Rhodium-or Nickel-Catalyzed Asymmetric Hydrogenation:Synthesis Of Chiral Nitrogenous Compounds

The asymmetric hydrogenation reaction catalyzed by chiral transition metal complexes is one of the most effective methods for synthesizing optically pure compounds and has been intensively explored over the past decades.Optically pure chiral amines,which can be used as resolving agents,chiral auxiliaries and key intermediates for synthesizing various bioactive molecules including natural and non-natural products,are very important in the organic synthesis.In this thesis,two new types of enamides have been designed for the Rh-catalyzed asymmetric hydrogenation.With the suitable chiral phosphine ligand,chiral amines can be obtained with excellent enantioselectivities in an efficient way.In addition,using the hydrogen bonding between the catalyst and the substrate,we have achieved an efficient and concise synthetic route to chiral ?-aminobutyric acids and their derivatives.Finally,the nickel-catalyzed asymmetric hydrogenation of Z/E isomeric mixtures of?-(acylamino)acrylates was developed,affording chiral ?-amino acid derivatives with excellent enantioselectivities,which declares that this nickel-catalyzed system can work as well as the precious metal-catalyzed system on the compatibility of Z/E mixtures.The detailed content is as follows:(1)We have developed a highly enantioselective hydrogenation of a-amino acrylonitriles to provide enantiomerically pure a-acylamino nitriles using a Rh-(S,S)-Me-DuPhos catalyst.Under mild conditions,a variety of substrates were converted to the a-acylamino nitriles with high yields and excellent enantioselectivities.On the basis of the various derivatizations of the cyano group,this reaction may therefore find use in diversity-oriented synthesis and medicinal chemistry.(2)With the assistance of hydrogen bonds,the first asymmetric hydrogenation of?-cyanocinnamic esters is developed,affording chiral ?-cyano esters with excellent enantioselectivities.This novel methodology provides an efficient and concise synthetic route to chiral chiral y-aminobutyric acids and their derivatives such as(S)-Pregabalin,(R)-Phenibut,(R)-Baclofen.(3)We have developed a highly enantioselective hydrogenation of tetrasubstituted cyclic enamides to provide enantiomerically pure cycloalkylamides using a Rh-Binapine catalyst.With the mild conditions,a variety of substrates was converted to the cycloalkylamides with excellent enantioselectivities.This methodology provides a concise route to the synthesis of cycloalkylamines.(4)Without any additives,we have developed a nickel-catalyzed asymmetric hydrogenation of Z/E isomeric mixtures of ?-alkyl and(?-aryl ?-(acylamino)acrylates,affording chiral ?-amino acid derivatives with excellent enantioselectivities.This method provides a concise route to the synthesis of ?-amino acids and their derivatives.