Diastereoselective Intramolecular α-Amidoalkylation Reactions of l -DOPA Derivatives. Asymmetric Synthesis of Pyrrolo[2,1- a ]isoquinolines (original) (raw)

2005, The Journal of Organic Chemistry

Contents of file 1 (current file) • General experimental methods S2 • (S)-(+)-2-tert-Butoxycarbonylamino-3-(3,4-dimethoxyphenyl)propionic acid methyl ester (3). S2 • (S)-(-)-[2-(3,4-Dimethoxyphenyl)-1-hydroxymethylethyl]carbamic acid tert-butyl ester (4) S3 • (S)-(-)-[1-(tert-Butyldiphenylsilyloxymethyl)-2-(3,4-dimethoxyphenyl)ethyl]carbamic acid tert-butyl ester (5a). S3 • (S)-(-)-[1-(Benzyloxymethyl)-2-(3,4-dimethoxyphenyl)ethyl]carbamic acid tert-butyl ester (5b) S4 • (S)-(-)-[1-(Methoxymethyl)-2-(3,4-dimethoxyphenyl)ethyl]carbamic acid tert-butyl ester (5c). S5 • Synthesis of amines 8a-c. General procedure S6 • Synthesis of succinimides 9a-c. General procedure S7 • (S)-(-)-1-[2-(3,4-Dimethoxyphenyl)-1-(hydroxymethyl)ethyl]pyrrolidine-2,5-dione (9d). S9 • References S10 Contents of file 2 • Copies of 1 H NMR and 13 C NMR of compounds S11 to S56 S1 General experimental methods: Melting points were determined in unsealed capillary tubes and are uncorrected. IR spectra were obtained on KBr pellets (solids) or CHCl 3 solution (oils). NMR spectra were recorded at 20-25 ˚C, running at 250 MHz for 1 H and 62.8 MHz for 13 C in CDCl 3 solutions. Assignment of individual 13 C resonances are supported by DEPT experiments. 1 H-{ 1 H} NOE experiments were carried out in the difference mode by irradiation of all the lines of a multiplet. 1 Mass spectra were recorded under electron impact at 70 eV. GC-MS analyses were performed using a TRB-1 column (methyl polysiloxane, 30 m × 0.25 mm × 0.25 µm). TLC was carried out with 0.2 mm thick silicagel plates. Visualization was accomplished by UV light. Flash column chromatography 2 on silica gel was performed with Kiesegel 60 (230-400 mesh). CSP HPLC was performed using Chiralcel OD or OJ columns (0.46 cm × 25 cm). All solvents used in reactions were anhydrous and purified according to standard procedures. 3 Organolithium reagents were titrated with diphenylacetic acid periodically prior to use. All air-or moisture-sensitive reactions were performed under argon; the glassware was dried (130 ˚C) and purged with argon. (S)-(+)-2-tert-Butoxycarbonylamino-3-(3,4-dimethoxyphenyl)-propionic acid methyl ester (3). NEt 3 (4.24 mL, 30.4 mmol)was added to a solution of L-DOPA (1) (5.00 g, 25.3 mmol) in dioxane/water (50%, 80 mL). (Boc) 2 O (6.64 g, 30.4 mmol) was added in one portion at 0 ºC, and the resulting mixture was sitirred at this temperature for 30 min, and at rt for 18 h. The solvent was removed under vacuum, and H 2 O (30 mL) and AcOEt (30 mL) were added. The aqueous phase was acidified with HCl 2M to pH = 1, and was extracted with AcOEt (3 × 20 mL). The combined organic extracts were washed with brine (3 × 20 mL), dried (Na 2 SO 4) and concentrated in vacuo to obtain the 2-tert-Butoxycarbonylamino-3-(3,4-dimethoxyphenyl)alanine (2) that was used without further purification. Over a solution of crude 2 in acetone (50 mL), K 2 CO 3 (12.25 g, 88.0 mmol) and Me 2 SO 4 (8.15 mL, 86.0 mmol) were added, and the mixture was refluxed for 48 h. The solvent was removed under vacuum, and the resulting white solid was disolved in CH 2 Cl 2 (30 mL). The solution was washed with brine (3 × 20 mL), dried (Na 2 SO 4) and concentrated in vacuo. Flash column chromatography (silicagel, 60% hexane/ethyl acetate) yielded S2