M. Amat, F. Subrizi, V. Elias, N. Llor, E. Molins, J. Bosch
FULL PAPER
1647, 2955 cm–1. HRMS calcd. for C29H32N2O [M + H]+:
425.2587; found 425.2583.
3382 cm–1. HRMS calcd. for C21H22N2O2 [M + H]+: 335.1759;
found 335.1749.
Data for 1-epi Derivatives and Partially Reduced Compounds 11 and
12
(R)-9-Benzyl-2-[(R)-2-hydroxy-1-phenylethyl]-1-methyl-3-oxo-
1,2,3,4-tetrahydropyrido[3,4-b]indole (12b): [α]2D2 = +18.25 (c = 1.2,
CHCl3). 1H NMR (400 MHz, CDCl3, 25 °C): δ = 1.29 (d, J =
6.4 Hz, 3 H, CH3), 3.68–3.79 (m, 2 H, 4-H, OH), 3.92 (m, 1 H, 4-
H), 4.03 (dt, J = 12.0, 4.3 Hz, 1 H, CH2OH), 4.26 (dt, J = 12.0,
7.4 Hz, 1 H, CH2OH), 4.46 (q, J = 6.4 Hz, 1 H, 1-H), 4.88 (dd, J
= 7.4, 4.3 Hz, 1 H, CHAr), 5.09 (d, J = 16.8 Hz, 1 H, NCH2), 5.29
(d, J = 16.8 Hz, 1 H, NCH2), 6.85–6.88 (m, 1 H, 5-H), 7.14–7.28
(m, 12 H, 6-H, 7-H, ArH), 7.53–7.56 (m, 1 H, 8-H) ppm. 13C NMR
(100.6 MHz, CDCl3, 25 °C): δ = 22.4 (CH3), 31.1 (C-4), 46.9
(CH2C6H5), 52.6 (C-1), 64.0 (CH2OH), 65.5 (CHCH2), 105.2 (C-
4a), 109.8 (C-8), 118.4 (C-5), 120.0 (C-6), 122.3 (C-7), 125.4 (C-
4b), 125.8 (C-o), 127.5 (C-o), 127.5 (C-p), 127.8 (C-p), 128.7 (C-m),
128.9 (C-m), 134.5 (C-8a), 136.6 (C-i), 136.9 (C-9a), 139.3 (C-i),
171.4 (CO) ppm. HRMS calcd. for C27H26N2O2 [M + H]+:
411.2067; found 411.2071.
(S)-2-[(R)-2-Hydroxy-1-phenylethyl]-1,9-dimethyl-1,2,3,4-tetrahy-
1
dropyrido[3,4-b]indole (1-epi-10a): H NMR (300 MHz, CDCl3,
25 °C, from a 10a/epi-10a mixture): δ = 1.36 (d, J = 6.9 Hz, 3 H,
CH3), 2.40–2.48 (m, 2 H, 4-H), 2.90–3.02 (m, 1 H, 3-H), 3.31 (m,
1 H, 3-H), 3.40 (s, 3 H, NCH3), 3.79 (dd, J = 6.0, 4.5 Hz, 1 H,
CH2OH), 4.30 (m, 1 H, 1-H), 7.05–7.48 (m, 9 H, ArH) ppm. 13C
NMR (75.4 MHz, CDCl3, 25 °C): δ = 18.4 (C-4), 19.2 (CH3), 29.1
(NCH3), 39.7 (C-3), 49.1 (C-1), 63.9 (CH2OH), 65.3 (CHAr), 106.2
(C-4a), 108.6 (C-8), 117.9 (C-5), 118.7 (C-6), 120.8 (C-7), 126.5 (C-
4b), 127.5 (C-p), 128.2 (C-m), 128.3 (C-o), 137.1 (C-9a), 137.5 (C-
i), 141.2 (C-8a) ppm.
(S)-9-Benzyl-2-[(R)-2-hydroxy-1-phenylethyl]-1-propyl-1,2,3,4-tetra-
hydropyrido[3,4-b]indole (1-epi-10c): [α]2D2 = –75.8 (c = 0.9, CHCl3).
