Alkali halides as nucleophilic reagent sources for N-directed palladium-catalysed ortho-C–H halogenation of s-tetrazines and other heteroaromatics?

RSC Advances Pub Date: 2022-10-26 DOI: 10.1039/D2RA06169D

Abstract

A general palladium-catalysed selective C–H halogenation reaction is reported, which was successfully achieved for a large variety of functionalized aromatic rings incorporating diverse N-directing groups. By using simple alkali halides of MX type as the nucleophilic reagent source (M = Li, Na, K, Cs and X = I, Br and Cl), and phenyliodanediacetate oxidant, clean C–H-iodination, bromination and chlorination reactions were performed. This general protocol of selective ortho-monohalogenation, which complements but contrasts with the classical methods using electrophilic reagents, is achievable in a short time (30 min) with microwave irradiation assistance. The reaction was extended to substrates bearing N-directing pyridine, pyrimidine, pyrazole, oxazoline, naphtho[1,2-d]thiazole, and azobenzene groups. Notably, the topical and selectivity-challenging s-tetrazine, as a nitrogen-rich heteroaromatic, was successfully halogenated by this protocol.

Graphical abstract: Alkali halides as nucleophilic reagent sources for N-directed palladium-catalysed ortho-C–H halogenation of s-tetrazines and other heteroaromatics
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