Studies On Palladium Catalyzed C(sp~3)-H Bond Activation/Functionalization

Palladium-catalyzed C(sp~3)-H bond activation/functionalization has received much attention in the past decade for its wide application in the construction of carbon-carbon bond,carbon-oxygen bond,carbon-nitrogen bond,carbon-halogen bond,carbon-sulfur bond,and other carbon-heteroatom bond.However,given the low ractivity,intramolecular ligands(directing groups)are often required to accelerate the inert C(sp~3)-H bond activation.This effective synthesis strategy enables the functionalization of inert C(sp~3)-H bonds,which have a good prospect about application in the synthesis of functional molecules and bio-active compounds.Alcohols are important fundamental chemicals,which are widely found in pharmaceuticals,spices,dyes,pesticides,polymer materials,and bioactive molecules.Thus,the direct and selective C(sp~3)-H bond functionalization of alcohols is of great interest to the chemical society.However,there are still several challenges remain due to low ractivity of alcohols.This dissertation describes the Pd-catalyzedb-selective C(sp~3)-H bond arylation of masked alcohols by the using of rational designed bidentate auxiliaries as exo-type directing groups.The bidentate monoanonic auxiliaries are crucial to facilate the C(sp~3)-H bond and stabilize the metalocycle,which enables the cross coupling arylation of alcohols with aromatic iodides for the first time.The transformation features high mono-arylation selectivity and broad substrate scope.Notably,the bidentate directing groups can be readily removed to give theb-arylated aliphatic alcohols,which significantly enhances the application perspective of our directing group in the selective C(sp~3)-H bond functionalization of alcohols.Moreover,theb-selective C(sp~3)-H bond acetoxylation of masked alcohols has alsobeen developed.The present transformation obviates the using of hypervalent iodines as oxidants in comparison with previous process.By using cheap persulfate as the external oxidant,acetoxylation of methyl C(sp~3)-H bonds features excellent regioselectivity and chemoselectivity.Acetoxylation of more challenging methylene C(sp~3)-H bonds takes place smoothly as well.The reaction is compatible with different types of alcohol derivatives.Moreover,the bidentate auxiliary can be readily removed to give theb-acetoxylated aliphatic alcohols.The hydrolysis of the acetoxylation product will give the corresponding alcohol under room temperature and alkaline conditions,which provides a general method for the synthesis of chemical differential 1,2-diols.