Asymmetric direct hydrogenation(ADH)is a straightforward and atom-economic methodology to achieve optically active compounds.The synthesis of chiral compounds bearing stereogenic centers has been well established.In c...Asymmetric direct hydrogenation(ADH)is a straightforward and atom-economic methodology to achieve optically active compounds.The synthesis of chiral compounds bearing stereogenic centers has been well established.In contrast,the construction of atropisomers,especially atropisomers bearing multiple chiral elements,has sporadically been explored.Herein,we report an innovative atroposelective iridium-catalyzed hydrogenation of N-arylindole ketones and heterobiaryl ketones via dynamic kinetic resolution(DKR)based on a Lewis acid-base interaction between the nitrogen atom and the carbonyl group of ketones,providing C-N and C-C atropisomers bearing multiple chiral elements with excellent enantioselectivities,diastereoselectivities and yields.The lynchpin of the DKR-ADH process stands in the newly developed planar-chiral tridentate PNO ligand,which ensures the excellent control of enantioselectivity and diastereoselectivity simultaneously.The synthetic utilization of this protocol is proved through stereospecific transformation to a tridentate PNN ligand bearing axial and central chirality,which shows promising potential in iridium-catalyzed asymmetric hydrogenation of simple ketones.展开更多
基金supported by the National Key Research and Development Program of China(2023YFA1507500)the National Natural Science Foundation of China(22171260,92356302)+1 种基金the Natural Science Foundation of Liaoning Province(2023-MS-009)the Dalian Institute of Chemical Physics(DICP I202442)。
文摘Asymmetric direct hydrogenation(ADH)is a straightforward and atom-economic methodology to achieve optically active compounds.The synthesis of chiral compounds bearing stereogenic centers has been well established.In contrast,the construction of atropisomers,especially atropisomers bearing multiple chiral elements,has sporadically been explored.Herein,we report an innovative atroposelective iridium-catalyzed hydrogenation of N-arylindole ketones and heterobiaryl ketones via dynamic kinetic resolution(DKR)based on a Lewis acid-base interaction between the nitrogen atom and the carbonyl group of ketones,providing C-N and C-C atropisomers bearing multiple chiral elements with excellent enantioselectivities,diastereoselectivities and yields.The lynchpin of the DKR-ADH process stands in the newly developed planar-chiral tridentate PNO ligand,which ensures the excellent control of enantioselectivity and diastereoselectivity simultaneously.The synthetic utilization of this protocol is proved through stereospecific transformation to a tridentate PNN ligand bearing axial and central chirality,which shows promising potential in iridium-catalyzed asymmetric hydrogenation of simple ketones.
