Pd(ii)-catalyzed meta-C–H bromination and chlorination of aniline and benzoic acid derivatives

Abstract

The classic electrophilic bromination leads to ortho- and para-bromination of anilines due to their electron-rich property. Herein we report the development of an unprecedented Pd-catalyzed meta-C–H bromination of aniline derivatives...

“Magic Chloro”: Profound Effects of the Chlorine Atom in Drug Discovery

“…Although this might not be possible on molecules that have many (hetero)­aromatic rings susceptible to chlorination, it should be possible to chlorinate many monosubstituted benzene rings at the para -position by electrophilic aromatic substitution (S E Ar) using an electrophilic chlorinating agent (Figure A). ortho -Selective functionalization should be achievable by directed ortho -metalation then trapping with an electrophilic chlorinating agent (Figure B); some Pd-catalyzed directed C–H chlorination and organocatalytic ortho -C–H chlorination protocols have also been developed. , Unless there is conveniently a strong electron-withdrawing group on the benzene ring to enforce meta -chlorination under S E Ar conditions, meta -selective chlorination is arguably the most difficult, and this has only been achieved recently by transition metal catalysis (Figure C). − For (hetero)­aromatic systems where conventional chlorinating agents such as N -chlorosuccinimide are not sufficiently reactive, new chlorinating reagents have been invented in the past decade (Figure D). , Other indirect methods such as C–H borylation followed by boron–chlorine substitution have also enabled the placement of chlorine atoms at positions that are often difficult to functionalize …”

“Magic Chloro”: Profound Effects of the Chlorine Atom in Drug Discovery

“…120,121 Unless there is conveniently a strong electron-withdrawing group on the benzene ring forcing a meta-chlorination under SEAr conditions, meta-selective chlorination is arguably the most difficult, and this has only been achieved recently by transition metal catalysis (Figure 7F). [122][123][124] For (hetero)aromatic systems where conventional chlorinating agents such as Nchlorosuccinimide is not sufficiently reactive, new chlorinating reagents have been invented in the past decade as well (Figure 7G). 125,126 Although there are likely more ways to chlorinate a molecule than to methylate a molecule, 2 there is arguably still room for methodological development in chlorination, especially for meta-chlorination, and chlorination of biaryls and fused (hetero)aromatic systems.…”

Palladium(II)-Catalyzed Remote meta-C–H Functionalization of Arenes Enabled by Multitasking Oxyamides as the Linker

“…Interestingly, it enabled positioning of the transition metal catalyst in the proximity of the remote meta -C–H bond. Subsequently, various nitrile-, N -heteroaryl-, and carboxy-based templates were then reported to furnish the meta -C–H functionalization of arenes by Maiti, Li, Jin, and Lu et al The aforementioned C–H bond substrates were linked to the directing templates by different linkage groups, such as esters, amides, and ethers, and were transformed into a singular category of meta -C–H functionalized products, including but not limited to carboxylic acids, amines, alcohols, and other analogous compounds . However, multifunctional linking groups have rarely been reported to activate meta -C–H bonds.…”