Samarium Diiodide Induced Cyclizations of Indolyl Ketones
FULL PAPER
1.99 (dt, Jꢀ7.5, 12.5 Hz, 1H; 8-H), 2.58 (ddd, J=7.5, 11.8, 18.6 Hz, 1H;
7-H), 2.70 (ddd, J=2.0, 7.5, 18.6 Hz, 1H; 7-H), 3.63 (s, 3H; OCH3), 4.16
(s, 1H; 10-H), 7.09 (t, Jꢀ7.4 Hz, 1H; 3-H), 7.13 (d, J=7.4 Hz, 1H; 1-H),
7.27 (dt, Jꢀ1.5, 8.1 Hz, 1H; 2-H), 8.27 ppm (d, J=8.1 Hz, 1H; 4-H);
13C NMR (125 MHz, CDCl3): d=19.9, 27.2 (2q; 10-CH3, 9-CH3), 30.8,
37.9 (2t; C-7, C-8), 52.8 (q; OCH3), 52.9 (s; C-10), 70.5 (s; C-9), 77.3 (d;
C-9a), 116.9, 123.4, 124.3, 128.8 (4d; C-4, C-1, C-2, C-3), 132.7, 142.1,
emental analysis calcd (%) for C21H27NO4Si (385.5): C 64.66, H 6.78, N
3.77; found: C 64.82, H 7.01, N 3.51.
Methyl
(9S*,9aR*,10S*)-10-(cyanomethyl)-9-hydroxy-9-methyl-6-oxo-
[1,2-a]indole-10-carboxylate (2j): Accord-
6,7,8,9,9a,10-hexahydropyrido
AHCTUNGTRENNUNG
ing to GP3, SmI2 solution (48.0 mL, 4.80 mmol), HMPA (4.00 g,
22.3 mmol), indole derivative 1 (546 mg, 2.00 mmol), and bromo acetoni-
trile (800 mg, 6.67 mmol) afforded after purification by column chroma-
tography on silica gel (Hex/EtOAc 4:1, 1:1, EtOAc) and HPLC com-
pound 2j (500 mg, 79%) as a colorless solid. M.p. 73–748C; 1H NMR
(500 MHz, CDCl3): d=1.30 (s, 3H; 9-CH3), 1.89 (ddd, J=1.7, 7.0,
13.0 Hz, 1H; 8-H), 2.07 (dt, Jꢀ7.0, 13.0 Hz, 1H; 8-H), 2.55–2.67 (m, 1H;
7-H), 2.73 (ddd, J=1.7, 7.0, 18.6 Hz, 1H; 7-H), 2.79 (s, 1H; OH), 3.31 (d,
J=17.1 Hz, 1H; 10-CH2), 3.40 (d, J=17.1 Hz, 1H; 10-CH2), 3.64 (s, 3H;
OCH3), 4.34 (s, 1H; 9a-H), 7.16 (dt, Jꢀ1.0, 7.6 Hz, 1H; 2-H), 7.31 (dd,
J=1.2, 7.6 Hz, 1H; 1-H), 7.38 (dt, Jꢀ1.2, 7.6 Hz, 1H; 3-H), 8.30 ppm (d,
J=8.2 Hz, 1H; 4-H); 13C NMR (125 MHz, CDCl3): d=20.0 (q; 9-CH3),
25.9, 31.0, 38.5 (3t; 10-CH2, C-7, C-8), 53.2 (s; C-10), 54.0 (q; OCH3),
70.5 (s; C-9), 74.1 (d; C-9a), 116.9 (s; CN), 117.4, 122.6, 124.9 (3d; C-4,
C-1, C-2), 129.0 (s; Ar), 130.0 (d; C-3), 142.7, 167.0, 171.5 ppm (3s; Ar,
À
167.4, 175.3 ppm (4s; 2Ar, C-7, CO2Me); IR (KBr): n˜ =3285 (O H),
À1
À
À
3065–3040 (=C H), 3000–2845 (C H), 1715, 1620 (C=O), 1600 cm
ACHTUNGTRENNUNG
(C=C); MS (ESI-TOF): m/z: calcd for C16H19NO4: 290.1387 [M+H]+,
312.1206 [M+Na]+, 328.0946 [M+K]+; found: 290.1399 [M+H]+,
312.1217 [M+Na]+, 328.0958 [M+K]+.
