Diastereoselective aldol reaction of 7-bromo-5-pyrido-1,4-benzodiazepin-2-one; Relative and absolute configuration of all stereoisomers

Aldol reaction of C(3) carbanion of 7-bromo-5-pyrido-1,4-benzodiazepin-2-on e (1) with representative aliphatic and aromatic aldehydes and ketones affo rded 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 ' -hyd roxy-2 ' -methylpropyl)-1-methyl-5-(2 ' -pyridyl)-2,3-dihydro-1H-1,4-benzod iazepin-2-one (6/7) with 60-85% diastereoselectivity. For prevailing diaste reomeric racemates (+/-)-2 and (+/-)-4, syn relative configuration is deduc ed, whereas the prevailing diastereomer (+/-)-7 has anti configuration. Con figurational assignment is based on H-1 NMR data and X-ray structure analys is, and the origin of inversion of diastereoselectivity is discussed. Racem ic mixtures were separated on chiral HPLC column, and on the basis of the C D spectra (3R) absolute configuration was determined for (+)-enantiomers, a nd (3S) configuration for (-)-enantiomers. Consequently, (3R,1 'S) configur ation is assigned to syn-(+)-enantiomers and (3R,1 'R)-configuration to ant i(+)-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 configurationally unstable.