Ligand Promoted meta-C–H Chlorination of Anilines and Phenols

Abstract

Pd-catalyzed meta-C–H chlorination of anilines and phenols is developed using norbornene as the mediator. The presence of heterocycles, including indole, thiophene and indazole, are tolerated. The identification of a new pyridone-based ligand is crucial for the success of this meta-C–H chlorination reaction. Subsequent diverse transformations of the chlorinated products demonstrate the versatility of meta-C–H chlorination.

Palladium(II)‐Initiated Catellani‐Type Reactions

“…The direct C−H chlorination of arenes is an appealing process to access synthetically versatile aryl chlorides. In 2016, the Yu group developed a meta ‐selective C−H chlorination of aniline and phenol derivatives with a pyridine‐type tether as the directing group that is co‐catalyzed by Pd II and Yu mediator 52 (Scheme a) . Aryl chlorosulfate 88 was exploited as the chlorination reagent, and the unique pyridine derivative 89 acted as the ligand of choice.…”

Palladium(II)‐Initiated Catellani‐Type Reactions

“…[16] Whereas ortho-selective C À Hf unctionalization reactions of arenes have been well developed, meta-selective CÀHf unctionalization remains ac hallenge. [19] As eparate approach using Pd II /NBE cooperative catalysis was developed by the groups of Yu,Dong, Zhao,Shi, Ferreira, and others, [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] who drew inspiration from the Catellani reaction. [19] As eparate approach using Pd II /NBE cooperative catalysis was developed by the groups of Yu,Dong, Zhao,Shi, Ferreira, and others, [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] who drew inspiration from the Catellani reaction.…”

“…[34] Aryl chlorosulfate 88 was exploited as the chlorination reagent, and the unique pyridine derivative 89 acted as the ligand of choice.U nder the optimized reaction conditions,alarge number of substrates bearing various functional groups were tolerated, delivering the corresponding meta-chlorinated products 90 in good to excellent yields.N otably,s ome medicinally important heterocyclic compounds,s uch as indole,t hiophene,a nd indazole derivatives,a re also competent substrates.M oreover,t he chlorinated products were transformed into aw ide range of synthetically useful synthons that are difficult to access through direct meta CÀHf unctionalization, for example, borylation and alkoxylation. [34] Aryl chlorosulfate 88 was exploited as the chlorination reagent, and the unique pyridine derivative 89 acted as the ligand of choice.U nder the optimized reaction conditions,alarge number of substrates bearing various functional groups were tolerated, delivering the corresponding meta-chlorinated products 90 in good to excellent yields.N otably,s ome medicinally important heterocyclic compounds,s uch as indole,t hiophene,a nd indazole derivatives,a re also competent substrates.M oreover,t he chlorinated products were transformed into aw ide range of synthetically useful synthons that are difficult to access through direct meta CÀHf unctionalization, for example, borylation and alkoxylation.…”

“…Recently,s everal elegant strategies have been developed to address this issue, [16g,i, 17-19] for example,s teric-hindrancesensitive borylation, [17] ruthenium-catalyzed meta-selective C À Hf unctionalization, [18] and the use of aU -shaped template. [19] As eparate approach using Pd II /NBE cooperative catalysis was developed by the groups of Yu,Dong, Zhao,Shi, Ferreira, and others, [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] who drew inspiration from the Catellani reaction. As shown in Scheme 10, by taking advantage of the directed ortho palladation and Catellanis It should be pointed out that in these meta-selective C À H functionalization processes,s toichiometric silver salts are usually needed, which may act as ab ase for the C À H activation steps,asanoxidant to prevent the formation of Pd 0 species,a sw ell as ahalogen anion scavenger to promote the formation of Pd IV species.F urther studies illustrated the use of this strategy in generating derivatives of phenylacetic acid, b-arylethylamines,b enzyl amines,a nilines,and phenols.…”

“…Thed irect C À Hc hlorination of arenes is an appealing process to access synthetically versatile aryl chlorides.In2016, the Yu group developed a meta-selective CÀHchlorination of aniline and phenol derivatives with ap yridine-type tether as the directing group that is co-catalyzed by Pd II and Yu mediator 52 (Scheme 23 a). [34] Aryl chlorosulfate 88 was exploited as the chlorination reagent, and the unique pyridine derivative 89 acted as the ligand of choice.U nder the optimized reaction conditions,alarge number of substrates bearing various functional groups were tolerated, delivering the corresponding meta-chlorinated products 90 in good to excellent yields.N otably,s ome medicinally important heterocyclic compounds,s uch as indole,t hiophene,a nd indazole derivatives,a re also competent substrates.M oreover,t he chlorinated products were transformed into aw ide range of synthetically useful synthons that are difficult to access through direct meta CÀHf unctionalization, for example, borylation and alkoxylation. Using as imilar strategy,t he meta-selective CÀHchlorination of benzylamine derivative 77…”