-1-
oxa-4-azaspiro[4.5]decane: diastereomeric ratio (27b/28b) 98:2;
total yield 99%; viscous yellow liquid; Rf 0.50 (20% EtOAc in
petroleum ether); [R]25D ) -11.83 (c 1.2, CHCl3); 1H NMR (CDCl3,
400 MHz) (NMR for major diastereomer) δ 7.81 (m, 2H), 7.66
(m, 2H), 7.31 (m, 5H), 4.97 (d, J ) 5.1 Hz, 1H), 4.01 (m, 1H),
2.38 (m, 2H), 2.23 (m, 1H), 1.76 (m, 6H), 1.29 (m, 1H), 0.82 (d,
J ) 6.6 Hz, 3H). Anal. Calcd for C21H24BrNO3S: : C, 56.00; H,
5.37; N, 3.11. Found: C, 56.19; H, 5.31; N, 3.03.
(2S,3R)-4-(4-Fluorobenzenesulfonyl)-3-methyl-2-phenyl-1-
oxa-4-azaspiro[4.5]decane: diastereomeric ratio (27c/28c) 95:5;
total yield 98%; viscous yellow liquid; Rf 0.61 (20% EtOAc in
petroleum ether); [R]25D ) +0.50 (c 1.7, CHCl3); 1H NMR (CDCl3,
400 MHz) (NMR for major diastereomer) δ 7.95 (m, 2H), 7.30
(m, 5H), 7.17 (m, 2H), 4.98 (d, J ) 5.1 Hz, 1H), 4.00 (m, 1H),
2.30 (m, 3H), 1.74 (m, 6H), 1.34 (m, 1H), 0.81 (br, 3H). Anal.
Calcd for C21H24FNO3S: C, 64.76; H, 6.21; N, 3.60. Found: C,
64.94; H, 6.29; N, 3.55.
Phenyl (2-phenyl-1-oxa-4-azaspiro[4.5]dec-4-yl)methanone
(30c): yield 52%; mp 144-147 °C; Rf 0.20 (10% EtOAc in
1
petroleum ether); FT IR (KBr) 1630, 1417, 1217, 1078 cm-1; H
NMR (CDCl3, 400 MHz) δ 7.45 (m, 2H), 7.34 (m, 8H), 5.03 (dd,
J ) 10.0, 5.6 Hz, 1H), 3.74 (br, 1H), 3.44 (t, J ) 10.0 Hz, 1H),
2.76 (m, 1H), 1.75 (m, 9H); 13C NMR (CDCl3, 100 MHz) δ 167.4,
138.0, 137.7, 129.6, 128.5, 128.3, 128.2, 126.3, 126.1, 97.0, 75.6,
56.3, 34.0, 31.0, 24.5, 23.1, 23.0. Anal. Calcd for C21H23NO2: C,
78.47; H, 7.21; N, 4.36. Found: C, 78.68; H, 7.15; N, 4.31.
3-Methyl-2-phenyl-1-oxa-4-azaspiro[4.5]decane-4-carboxyl-
ic acid benzyl ester (32a): yield 50%; viscous liquid; Rf 0.44 (10%
EtOAc in petroleum ether); [R]25 ) +33.16 (c 1.6, CHCl3); FT
D
1
IR (neat) 1708, 1408, 1206, 1124, 1055 cm-1; H NMR (CDCl3,
400 MHz) δ 7.26 (m, 10H), 5.19 (m, 2H), 4.22 (m, 1H), 2.57 (m,
1H), 2.37 (m, 1H), 1.63 (m, 9H), 0.77 (d, J ) 6.6 Hz, 3H); 13C
NMR (CDCl3, 100 MHz) δ 152.1, 136.8, 128.5, 128.1 (2C), 127.9,
127.8, 127.5, 126.1, 94.6, 77.7, 66.4, 56.3, 35.9, 32.1, 25.7, 23.4,
23.3, 15.9; MS (FAB) 366 (M+ + 1). Anal. Calcd for C23H27NO3:
C, 75.59; H, 7.45; N, 3.83. Found: C, 75.78; H, 7.40; N, 3.88.
3-Methyl-2-phenyl-1-oxa-4-azaspiro[4.5]decane-4-carboxyl-
ic acid ethyl ester (32b): yield 48%; viscous liquid; Rf 0.14 (5%
(2S,3R)-4-Methanesulfonyl-3-methyl-2-phenyl-1-oxa-4-azaspiro-
[4.5]decane: diastereomeric ratio (27d/28d) 94:6; total yield 84%;
dense liquid; Rf 0.39 (20% EtOAc in petroleum ether); [R]25
)
D
J. Org. Chem, Vol. 72, No. 6, 2007 2141