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Convenient Synthesis of Biphenyl-2-carboxylic Acids via the Nucleophilic Aromatic Substitution Reaction of 2-Methoxybenzoates by Aryl Grignard Reagents

1993; Oxford University Press; Volume: 66; Issue: 10 Linguagem: Inglês

10.1246/bcsj.66.3034

1348-0634

Tetsutaro Hattori, Takatsugu Suzuki, Noriyuki Hayashizaka, Nobuyuki Koike, Sotaro Miyano,

Synthesis of heterocyclic compounds

Abstract Nucleophilic aromatic substitution (SNAr) of 2-methoxybenzoic esters derived from 2,6-dialkylphenols by aryl Grignard reagents affords 1,1′-biphenyl-2-carboxylates in excellent yields by proper choice of the bulk of the 2,6-dialkyl-substituents. The phenoxyl protecting groups can be easily removed from the resulting biphenyl-2-carboxylates to the free acids by treatment with potassium hydroxide in aqueous ethanol (2,4,6-trimethylphenyl and 2,6-diisopropylphenyl esters) or sodium methoxide in toluene–hexamethylphosphoric triamide (2,6-di-t-butyl-4-methylphenyl esters). The regioselective biphenyl coupling reaction via the SNAr process is utilized for the key-step construction of the biphenyl skeleton in a formal synthesis of cannabinol.