Carbon-Center Radical Enabled Oxidative Alkylation/Alkoxycarbonylation Of Furans

The conversion of compounds from biomass into high value-added chemicals is an important research area with the potential to reduce global dependence on fossil resources.Furans,which are among the principal products obtained from the biomass feedstocks,can be further converted into other high value-added products because they can act as dienes,enol ethers,and carbonyl compounds.Therefore,the development of new methods for conversion of furan and its derivatives to widely used chemicals has become one of the research hotspots in recent years.After decades of development,radical chemistry has been one of the most energetic and creative research.The strategy of using carbon-centered radicals to efficiently construct C—C bonds has proved to be a powerful tool.Among them,the strategy of directly coupling two different C—H bonds to form new C—C bonds through oxidative cleavage is favored by researchers due to their excellent step and atom economy.However,furan,as a weakly aromatic electron-rich aromatic ring,is difficult to form stable furan radicals under the oxidizing atmosphere,and it is favored to lose electrons to form cation resulting in ring-opening or polymerization.At present,using carbon-centered radicals to achieve the selective functionalization or dearomatization of furan under oxidizing atmosphere still has great challenges.We envisage that introducing an acyl group on the furan ring can strengthen the conjugated?-bond,thereby stabilizing the furan radical intermediate.On the other hand,acyl-substituted furan derivatives such as furfural and furoic acid are very easy to obtain from renewable resources and belong to cheap chemicals.However,the conventional alkylation of acyl furans involves the protection and deprotection of functional groups.If the alkylated products can be obtained directly from the acyl-substituted furan derivatives,it will be extremely step-economical.In this doctoral dissertation,firstly,the conversions of furan compounds are introduced.Secondary,we further introduce the reactions between carbon radical species and heteroaromatic compounds.This doctoral dissertation focuses on the transition-metal-catalyzed functionalization and dearomatization of furans under oxidizing atmosphere through radical pathway,thereby synthesizing a series of functional and high value-added molecules.The results of the main research are shown as follow:Iron-catalyzed radical alkylation of furans has been developed in the second chapter.By using acyl-furan derived from renewable resources as the starting materials,cheap and readily available fatty aldehydes as the alkylating reagents,various?-alkyl-?'-acyl furans can be sustainably obtained via radical pathway between ferrous chloride and di-tert-butyl peroxide.The mechanism research shows that the aliphatic aldehydes undergo the C—C bond cleavage and decarbonylation to form an alkyl radical.This method can be compatible with primary,secondary and tertiary carbon radicals at the same time,and the gram-scale synthesis shows the application potential.The copper-promoted radical alkoxycarbonylation reaction of furans has been described in the third chapter.By using furoate derived from the C₅ biomass platform as the starting material,copper acetate as the additive,tert-butyl peroxybenzoate as the oxidant,and chloroform as an operable C₁ source,various FDCA derivatives were efficiently synthesized in the presence of alcohols.This method avoids the use of precious metals or stoichiometric alkali metals,and it was found as the first exertion of radical pathway to construct FDCA derivatives based on C₅ platform.Mechanism experiments reveal that copper additive that has been treated in this reaction engage and benefit in three significant processes.Wide applicability for heteroaryl carboxylates,and success in gram-scale synthesis encourage it to be promising application.Copper-catalyzed dearomatization of furan via radical pathway for the construction of dihydrofuran-2,3'-spirooxindole has been described in the fourth chapter.In this method,N-arylfuranamides as starting materials,di-tert-butyl peroxide as the oxidant,copper acetylacetonate as the catalyst,and chloroform as both alkyl radical precursor and solvent,a series of dihydrofuran-2,3'-spirooxindoles were synthesized efficiently through radical migration.Importantly,this method undergoes a radical pathway to construct dual carbon-carbon bonds in one step,and realizes the 2,5-alkyl arylation reaction of furan.