A Short Synthesis of an Apogalanthamine Analogue
FULL PAPER
Synthesis of Benzyl [2-(3Ј-Chloro-4,5-dimethoxybiphenyl-2-yl)ethyl]-
carbamate (5c): Compound 5c was synthesized from amine 3 87%) as a pale yellow oil. H NMR (400 MHz, CDCl3): δ ϭ 2.78
(197 mg) and (3-chlorophenyl)boronic acid (4c, 101 mg, 0.65 mmol, (t, J ϭ 7.0 Hz, 2 H), 3.29 (dd, J ϭ 7.0 Hz, 2 H), 3.86 (s, 3 H), 3.88
ether/hexane (1:1)] afforded analytically pure product (210 mg,
1
1.3 equiv.). Column chromatography [silica gel, diethyl ether/hex-
ane (1:1)] afforded analytically pure product (183 mg, 86%) as a
pale yellow oil. H NMR (400 MHz, CDCl3): δ ϭ 2.73 (t, J ϭ 6.4
(s, 3 H), 4.78 (br. s, NH), 5.05 (s, 2 H), 6.75 (s, 1 H), 6.79 (s, 1 H),
7.03 (d, J ϭ 8.0 Hz, 2 H), 7.09 (d, J ϭ 7.7 Hz, 2 H), 7.24 (d, J ϭ
8.4 Hz, 2 H), 7.36 (m, 7 H) ppm. 13C NMR (100 MHz, CDCl3):
1
Hz, 2 H), 3.26 (q, J ϭ 6.4 Hz, 2 H), 3.84 (s, 3 H), 3.85 (s, 3 H), δ ϭ 33.0, 41.9, 55.8, 55.9, 65.0, 112.4, 113.4, 118.3, 119.0, 123.3,
3.86 (s, 3 H), 4.84 (br. s, NH), 5.05 (s, 2 H), 6.69 (s, 1 H), 6.78 (s, 126.8, 127.9, 128.0, 128.4, 129.7, 130.6, 132.0, 133.9, 136.1, 141.0,
1 H), 7.23 (m, 5 H), 7.42 (d, J ϭ 8.7 Hz, 1 H), 7.55 (d, J ϭ 8.7 147.1, 148.1, 156.3, 156.9 ppm. DEPT (100 MHz, CDCl3): δ ϭ
Hz, 1 H), 7.83 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ Ϫ33.3, Ϫ42.4, 56.3, 56.4, Ϫ65.6, 113.0, 113.9, 119.5, 123.9, 127.4,
32.8, 42.0, 55.8, 56.1, 66.7, 112.7, 113.4, 119.8, 127.1, 127.7, 128.0,
128.1, 128.5, 129.4, 129.5, 133.6, 134.1, 143.2, 147.3, 148.7, 156.5,
157.8, ppm. DEPT (100 MHz, CDCl3): δ ϭ Ϫ32.9, Ϫ42.1, 55.9,
56.0, Ϫ66.5, 113.6, 126.9, 127.9, 128.0, 128.3, 128.5, 129.4 ppm.
LR-MS (EI) [Mϩ]: 425, 91 (100%).
128.5, 128.9, 130.2, 131.1, 132.4 ppm. LR-MS (EI): [Mϩ]: 483, 91
(100%).
Synthesis of Benzyl [2-(4Ј-Hydroxymethyl-4,5-dimethoxybiphenyl-2-
yl)ethyl]carbamate (5i): Compound 5i was synthesized from amine
3 (197 mg) and [(4-hydroxymethyl)phenyl]boronic acid (4i, 99 mg,
0.65 mmol, 1.3 equiv.). Column chromatography [silica gel, diethyl
Synthesis of Benzyl [2-(4Ј-Chloro-4,5-dimethoxybiphenyl-2-yl)ethyl]-
carbamate (5d): Compound 5d was synthesized from amine 3 ether/hexane (1:1)] afforded analytically pure product (166 mg,
1
(197 mg) and (4-chlorophenyl)boronic acid (4d, 101 mg, 79%) as a colorless oil. H NMR (400 MHz, CDCl3): δ ϭ 2.73 (t,
0.65 mmol, 1.3 equiv.). Column chromatography [silica gel, diethyl
J ϭ 7.0 Hz, 2 H), 3.22 (dd, J ϭ 7.0 Hz, 2 H), 3.82 (s, 3 H), 3.86
ether/hexane (1:1)] afforded analytically pure product (179 mg,
(s, 3 H), 4.2 (br. s, OH), 4.69 (s, 2 H), 4.76 (br. s, NH), 5.01 (s, 2
