H. Saitoh et al. / Tetrahedron 68 (2012) 2481e2495
2493
1H NMR
d
1.53e1.61 (m, 3H), 1.74 (ddd, J¼4.4, 11.2, 14.0 Hz, 1H),
AcOEt); IR (KBr) 2917, 2234 (CN), 1610, 1513, 1255, 1098, 1085, 1057,
1031, 952, 843 cmꢀ1; 1H NMR
1.85e1.96 (m, 2H), 2.31 (ddd, J¼4.3, 11.2, 14.6 Hz, 1H), 2.43 (s, 3H),
2.67e2.70 (m, 1H), 3.87e3.95 (m, 4H), 4.53 (s, 1H), 4.61 (s, 1H),
7.33e7.46 (m, 9H); Anal. Calcd for C24H26ClNO3S: C, 64.92; H, 5.90;
Cl, 7.99; N, 3.15; S, 7.22, found: C, 64.81; H, 5.87; Cl, 7.91; N, 3.14; S,
7.15.
d
1.50e1.64 (m, 3H), 1.73 (ddd, J¼4.4,
11.2, 14.0 Hz, 1H), 1.82e1.96 (m, 2H), 2.28 (ddd, J¼4.2, 11.0, 14.4 Hz,
1H), 2.43 (s, 3H), 2.60e2.70 (m, 1H), 3.82 (s, 3H), 3.87e3.96 (m, 4H),
4.52 (s, 1H), 4.56 (s, 1H), 6.90 (d, J¼8.8 Hz, 2H), 7.34 (d, J¼8.1 Hz,
2H), 7.35 (d, J¼8.8 Hz, 2H), 7.46 (d, J¼8.1 Hz, 2H); Anal. Calcd for
C25H28ClNO4S: C, 63.35; H, 5.95; Cl, 7.48; N, 2.95; S, 6.76, found: C,
62.94; H, 5.89; Cl, 7.40; N, 2.97; S, 6.72.
3.1.37. (1R*,2R*)-2-Phenyl-7,10-dioxadispiro[2.2.4.2]dodecane-1-
carbonitrile (43). Colorless oil; IR (neat) 2952, 2886, 2232 (CN),
1499, 1447, 1138, 1092, 1035, 921, 739, 702 cmꢀ1
;
1H NMR
3.1.43. (2R*)-2-{8-[(S*)-Chloro((RS*)-p-tolylsulfinyl)methyl]-1,4-
dioxaspiro[4.5]decan-8-yl}-2-(4-fluorophenyl)acetonitrile
(46cL). Yield (60%); colorless crystal; mp 160.5e161.0 ꢁC (hexane/
AcOEt); IR (KBr) 2935, 2237 (CN), 1600, 1509, 1240, 1158, 1079, 933,
d
1.31e1.41 (m, 2H), 1.69 (d, J¼8.6 Hz, 1H), 1.71e1.88 (m, 5H), 2.16
(ddd, J¼4.6, 11.2, 13.0 Hz, 1H), 2.47 (d, J¼8.6 Hz, 1H), 3.94e4.02 (m,
4H), 7.24e7.29 (m, 1H), 7.32e7.39 (m, 4H); MS (EI) m/z (%) 269 (Mþ,
45), 241 (12), 140 (25), 125 (16), 115 (10), 99 (84), 86 (100); HRMS
(EI) calcd for C17H19NO2: 269.1416, found: 269.1415.
841, 814 cmꢀ1; 1H NMR
d 1.54e2.01 (m, 6H), 2.31e2.41 (m,1H), 2.44
(s, 3H), 2.60e2.69 (m, 1H), 3.86e3.97 (m, 4H), 4.64 (s, 1H), 4.68 (br
s, 1H), 7.13 (t, J¼8.6 Hz, 2H), 7.33 (d, J¼8.2 Hz, 2H), 7.47 (dd, J¼5.1,
8.6 Hz, 2H), 7.62 (d, J¼8.2 Hz, 2H); Anal. Calcd for C24H25ClFNO3S: C,
62.40; H, 5.45; Cl, 7.67; F, 4.11; N, 3.03; S, 6.94, found: C, 62.24; H,
5.35; Cl, 7.67; F, 4.15; N, 3.00; S, 6.86.
3.1.38. (1R*,2S*)-2-Phenyl-7,10-dioxadispiro[2.2.4.2]dodecane-1-
carbonitrile (44). Colorless crystal; mp 114.0e114.5 ꢁC (hexane/
AcOEt); IR (KBr) 2952, 2231 (CN), 1441, 1262, 1126, 1088, 1034, 907,
705 cmꢀ1
;
1H NMR
d
1.17 (td, J¼6.0, 12.6 Hz, 1H), 1.43 (td, J¼6.8,
13.7 Hz, 1H), 1.49e1.56 (m, 2H), 1.73 (d, J¼5.5 Hz, 1H), 1.82e1.94 (m,
3H), 1.99e2.05 (m, 1H), 2.62 (d, J¼5.5 Hz, 1H), 3.89e3.99 (m, 4H),
7.16 (d, J¼7.4 Hz, 2H), 7.24e7.34 (m, 3H); MS (EI) m/z (%) 269 (Mþ,
42), 140 (27), 125 (18), 99 (78), 86 (100); HRMS (EI) calcd for
C17H19NO2: 269.1416, found: 269.1415.
