[3+3] Cycloaddition Strategy to Functionalized Piperidines
ES): 292 (MH+, 100%), 250 (38%). Anal. Calcd for C16H21
NO2S: C, 65.95; H, 7.26; N, 4.81. Found: C, 65.71; H, 7.44;
N, 4.77.
-
34 was isolated as a white solid, mp 185-187 °C. 1H NMR
(250 MHz, CDCl3): δ 1.55 (2H, t, J ) 6.5 Hz), 1.80-1.91 (2H,
m), 2.21 (2H, t, J ) 6.5 Hz), 2.29-2.39 (2H, m), 2.42 (3H, s),
2.46 (3H, s), 2.60-2.73 (2H, m), 3.37 (2H, dt, J ) 12.0, 4.5
Hz), 4.12 (2H, s), 4.80 (1H, br), 4.89 (1H, br), 7.23 (2H, d, J )
8.0 Hz), 7.33 (2H, d, J ) 8.0 Hz), 7.62 (4H, d, J ) 8.0 Hz). 13C
NMR (62.9 MHz, CDCl3): δ 21.5, 21.6, 27.3, 31.6, 33.1, 42.5,
48.6, 58.9, 111.1, 127.1, 127.7, 129.6, 129.7, 133.1, 140.2, 140.9,
143.1, 143.6. FTIR (CH2Cl2): 2925 (m), 2854 (m), 1596 (w),
1456 (w), 1330 (m), 1166 (s), 1091 (m) cm-1. m/z (FAB): 475
(MH+, 12%), 155 (34%). HRMS (FAB) calcd for C24H31N2O4S2
475.1725, found 475.1746.
3-Meth ylen e-1-(tolu en e-4-su lfon yl)-octa h yd r o-[1]p yr i-
d in e (38). Following the representative procedure, 38 was
isolated as a white solid, mp 127-129 °C. 1H NMR (250 MHz,
CDCl3): δ 0.80-2.25(8H, m), 2.20-2.31 (1H, m), 2.39-2.52
(1H, m), 2.45 (3H, s), 2.87 (1H, d, J ) 12.0 Hz), 4.27 (1H, d, J
) 12.0 Hz), 4.86 (1H, br), 4.96 (1H, br), 7.34 (2H, d, J ) 8.0
Hz), 7.67 (2H, d, J ) 8.0 Hz). 13C NMR (62.9 MHz, CDCl3): δ
20.5, 21.5, 27.4, 38.0, 46.1, 54.7, 64.2, 112.3, 128.0, 129.6, 132.9,
141.1, 143.5. FTIR (CH2Cl2): 2952 (m), 1600 (w), 1494 (w),
1454 (w), 1351 (s), 1168 (s), 1094 (m) cm-1. m/z (EI): 291 (M+,
82%), 262 (65%), 155 (33%), 136 (74%), 91 (100%). HRMS (EI)
calcd for C16H21NO2S (M+) 291.1293, found 291.1295.
3-Met h ylen e-1-(t olu en e-4-su lfon yl)-d eca h yd r oq u in o-
lin e (39). Following the representative procedure, 39 was
isolated as a white solid, mp 92-93 °C. 1H NMR (250 MHz,
CDCl3): δ 0.82-1.01 (1H, m), 1.09-1.77 (8H, m), 2.03-2.20
(1H, m), 2.20-2.31 (1H, m), 2.38 (3H, s), 2.78 (1H, td, J )
10.5, 3.5 Hz), 3.94 (1H, d, J ) 16.0 Hz), 4.10 (1H, d, J ) 16.0
Hz), 4.77 (1H, br), 4.77 (1H, br), 7.25 (2H, d, J ) 8.0 Hz), 7.66
(2H, d, J ) 8.0 Hz). 13C NMR (62.9 MHz, CDCl3): δ 21.5, 25.6,
25.7, 33.0, 33.4, 36.4, 39.5, 49.1, 62.9, 109.8, 127.6, 129.3, 142.3,
143.0. FTIR (CH2Cl2): 3055 (m), 2930 (m), 1737 (w), 1450 (m),
1422 (m), 1339 (m), 1272 (s), 1161 (s), 1091 (m) cm-1. m/z
(EI): 305 (M+, 65%), 262 (98%), 155 (32%), 150 (37%), 91
(100%). Anal. Calcd for C17H23NO2S: C, 66.85; H, 7.59; N, 4.59.
