Trichloromethylation And Chlorination Of C-H Bonds

Among the natural products,the compounds containing a trichloromethyl functional group exhibit excellent biological activity.In addition,trichloromethyl can be readily converted to a variety of one-carbon functional groups including methyl,chloromethyl,dichloromethyl,trifluoromethyl,carboxyl groups,as well as carboxylate.Therefore,the trichloromethylation reaction is of great importance both in the field of total synthes is of natural products and in the field of synthetic methods.In this paper,we have studied the direct trichloromethylation reaction of C-H bond.This paper includes the following four parts:In the first part,we review the trichloromethylation reactions reported in the literature,including 1,2-addition and 1,4-addition reactions of trichloromethyl anions,atom transfer radical addition reaction of CHCl₃ and CCl₄ with terminal olefins,cross-coupling reation,trichloromethylation of aromatic hydrocarbons,α-trichloromethylation of carbonyl,trichloromethylation of MBH-fluorides.In the second part,we designed and tried to synthesie a series of hypervalent iodine-based trichloromethylation reagents.The experimental results showed that this type trichloromethyl reagents are unstable.In the third,part we studied the oxidation of trichloromethylation of tertiary amines and found that when 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone（DDQ）was used as the oxidant and trimethyl（trichloromethyl）silane as the source of trichloromethyl,the N-substituted tetrahydroisoquinoline substrates could be instantaneously and quantitatively converted to the trichloromethyl substituted products.This reaction has unique regioselectivity,and can be scaled up to the gram scale without a decrease in the yield,and is compatible with various functional groups,including benzyl,allyl,propargyl and ester substituents.In addition,the reaction is also applicable to N-substituted-4,5,6,7-tetrahydrothieno[3,2-c]pyridine substrates.Finally,we also convert the trichloromethyl group of the target product to dichloromethyl,dichloromethylene,methylene and carboxylate groups under mild conditions.This reaction is expected to replace the highly toxic cyanation reaction,providing a new way for the synthesis of carboxylic acids and their derivatives.In the fourth part,we studied the direct trichloromethylation of N-heteroaryl-directed C（sp²）-H bond and found that in the presence of Cu（OAc）₂,using TMSCCl₃ as trichloromethylating reagent,an ortho-chloro product was obtained instead of the target product.Thus,we have developed a direct chlorination reaction of aryl C-H with TMSCCl₃ as the chlorine source.The reaction has high monochloro/dichlorination selectivity and regioselectivity...