Data for methyl (9S*,9aR*,10R*)-9-hydroxy-9,10-dimethyl-6-oxo-
6,7,8,9,9a,10-hexahydropyridoACHTUNGTRNEUNG
[1,2-a]indole-10-carboxylate (2c): 1H NMR
(500 MHz, CDCl3): d=1.25, 1.62 (2 s, each 3H; 10-CH3, 9-CH3), 1.94
(ddd, J=2.4, 7.4, 12.8 Hz, 1H; 8-H), 2.03 (dt, Jꢀ7.0, 12.8 Hz, 1H; 8-H),
2.62 (ddd, J=7.4, 11.8, 18.6 Hz, 1H; 7-H), 2.76 (ddd, J=2.4, 7.0, 18.6 Hz,
1H; 7-H), 3.86 (s, 3H; OCH3), 4.79 (s, 1H; 9a-H), 7.10 (dt, Jꢀ1.1,
7.3 Hz, 1H; 2-H), 7.29 (t, Jꢀ7.3 Hz, 1H; 3-H), 7.34 (dd, J=1.6, 8.2 Hz,
1H; 1-H), 8.27 ppm (d, J=8.2 Hz, 1H; 4-H); 13C NMR (100 MHz,
CDCl3): d=21.8, 23.2 (2q; 10-CH3, 9-CH3), 31.3, 39.9 (2t; C-7, C-8), 53.2
(q; OCH3), 55.1 (s; C-10), 70.86 (d; C-9a), 70.89 (s; C-9), 117.0, 123.3,
124.6, 128.9 (4d; C-4, C-1, C-2, C-3), 133.4, 140.6, 168.1, 175.5 ppm (4s;
À
À
C-6, CO2Me); IR (KBr): n˜ =3400 (O H), 3040 (=C H), 3000–2850
À
(C H), 2250 (CꢁN), 1730, 1660–1635 (C=O), 1595 (C=C) cmÀ1; elemen-
tal analysis calcd (%) for C17H18N2O4 (314.3): C 64.96, H 5.77, N 8.91;
found: C 64.61, H 5.61, N 8.65.
À
2Ar, C-7, CO2Me); IR (KBr): n˜ =3290 (OH), 3065–3035 (=C H), 3000–
Benzyl
(9S*,9aR*,10S*)-10-(cyanomethyl)-9-hydroxy-9-methyl-6-oxo-
[1,2-a]indole-10-carboxylate (15): Accord-
À1
À
2835 (C H), 1720, 1625 (C=O), 1590 cm (C=C); MS (ESI-TOF): m/z:
6,7,8,9,9a,10-hexahydropyrido
AHCTUNGTRENNUNG
calcd for C16H19NO4: 312.1206 [M+Na]+; found: 312.1208 [M+Na]+.
ing to GP3, SmI2 (50.0 mL, 5.00 mmol), HMPA (3.60 g, 20.1 mmol),
indole derivative 14 (700 mg, 2.00 mmol), and bromo acetonitrile (1.00 g,
8.34 mmol) furnished after workup and purification by column chroma-
tography on silica gel (Hex/EtOAc 3:1, 1:1, EtOAc) compound 15
(670 mg, 85%) as a colorless solid. M.p. 72–758C; 1H NMR (500 MHz,
CDCl3): d=1.24 (s, 3H; 9-CH3), 1.85 (ddd, J=1.7, 7.0, 12.7 Hz, 1H; 7-
H), 2.04 (dt, Jꢀ7.0, 12.7 Hz, 1H; 7-H), 2.53 (ddd, J=7.0, 12.7, 18.5 Hz,
1H; 8-H), 2.69 (ddd, J=1.7, 7.0, 18.5 Hz, 1H; 8-H), 2.79 (brs, 1H; OH),
3.34 (d, J=17.2 Hz, 1H; 10-CH2), 3.38 (d, J=17.2 Hz, 1H; 10-CH2), 4.36
(s, 1H; 9a-H), 4.95 (d, J=12.7 Hz, 1H; OCH2Ph), 5.22 (d, J=12.7 Hz,
1H; OCH2Ph), 6.95–6.99 (m, 2H; Ar), 7.14 (dt, Jꢀ0.9, 7.4 Hz, 1H; 2-H),
7.24–7.27 (m, 4H; Ar, 1-H), 7.38 (dt, Jꢀ1.2, 7.4 Hz, 1H; 3-H), 8.31 ppm
