Original scientific paper

Diastereoselective Aldol Reaction of 7-Bromo-5-pyrido-1,4-benzodiazepin-2-one; Relative and Absolute Configuration of All Stereoisomers

Maja Majerić-Elenkov ; Ruđer Bošković Institute, P.O. Box 180, Bijenička 54, 10002 Zagreb, Croatia
Dinko Žiher ; PLIVA d.d., Research and Development, Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia
Aleksandar Višnjevac ; Ruđer Bošković Institute, P.O. Box 180, Bijenička 54, 10002 Zagreb, Croatia
Zdenko Hameršak ; Ruđer Bošković Institute, P.O. Box 180, Bijenička 54, 10002 Zagreb, Croatia
Biserka Kojić-Prodić ; Ruđer Bošković Institute, P.O. Box 180, Bijenička 54, 10002 Zagreb, Croatia
Vitomir Šunjić ; Ruđer Bošković Institute, P.O. Box 180, Bijenička 54, 10002 Zagreb, Croatia

Abstract

Aldol reaction of C(3) carbanion of 7-bromo-5-pyrido-1,4-benzodia-zepin-2-one (1) with representative aliphatic and aromatic aldehydes and ketones afforded racemic mixtures syn/anti-7-bromo-3-(1'-hydroxy-1'-phenylmethyl)-1-methyl-5-(2'-pyridyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one (2/3), syn/anti-7-bromo-3-(1'-hydroxy-1'-phenylethyl)-1-methyl-5-(2'-pyridyl)-2,3-dihydro-1H-1,4-benzodiazepin -2-one (4/5) and syn/anti-7-bromo-3-(1'-hydroxy-2'-methylpropyl)-1-methyl-5-(2'-pyridyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one (6/7) with 60-85% diastereoselectivity. For prevailing diastereomeric racemates (±)-2 and (±)-4, syn relative configuration is deduced, whereas the prevailing diastereomer (±)-7 has anti configuration. Configurational assignment is based on NMR data and X-ray structure analysis, and the origin of inversion of diastereoselectivity is discussed. Racemic mixtures were separated on chiral HPLC column, and on the basis of the CD spectra (3R) absolute configuration was determined for (+)-enantiomers, and (SS) configuration for (-)-enantiomers. Consequently, (3R,1'S) configuration is assigned to syn-(+)-enantiomers and (3R,1'R)-configuration to anti-(+)-enantiomers. In an attempt to use enantiomerically pure compounds 2-7 as catalysts in asymmetric alkylation of benzaldehyde by diethylzinc, these ligands proved chemically and configuration-ally unstable.

Keywords

1,4-benzodiazepines; enantioseparation; HPLC chiral chromatography; relative and absolute configuration

Hrčak ID:

131925

URI

https://hrcak.srce.hr/131925

Publication date:

1.8.2001.

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