Synthesis Of Quinoline And Chromone Derivatives Via Photocatalytic C(sp~2)-H Alkylation

C-C bond is the most basic type of chemical bonds in organic chemistry and the research about synthesizing C-C bonds has never been stopped.The method of constructing C-C bond by transition-metal-catalyzed cross-coupling requires pre-functionalization of substrates,which increases the reaction steps and reduces the atom economy.The construction of C-C bond through C-H bond direct functionalization is simpler and more efficient than the classic cross-coupling reactions.However,the protocols for the alkylation of C-H bond such as transition-metal-catalyzed C-H bond alkylation and oxidant-induced radical C-H bond alkylation reaction are subject to demanding reaction conditions.Due to the mild conditions,environmental protection and other characteristics,the photocatalytic C-H bond alkylation has gradually become a hot research direction recently.Quinoline and chromone derivatives exist widely in various natural products and synthesized medicines due to their remarkable pharmacological activity.This thesis introduces two C?sp²?-H alkylation reactions based on photocatalysis,and applies them to the synthesis of quinoline and chromone derivatives.The specific research content is divided into the following three aspects:The first chapter mainly introduces the research progress of C-H bond direct alkylation in China and abroad,including transition-metal-catalyzed C-H bond alkylation and radical C-H bond alkylation.In addition,this chapter highlights a hot research field:Photocatalytic C-H bond alkylation and its application in constructing C?sp²?-C?sp³?and C?sp³?-C?sp³?bonds.The second chapter mainly introduces a visible-light-triggered alkylation of 8-aminoquinoline derivatives.In this chapter,32 examples of 2-alkyl or 2,4-dialkyl-8-aminoquinoline amides were synthesized in moderate to good yields?33?82%?under the irradiation of white light,fac-Ir?ppy?₃ as the photosensitizer and NHP ester?N-alkanoyloxyphthalimide?as the alkyl radical donor.This novel reaction system is mild,oxidant-free,and it's adapted to primary,secondary and tertiary radicals.The system was up to gram scale successfully,which is a method for synthesizing alkylated quinoline derivatives with good application prospects.The chapter 3 describes a visible-light-driven C?sp²?-H tandem alkylation/cyclization reaction and its application to the synthesis of chromones.With O-allyl salicylaldehyde as the starting substrates and NHP esters as the alkylating agent,13 examples of 3-alkylated chroman-4-ones were synthesized at room temperature in moderate to good yields?40?83%?only needing 1 mol%of the photosensitizer Ir[d F?CF₃?ppy]₂?dtbbpy?PF₆,and the system was up to gram scale successfully.This tandem alkylation/cyclization reaction is mild and easy to operate,which provides a new idea for the synthesis of alkylated chroman-4-one compounds.To summarize the full text,two cases of photocatalytic C?sp²?-H bond alkylation were developed and applied to the synthesis of quinoline and chromone derivatives respectively.Looking forward to the future research direction of C-H bond alkylation catalyzed by visible light,developing a cleaner and more efficient catalytic system is one of the key research areas.