(dd, J=0.4, 8.2 Hz, 1H, 4-H); 13C NMR (100 MHz, CDCl3): d=20.2 (q;
9a-CH3), 25.6, 30.9, 38.4 (3t; 10-CH2, C-7, C-8), 54.3 (s; C-10), 67.7 (t;
OCH2), 70.6 (s; C-9), 74.1 (d; C-9a), 116.8 (s; CN), 117.5, 122.6, 124.8
(3d; C-4, C-1, C-2), 127.3*, 128.3, 128.5* (3d; Ar), 129.1 (s; Ar), 130.1
(d; C-3), 134.0, 142.8, 167.0, 170.7 ppm (4s; 2Ar, C-6, CO2Bn) (*double
Methyl
(9S*,9aR*,10S*)-10-benzyl-9-hydroxy-9-methyl-6-oxo-
[1,2-a]indole-10-carboxylate (2 f): Accord-
6,7,8,9,9a,10-hexahydropyrido
AHCTUNGTRENNUNG
ing to GP3, SmI2 solution (24.0 mL, 2.40 mmol), HMPA (1.60 g,
8.93 mmol), indole derivative 1 (273 mg, 1.00 mmol), and benzyl bromide
(1.00 g, 5.88 mmol) furnished after purification by column chromatogra-
phy on silica gel (Hex/EtOAc 4:1, 1:1, EtOAc) compound 2 f (255 mg,
70%) as a colorless solid. M.p. 190–1928C; 1H NMR (500 MHz, CDCl3):
d=1.19 (s, 3H; 9-CH3), 1.86 (ddd, J=3.6, 7.7, 13.3 Hz, 1H; 8-H), 1.97
(ddd, J=7.7, 10.4, 13.3 Hz, 1H; 8-H), 2.53 (ddd, J=7.7, 10.4, 18.3 Hz,
1H; 7-H), 2.66 (ddd, J=3.6, 7.7, 18.3 Hz, 1H; 7-H), 3.34 (d, J=13.7 Hz,
1H; 10-CH2), 3.68 (d, J=13.7 Hz, 1H; 10-CH2), 3.71 (s, 3H; OCH3), 3.91
(s, 1H; OH), 4.35 (s, 1H; 9a-H), 6.94–6.98 (m, 3H, 1-H; Ar), 7.04 (dt, J
ꢀ0.9, 7.7 Hz, 1H; 2-H), 7.18–7.22 (m, 3H; Ar), 7.29 (dt, Jꢀ1.3, 7.7 Hz,
1H; 3-H), 8.23 ppm (d, J=8.2 Hz, 1H; 4-H); 13C NMR (100 MHz,
CDCl3): d=20.7 (q, 9-CH3), 30.9, 37.8, 46.2 (3t; C-7, C-8, 10-CH2), 53.1
(q; OCH3), 58.5, 70.8 (2s; C-10, C-9), 73.0 (d; C-9a), 116.5, 123.3, 126.2,
127.3*, 128.3* (5d; C-4, C-2, C-1, Ar), 129.0 (s; Ar), 129.0, 131.1 (2d;
C-3, Ar), 135.0, 142.6, 167.9, 175.5 ppm (4s; 2Ar, C-6, CO2Me) (*double
À
À
À
intensity); IR (KBr): n˜ =3385 (O H), 3065–2880 (=C H, C H), 2255
(CꢁN), 1730, 1660–1640 (C=O), 1595 cmÀ1 (C=C); MS (ESI-TOF): m/z:
calcd for C23H22N2O4: 391.1658 [M+H]+, 413.1477 [M+Na]+, 429.1217
[M+K]+; found: 391.1666 [M+H]+, 413.1481 [M+Na]+, 429.1225
[M+K]+; elemental analysis: calcd (%) for C23H22N2O4 (390.4): C 70.75,
H 5.68, N 7.17; found: C 70.20, H 5.58, N 7.31.
À
À
intensity); IR (ATR): n˜ =3495 (O H), 3060–3000 (=C H), 2945–2870
À1
À
(C H), 1710, 1660 (C=O), 1595 cm (C=C); MS (ESI-TOF): m/z: calcd
for C22H23NO4: 388.1519 [M+H]+, 404.1259 [M+Na]+; found: 388.1511
[M+H]+, 404.1254 [M+Na]+.