3.1.44. (2R*)-2-{8-[(R*)-Chloro((RS*)-p-tolylsulfinyl)methyl]-1,4-
dioxaspiro[4.5]decan-8-yl}-2-(4-fluorophenyl)acetonitrile
(46cP). Yield (20%); colorless crystal; mp 164.0e164.5 ꢁC (hexane/
AcOEt); IR (KBr) 2967, 2239 (CN), 1606, 1509, 1239, 1158, 1104,
1066, 1034, 942, 885, 832, 813 cmꢀ1; 1H NMR
d 1.43e1.58 (m, 3H),
1.71 (ddd, J¼4.3, 12.1, 14.1 Hz, 1H), 1.78e1.99 (m, 2H), 2.36 (ddd,
J¼4.4, 12.1, 14.5 Hz, 1H), 2.44 (s, 3H), 2.64e2.76 (m, 1H), 3.86e3.98
(m, 4H), 4.58 (s, 1H), 4.63 (s, 1H), 7.07 (t, J¼8.6 Hz, 2H), 7.35 (d,
J¼8.3 Hz, 2H), 7.44 (dd, J¼5.2, 8.6 Hz, 2H), 7.48 (d, J¼8.3 Hz, 2H);
Anal. Calcd for C24H25ClFNO3S: C, 62.40; H, 5.45; Cl, 7.67; F, 4.11; N,
3.03; S, 6.94, found: C, 62.09; H, 5.41; Cl, 7.59; F, 4.16; N, 3.01; S,
6.86.
3.1.39. (2R*)-2-{8-[(S*)-Chloro((RS*)-p-tolylsulfinyl)methyl]-1,4-
dioxaspiro[4.5]decan-8-yl}-2-(p-tolyl)acetonitrile
(46aL). Yield
(79%); colorless crystal; mp 162.5e163.0 ꢁC (hexane/AcOEt); IR
(KBr) 2934, 2868, 2231 (CN), 1514, 1455, 1375, 1155, 1105, 1081,
1058, 1036, 933, 813 cmꢀ1; 1H NMR
d 1.62e1.70 (m, 1H), 1.72e1.80
(m, 2H), 1.85e2.02 (m, 3H), 2.30e2.50 (m, 1H), 2.38 (s, 3H), 2.44 (s,
3H), 2.56e2.66 (m, 1H), 3.85e3.97 (m, 4H), 4.59 (s, 1H), 4.64 (br s,
1H), 7.22 (d, J¼8.0 Hz, 2H), 7.32 (d, J¼7.9 Hz, 2H), 7.36 (d, J¼7.9 Hz,
2H), 7.61 (d, J¼8.0 Hz, 2H); Anal. Calcd for C25H28ClNO3S: C, 65.56;
H, 6.16; Cl, 7.74; N, 3.06; S, 7.00, found: C, 65.44; H, 6.08; Cl, 7.85; N,
3.05; S, 6.92.
3.1.45. (2R*)-2-{8-[(S*)-Chloro((RS*)-p-tolylsulfinyl)methyl]-1,4-
dioxaspiro[4.5]decan-8-yl}-2-(4-chlorophenyl)acetonitrile (46dL). 4-
Chloroacetonitrile (5 equiv) and LDA (5 equiv) were used. Yield
(36%); colorless crystal; mp 122.0e122.5 ꢁC (hexane/AcOEt); IR
(KBr) 2938, 2233 (CN), 1742, 1596, 1489, 1375, 1242, 1155, 1095,
3.1.40. (2R*)-2-{8-[(R*)-Chloro((RS*)-p-tolylsulfinyl)methyl]-1,4-
1056, 810 cmꢀ1 1H NMR
; d 1.62e2.00 (m, 6H), 2.32e2.42 (m, 1H),
dioxaspiro[4.5]decan-8-yl}-2-(p-tolyl)acetonitrile
(46aP). Yield
2.44 (s, 3H), 2.55e2.71 (m, 1H), 3.85e3.96 (m, 4H), 4.65 (s, 1H), 4.68
(br s,1H), 7.34 (d, J¼8.1 Hz, 2H), 7.38e7.46 (m, 4H), 7.63 (d, J¼8.1 Hz,
2H); MS (FABþ) m/z (%) 478 ([MþH]þ, 60), 338 (12), 246 (23), 154
(71), 93 (100); HRMS (FABþ) calcd for C24H26Cl2NO3S: 478.1010,
found: 478.1011.
