Thed irect arylation of N-substituted obromobenzanilides and benzenesulfonamides via C À Hb ondf unctionalization hasb eend eveloped using very low catalyst loadings.T his novel cost-effective and more sustainable method relies on aP CN-type palladium pincerc omplexa sahighly active palladium source,p roviding ag enerala nd efficient access to phenanthridinones,b iaryl sultams and related heterocyclic systems. Theb eneficial effect of water as cosolvent has been observed in this process,w hich is not seriously influencedb y electronice ffects at the arene moieties or sterically demanding substituents at the amide or sulfonamide nitrogen. In addition, an umber of experiments (kinetic plot, poisoning assays,T EM,E SI) have been performed in order to understand the role of the employed palladium complex in this reaction.Palladium-catalyzed direct functionalization of C À H bonds has emerged over the last years as am odern and sustainablet ool in organic synthesis. [1] Thei ncreasing demand for greenc hemistry in industry as well as in academia has lead to the development of innovative,e nvironmentally friendly and highly efficient synthetic strategies. [2] Thus,r egarding both atom and stepe conomy,t he formationo fc arbon-carbon bonds throughC À Hf unctionalization hasa ppeared as ac onvenient methodology with broad applicationi n total synthesis and medicinal chemistry. [3] Phenanthridinones are important structural scaffolds found in manyn atural productst hat exhibit remarkable biological andp harmaceutical properties. [4] In the last years,n ovel alternative synthetic approachesh aveb eend evelopedt ot he synthesis of the phenanthridinone core and related lactams,m ost of them based on palladium-catalyzed direct functionalization of arenes. [5] Although recent efforts have been focused on the discovery of complementary routes in order to avoid the substantial costs associated to the relativeb ig amounts of catalysts required( 2-10 mol %), [6] still, the palladium-catalyzed intramolecular direct C À Ha rylation reactionh as provedt ob e one of the most versatile,r eliablea nd efficient method for the access of phenanthridinones.F urthermore,r elatedh eterobiaryls and biaryl heterocyclic compounds as wella sb iaryl sultams have been successfullyp repared under equivalent direct arylation procedures. [6a, 7a-c] Therefore,i tw ould be desirable to develop an ovel palladium-catalyzed approachf or the direct functionalization of arenes using very low catalyst loadings, [7d-e] which would provide ac ost-effective and environmentally very attractivep rocedure for the preparation of such compounds.M oreover, considering the problems associated to the minuteq uantities of metal particles usually detected in the productso f transitionm etal catalyzed reactions, [8] such method wouldp revent metal contamination of the product and therefore be of addedi nterest regarding its potential applicationinm edicinal chemistry.Our group hasa mple experience in the synthesis and applicationo fp incer-type palladium complexes as ve...
