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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
Author(s) -
Hameršak Zdenko,
Gašo Dajana,
Kovač Spomenka,
HergoldBrundić Antonija,
Vicković Ivan,
Šunjić Vitomir
Publication year - 2003
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200390181
Subject(s) - diastereomer , chemistry , aryl , hydrolysis , high performance liquid chromatography , homogeneous , stereochemistry , diphenylphosphine , organic chemistry , medicinal chemistry , catalysis , phosphine , physics , alkyl , thermodynamics
Aldol reaction of 7‐chloro‐1,3‐dihydro‐1‐methyl‐5‐phenyl‐2 H ‐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‐2 H ‐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 [Rh I (cod)(diphos‐4)]ClO 4 (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 ( 1 H‐NMR). The relative configurations were assigned by means of 1 H‐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.