Spiro- and Bicycloannulation of 2-Hydroxy-dihydropyrans
CH(CH3)2], 4.08 (tt, J = 11.6, 4.3 Hz, 1 H, CHCl), 6.91 (d, J =
2.4 Hz, 1 H, CH=C-S), 7.47–7.57 (m, 3 H, Ph), 7.83–7.86 (m, 2 H,
Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.5 (d), 17.5 (d), 20.9
(u), 21.2 (d), 21.4 (d), 26.7 (d), 28.6 (d), 30.0 (d), 33.5 (u), 35.9 (u),
42.1 (u), 44.2 (d), 55.8 (d), 71.6 (d), 76.5 (u), 127.4 (d), 128.8 (d),
NMR (100 MHz, CDCl3): δ = 15.3 (d), 21.6 (d), 21.9 (u), 25.1 (u),
26.5 (u), 29.4 (d), 29.9 (d), 31.9 (u), 32.0 (u), 34.5 (u), 36.1 (u), 41.3
(u), 43.1 (d), 56.7 (d), 74.6 (d), 78.0 (u), 126.7 (d), 128.8 (d), 131.8
(d) ppm. IR (CHCl ): ν = 3012 (w), 2936 (s), 2868 (s), 2800 (w),
˜
3
1590 (m), 1449 (s), 1385 (w), 1236 (s), 1146 (s), 1108 (s), 1079 (s),
1049 (s), 963 (w), 860 (s) cm–1. MS (EI, 70 eV): m/z (%) = 438 (3),
437 (7), 436 (9), 435 [M]+ (15), 401 (27), 349 (23), 400 (100), 382
(11), 358 (21), 357 (21), 356 (49), 321 (22), 301 (14), 299 (14), 286
(14), 285 (27), 284 (29), 283 (15), 265 (16), 255 (10), 250 (22), 249
(14), 245 (14), 237 (36), 201 (12), 185 (16), 181 (12), 173 (17), 169
(11), 156 (13), 147 (12), 145 (13), 143 (13), 139 (14), 131 (23), 129
(12), 125 (36), 117 (19), 115 (11), 109 (14), 107 (18), 105 (26), 95
(16), 93 (16), 91 (42), 81 (26). HRMS (EI): calcd. for
C24H34ClNO2S 435.1998; found 435.2001.
132.1 (d), 141.3 (u), 141.8 (d), 144.5 (u) ppm. IR (in CHCl ): ν =
˜
3
2960 (s), 2874 (s), 2803 (w), 1449 (s), 1386 (m), 1370 (m), 1110 (w),
1082 (w), 1037 (s), 952 (m), 852 (s) cm–1. MS (EI, 70 eV): m/z (%)
= 426 (2), 425 (4), 424 (5), 423 [M]+ (10), 389 (26), 388 (100), 225
(13), 155 (14), 138 (9), 124 (9). HRMS (EI): calcd. for
C23H34ClNO2S 423.1998; found 423.1998.
