Pd-Catalyzed Selective Oxycyclization–Alkene Addition Cascades
sentative procedure for a reaction time of 18 h. The crude product
was purified by flash chromatography (silica gel saturated with
Et3N; hexanes/EtOAc/Et3N, from 95:3:2 to 92:6:2) to afford 6e
2.69 (m, 2 H), 2.81–2.86 (m, 2 H), 7.17 (d, J = 8.4 Hz, 2 H), 7.34
(d, J = 7.9 Hz, 1 H), 7.43 (t, J = 7.5 Hz, 1 H), 7.59–7.64 (m, 3 H),
8.38 (d, J = 7.9 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
(113 mg, 92 %) as a yellow solid; m.p. 123–124 °C. 1H NMR 14.0 (CH3), 19.7 (CH2), 22.3 (CH2), 27.4 (CH2), 28.6 (CH2), 30.0
(300 MHz, CDCl3): δ = 2.11 (s, 3 H), 2.66–2.71 (m, 2 H), 2.88– (CH3), 30.1 (CH2), 31.4 (CH2), 42.8 (CH2), 106.1 (C), 109.9 (C),
2.93 (m, 2 H), 4.69 (s, 2 H), 7.21–7.26 (m, 1 H), 7.30–7.39 (m, 4
119.6 (C), 121.8 (CH), 123.0 (C), 123.3 (2 CH), 127.5 (CH), 128.0
H), 7.40–7.47 (m, 7 H), 7.56 (ddd, J = 7.9, 7.4, 1.4 Hz, 1 H), 8.42 (CH), 132.7 (2 CH), 133.0 (CH), 134.1 (C), 151.4 (C), 151.8 (C),
(dd, J = 7.9, 1.0 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ
152.6 (C), 207.2 (C) ppm. IR (film): ν = 2222 (m, CϵN), 1715 (m),
˜
= 20.8 (CH2), 30.0 (CH3), 43.5 (CH2), 50.1 (CH2), 110.6 (C), 122.4 1660 (s), 1629 (s), 1592 (s) cm–1. MS (EI): m/z (%) = 400 (100)
(CH), 124.9 (C), 126.4 (CH), 127.4 (CH), 127.8 (CH), 127.9 (CH), [M]+, 357 (16), 344 (23), 343 (89), 330 (11), 315 (18), 287 (19), 285
128.3 (CH), 128.6 (CH), 128.9 (CH), 129.4 (CH), 131.9 (CH), 133.1 (12), 274 (13), 273 (68), 272 (36), 271 (17), 260 (39), 259 (10), 257
(C), 134.0 (C), 141.2 (C), 150.5 (C), 151.0 (C), 207.5 (C) ppm. IR
(22), 255 (15), 245 (37), 244 (25), 243 (39), 242 (28), 232 (18), 231
(film): ν = 1714 (s), 1658 (s), 1604 (m) cm–1. MS (EI): m/z (%) = (92), 230 (14), 229 (39), 225 (28). HRMS (EI): calcd. for
˜
381 (24) [M]+, 290 (15), 105 (46), 91 (100), 77 (10). HRMS (EI):
calcd. for C26H23NO2 [M]+ 381.1729; found 381.1721.
C26H28N2O2 [M]+ 400.2151; found 400.2153. Alternatively, the re-
action was conducted by using compound 3h[6a] (57.0 mg,
0.172 mmol), 3-buten-2-one (84 μL, 1.035 mmol), and PdI2
(3.10 mg, 8.6 μmol; Table 2, Entry 5), and the crude product was
purified by flash chromatography (silica gel saturated with Et3N;
hexanes/EtOAc/Et3N, from 92:7:1 to 40:59:1) to afford 7h[2]
(39.5 mg, 75%), 6h (8.5 mg, 15%), and 8h[8] (20 mg, 62%).