1H NMR (400 MHz, CDCl3, 25 °C): δ = 0.68 (t, J = 7.5 Hz, 3
H, CH3), 1.15–1.30 (m, 2 H, CH2CH2CH3), 1.54–1.61 (m, 1 H,
CH2CH2CH3), 1.73–1.79 (m, 1 H, CH2CH2CH3), 2.64 (dm, J =
16.0 Hz, 1 H, H-4), 3.07 (ddd, J = 16.0, 10.4, 7.2 Hz, 1 H, H-4),
3.41 (m, 2 H, H-3), 3.47 (t, J = 9.2 Hz, 1 H, H-1), 3.74 (dd, J =
6.0, 3.2 Hz, 1 H, CHAr), 3.84 (dd, J = 11.0, 3.2 Hz, 1 H, CH2OH),
4.03 (dd, J = 11.0, 6.0 Hz, 1 H, CH2OH), 4.91 (d, J = 16.8 Hz, 1
H, NCH2), 4.96 (d, J = 16.8 Hz, 1 H, NCH2), 6.79 (m, 2 H, ArH),
7.10–7.20 (m, 11 H, ArH, H-Ind), 7.53 (m, 1 H, H-8) ppm. 13C
NMR (100.6 MHz, CDCl3, 25 °C): δ = 13.9 (CH3), 17.4 (C-4), 19.8
(CH2CH3), 36.9 (CH2CH2CH3), 39.6 (C-3), 46.4 (NCH2), 53.2 (C-
1), 64.4 (CH2OH), 64.7 (CHAr), 107.0 (C-4a), 109.6 (C-8), 118.0
(C-5), 119.2 (C-6), 121.3 (C-7), 126.1 (C-o), 127.2 (C-p), 127.6 (C-
4b), 128.8 (C-p), 128.6 (C-m), 128.7 (C-m), 136.9 (C-i), 137.0 (C-
8a), 137.6 (C-i), 140.9 (C-9a) ppm. EM (IQ+): m/z %: 424 (1), 393
(10), 381 (100), 288 (16), 261 (39), 169 (20), 103 (16), 91 (95).
(R)-2-[(R)-2-Hydroxy-1-phenylethyl]-1-methyl-1,2,3,4-tetrahydro-
pyrido[3,4-b]indole (13b): NH3 (30 mL) was condensed at –78 °C
into a three-necked round-bottomed condenser fitted with a cold
finger charged with dry ice/acetone. The temperature was raised to
–33 °C, and a solution of amine 10b (90 mg, 0.23 mmol) in THF
(2 mL) was added. Sodium metal was then added in small portions
until the blue color persisted. The mixture was stirred at –33 °C for
1 min. The reaction was quenched by addition of solid NH4Cl until
the blue color disappeared. The mixture was stirred at room temp.
for 4 h. The resulting residue was digested at room temp. with
CH2Cl2, poured into water, and extracted with CH2Cl2. The com-
bined organic extracts were dried and concentrated. Flash
chromatography (hexane/EtOAc 8:2) of the residue afforded 13b
1
(54 mg, 77%) as a white solid. [α]2D2 = +21.2 (c = 0.99, CHCl3). H
NMR (400 MHz, CDCl3, 25 °C): δ = 1.59 (d, J = 6.6 Hz, 3 H,
CH3), 2.40 (ddd, J = 12.3, 8.4, 5.1 Hz, 1 H, 3-H), 2.67 (m, 2 H, 4-
H), 3.25 (dt, J = 12.3, 4.2 Hz, 1 H, 3-H), 3.77 (dd, J = 10.5, 4.8 Hz,
1 H, CH2OH), 4.10 (dd, J = 10.5, 9.0 Hz, 1 H, CH2OH), 4.11 (q,
J = 6.6 Hz, 1 H, 1-H), 4.25 (dd, J = 9.0, 4.8 Hz, 1 H, CHAr), 7.06–
7.15 (m, 2 H, 6-H, 7-H), 7.24–7.35 (m, 6 H, 8-H, ArH), 7.43 (m, 1
H, 5-H), 7.65 (br. s, 1 H, NH) ppm. 13C NMR (100.6 MHz, CDCl3,
25 °C): δ = 19.7 (CH3), 21.4 (C-4), 42.2 (C-3), 50.5 (C-1), 60.9
(CH2OH), 62.8 (CHAr), 108.3 (C-4a), 110.7 (C-8), 118.1 (C-5),
119.4 (C-7), 121.5 (C-6), 127.0 (C-4b), 128.0 (C-p), 128.4 (C-o),
129.0 (C-m), 136.0 (C-i), 136.1 (C-8a), 136.2 (C-9a) ppm. IR (KBr):
(3R,11bS)-11,11b-Dimethyl-3-phenyl-3,5,6,11b-tetrahydro-2H-ox-
azolo[3Ј,2Ј:1,2]pyrido[3,4-b]indole (11a): [α]2D2 = –96.6 (c = 1.0,
CHCl3). 1H NMR (400 MHz, CDCl3, 25 °C): δ = 1.78 (s, 3 H,
CH3), 2.44 (dd, J = 16.0, 4.8 Hz, 1 H, 6-H), 2.91 (ddd, J = 16.0,
12.0, 5.6 Hz, 1 H, 6-H), 3.09 (dd, J = 14.4, 5.6 Hz, 1 H, 5-H), 3.17
(ddd, J = 14.4, 12.0, 5.2 Hz, 1 H, 5-H), 3.70 (t, J = 7.6 Hz, 1 H,
2-H), 3.80 (s, 3 H, NCH3), 3.97 (t, J = 7.6 Hz, 1 H, 2-H), 4.17 (t,
J = 7.6 Hz, 1 H, 3-H), 7.04 (ddd, J = 14.4, 7.2, 0.8 Hz, 1 H, 9-H),
7.16 (ddd, J = 14.4, 7.5, 1.2 Hz, 1 H, 8-H), 7.23–7.28 (m, 5 H,
ArH), 7.43 (d, J = 7.5 Hz, 1 H, 7-H) ppm. 13C NMR (100.6 MHz,
CDCl3, 25 °C): δ = 16.2 (C-6), 26.7 (CH3), 30.8 (NCH3), 40.9 (C-
5), 61.3 (C-3), 72.8 (C-2), 92.1 (C-11b), 107.2 (C-6a), 109.0 (C-10),
118.7 (C-7), 119.0 (C-9), 121.9 (C-8), 126.0 (C-6b), 127.7 (C-p),
127.5 (C-o), 127.8 (C-p), 136.0 (C-i), 137.4 (C-11a), 140.1 (C-
ν = 1454, 1644, 3440 cm–1. HRMS calcd. for C H N O [M +
˜
20 22
2
H]+: 307.1805; found 307.1790.