Methyl (9S*,9aR*,10S*)-9-hydroxy-9-methyl-6-oxo-10-[3-(trimethylsilyl)-
Benzyl (9R*,9aR*,10S*)-9-[2-(tert-butyldimethylsiloxy)ethyl]-10-(cyano-
prop-2-ynyl]-6,7,8,9,9a,10-hexahydropyrido
G
methyl)-9-hydroxy-6-oxo-6,7,8,9,9a,10-hexahydropyridoACTHNGUTER[NNUG 1,2-a]indole-10-
(2i): According to GP3, SmI2 solution (24.0 mL, 2.40 mmol), HMPA
(1.90 g, 10.6 mmol), indole derivative 1 (280 mg, 1.03 mmol), and (3-bro-
moprop-1-ynyl)trimethylsilane (800 mg, 4.34 mmol) provided after purifi-
cation by column chromatography on silica gel (Hex/EtOAc 4:1, 1:1,
EtOAc) compound 2i (340 mg, 86%) as a colorless solid. M.p. 132–
carboxylate (23c): According to GP3, SmI2 solution (12.0 mL,
1.20 mmol), HMPA (2.00 g, 11.2 mmol), indole derivative 22c (500 mg,
1.00 mmol), and bromo acetonitrile (1.00 g, 8.34 mmol) afforded after pu-
rification by column chromatography on silica gel (Hex/EtOAc 9:1, 4:1,
1:1) 23c (460 mg, 86%) as a colorless solid. M.p. 98–1018C; 1H NMR
1
1338C; H NMR (500 MHz, CDCl3): d=0.05 (s, 9H; SiCH3), 1.22 (s, 3H;
(500 MHz, CDCl3): d=0.09 (s, 6H; SiCH3), 0.90 (s, 9H; SiCACHTNGUTERNNU(G CH3)3), 1.60
9-CH3), 1.88 (ddd, J=2.3, 7.7, 13.1 Hz, 1H; 8-H), 2.01 (dt, Jꢀ7.3,
12.3 Hz, 1H; 8-H), 2.51–2.62 (ddd, J=7.7, 11.6, 18.5 Hz, 1H; 7-H), 2.72
(ddd, J=2.2, 7.7, 18.5 Hz, 1H; 7-H), 2.96 (d, J=16.9 Hz, 1H; 10-CH2),
3.19 (d, J=16.9 Hz, 1H; 10-CH2), 3.62 (s, 1H; OH), 3.70 (s, 3H; OCH3),
4.31 (s, 1H; 9a-H), 7.09 (dt, Jꢀ 0.6, 7.6 Hz, 1H; 2-H), 7.30 (dt, Jꢀ0.8,
7.9 Hz, 1H, 3-H), 7.46 (dd, J=0.6, 7.6 Hz, 1H; 1-H), 8.27 ppm (d, J=
8.2 Hz, 1H; 4-H); 13C NMR (100 MHz, CDCl3): d=À0.2 (q; SiCH3), 20.1
(q; 9-CH3), 30.8, 31.8, 37.8 (3t; C-7, C-8, 10-CH2), 53.0 (q; OCH3), 56.4,
70.4 (2s; C-10, C-9), 74.3 (d; C-9a), 89.4, 101.9 (2s; CꢁCTMS), 116.6,
124.0, 124.7, 129.1 (4d; C-4, C-1, C-2, C-3), 130.0, 142.4, 167.4, 173.9 ppm
(td, Jꢀ2.2, 14.5 Hz, 1H; 9-CH2), 1.71 (dt, Jꢀ4.9, 15.0 Hz, 1H; 9-CH2),
1.97 (dt, Jꢀ5.7, 13.6 Hz, 1H; 8-H), 2.19 (ddd, J=1.6, 6.3, 13.6 Hz, 1H; 8-
H), 2.32 (ddd, J=6.3, 13.6, 18.5 Hz, 1H; 7-H), 2.67 (ddd, J=1.6, 6.3,
18.5 Hz, 1H; 7-H), 3.43 (d, J=17.2 Hz, 1H; 10-CH2), 3.46 (d, J=17.2 Hz,
1H; 10-CH2), 3.56 (ddd, Jꢀ2.2, 4.9, 10.5 Hz, 1H; CH2OTBS), 3.74 (dt, J
ꢀ2.2, 11.5 Hz, 1H; CH2OTBS), 4.36 (s, 1H; OH), 4.48 (s, 1H; 9a-H),
5.03, 5.06 (AB system, JAB =12.4 Hz, 2H; OCH2Ph), 7.01–7.05 (m, 2H;
Ar), 7.14 (dt, Jꢀ0.8, 7.7 Hz, 1H; 2-H), 7.22–7.26 (m, 4H; Ar, 1-H), 7.37
(dt, Jꢀ1.2, 7.6 Hz, 1H; 3-H), 8.31 ppm (d, J=8.1 Hz, 1H; 4-H);
13C NMR (100 MHz, CDCl3): d=À5.7, À5.6 (2q; SiCH3), 17.9 (s; SiC-
À
À
(4s; 2Ar, C-6, CO2Me); IR (ATR): n˜ =3380 (O H), 3250–3010 (=C H),
G
ACHTUGNTERN(NUNG CH3)3), 30.9, 31.0, 32.8 (3t; C-7,
À1
À
2990–2895 (C H), 2175 (CꢁC), 1735, 1630 (C=O), 1595 cm (C=C); el-
Chem. Eur. J. 2011, 17, 9720 – 9730
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
9727