4-[(Z)-3-Hexyl-1-(phenylimino)-1H-isochromen-4-yl]butan-2-one
(6f): Compound 3f[7a] (100 mg, 0.327 mmol) was used in the repre-
sentative procedure for a reaction time of 16 h. The crude product
was purified by flash chromatography (silica gel saturated with
Et3N; hexanes/EtOAc/Et3N, 98.5:0.5:1 to 98:1:1) to afford 6f
1
4-[(Z)-1-(4-Chlorophenylimino)-3-hexyl-1H-isochromen-4-yl]butan-
2-one (6i): Compound 3i[6a] (100 mg, 0.294 mmol) was used in the
representative procedure for a reaction time of 18 h. The crude
product was purified by flash chromatography (silica gel saturated
with Et3N; hexanes/EtOAc/Et3N, from 98.5:0.5:1 to 97:2:1) to af-
(117 mg, 95%) as a yellow oil. H NMR (300 MHz, CDCl3): δ =
0.87 (m, 3 H), 1.24–1.31 (m, 6 H), 1.45–1.52 (m, 2 H), 2.18 (s, 3
H), 2.41 (t, J = 7.4 Hz, 2 H), 2.63–2.69 (m, 2 H), 2.79–2.85 (m, 2
H), 7.07 (t, J = 7.3 Hz, 1 H), 7.15 (d, J = 7.3 Hz, 2 H), 7.28–7.41
(m, 4 H), 7.53–7.59 (m, 1 H), 8.41 (dd, J = 7.8, 0.8 Hz, 1 H) ppm.
13C NMR (75.5 MHz, CDCl3): δ = 14.0 (CH3), 19.8 (CH2), 22.4
(CH2), 27.3 (CH2), 28.7 (CH2), 30.1 (CH3), 30.2 (CH2), 31.5 (CH2),
43.0 (CH2), 109.1 (C), 121.5 (CH), 122.7 (2 CH), 123.3 (CH), 123.9
(C), 127.2 (CH), 127.8 (CH), 128.5 (2 CH), 132.3 (CH), 133.9 (C),
1
ford 6i (110 mg, 91%) as a yellow solid; m.p. 62–63 °C. H NMR
(300 MHz, CDCl3): δ = 0.85–0.90 (m, 3 H), 1.25–1.30 (m, 6 H),
1.45–1.52 (m, 2 H), 2.18 (s, 3 H), 2.41 (t, J = 7.4 Hz, 2 H), 2.63–
2.68 (m, 2 H), 2.80–2.85 (m, 2 H), 7.09 (d, J = 8.7 Hz, 2 H), 7.27–
7.32 (m, 3 H), 7.37–7.42 (m, 1 H), 7.55–7.60 (m, 1 H), 8.38 (d, J
= 8.0 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 14.0
(CH3), 19.8 (CH2), 22.4 (CH2), 27.4 (CH2), 28.7 (CH2), 30.1 (CH3),
30.1 (CH2), 31.5 (CH2), 42.9 (CH2), 109.4 (C), 121.6 (CH), 123.6
(C), 124.1 (2 CH), 127.3 (CH), 127.8 (CH), 128.3 (C), 128.5 (2
CH), 132.5 (CH), 133.9 (C), 145.4 (C), 150.6 (C), 152.7 (C), 207.4
146.8 (C), 150.1 (C), 152.7 (C), 207.5 (C) ppm. IR (film): ν = 1717
˜
(s), 1660 (s), 1631 (s) cm–1. MS (EI): m/z (%) = 376 (20), 375 (77)
[M]+, 332 (14), 319 (22), 318 (100), 290 (12), 262 (12), 248 (22), 247
(12), 235 (14), 225 (16), 220 (18), 219 (12), 218 (27), 217 (19), 207
(15), 206 (74), 205 (10), 204 (31). HRMS (EI): calcd. for
C25H29NO2 [M]+ 375.2198; found 375.2197.
(C) ppm. IR (film): ν = 1716 (m), 1659 (s), 1630 (s) cm–1. MS (EI):
˜
m/z (%) = 411 (35) [M, 37Cl]+, 410 (29), 409 (100) [M, 35Cl]+, 366
(17), 354 (33), 353 (23), 352 (97), 324 (18), 296 (17), 284 (11), 283
(11), 282 (36), 281 (15), 280 (11), 269 (21), 266 (14), 256 (11), 255
(11), 254 (27), 253 (22), 252 (19), 242 (28), 241 (18), 240 (76), 238
(17), 225 (27), 218 (13), 217 (17), 205 (16), 204 (31), 203 (13).
HRMS (EI): calcd. for C25H2835ClNO2 [M]+ 409.1809; found
409.1808; calcd. for C25H2837ClNO2 [M]+ 411.1779; found
411.1782.
