Regioselective Arene Functionalization: Simple Substitution of Carboxylate by Alkyl Groups

Arenes with various alkyl side‐chains were synthesized in high yields and excellent regioselectivities. Starting from toluic and naphthoic acids, the carboxylate group was conveniently substituted by alkyl halides by Birch reduction and subsequent decarbonylation. The method is characterized by inexpensive starting materials and reagents, and methylation of arenes was realized. Besides simple alkyl substituents, the scope of arene functionalization was extended by benzyl, fluoro, amino, and ester groups. We were able to control the alkylation of 1‐naphthoic acid during Birch reduction by the addition of tert‐butanol. This allowed the regioselective synthesis of mono and bis‐substituted naphthalenes from the same starting material. Mono or bis, that is the question: Starting from 1‐naphthoic acid, alkyl groups are introduced in only a few steps by Birch reduction and subsequent decarbonylation. High yields and excellent selectivities are obtained, and the degree of alkylation is simply controlled by the addition of tert‐butanol (see scheme). Various other aromatic precursors and functional groups are tolerated during this ipso substitution.