Lipase-catalysed kinetic resolution as the key step in the synthesis of a new class of optically active 5,6-trans-9,10-dihydrophenanthroline derivatives

New atropisomeric 5,6-trans-9,10-dihydrophenanthroline amino- and hydroxy-derivatives 3-7 possessing two additional stereogenic centres were obtained in high enantiomeric purity by lipase-catalysed kinetic resolution of the corresponding easily accessible racemates. Lipase from Pseudomonas fluorescens (Lipase AK) showed good enantioselectivity (E > 200) in the esterification reaction of trans-5-azido-6-hydroxyl derivative (+/-)-7, giving access to the enantioforms (+)- and (-)-7 isolated with ee = 97% and ee >98%, respectively. The chemical reduction of azide group furnished the homochiral amino derivatives (+)- and (-)-4 without a loss in enantiomeric purity. For all the substrates investigated, lipase AK( revealed a stereopreference for the enantiomer with a (P,R,R)-configuration. (C) 2008 Elsevier Ltd. All rights reserved.