Stereochemistry of 9-phenyl-hexahydro-1H-indeno[2,1-c]pyridines

Abstract

Catalytic reduction of 2-methyl-9-phenyl-2,3-dihydro-1H-indeno[2,1-c]pyridine (II) and the corresponding 2,3,4,9-tetrahydro-analogue, phenindamine (I), proceeds stereospecifically to give the sterically crowded all-cis-2,3,4,4a,9,9a-hexahydro-derivative (III). Treatment of this with alkali epimerises the C-9 centre to give the thermodynamically more stable substance (IV) with the hydrogen atoms at C-9 and C-9a now disposed trans to one another with consequent relief of steric compression. These stereochemical assignments are based on deuterium exchange studies with the two epimers under varying alkaline conditions and have been confirmed by a stereospecific synthesis of (III).