Visible Light Induced Intermolecular [2+2] Photocycloaddition Of Chalcones With 2,3-dimethyl-1,3-butadiene And Acylation Reaction Of Imidazo[1,2-a]pyridine

In the face of resource shortage and environmental pollution,it is urgent to find sustainable green energy.As a kind of energy that can be obtained from the sun continuously,visible light is easy to get,inexhaustible and green,so its development and utilization are attracting more and more attention.Photocatalysis as a green catalytic method,has been widely used in chemical synthesis.Scientists use photosensitizers to make the reactions possible for the substances that cannot directly absorb light.Photocatalysis can achieve many different types of chemical reactions,such as reductive amination,acylation,halogenation and alkylation etc.However,most photocatalytic reactions require expensive,toxic and post-processing complicated metal complex?eg:Ru,Ir etc?as photosensitizer,and potential hazards and environmental pollution make their applications limited.Therefore,it is important to choose cheap,easy to handle organic dyes or even without photosensitizer.Olefin is a kind of widely and important chemical raw material.The bifunctionalization of C?sp²?=C?sp²?of olefin can rapidly increase the complexity of molecules and build complex molecules.In photocatalytic reactions,C=C can be used as a radical acceptor,or be oxidized to a radical cation,or be reduced to a radical anion,even being directly induced by visible light to produce double radicals.In addition,visible light can also catalyze the C?sp²?-H functionalization reaction.All of these properties make C=C widely studied in the field of photocatalysis.In the second chapter of this thesis,the intermolecular[2+2]photocycloaddition of chalcones with 2,3-dimethyl-1,3-butadiene under visible-light irradiation for the synthesis of cyclobutane derivatives was described.Since many ketenes do not absorb in the visible region,and the traditional methods for the ketene[2+2]cycloaddition reaction require high-energy ultraviolet lamp or high-pressure mercury lamp as light source.Visible light initiated ketene[2+2]cycloaddition reactions need by means of photosensitizers through triplet energy transfer or single electron transfer pathway to finish.Solvents are important mediators for organic reactions,but solvents are mostly toxic and can pollute the environment.Avoiding the use of solvents is beneficial to environmental protection.Therefore,we tried to carry out the intermolecular[2+2]photocycloaddition reaction under neat reaction conditions.We selected chalcone and2,3-dimethyl-1,3-butadiene as a model reaction,and obtained the optimal conditions after screening the light source,molar ratio and reaction time.The substrates scope of the reaction was explored under the optimized reaction conditions,and thirteen cyclobutane derivatives were obtained with yields of up to 72%.The reaction proceeded with high regioselectivity and moderate to high stereoselectivity.Based on the mechanism studies and density functional theory?DFT?calculations,a possible reaction mechanism was proposed.The ground state chalcone?S₀?absorbs energy into the first excited singlet state?S₁?under visible light irradiation,and then undergoes a rapid intersystem crossing?ISC?to form the excited triplet state?T₁?.It reacts with 2,3-dimethyl-1,3-butadiene to generate1,4-diradical intermediates?DR1,DR2?,which finally obtained a cyclobutane derivative via ring closure.This work provides a greener and simpler method for the synthesis of photocatalytic cyclobutane derivatives.In the third chapter of this thesis,the visible light induced selective C3 acylation of imidazo[1,2-a]pyridine to synthesize imidazo[1,2-a]pyridin-3-yl?phenyl?methanone was explored.Imidazo[1,2-a]pyridine is the core skeleton of many marketed medicines,and its medicinal activity is significantly affected by the imidazo[1,2-a]pyridine C3 functional group.Imidazo[1,2-a]pyridine 3-yl?phenyl?methanone is the structural unit of an anticancer drug and a calcium channel blocker.Therefore,it is necessary to explore methods for C3 functionalization of imidazo[1,2-a]pyridine.We chose imidazo[1,2-a]pyridine and nitrone as substrates,Mes-Acr⁺ClO₄^-as catalyst,and white light as light source,realized the selective C3 acylation of imidazo[1,2-a]pyridine.After condition screening,the optimal conditions were obtained.Under the optimal conditions,the universality of the reaction was explored.Eighteen products were obtained with medium yields.Based on control experiments,fluorescence quenching experiments and intermediate conversion etc,a possible reaction mechanism was proposed.Under the irradiation of visible light,photocatalyst Mes-Acr⁺converted to its excited state.The C=C on the imidazo[1,2-a]pyridine ring is oxidized by Mes-Acr^+*to generate a radical cation,which then addition to nitrone to produce an intermediate.The intermediate loses nitrosobenzene and proton to generate benzyl radical.The benzyl radical is captured by superoxide radical anion,then combines with a proton and loses one molecule of water to form the desired product.This is the first report on the selective C3 acylation of imidazo[1,2-a]pyridine vis photoredox catalysis.This work provides a novel method for the C3 acylation of imidazo[1,2-a]pyridine.