1
84%) as a yellowish oil. H NMR (400 MHz, CDCl3): δ ϭ 2.74 (t, H), 6.70 (s, 1 H), 6.77 (s, 1 H), 7.25 (d, J ϭ 8.0 Hz, 2 H), 7.30 (d,
J ϭ 6.6 Hz, 1 H), 3.27 (dd, J ϭ 6.6 Hz, 2 H), 3.86 (s, 3 H), 3.88 J ϭ 8.0 Hz, 2 H), 7.35 (m, 5 H) ppm. 13C NMR (100 MHz,
(s, 3 H), 4.73 (br. s, NH), 5.05 (s, 2 H), 6.69 (s, 1 H), 6.79 (s, 1 H),
CDCl3): δ ϭ 32.8, 41.9, 55.8, 55.9, 64.8, 65.0, 112.6, 113.5, 126.8,
7.22 (d, J ϭ 8.0 Hz, 2 H), 7.35 (m, 7 H) ppm. 13C NMR (100 MHz, 127.4, 128.0, 128.4, 129.4, 131.9, 134.4, 139.7, 140.6, 141.0, 147.2,
CDCl3): δ ϭ 32.8, 41.9, 55.8, 55.9, 65.2, 112.5, 113.2, 126.9, 127.5, 148.2, 156.2 ppm. DEPT (100 MHz, CDCl3): δ ϭ Ϫ32.9, Ϫ42.0,
128.0, 128.5, 130.6, 132.0, 132.9, 133.3, 136.4, 139.7, 148.4, 55.9, 56.0, Ϫ64.9, Ϫ65.1, 112.7, 113.5, 126.9, 127.5, 128.4, 129.5,
156.1 ppm. DEPT (100 MHz, CDCl3): δ ϭ Ϫ33.3, Ϫ42.4, 56.3, 132.0 ppm. LR-MS (EI) [Mϩ]: 421, 91 (100%).
56.4, Ϫ65.7, 113.0, 113.7, 127.4, 128.5, 129.1, 131.1, 132.4 ppm.
Synthesis of Benzyl [2-(2-Furan-2-yl-4,5-dimethoxyphenyl)ethyl]car-
bamate (5j): Compound 5j was synthesized from amine 3 (197 mg)
and 2-furylboronic acid (4j, 73 mg, 0.65 mmol, 1.3 equiv.). Column
LR-MS (EI) [Mϩ]: 425, 390, 91 (100%).
Synthesis of Benzyl [2-(4,5,3Ј-Trimethoxybiphenyl-2-yl)ethyl]carba-
mate (5f): Compound 5f was synthesized from amine 3 (197 mg) chromatography [silica gel, diethyl ether/hexane (1:1)] afforded ana-
and (3-methoxyphenyl)boronic acid (4f, 99 mg, 0.65 mmol, 1.3 lytically pure product (162 mg, 79%) as a pale yellow oil. 1H NMR
equiv.). Column chromatography [silica gel, diethyl ether/hexane
(400 MHz, CDCl3): δ ϭ 2.74 (t, J ϭ 6.7 Hz, 2 H), 3.25 (dd, J ϭ
(1:1)] afforded analytically pure product (187 mg, 89%) as a pale
6.7 Hz, 2 H), 3.81 (s, 3 H), 3.83 (s, 3 H), 4.75 (br. s, NH), 5.02 (s,
1
yellow oil. H NMR (400 MHz, CDCl3): δ ϭ 2.96 (t, J ϭ 7.0 Hz, 2 H), 6.70 (s, 1 H), 6.76 (s, 1 H), 6.85 (m, 3 H), 7.30 (m, 5 H) ppm.
2 H), 3.43 (dd, J ϭ 6.7 Hz, 2 H), 3.83 (s, 3 H), 3.84 (s, 3 H), 3.88 13C NMR (100 MHz, CDCl3): δ ϭ 32.8, 42.0, 55.9, 56.0, 66.6,
(s, 3 H), 4.87 (br. s, NH), 5.08 (s, 2 H), 6.48 (s, 1 H), 6.73 (s, 1 H),
112.7, 113.5, 115.2, 121.9, 126.9, 128.2, 128.5, 129.3, 134.6, 136.6,
7307 (s, 1 H), 7.40 (m, 8 H) ppm. 13C NMR (100 MHz, CDCl3): 142.9, 147.3, 148.4, 156.4, 159.5 ppm. DEPT (100 MHz, CDCl3):
δ ϭ 33.8, 41.8, 55.8, 55.9, 56.0, 65.2, 107.3, 112.2, 112.4, 111.3, δ ϭ Ϫ32.8, Ϫ42.1, 55.9, 56.0, Ϫ66.6, 112.4, 112.7, 113.5, 115.2,
111.6, 111.9, 120.6, 123.0, 127.5, 128.0, 128.5, 136.5, 141.6, 147.4,
121.9, 128.0, 128.5, 129.3 ppm. LR-MS (EI) [Mϩ]: 381, 91 (100%).