Chlorinated Compound 21: [α]D = –40.5 (c = 1.00, CH2Cl2); Rf =
1
0.10 (EtOAc/cyclohexane 5:95), H NMR (400 MHz, CDCl3): δ =
0.84 (d, J = 6.9 Hz, 3 H, CH3), 0.85 (d, J = 6.9 Hz, 3 H, CH3),
1.04 (d, J = 6.9 Hz, 3 H, CH3), 1.10 (d, J = 6.9 Hz, 3 H, CH3),
1.63–1.77 {m, 3 H, CH[CH(CH3)2]-COH-CH(CH3)2, CHH-
CHCl}, 1.87–1.96 (m, 2 H, CH2-CH2-CHCl-CHH), 2.04 (tt, J =
14.1, J = 3.2 Hz, 1 H, CHH-CHCl), 2.15 (tt, J = 13.1, J = 3.2 Hz,
1 H, CHCl-CHH), 2.30 (m, J = 9.7, 2.6 Hz, 1 H, C=CH-CH), 2.60
(m, J = 14.1, 4.0 Hz, 2 H, CHH-CH2-CHCl-CH2-CHH), 2.81 (s, 3
H, N-CH3), 3.38 (dd, J = 9.7, 2.3 Hz, 1 H, C=CH-CH-CHO), 4.42
(quint, J = 2.9 Hz, 1 H, CHCl), 6.96 (d, J = 2.4 Hz, 1 H, CH=C-
S), 7.46–7.55 (m, 3 H, Ph), 7.88–7.92 (m, 2 H, Ph) ppm. 13C NMR
(75 MHz, CDCl3): δ = 14.6 (d), 17.5 (d), 21.3 (d), 21.5 (d), 26.3
(d), 26.9 (d), 28.9 (u), 29.0 (d), 29.1 (d), 30.0 (u), 44.4 (d), 58.8 (d),
71.6 (d), 74.4 (u), 127.8 (d), 128.9 (d), 132.2 (d), 141.4 (u), 141.5
Chlorinated Compound 23: Rf = 0.19 (EtOAc/cyclohexane 5:95). 1H
NMR (400 MHz, CDCl3): δ = 0.92 (d, J = 6.9 Hz, 3 H, CH3), 1.07
(d, J = 6.9 Hz, 3 H, CH3), 0.97–1.09 (m, 1 H), 1.30–1.57 (m, 4 H),
1.68 (t, J = 13.6 Hz, 2 H), 1.76–1.96 (m, 7 H), 2.04–2.24 (m, 3 H),
2.29 (tt, J = 13.8, J = 3.6 Hz, 1 H), 2.81 (s, 3 H, N-CH3), 3.04 (dd,
J = 12.9 Hz, 1 H), 3.19 (dd, J = 9.3, 2.0 Hz, 1 H), 3.42 (t, J =
10.8 Hz, 1 H), 3.62 (d, J = 14.2 Hz, 1 H), 4.48 (quint, J = 2.5 Hz,
1 H, CHCl), 7.47–7.56 (m, 3 H, Ph), 7.89–7.94 (m, 2 H, Ph) ppm.
IR (CHCl ): ν = 2933 (s), 2870 (s), 2800 (w), 1726 (w), 1590 (w),
˜
3
1446 (s), 1384 (w), 1266 (m), 1239 (s), 1147 (m), 1106 (m), 1078
(m), 1047 (m), 921 (w), 863 (m) cm–1. MS (EI, 70 eV): m/z (%) =
437 (6), 436 (6), 435 (14), 406 (12), 405 (11), 404 (20), 400 (28), 389
(12), 387 (15), 359 (12), 358 (41), 357 (41), 356 (100), 355 (23), 339
(11), 332 (11), 320 (10), 301 (18), 299 (24), 287 (15), 286 (31), 285
(53), 284 (70), 283 (33), 282 (13), 281 (20), 280 (16), 279 (14), 265
(12), 255 (23), 249 (14), 239 (15), 237 (44), 223 (10), 209 (11), 208
(10), 201 (10), 181 (15), 173 (15), 169 (15), 168 (10), 167 (10), 156
(18), 155 (10), 149 (10), 147 (16), 145 (21), 143 (12), 142 (12), 141
(11), 139 (33), 135 (11), 133 (12), 131 (30), 129 (17), 125 (56), 119
(14), 117 (26), 115 (14), 109 (19), 107 (25), 106 (12), 105 (36), 97
(18), 95 (19). HRMS (EI): calcd. for C24H34ClNO2S 435.1998;
found 435.2019.
(d), 145.8 (u) ppm. IR (CHCl ): ν = 2960 (s), 2877 (s), 2804 (w),
˜
3
1447 (s), 1384 (w), 1246 (s), 1151 (s), 1110 (w), 1083 (w), 1030 (m),
1003 (m), 950 (w), 921 (w), 852 (m) cm–1. MS (EI, 70 eV): m/z (%)
= 426 (4), 425 (12), 424 (11), 423 [M]+ (30), 389 (10), 388 (40), 382
(19), 381 (14), 380 (49), 354 (9), 353 (16), 352 (26), 351 (30), 227
(29), 226 (14), 225 (85), 161 (11), 157 (11), 156 (100), 147 (15), 145
(10), 140 (22), 139 (68), 125 (72), 119 (18), 117 (11), 107 (18), 106
(15), 105 (27), 97 (19), 93 (11), 91 (27), 81 (26), 79 (25), 78 (13),
77 (27). HRMS (EI): calcd. for C23H34ClNO2S 423.1998; found
423.1996.
(8R,9S,E)-1-Hydroxy-8-isopropyl-10-methyl-6-[(R)-N-methyl-S-
phenyl-sulfonimidoyl]-9-(triethylsilyloxy)undec-6-en-5-one (24):
Treatment of alkenylsulfoximine 1a (300 mg, 0.71 mmol) and δ-va-
lerolactone (140 mg, 1.40 mmol) as described in GP9 afforded, af-
ter purification by flash chromatography (EtOAc/n-hexane 1:2), hy-
droxy ketone 24 (350 mg, 94%) as a colorless oil. [α]D = –72.7 (c
= 1.00, CH2Cl2); Rf = 0.16 (EtOAc/n-hexane 1:2). 1H NMR
(400 MHz, CDCl3): δ = 0.60 (q, J = 7.9 Hz, 6 H, Si-CH2CH3), 0.69
(d, J = 6.8 Hz, 3 H, CH3), 0.75 (d, J = 6.8 Hz, 3 H, CH3), 0.78 (d,
J = 6.8 Hz, 3 H, CH3), 0.90 (d, J = 6.8 Hz, 3 H, CH3), 0.97 (t, J
= 7.9 Hz, 9 H, Si-CH2CH3), 1.50 [sept, J = 6.8 Hz, 1 H, C=CH-
CH-CH(CH3)2], 1.55–1.76 [m, 5 H, CO-CH2-CH2-CH2, CHOSi-
(1S,1ЈS,3S,8aЈR)-3-Chloro-1Ј-isopropyl-4Ј-[(R)-N-methyl-S-phenyl-
sulfonimidoyl]-1Ј,5Ј,6Ј,7Ј,8Ј,8aЈ-hexahydro-spiro[cyclohexane-1,3Ј-
isochromene] (22) and (1R,1ЈS,4S,8aЈR)-4-Chloro-1Ј-isopropyl-4Ј-
[(R)-N-methyl-S-phenyl-sulfonimidoyl]-1Ј,5Ј,6Ј,7Ј,8Ј,8aЈ-hexahydro-
spiro[cyclohexane-1,3Ј-isochromene] (23): Treatment of hemiketal
10b (60 mg, 0.14 mmol) with TiCl4 (82 mg, 0.43 mmol) as described
in GP8 afforded an 8:1 mixture (1H NMR: NMe) of chlorinated
compounds 22 and 23 (51 mg, 84 %). Separation by flash
chromatography (EtOAc/cyclohexane 1:9) gave chlorinated com-
pound 22 (42 mg, 69%) and chlorinated compound 23 (3 mg, 5%)
as colorless oils.