(20%); colorless crystal; mp 174.5e175.0 ꢁC (hexane/AcOEt); IR
(KBr) 2953, 2936, 2884, 2234 (CN), 1453, 1161, 1086, 1058, 936,
811 cmꢀ1
;
1H NMR
d
1.50e1.63 (m, 3H), 1.74 (ddd, J¼4.2, 10.9,
14.1 Hz, 1H), 1.84e1.96 (m, 2H), 2.27 (ddd, J¼4.1, 11.2, 14.5 Hz, 1H),
2.37 (s, 3H), 2.43 (s, 3H), 2.62e2.70 (m, 1H), 3.85e3.98 (m, 4H), 4.52
(s, 1H), 4.57 (s, 1H), 7.19 (d, J¼8.0 Hz, 2H), 7.31 (d, J¼8.0 Hz, 2H), 7.34
(d, J¼8.0 Hz, 2H), 7.46 (d, J¼8.0 Hz, 2H); Anal. Calcd for
C25H28ClNO3S: C, 65.56; H, 6.16; Cl, 7.74; N, 3.06; S, 7.00, found: C,
65.20; H, 6.14; Cl, 7.82; N, 3.02; S, 6.86.
3.1.46. (2R*)-2-{8-[(R*)-Chloro((RS*)-p-tolylsulfinyl)methyl]-1,4-
dioxaspiro[4.5]decan-8-yl}-2-(4-chlorophenyl)acetonitrile
(46dP). Yield (12%); colorless crystal; mp 126.5e127.0 ꢁC (hexane/
AcOEt); IR (KBr) 2945, 2242 (CN), 1592, 1490, 1155, 1092, 1016, 836,
806 cmꢀ1
;
1H NMR
d
1.44e1.60 (m, 3H), 1.71 (ddd, J¼4.3, 12.3,
3.1.41. (2R*)-2-{8-[(S*)-Chloro((RS*)-p-tolylsulfinyl)methyl]-1,4-
dioxaspiro[4.5]decan-8-yl}-2-(4-methoxyphenyl)acetonitrile
(46bL). Yield (64%); colorless crystal; mp 151.0e151.5 ꢁC (hexane/
AcOEt); IR (KBr) 2942, 2232 (CN), 1734, 1611, 1512, 1257, 1180, 1103,
14.1 Hz, 1H), 1.77e1.86 (m, 1H), 1.87e1.98 (m, 1H), 2.37 (ddd, J¼4.4,
12.3, 14.6 Hz, 1H), 2.44 (s, 3H), 2.67e2.78 (m, 1H), 3.86e3.98 (m,
4H), 4.59 (s, 1H), 4.63 (s, 1H), 7.32e7.43 (m, 6H), 7.48 (d, J¼8.2 Hz,
2H); MS (FABþ) m/z (%) 478 ([MþH]þ, 100), 246 (11), 185 (33), 154
(36), 93 (50); HRMS (FABþ) calcd for C24H26Cl2NO3S: 478.1010,
found: 478.1010.
1054, 932, 837, 815 cmꢀ1; 1H NMR
d
1.66 (ddd, J¼3.7, 11.2, 14.9 Hz,
1H), 1.72e1.79 (m, 2H), 1.90 (dt, J¼3.8, 12.9 Hz, 1H), 1.98 (ddd, J¼4.0,
12.0, 13.7 Hz, 2H), 2.30e2.40 (m, 1H), 2.43 (s, 3H), 2.60e2.66 (m,
1H), 3.84 (s, 3H), 3.89e3.95 (m, 4H), 4.56 (s, 1H), 4.65 (br s,1H), 6.94
(d, J¼8.7 Hz, 2H), 7.31 (d, J¼8.2 Hz, 2H), 7.39 (d, J¼8.7 Hz, 2H), 7.61
(d, J¼8.2 Hz, 2H); Anal. Calcd for C25H28ClNO4S: C, 63.35; H, 5.95; Cl,
7.48; N, 2.95; S, 6.76, found: C, 62.82; H, 5.87; Cl, 7.34; N, 2.96; S,
6.67.
3.1.47. (2R*)-2-{8-[(S*)-Chloro((RS*)-p-tolylsulfinyl)methyl]-1,4-
dioxaspiro[4.5]decan-8-yl}-2-(2-naphthyl)acetonitrile
(46eL). (2-
Naphthyl)acetonitrile (5 equiv) and LDA (5 equiv) were used.
Yield (45%); colorless crystal; mp 118.0e118.5 ꢁC (hexane/AcOEt);
IR (KBr) 2939, 2230 (CN), 1598, 1494, 1452, 1375, 1156, 1102, 1056,
814, 743 cmꢀ1; 1H NMR
d 1.63e2.13 (m, 6H), 2.40e2.51 (m,1H), 2.43
3.1.42. (2R*)-2-{8-[(R*)-Chloro((RS*)-p-tolylsulfinyl)methyl]-1,4-
dioxaspiro[4.5]decan-8-yl}-2-(4-methoxyphenyl)acetonitrile
(46bP). Yield (32%); colorless crystal; mp 162.0e162.5 ꢁC (hexane/
(s, 3H), 2.60e2.74 (m,1H), 3.82e3.94 (m, 4H), 4.72 (br s,1H), 4.84 (s,
1H), 7.30 (d, J¼8.1 Hz, 2H), 7.52e7.57 (m, 3H), 7.59 (d, J¼8.1 Hz, 2H),
7.86e7.96 (m, 4H); MS (FABþ) m/z (%) 494 ([MþH]þ, 60), 354 (13),