Nickel-catalyzed Asymmetric Electrochemical Reactions

Electrochemical synthesis and asymmetric catalysis are two important disciplines in organic chemistry that have found significant applications.Electrochemistry has advanced tremendously as a platform for the identification of novel synthetic transformations in recent years.Combining asymmetric catalytic strategies with electrochemical organic synthesis can be used to tackle several tough difficulties in traditional asymmetric catalysis using the benefits of organic electrochemistry,which is of great research significance for opening up new reaction modes and realizing efficient,green,and sustainable catalytic asymmetric electrochemical synthesis.This dissertation focuses on the asymmetric α-functionalization of carbonyl compounds induced by chiral catalysts in combination with electrochemical reactions.Initially,we achieved an electrochemical asymmetric benzylation process using an effective combination of chiral Lewis acid catalysts and electrochemistry to catalytic activation of 2-acyl imidazoles.The benzylation products can be used to afford tetrahydroisoquinoline compounds with antibacterial properties.Mechanistic studies suggest that the Lewis-acid-bound radical intermediate from a single electron anodic oxidation selectively reacts with the benzylic radical species to generate the desired adducts.Asymmetric induction is realized through the radical-radical coupling of a chiral Lewis-acid-bound radical with an electrochemically formed benzylic radical species.As an important family of natural compounds,isopamine alkaloids with a tetracyclic tetrahydroisoquinoline core structure made of biphenyl cycloazabicyclo[3.2.2]nonane have been widely used in the treatment of various neurological diseases.The chiral Lewis acid-catalyzed enantioselective electrochemical anodic coupling process was introduced as a vital step in the described formal synthesis of isopavine alkaloids.Direct functionalization of catechol derivatives with 2-acyl imidazoles was developed to provide a wide range of desirable chiral α,αdiaryl carbonyl building blocks with good reactivity and stereoselectivity.The application of this unique enantioselective electrochemical procedure in the enantioselective formal synthesis of(+)-Amurensinine exemplifies its applicability.Finally,we developed a new electrolytic system that redirects standard ionic reactivity to new catalytic functions,allowing mechanistically distinct single-electron transfer-based enantioselective routes to exhibit a completely new pattern of reactivity electricity-driven asymmetric catalysis as a privileged chiral platform for enantioselective Keck radical allylation.Mechanistic investigations suggest that Nicatalyzed nucleophile activation prompted a selective single-electron transfer mechanism,resulting in a chiral catalyst-bound radical cation intermediate,which might be used as an alternate technique for developing stereocontrolled radical reactions.The feasibility of designing a reaction based on this privileged chiral platform is demonstrated,and the allylation product can then be used to create a CCR2 antagonist.