Chlorinated Compound 22: [α]D = +119.6 (c = 1.00, CH2Cl2); Rf = CH(CH3)2], 2.11 (ddd, J = 11.2, 8.6, 1.4 Hz, 1 H, C=CH-CH), 2.65
0.20 (EtOAc/cyclohexane 5:95). 1H NMR (400 MHz, C6D6): δ =
0.45–0.58 (m, 2 H, CHH-CH2-CHH-CH2-C=C), 0.90 (dt, J = 14.3,
(td, J = 18.6, 6.8 Hz, 1 H, CO-CHH), 2.80 (s, 3 H, N-CH3), 2.90
(td, J = 18.6, 7.0 Hz, 1 H, CO-CHH), 3.60 (dd, J = 6.7, 1.4 Hz, 1
7.2 Hz, 1 H, CHH-CH2-CH2-C=C), 0.89 (d, J = 6.9 Hz, 3 H, CH3), H, CH-OSi), 3.64 (t, J = 6.7 Hz, 2 H, CH2-OH), 6.86 (d, J =
0.98 (d, J = 6.9 Hz, 3 H, CH3), 1.19 (dt, J = 13.0, 4.2 Hz, 1 H,
11.2 Hz, 1 H, CH=C-S), 7.44–7.59 (m, 3 H, Ph), 7.83–7.88 (m, 2
CHH-CH2-CH2-C=C), 1.25 (m, 2 H, CHH-CHH-C=C), 1.41 (d, J H, Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 5.5 (u), 7.1 (d),
= 13.2 Hz, 1 H, CHH-CH2-CH2-CH2-C=C), 1.48 (m, 1 H, CClH- 18.4 (d), 18.9 (d), 19.4 (u), 21.1 (d), 21.4 (d), 29.3 (d), 29.6 (d), 31.7
CH2-CHH), 1.56 [dtd, J = 11.5, 6.9, 2.4 Hz, 1 H, CH-(CH3)2], 1.75
(u), 33.5 (d), 44.1 (u), 48.8 (d), 62.3 (u), 77.9 (d), 128.4 (d), 128.8
(d, J = 12.8 Hz, 1 H, CClH-CH2-CH2-CHH), 1.88 (m, 3 H, CH- (d), 132.5 (d), 139.4 (u), 143.1 (u), 148.1 (d), 200.6 (u) ppm. IR
CHO-CH, CClH-CHH-CHH-CH2), 2.20 (m, 1 H, CClH-CHH),
2.82 (s, 3 H, N-CH3), 2.83 (m, 1 H, CHH-CClH), 3.03 (dd, J =
(CHCl ): ν = 3408 (m), 2958 (s), 2808 (m), 1698 (s), 1616 (w), 1465
˜
3
(s), 1411 (w), 1249 (s), 1375 (m), 1253 (s), 1152 (s), 1081 (s), 1011
9.3, 2.5 Hz, 1 H, CH-O), 3.44 (m, 1 H, CClH-CH2-CH2-CHH), (m), 858 (w), 800 (w) cm–1. MS (EI, 70 eV): m/z (%) = 524 [M +
3.52 (dd, J = 13.2, 12.5 Hz, 1 H, CHH-CClH), 3.68 (ddd, J = 13.8,
1]+ (6), 523 (3), 494 (5), 480 (5), 368 (8), 339 (7), 338 (13), 337 (48),
3.5, 2.4 Hz, 1 H, CHH-C=C), 4.38 (tt, J = 11.6, 4.2 Hz, 1 H, 336 (100), 322 (19), 294 (21), 283 (14), 270 (18), 267 (10), 187 (40),
CHCl), 6.94–6.97 (m, 3 H, Ph), 7.92–7.96 (m, 2 H, Ph) ppm. 13C 159 (31), 156 (24), 125 (27), 115 (57), 111 (10), 107 (17), 103 (21), 87
Eur. J. Org. Chem. 2014, 529–553
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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