Polar Heterobenzylic C(sp³)-H Chlorination Pathway Enabling Efficient Diversification of Aromatic Nitrogen Heterocycles.

ABSTRACT: Site-selective radical reactions of benzylic C-H bonds are now highly effective methods for C(sp³-H) functionalization and cross-coupling. The existing methods, however, are often ineffective with heterobenzylic C-H bonds in alkyl-substituted pyridines and related aromatic heterocycles that are prominently featured in pharmaceuticals and agrochemicals. Here, we report new synthetic methods that leverage polar, rather than radical, reaction pathways to enable the selective heterobenzylic C-H chlorination of 2- and 4-alkyl-substituted pyridines and other heterocycles. Catalytic activation of the substrate with trifluoromethanesulfonyl chloride promotes the formation of enamine tautomers that react readily with electrophilic chlorination reagents. The resulting heterobenzyl chlorid

SUBMITTER: Maity S 

PROVIDER: S-EPMC10629438 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature