Convenient Entry to α-Amino-β-hydroxy-γ-methyl Carboxylic Acids. Diastereoselective Formation and Directed Homogeneous Hydrogenation of 3-(3-Aryl-1-hydroxy-2-methylprop-2-enyl)-1,4-benzodiazepin-2-ones

Aldol reaction of 7‐chloro‐1,3‐dihydro‐1‐methyl‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2‐one (1) with 4‐substituted α‐methylcinnamaldehydes 2–5 afforded a mixture of threo‐ and erythro‐3‐(3‐aryl‐1‐hydroxy‐2‐methylprop‐2‐enyl)‐7‐chloro‐1,3‐dihydro‐1‐methyl‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2‐ones 6–13. The chroma...

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Published in:Helvetica chimica acta 2003-06, Vol.86 (6), p.2247-2257
Main Authors: Hameršak, Zdenko, Gašo, Dajana, Kovač, Spomenka, Hergold-Brundić, Antonija, Vicković, Ivan, Šunjić, Vitomir
Format: Article
Language:English
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Summary:Aldol reaction of 7‐chloro‐1,3‐dihydro‐1‐methyl‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2‐one (1) with 4‐substituted α‐methylcinnamaldehydes 2–5 afforded a mixture of threo‐ and erythro‐3‐(3‐aryl‐1‐hydroxy‐2‐methylprop‐2‐enyl)‐7‐chloro‐1,3‐dihydro‐1‐methyl‐5‐phenyl‐2H‐1,4‐benzodiazepin‐2‐ones 6–13. The chromatographically separated threo diastereoisomers 6, 8, 10, and 12 and erythro diastereoisomers 7, 9, 11, and 13 were submitted to ‘directed' homogeneous hydrogenation catalyzed by [RhI(cod)(diphos‐4)]ClO4 (cod=cycloocta‐1,5‐diene, diphos‐4=butane‐1,4‐diylbis[diphenylphosphine]. From the erythro‐racemates 9, 11, and 13, the erythro,erythro/erythro,threo‐diastereoisomer mixtures 16/17, 20/21, and 24/25 were obtained in ratios of 20 : 80 to 28 : 72 (HPLC), which were separated by chromatography. From the threo racemates 8, 10, and 12, the threo,threo/threo,erythro‐diastereoisomer mixtures were obtained in a ratio of ca. 25 : 75 (1H‐NMR). The relative configurations were assigned by means of 1H‐NMR data and X‐ray crystal‐structure determination of 21. Hydrolysis of 21 afforded the diastereoisomerically pure N‐(benzyloxy)carbonyl derivative 27 of α‐amino‐β‐hydroxy‐γ‐methylpentanoic acid 26, representative of the novel group of polysubstituted α‐amino‐β‐hydroxycarboxylic acids.
ISSN:0018-019X
1522-2675
DOI:10.1002/hlca.200390181