Substitutions by nucleophilic free radicals: A new general reaction of heteroaromatic bases

Abstract

The substitution of protonated heteroaromatic bases by nucleophilic carbon‐centered radicals has been developed as one of the most general reactions in the heterocyclic series; its great interest results from the fact that it reproduces most of the numerous aspects of the Friedel‐Crafts aromatic substitution, but with opposite reactivity and selectivity. The most recent developments, concerning the generation of free radicals by iodine and hydrogen abstraction and decarboxylation of carboxylic acids are particularly discussed. Some processes of high synthetic value were designed on the basis of the kinetic and thermodynamic features of all the elementary steps involved in complex but selective chain processes. New general procedures for the monosubstitution in the homolytic alkylation and acylation are reported and discussed.

Übergangsmetallfreie BF3‐vermittelte oxidative und nichtoxidative Kreuzkupplung von Pyridinen

“…[1] Bisher wurden weitestgehend übergangsmetallkatalysierte Kreuzkupplungsmethoden für die Funktionalisierung von Pyridinen angewendet. Kürzlich berichteten wir, dass 3-substituierte Pyridine des Typs 1 eine BF 3 -vermittelte [4] oxidative Kreuzkupplung [5,6] in Position 4 mit verschiedenen Alkyl-und Arylmagnesiumoder Alkyl-und Arylzinkreagentien eingehen und über ein Intermediat des Typs 2 zu 3,4-disubstituierten Pyridinen des Typs 3 führen (Schema 1). Kürzlich berichteten wir, dass 3-substituierte Pyridine des Typs 1 eine BF 3 -vermittelte [4] oxidative Kreuzkupplung [5,6] in Position 4 mit verschiedenen Alkyl-und Arylmagnesiumoder Alkyl-und Arylzinkreagentien eingehen und über ein Intermediat des Typs 2 zu 3,4-disubstituierten Pyridinen des Typs 3 führen (Schema 1).…”

Six‐Membered Heterocycles: Triazines, Tetrazines and Other Polyaza Systems

“…Makosza [113] has developed a method named vicarious nucleophilic substitution of hydrogen to transform 1,2,3-triazinium 2-dicyanomethylylides 65 into 5-benzenesulfonylmethyltriazines 75 [71,114] by a radical reaction (Scheme 20.18). Radical nucleophilic carbamoylation, which was developed by Minisci [115], has been applied to triazinium dicyanomethylides to form 5-carbamoyl-1,2,3-triazines 76 [70,116].…”

Six‐Membered Heterocycles: Quinoline and Isoquinoline

“…The replacement of hydrogen at C1 through homolytic processes is also possible in 116, with the Minisci reaction being by far the most important approach [430]. Since 116 is a p-deficient heterocycle, nucleophilic free radicals such as hydroxymethyl, alkyl, and acyl give better results.…”