Isomerization‐Asymmetric Hydrogenation Sequence Converting Racemic β‐Ylidenecycloalkanols into Stereocontrolled β‐Substituted Cycloalkanols Using a Ru Catalytic System with Dual Roles

Racemic β‐ylidenecycloalkanols were transformed into the cis‐β‐substituted cycloalkanols with high enantio‐ and diastereoselectivities through an isomerization‐asymmetric hydrogenation sequence with the (4,4′‐bi‐1,3‐benzodioxole)‐5,5′‐diylbis[di(3,5‐xylyl)phosphine (DM‐Segphos)/2‐dimethylamino‐1‐phenylethylamine (DMAPEN)‐ruthenium(II) catalyst; such transformation hardly proceeded by single‐step asymmetric hydrogenation. The reaction was usually carried out with a substrate‐to‐catalyst molar ratio of 500 under 4 to 10 atm of H2 to afford the products in cis/trans ratio up to 99:1 and 98% ee. Mechanistic experiments suggested that this catalytic system reversibly formed two reactive species, types (I) and (II), through a ruthenacyclic amide intermediate. The amide complex and allylic alcohol reacted to afford the allylic alkoxide complex with partial or full removal of diamine (type (I)), and this type (I) complex catalyzed isomerization of the allylic alcohols into the racemic α‐substituted ketones. The RuH2 complex with chelation of diamine (type (II)) formed by reaction of the amide complex and hydrogen promoted asymmetric hydrogenation of racemic α‐substituted ketone into the stereocontrolled β‐substituted cycloalkanols through dynamic kinetic resolution.