78498-83-6Relevant academic research and scientific papers
syn/anti Diastereoselectivity in the aldol reaction of aldehydes with the C(3) carbanion of 1,3-dihydro-2H-1,4-benzodiazepin-2-one
Markovic, Dean,Hamersak, Zdenko,Visnjevac, Aleksandar,Kojic-Prodic, Biserka,Sunjic, Vitomir
, p. 603 - 615 (2007/10/03)
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°afforded threo/erythro diastereoisomers 3-16 of 7-chloro-1,3-dihydro-3-(hydroxymethyl)-1-methyl-5-phenyl-2H-1,4- benzodiazepinones, 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. 1H-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 threo and erythro of the diastereoisomers 5 and 6, respectively, were established by single-crystal X-ray analysis, confirming the assignment based on the 1H-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-β-hydroxy-phenylalanine 17, whereas from 4, the N-(benzyloxy)carbonyl derivative 18 of erythro-β- 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 α-amino-β-hydroxy carboxylic acids and their congeners of biological importance.
