Studies On Nickel/Photoredox-Catalyzed Enantioselective C(sp~3)-H Acylation

The merger of transition metal catalysis and photocatalysis was termed as metallaphotoredox catalysis.By using this strategy,common functional groups(e.g.,carboxylic acids,organoboron reagents,aldehydes,or organohalides)can be readily converted into reactive radical species to engage in transition metal-catalyzed bondforming reactions under exceptionally mild conditions.In this context,nickel metallaphotoredox catalysis has enabled many modular approaches for the formation of C-C and C-heteroatom bonds.However,the high reactivity of radical species has posed significant challenges for congrolling the stereoselectivity of these reactions,and the enantiselective nickel/photoredox-catalyzed cross-coupling remains challenging,especially for the asymmetric C(sp3)-H functionalization.The thesis is focused on the investigation of enantioselective C(sp3)-H acylation for the synthesis of chiral ketone via the combination of nickel/photoredox catalysis and carboxylic acid in situ-activation strategy.These achievements provide new ideas for the development of nicel/photoredox-catalyzed enantioselective C(sp3)-IH functionalization.The results obtained in this thesis are as follows:First,a nickel/photoredox-catalyzed asymmetric α-amino C(sp3)-H acylation has been achieved,providing a new approach for the synthesis of chiral α-amino ketones from commercially available carboxylic acids and readily available N-alkyl benzamides.This method features excellent yields and enantioselectivies,good functional group compatibility,and is applicable to gram scale synthesis and late-stage functionalization.(?)Second,an enantioselective benzylic C(sp3)-H acylation via dual nickel and photoredox catalysis has been achieved for the synthesis of enantioenriched a-aryl ketones.Advantages associated with this method include(1)commercial availability and low cost of both available coupling partners,(2)broad substrate scope and excellent functional group tolerance,and(3)the applicability to late-stage functionalization of medicinally relevant molecules,and to parallel synthesis of drug analogs.#12Third,a nickel/photoreodox-catalyzed α-oxy C(sp3)-H acylation has been accomplished.The synthesis of enantioenriched α-oxy ketones is achieved with similar metallaphotoredox strategy by using common ethers as the nucleophile coupling partner.