Enantioselective Rh Catalyzed Arylation Of N-Heteroaryl Ketones And Pd Catalyzed Cyanation Of Halogenated (Hetero) Aromatics

In this thesis,based on the new ligands derived from the benzoxaphosphine skeleton,we have developed a universal and efficient organometallic catalytic reaction and studied organic synthesis methodology containing N-heteroaromatic ring molecules.In the first part,the rhodium-catalyzed asymmetric arylation of N-heteroaryl ketones was realized.In the second part,the palladium catalyzed cyanation of halogenated(heteroaromatic)aromatics reaction is being explored.1.The enantioselective addition of arylboronic acids to N-heteroaryl ketones provides a convenient access to chiral α-heteroaryl tertiary alcohols,yet addition reactions of this type have been challenging due to catalyst deactivation.In this report,an efficient rhodium-catalyzed addition of arylboronic acids to N-heteroaryl ketones is established,affording a variety of valuable α-heteroaryl alcohols with excellent functional group compatibility.The employment of Wing Phos ligand containing two anthryl groups is crucial for this transformation.Especially,a range of chiral benzoxazolyl-substituted tertiary alcohols were formed with excellent ee values and yields by employing a Rh loading as low as 0.3 mol%,which can serve as practical protocol to furnish a series of chiral α-hydroxy acids after hydrolysis.2.Palladium-catalyzed cyanidation of halogenated(hetero)aromatics with large steric hindrance.Heteroaromatic nitrile compounds have important value in biomedicine,and the development of efficient preparation of heteroaromatic nitrile compounds assists in the development of new drugs.However,active molecules generally contain complex structures,and different regioselectivity results from the order in which functional groups are introduced.In addition,due to the poisoning of the catalyst by the cyanide sources and the aromatic nitrile products,as well as the inhibition of the catalytic reaction by the steric hindrance groups of the substrate,the cyanide reaction of aromatic halides with both large steric hindrance and heteroatoms has not yet achieved ideal results.Therefore,developing a universal catalytic system is crucial.We achieved palladium catalyzed cyanide reaction of large steric hindrance(hetero)aryl bromide compounds by screening ligands,precatalysts,and cyanide sources,achieving almost quantitative conversion of various substrates.Other types of halogenated substrates is currently being studied.