Found: C, 66.86; H, 7.65; N, 4.54.
6-Ben zyl-5-(tolu en e-4-su lfon yl)-1-oxa -5-a za -sp ir o[2.5]-
octa n e (43). A 0.062 M solution of dimethyldioxirane in
acetone (11.77 mL, 0.73 mmol, 5 equiv) was added to a solution
of 14 (50 mg, 0.15 mmol, 1 equiv) in CH2Cl2 (15 mL) at 0 °C
via syringe. The reaction was stirred at 0 °C for 1 h and then
allowed to warm to room temperature overnight. The reaction
mixture was then concentrated in vacuo and purification by
flash chromatography providing epoxides 43a (35 mg, 67%)
and 43b (12 mg, 24%) as colorless oils.
(R )-2-I s o p r o p y l-1-(4-m e t h o x y -b e n ze n e s u lfo n y l)-5-
m eth ylen e-p ip er id in e (22). Following the representative
procedure, 22 was isolated as a white solid, mp 115-117 °C.
1
[R]25 -43.33 (c 0.60, CH2Cl2). H NMR (250 MHz, CDCl3): δ
D
0.87 (3H, d, J ) 6.5 Hz), 0.96 (3H, d, J ) 6.5 Hz), 1.05-1.26
(1H, m), 1.55-1.74 (1H, m), 1.82-2.24 (3H, m), 3.35-3.49 (1H,
m), 3.58 (1H, d, J ) 16.0), 3.80 (3H, s), 4.22 (1H, d, J ) 16.0),
4.56 (1H, br), 4.66 (1H, br), 6.84 (2H, d, J ) 9.0 Hz), 7.67 (2H,
d, J ) 9.0 Hz). 13C NMR (100.6 MHz, CDCl3): δ 19.6, 20.1,
25.0, 26.7, 27.3, 47.0, 55.5, 59.1, 110.2, 113.8, 129.4, 133.0,
141.2, 162.4. FTIR (CH2Cl2): 3052 (w), 2929 (w), 1598 (w), 1499
(w), 1421 (w), 1336 (w), 1260 (s), 1158 (w), 1094 (w) cm-1. m/z
(FAB): 310 (MH+), 266 (60%), 171 (100%), 138 (25%), 123
(61%). Anal. Calcd for C16H23NO3S: C, 62.11; H, 7.49; N, 4.53.
Found: C, 61.84; H, 7.66; N, 4.33.
(R)-2-P r op yl-5-m eth ylen e-1-(4-m eth oxy-ben zen esu lfo-
n yl)-p ip er id in e (24). Following the representative procedure,
24 was isolated as a white solid, mp 112-113 °C. [R]25 39.52
D
1
(c 0.99, CH2Cl2). H NMR (250 MHz, CDCl3): δ 0.94 (3H, t, J
) 7.5 Hz), 1.19-1.52 (5H, m), 1.62-1.76 (1H, m), 1.97 (1H,
dt, J ) 14.0, 4.0 Hz), 2.05-2.26 (1H, m), 3.68 (1H, d, J ) 15.5
Hz), 3.81-3.99 (1H, m), 3.86 (3H, s), 4.20 (1H, d, J ) 15.5
Hz), 4.66 (1H, br), 4.75 (1H, br), 6.93 (2H, d, J ) 9.0 Hz), 7.73
(d, 2H, J ) 9.0 Hz). 13C NMR (62.9 MHz, CDCl3): δ 13.9, 19.5,
27.3, 28.0, 32.3, 46.5, 52.4, 55.5, 110.3, 113.9, 129.4, 132.9,
141.3, 162.4. FTIR (CH2Cl2): 3077 (w), 2960 (w), 2874 (w), 1598
(m), 1498 (m), 1338 (m), 1265 (s), 1157 (s), 1094 (m) cm-1. m/z
(EI): 309 (M+, 4%), 266 (100%), 171 (39%), 107 (12%). HRMS
(EI) calcd for C16H23NO3S (M+) 309.1399, found 309.1388.