(R)-2-[(R)-2-Hydroxy-1-phenylethyl]-1-propyl-1,2,3,4-tetrahydropyr-
ido[3,4-b]indole (13c): Compound 13c (105 mg, 70%) was obtained
in the same way as in the above preparation of 13b (reaction time
10 min), from 10c (190 mg, 0.45 mmol) in THF (2 mL), sodium,
10a) ppm. IR (KBr): ν = 1382, 1470, 2927, 2934 cm–1. HRMS
˜
calcd. for C21H22N2O [M + H]+: 319.1810; found 319.1817.
(R)-2-[(R)-2-Hydroxy-1-phenylethyl]-1,9-dimethyl-3-oxo-1,2,3,4-tetra- and liquid NH3 (30 mL), as a white solid after flash chromatog-
hydropyrido[3,4-b]indole (12a): [α]2D2 = +70.8 (c = 0.5, CHCl3). 1H
NMR (400 MHz, CDCl3, 25 °C): δ = 1.38 (d, J = 6.4 Hz, 3 H,
CH3), 3.51 (s, 3 H, NCH3), 3.70 (d, J = 19.2 Hz, 1 H, 4-H), 3.82
raphy (hexane/EtOAc 95:5). [α]2D2 = +2.1 (c = 1.0, CHCl3). 1H
NMR (400 MHz, CDCl3, 25 °C): δ = 0.95 (t, J = 7.6 Hz, 3 H,
CH3), 1.30 (m, 1 H, CH2CH3), 1.53 (m, 1 H, CH2CH3), 1.72 (m,
(d, J = 19.2 Hz, 1 H, 4-H), 4.11 (dd, J = 12.0, 3.5 Hz, 1 H, 1 H, CH2CH2CH3), 2.07 (m, 1 H, CH2CH2CH3), 2.50–2.68 (m, 2
CH2OH), 4.37 (dd, J = 12.0, 7.2 Hz, 1 H, CH2OH), 4.83 (dd, J = H, 4-H), 2.65 (m, 1 H, 3-H), 3.25 (m, 1 H, 3-H), 3.80 (dd, J = 11.3,
7.2, 3.5 Hz, 1 H, CHAr), 7.07–7.09 (m, 1 H, 6-H), 7.15–7.38 (m, 6 5.2 Hz, 1 H, CH2OH), 4.01 (t, J = 11.3 Hz, 1 H, CH2OH), 4.10
H, 7-H, 8-H, ArH), 7.43 (d, J = 8.0 Hz, 1 H, 5-H) ppm. 13C NMR
(100.6 MHz, CDCl3, 25 °C): δ = 22.3 (CH3), 29.6 (C-4), 30.8
(NCH3), 53.0 (C-1), 64.3 (CHCH2), 66.1 (CH2OH), 103.9 (C-4a),
109.2 (C-8), 118.3 (C-5), 119.7 (C-6), 122.0 (C-7), 125.0 (C-4b),
(m, 1 H, CHAr), 7.03 (ddd, J = 7.2, 7.2,1.2 Hz, 1 H, 6-H), 7.07
(ddd, J = 8.0, 8.0, 1.6 Hz, 1 H, 7-H), 7.32 (m, 6 H, 8-H, ArH),
7.42 (d, J = 7.6 Hz, 1 H, 5-H), 7.71 (s, 1 H, NH) ppm. 13C NMR
(100.6 MHz, CDCl3, 25 °C): δ = 14.4 (CH3), 18.1 (CH2CH3), 35.5
127.3 (C-p), 128.2 (C-m), 128.7 (C-o), 134.0 (C-9a), 136.7 (C-8a), (CH2CH2CH3), 41.5 (C-3), 54.6 (C-1), 62.1 (CH2OH), 63.4
137.9 (C-i), 171.6 (CO) ppm. IR (KBr): ν = 1469, 1621, 2929, (CHAr), 109.1 (C-4a), 110.6 (C-8), 117.3 (C-5), 119.3 (C-7), 121.4
˜
1840
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1835–1842