Naslov
Syn/anti diatereoselectivity in the aldol reaction of aldehydes with the C(3) carbanion of 1,3-dihydro-2H-1,4-benzodiazepin-2-one

Autori
Marković, Dean ; Hameršak, Zdenko ; Višnjevac, Aleksandar ; Kojić-Prodić, Biserka ; Šunjić, Vitomir

Izvornik
Helvetica chimica acta (0018-019X) 83 (2000), 3; 603-615

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Alpha-amino-acids; Enantioselective synthesis; Carbonyl-compounds; Condensation; Alkoxy

Sažetak
The aldol reaction of the C(3) carbanion of 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one (2) with a series of aromatic and aliphatic aldehydes at -78 degrees afforded threolerythro diastereoisomers 3-16 of 7-chloro-1,3-dihydro-3-(hydroxymethyl)-1-methyl-5-phenyl-2H-1,4-benzodiazepin ones, substituted at the C(3) side chain, in a ratio from 55:45 to 94:6 (Scheme 1). Lewis acids exhibited limited effect on the syn/ anti diastereoselectivity of this reaction, and kinetic control of the reaction was confirmed. H-1-NMR Data suggested the assignment of the threo relative configuration to the first-eluted diastereoisomers 3, 5, 7,and 9 on reversed-phase HPLC, and the erythro configuration to the second-eluted counterparts 4, 6, 8, and 10, respectively. The structures and relative configurations three and erythro of the diastereoisomers 5 and 6, respectively, were established by single-crystal X-ray analysis, confirming the assignment based on the H-1-NMR data. A tentative mechanistic explanation of the diastereoselectivity invokes the enolate anion of 1,3-dihydro-2H-1,4-benzodiazepin-2-one as the reactive species (Scheme 2). Acid-catalyzed hydrolytic ring opening of 3 afforded threo-beta-hydroxy-phenylalanine 17, whereas from 4, the N-(benzyloxy)carbonyl derivative 18 of erythro-beta-hydroxy-phenylalanine was obtained (Scheme 3); in both cases, neither elimination of H2O from the C(3)-CHOH moiety nor epimerization at C(3) were observed. This result opens a new pathway to various configurationally uniform alpha-amino-beta-hydroxy carboxylic acids and their congeners of biological importance.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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