148.7, 153.4, 156.3 ppm. DEPT (100 MHz, CDCl3): δ ϭ Ϫ34.3, HR-MS (EI) : C22H23NO5 found 381.15768, calcd. 381.15762.
Ϫ42.3, 56.2, 56.3, 56.4, Ϫ66.9, 112.1, 112.4, 113.8, 121.1, 127.4,
Synthesis of Benzyl [2-(4,5-Dimethoxy-2-pyridin-4-ylphenyl)ethyl]-
carbamate (5k): Compound 5k was synthesized from amine 3
(197 mg, 0.5 mmol) and (benzofuran-2-yl)boronic acid (4k, 80 mg,
128.4, 128.9, 130.8, 142.0 ppm. LR-MS (EI) [Mϩ]: 421, 91 (100%).
Synthesis of Benzyl [2-(4,5,4Ј-Trimethoxybiphenyl-2-yl)ethyl]carba-
mate (5g): Compound 5g was synthesized from amine 3 (197 mg, 0.65 mmol, 1.3 equiv.). Column chromatography [silica gel, di-
0.5 mmol) and (4-methoxyphenyl)boronic acid (4g, 99 mg, chloromethane Ϫ methanol (19:1)] afforded analytically pure prod-
0.65 mmol, 1.3 equiv.). Column chromatography [silica gel, diethyl
uct (176 mg, 90%) as a yellow oil. 1H NMR (300 MHz, CDCl3):
ether/hexane (1:1)] afforded analytically pure product (183 mg,
87%) as a pale yellow oil. H NMR (400 MHz, CDCl3): δ ϭ 2.74 H), 3.88 (s, 3 H), 4.81 (br. s, 1 H), 5.00 (s, 2 H), 6.68 (s, 1 H), 6.80
δ ϭ 2.75 (t, J ϭ 7.3 Hz, 2 H), 3.28 (q, J ϭ 7.3 Hz, 2 H), 3.86 (s, 3
1
(t, J ϭ 7.3 Hz, 1 H), 3.25 (dd, J ϭ 6.6 Hz, 2 H), 3.83 (s, 3 H), 3.84
(s, 3 H), 3.86 (s, 3 H), 4.66 (br. s, 1 H), 5.04 (s, 2 H), 6.71 (s, 1 H),
(s, 1 H), 7.33 (m, 6 H), 7.46 (dt, 1J ϭ 7.32, 2J ϭ 2.93 Hz, 1 H),
2
7.55 (dt, 1J ϭ 7.32, J ϭ 1.47 Hz, 1 H), 7.67 (dd, J ϭ 7.32, 6.59
6.76 (s, 1 H), 6.92 (d, J ϭ 8.8 Hz, 2 H), 7.20 (m, 5 H) ppm. 13C Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 32.7, 42.0, 55.9,
NMR (100 MHz, CDCl3): δ ϭ 32.8, 41.9, 55.2, 55.8, 55.9, 65.2, 56.0, 66.6, 112.6, 113.7, 128.0, 128.1, 128.4, 128.5, 128.5, 131.2,
112.5, 113.6, 114.7, 126.9, 127.5, 127.9, 128.0, 128.2, 128.5, 131.7,
131.3, 131.9, 131.9, 132.0, 132.1, 147.5, 149.33, 156.1 ppm. DEPT
134.3, 136.5, 140.8, 147.1, 148.0 ppm. DEPT (100 MHz, CDCl3): (75 MHz, CDCl3): δ ϭ Ϫ33.2, Ϫ42.4, 56.4, 56.4, Ϫ67.0, 113.1,
δ ϭ Ϫ33.2, Ϫ42.4, 55.7, 56.3, 56.4, Ϫ65.7, 112.9, 114.0, 127.4,
113.1, 128.5, 128.8, 129.0, 132.6, 149.8 ppm. LR-MS (EI) [Mϩ]:
392, 91 (100%).
128.0, 128.5, 128.9, 130.8 ppm. LR-MS (EI) [Mϩ]: 421, 91 (100%).
Synthesis of Benzyl [2-(4,5-Dimethoxy-4Ј-phenoxybiphenyl-2-yl)-
ethyl]carbamate (5h): Compound 5h was synthesized from amine 3
(197 mg) and (4-phenoxyphenyl)boronic acid (4h, 139 mg,
0.65 mmol, 1.3 equiv.). Column chromatography [silica gel, diethyl
Synthesis of Benzyl [2-(2Ј-Formyl-4,5-dimethoxybiphenyl-2-yl)ethyl]-
carbamate (7): Compound 3 (197 mg, 0.5 mmol), (2-formylphe-
nyl)boronic acid (6, 97.5 mg, 0.65 mmol, 1.3 equiv.), and tetrakis-
(triphenylphosphane)palladium(0) (29 mg, 5 mol %) were sus-
Eur. J. Org. Chem. 2004, 3277Ϫ3285
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3283