An Ir-catalyzed enantioselective hydrogenation of challenging tetrasubstituted exocyclic olefins is disclosed.This new catalytic system tolerates a broad substrate scope and affords valuable chiral cyclic β-amino est...An Ir-catalyzed enantioselective hydrogenation of challenging tetrasubstituted exocyclic olefins is disclosed.This new catalytic system tolerates a broad substrate scope and affords valuable chiral cyclic β-amino esters possessing two vicinal stereocenters in high yields and excellent enantioselectivities and diastereoselectivities(up to 94% yield,96% ee,99:1 dr).Control experiments and deuterium-labeling reactions reveal an iminium hydrogenation mechanism upon Brønsted acid-promoted tautomerization of the C=C double bond to cycliciminium intermediates.Density functional theory calculations showcase that the excellent selectivities are derived from C-H…π interaction between the substrate and the chiral ligand.Application in gram-scale preparation of dexmethylphenidate with up to 1500 turnover number is also demonstrated,showing the promising potential of Ir-catalyzed enantioselective hydrogenation in drug synthesis.展开更多
基金The National Natural Science Foundation of China(grant no.21991113)the Stable Support Plan Program of Shenzhen Natural Science Fund(program contract no.20200925161222002)+1 种基金Guangdong Basic and Applied Basic Research Foundation(grant nos.2021A1515110808 and 2021B1515020062)Guangdong Provincial Key Laboratory of Catalysis(grant no.2020B121201002).
文摘An Ir-catalyzed enantioselective hydrogenation of challenging tetrasubstituted exocyclic olefins is disclosed.This new catalytic system tolerates a broad substrate scope and affords valuable chiral cyclic β-amino esters possessing two vicinal stereocenters in high yields and excellent enantioselectivities and diastereoselectivities(up to 94% yield,96% ee,99:1 dr).Control experiments and deuterium-labeling reactions reveal an iminium hydrogenation mechanism upon Brønsted acid-promoted tautomerization of the C=C double bond to cycliciminium intermediates.Density functional theory calculations showcase that the excellent selectivities are derived from C-H…π interaction between the substrate and the chiral ligand.Application in gram-scale preparation of dexmethylphenidate with up to 1500 turnover number is also demonstrated,showing the promising potential of Ir-catalyzed enantioselective hydrogenation in drug synthesis.