4-[(Z)-3-Hexyl-1-(4-methoxyphenylimino)-1H-isochromen-4-yl]but-
an-2-one (6g): Compound 3g[7a] (100 mg, 0.298 mmol) was used in
the representative procedure for a reaction time of 18 h. The crude
product was purified by flash chromatography (silica gel saturated
with Et3N; hexanes/EtOAc/Et3N, 97:2:1 to 91:8:1) to afford 6g
1
(117 mg, 97%) as a yellow oil. H NMR (300 MHz, CDCl3): δ =
0.85–0.90 (m, 3 H), 1.27–1.35 (m, 6 H), 1.51–1.58 (m, 2 H), 2.18
(s, 3 H), 2.42–2.47 (m, 2 H), 2.63–2.68 (m, 2 H), 2.80–2.85 (m, 2
H), 3.82 (s, 3 H), 6.89 (dd, J = 8.9, 2.1 Hz, 2 H), 7.19–7.29 (m, 3
H), 7.37 (t, J = 7.6 Hz, 1 H), 7.51–7.56 (m, 1 H), 8.40 (d, J =
7.9 Hz, 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 14.0 (CH3),
19.9 (CH2), 22.4 (CH2), 27.5 (CH2), 28.8 (CH2), 30.1 (CH3), 30.2
(CH2), 31.6 (CH2), 43.0 (CH2), 55.4 (CH3), 109.1 (C), 113.7 (2 CH),
121.5 (CH), 124.3 (2 CH, 1 C), 127.2 (CH), 127.6 (CH), 132.0
(CH), 133.7 (C), 139.6 (C), 149.5 (C), 152.7 (C), 155.9 (C), 207.6
4-[(Z)-3-Phenyl-1-(p-tolylimino)-1H-isochromen-4-yl]butan-2-one
(6j): Compound 3j[15] (100 mg, 0.321 mmol) was used in the repre-
sentative procedure for a reaction time of 17 h. The crude product
was purified by flash chromatography (silica gel saturated with
Et3N; hexanes/EtOAc/Et3N, from 95:4:1 to 92:7:1) to afford 6j
[85 % yield estimated by 1H NMR analysis using (3,4-dimeth-
oxyphenyl)acetonitrile as an internal standard; the isomeric rela-
tionship was confirmed by HPLC/HRMS analysis]. Column
chromatography was repeated to afford pure 6j as a yellow solid for
(C) ppm. IR (film): ν = 1716 (m), 1657 (s), 1632 (s), 1505 (s) cm–1.
˜
MS (EI): m/z (%) = 405 (100) [M]+, 390 (14), 349 (13), 348 (49),
237 (13), 236 (72), 234 (14), 204 (11), 123 (14). HRMS (EI): calcd.
for C26H31NO3 [M]+ 405.2304; found 405.2306.
1
characterization; m.p 139–141 °C. H NMR (300 MHz, CDCl3): δ
= 2.12 (s, 3 H), 2.30 (s, 3 H), 2.67–2.73 (m, 2 H), 2.91–2.96 (m, 2
4-[3-Hexyl-4-(3-oxobutyl)isochromen-1-ylidene]-(Z)-aminobenzo- H), 7.08 (d, J = 8.0 Hz, 2 H), 7.17 (d, J = 8.2 Hz, 2 H), 7.38–7.48
nitrile (6h): Compound 3h[6a] (100 mg, 0.303 mmol) was used in (m, 7 H), 7.60 (t, J = 7.7 Hz, 1 H), 8.48 (d, J = 7.9 Hz, 1 H) ppm.
the representative procedure for a reaction time of 18 h. The crude
product was purified by flash chromatography (silica gel saturated
with Et3N; hexanes/EtOAc/Et3N, 95:4:1 to 87:12:1) to afford 6h
13C NMR (75.5 MHz, CDCl3): δ = 20.6 (CH2), 20.9 (CH3), 29.8
(CH3), 43.3 (CH2), 110.0 (C), 122.3 (CH), 123.1 (2 CH), 124.7 (C),
127.9 (2 CH), 128.4 (2 CH), 128.7 (2 CH), 129.1 (2 CH), 129.2
(113 mg, 93 %) as a yellow solid; m.p. 93–95 °C. 1H NMR (CH), 132.2 (CH), 133.0 (C), 133.4 (C), 133.6 (C), 143.4 (C), 149.0
(300 MHz, CDCl3): δ = 0.85–0.89 (m, 3 H), 1.17–1.30 (m, 6 H), (C), 150.3 (C), 207.2 (C) ppm. IR (film): ν = 1713 (s), 1655 (s),
˜
1.41–1.47 (m, 2 H), 2.18 (s, 3 H), 2.42 (t, J = 7.4 Hz, 2 H), 2.64–
1630 (s), 1603 (m) cm–1. MS (EI): m/z (%) = 381 (99) [M]+, 325
Eur. J. Org. Chem. 2015, 6298–6305
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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