Palladium‐ and Copper‐Catalyzed Site Selective Monoamination of Dibromobenzoic Acid

Abstract

Abstract:The carboxylate anion has been used as a directing group in the aromatic amination of electronically equivalent aryl bromides to afford selective ortho-substituted derivatives (> 99:1 selectivity; 60-80% yield) in the case of copper(I) catalysis. The solvent, base and equivalents of base were important factors in the success of this reaction. Complementary selectivity was achieved with palladium catalysis where the para-substituted derivatives were produced selectively (> 99% selectivity, 70-80% yield).

Facile synthesis of indolo[3,2-a]carbazoles via Pd-catalyzed twofold oxidative cyclization

“…The desired methyl 2,4-dianilinobenzoates ( 2a–e ) were obtained in good to excellent yield. In a parallel synthesis, using the Houpis protocol [15], Cu-catalyzed selective monoaminations of the 2,4-dibromobenzoic acid at the 2-position were achieved. After methyl esterification of ortho-aminated benzoic acids, substrates 4a and b were treated with other anilines under the previous Buchwald–Hartwig conditions to afford methyl 2,4-dianilinobenzoate ( 2f–p ) with various substituents at the aniline moieties.…”

Site-Selective Cross-Coupling of Polyhalogenated Arenes and Heteroarenes with Identical Halogen Groups

“…Upon adding DPEPhos to the reaction mixture, the para-coupled product (136) Houpis and coworkers then attempted to extend the scope of the coordinating ability of the carboxylate group to other transformations such as Pd-catalyzed amination. 156 Their study included coupling reactions between 2,4-dibromobenzoic acid 134 and various electronically and sterically diverse amines (Scheme 38A). They observed that under the previously disclosed conditions to obtain para selectivity, they isolated the expected coupled product (137) when benzylamine was treated with 134.…”

“…Houpis and coworkers then attempted to extend the scope of the coordinating ability of the carboxylate group to other transformations such as Pd-catalyzed amination . Their study included coupling reactions between 2,4-dibromobenzoic acid 134 and various electronically and sterically diverse amines (Scheme A).…”

Catalytic Selective Synthesis

“…This concept has also been successfully applied to site-selective cross-coupling of boronic acids and dichloro heterocycles such as 184 (Scheme 45 d) [179] and site-selective monoamination of dibromobenzoic acid 183 with Pd versus Cu catalysts (Scheme 45 e). [180]…”