7-Met h ylen e-5-(t olu en e-4-su lfon yl)-5-a za -sp ir o[3.5]-
n on a n e (31). Following the representative procedure, 31 was
isolated as a white solid, mp 109-110 °C. 1H NMR (250 MHz,
CDCl3): δ 1.55-1.72 (2H, m), 1.69 (2H, t, J ) 6.5 Hz), 1.90-
2.03 (2H, m), 2.27 (2H, t, J ) 6.5 Hz), 2.40 (3H, s), 2.44 (2H,
ddd, J ) 20.5, 10.0, 3.0 Hz), 3.90 (2H, s), 4.75(1H, br), 4.88
(1H, br), 7.23 (2H, d, J ) 8.5 Hz), 7.68 (2H, d, J ) 8.5 Hz). 13
C
NMR (62.9 MHz, CDCl3): δ 14.6, 21.5, 29.2, 31.6, 33.6, 49.5,
60.3, 110.8, 127.3, 129.4, 140.2, 141.1, 142.7. FTIR (CH2Cl2):
2940 (m), 1598 (w), 1443 (w), 1337 (s), 1156 (s), 1091 (m) cm-1
.
m/z (EI): 291 (M+, 4%), 198 (91%), 155 (5%), 136 (17%). Anal.
Calcd for C16H21NO2S: C, 65.95; H, 7.26; N, 4.81. Found: C,
65.90; H, 7.42; N, 4.82.
8-Met h ylen e-6-(t olu en e-4-su lfon yl)-6-a za -sp ir o[4.5]-
d eca n e (32). Following the representative procedure, 32 was
isolated as a white solid, mp 95-97 °C. 1H NMR (250 MHz,
CDCl3): δ 1.43-1.87 (8H, m), 1.94-2.20 (2H, m), 2.34 (2H, t,
J ) 6.5 Hz), 2.41 (3H, s, ArCH3), 4.19 (2H, s, C7-H), 4.83 (1H,
br, CdCHH), 4.94 (1H, br, CdCHH), 7.24 (2H, d, J ) 8.0 Hz,
ArH), 7.70 (2H, d, J ) 8.0 Hz, ArH). 13C NMR (62.9 MHz,
CDCl3): δ 21.5, 22.6, 29.4, 34.7, 36.0, 51.2, 68.0, 110.6, 127.2,
129.3, 140.7, 142.1, 142.5. FTIR (CH2Cl2): 2951 (m), 1598 (w),
1450 (w), 1328 (s), 1156 (s), 1091 (s) cm-1. m/z (EI): 305 (M+,
(2R,6S)-6-Ben zyl-5-(t olu en e-4-su lfon yl)-1-oxa -5-a za -
sp ir o[2.5]octa n e (43a ): [R]25 -31.79 (c 0.98, CH2Cl2). 1H
D
NMR (250 MHz, CDCl3): δ 1.26-1.38 (1H, m), 1.67-1.92 (2H,
m), 2.23 (1H, td, J ) 13.0, 5.0 Hz), 2.43 (3H, s), 2.63 (1H, dd,
J ) 4.5, 1.5 Hz), 2.74-2.81 (1H, m), 2.74-2.79 (2H, m), 2.82-
2.96 (2H, m), 3.33 (1H, d, J ) 14.0 Hz), 3.49 (1H, app dd, J )
14.0, 1.5 Hz), 4.30-4.41 (1H, m), 7.16 (2H, d, J ) 8.0 Hz),
7.21-7.32 (5H, m), 7.56 (2H, d, J ) 8.0 Hz). 13C NMR (62.9
MHz, CDCl3): δ 21.5, 26.4, 26.5, 35.7, 45.8, 53.7, 55.7, 118.8,
126.6, 127.1, 128.7, 129.1, 129.7, 137.4, 137.9, 143.3. FTIR
(CH2Cl2): 3024 (w), 2948 (w), 2862 (w), 1599 (w), 1495 (w),
1453 (w), 1338 (m), 1158 (s), 1095 (m), 966 (m) cm-1. m/z (TOF
ES): 358 (100%, MH+). HRMS (TOF ES) calcd for C20H24NO3S
(MH+) 358.1477, found 358.1480.
