Enantioselective Reductive Cyclization of 1,6-Enynes via Rhodium-Catalyzed Asymmetric Hydrogenation:C-C Bond Formation Precedes Hydrogen Activation

摘要

Although elemental hydrogen is the cleanest and most cost-effective reductant available,the capture of organometallic species generated via hydrogenation has,until recently,only been achieved through migratory insertion of carbon monoxide (alkene hydro-formylation and the Fischer-Tropsch reactions).The principal challenge posed by hydrogen-mediated C-C bond formation involves partitioning of conventional hydrogenation and reductive coupling manifolds.Initial studies from our lab on hydrogen-mediated reductive aldol coupling demonstrate that conventional hydrogenation pathways are suppressed through the use of cationic rhodium precatalysts and mild basic additives.Such conditions are believed to induce heterolytic hydrogen activation.Subsequently developed reductive couplings of a-keto aldehydes to 1,3-dienes,1,3-enynes,and 1,3-diynes retain the requirement of a cationic rhodium precatalyst,yet proceed in the absence of basic additives,suggesting heterolytic hydrogen activation may not be operative.