Study On C3 Position Functionalization And Decarboxylation Of Benzofuranone

The benzofuranone skeleton is widely present in various natural products,drug molecules and antioxidants.Therefore,developing new methods for the synthesis and transformation of benzofuranones is of great significance.Among them,3-aryl substituted benzofuranones have received extensive attention from researchers due to their C3 position combining a benzyl carbon center and a tertiary carbon center,which can form stable carbon cations,carbon anions or radicals.In previous work,our research group achieved selective arylation and alkenylation of the C3 position of benzofuranones through the coupling or addition reactions of the C-H bond of3-aryl substituted benzofuranones activated by transition metals with other active groups such as heterocyclic aromatics,alkenes and alkynes.However,the universality of the above reaction system still needs to be further expanded.Based on a large number of literature research results and the research achievements of our research group,this dissertation uses the characteristic of the C3 position of benzofuranones connected to lactone carbonyl to develop new methods for the functionalization and ester conversion of benzofuranones with high functional group tolerance through systematic regulation of the catalytic reaction system.These methods include（1）benzyl and aryl substitution of benzofuranones at the C3 position without the participation of transition metals,（2）copper-catalyzed linear alkenylation of benzofuranones at the C3 position,（3）nickel-catalyzed decarboxylation and oxidation of benzofuranones and（4）palladium-catalyzed decarboxylation and hydrogenation of benzofuranones.The main research results obtained are as follows:（1）To address the challenge of selective benzylations of benzofuranones,the unique functionality of benzofuranones as carbon radical trapping agents was utilized.Stable benzyl radicals were generated by the reaction of toluene derivatives with tert-butyl peroxide at high temperature,and the high selective cross-dehydrogenative coupling of the C（sp3）-H bond of benzofuranones and the C（sp3）-H bond of toluene derivatives was achieved through radical coupling reactions.A new method for the synthesis of benzylated benzofuranone quaternary carbon compounds with transition metal-free was developed.This method produced 29 3-benzyl-substituted benzofuranone quaternary carbon compounds with moderate to good yields,and exhibited good substrate tolerance for both electron-donating and electron-withdrawing groups in benzofuranone and toluene substrates.The method could be scaled up to 5 mmol and obtained the product in65%yield.This method can also be extended to the highly selective cross-dehydrogenative coupling reaction of the C3（sp3）-H bond of benzofuranones and the ortho C（sp2）-H bond of phenols,achieving C3-arylation of phenols with benzofuranones.Finally,based on literature reports and control experiments,we speculated that the reaction may proceed through radical coupling and radical transfer pathways.（2）To address the challenge of highly selective tandem alkenylation of benzofuranones,we developed a novel method for the preparation of 1,3-butadiene benzofuranone quaternary carbon compounds and 1,3,5-hexatriene benzofuranone quaternary carbon compounds using copper-catalyzed oxidation to generate stable quaternary carbon allyl radicals under solvent-free conditions.By carefully controlling the catalytic reaction system and reactant ratio,we were able to achieve precise control over the reaction selectivity.This method utilizes 3-aryl substituted benzofuranone and phenylacetylene as reactants,Cu I as a catalyst,and di-tert-butyl peroxide as an oxidant,and exhibits excellent substrate tolerance for benzofuranone and phenylacetylene substrates containing both electron-donating and electron-withdrawing groups.Based on literature reports and control experiments,we speculated that the allyl radicals formed by the addition of benzofuranone radicals and phenylacetylene will continue to add to phenylacetylene,ultimately leading to the formation of polyene quaternary carbon products through radical transfer.（3）To address the challenge of highly selective decarboxylation and oxidant of benzofuranone,a method was developed for the high selective synthesis of 2-hydroxybenzophenone compounds using the benzyl carbon center at the C3position of 3-aryl substituted benzofuranones connected to the lactone.This method involves the nickel-catalyzed cooperative activation of the C-O bond of lactone and the C-H bond at the C3 position,and was used to high selectivity decarboxylation of benzofuranone.The reaction used benzofuranone as the starting material,Ni Cl₂ as the catalyst,sodium carbonate as the base,and tert-butyl hydroperoxide as the oxidant,and produced 25 2-hydroxybenzophenone compounds with electron-donating and electron-withdrawing groups in 22%to 99%yields with good substrate tolerance.The reaction also produced gram-scale product in 77%yield.These compounds could be used to prepare a series of biologically active molecular skeleton structures through esterification,cyclization and dehydroxylation.Based on literature research and control experiments such as radical trapping and carbon dioxide trapping,we speculated the reaction may involve nickel insertion into the C-O bond,carbonyl migration,ring-opening and decarboxylation.（4）To address the challenge of highly selective decarboxylative and hydrogenation of benzofuranone,a method was developed for the high selective synthesis of 2-hydroxydiarylmethanes using the benzyl carbon center at the C3position of 3-aryl substituted benzofuranones connected to the lactone.This method involves the palladium-catalyzed cooperative activation of C-Br and C-O bonds,and was used to high selectivity coupling and decarboxylation of benzofuranone.The reaction employed 3-bromo-substituted benzofuranone and arylboronic acid as reactants,Pd（^tBu₃P）₂ as the catalyst,potassium hydroxide as the base,tetrabutylammonium bromide as the additive,toluene and water as solvents,and water or arylboronic acid as possible hydrogen sources.The method exhibited good substrate tolerance towards benzofuranone and arylboronic acid substrates containing both electron-donating and electron-withdrawing groups,and produced 30 2-hydroxydiarylmethane compounds in 34 to 99%yield.The reaction could be scaled up to 10 mmol with 83%yield.The product is transformed by etherification,esterification and dehydroxylation to prepare a range of diarylmethanes.Based on literature reports and control experiments,we speculated the reaction may involve the process of coupling,palladium insertion into the C-O bond,carbonyl migration,ring-opening and decarboxylation.