1%), 198 (79%), 155 (100%), 150 (58%). HRMS calcd for C17H23
-
NO2SNa (MNa+) 328.1336, found 328.1341.
3-Met h ylen e-1-(t olu en e-4-su lfon yl)-1-a za -sp ir o[5.5]-
u n d eca n e (33). Following the representative procedure, 33
was isolated as a white solid, mp 98-100 °C. 1H NMR (250
MHz, CDCl3): δ 1.16-1.39 (2H, m), 1.53-1.65 (4H, m), 1.70-
1.86 (4H, m), 2.02-2.17 (2H, m), 2.25 (2H, t, J ) 6.0 Hz), 2.41
(3H, s), 4.20 (2H, s), 4.81 (1H, br), 4.89 (1H, br), 7.24 (2H, d,
J ) 8.0 Hz), 7.69 (2H, d, J ) 8.0 Hz). 13C NMR (62.9 MHz,
CDCl3): δ 21.5, 22.8, 25.2, 27.2, 31.2, 33.5, 48.2, 62.2, 109.7,
126.8, 129.3, 141.4, 142.3, 142.8. FTIR (CH2Cl2): 2933 (m),
1599 (w), 1452 (w), 1317 (m), 1152 (s), 1091 (m) cm-1. m/z
(CI): 320 (MH+, 9%), 199 (21%), 164 (25%), 149 (100%). Anal.
Calcd for C18H25NO2S: C, 67.67; H, 7.89; N, 4.38. Found: C,
67.80; H, 7.99; N, 4.42.
(2S,6S)-6-Be n zyl-5-(t olu e n e -4-su lfon yl)-1-oxa -5-a za -
sp ir o[2.5]octa n e (43b): [R]25D -2.55 (c 0.98, CH2Cl2). 1H NMR
(250 MHz, CDCl3): δ 1.04-1.17 (1H, m), 1.36-1.60 (2H, m),
2.25 (1H, td, J ) 13.5, 5.0 Hz), 2.38 (3H, s), 2.67 (1H, d, J )
4.5 Hz), 2.75 (1H, d, J ) 4.5 Hz), 2.98 (2H, d, J ) 8.0 Hz),
3.48 (1H, d, J ) 14.5 Hz), 3.73 (1H, d, J ) 14.5 Hz), 4.06-
4.19 (1H, m), 7.14-7.34 (7H, m), 7.78 (2H, d, J ) 8.0 Hz). 13C
NMR (62.9 MHz, CDCl3): δ 21.6, 22.8, 25.4, 36.1, 47.1, 51.7,
53.7, 55.3, 126.7, 127.5, 128.7, 129.2, 129.5, 137.7, 138.1, 143.1.
FTIR (CH2Cl2): 3028 (w), 2951 (w), 2862 (w), 1599 (w), 1496
(w), 1454 (w), 1335 (m), 1159 (s), 1097 (m), 964 (m) cm-1. m/z
3-Meth ylen e-1,9-bis(tolu en e-4-su lfon yl)-1,9-diaza-spir o-
[5.5]u n d eca n e (34). Following the representative procedure,
J . Org. Chem, Vol. 68, No. 11, 2003 4291