Application of organolithium and related reagents in synthesis. Part 25: Novel specific synthesis of the 4-arylisochroman-3-acetic acids via conversion of benzoic acids

The transformation of the benzanilides 1 into 4-arylisochroman-3-acetic acids 8 applying the following sequence of reactions is described. At first, the 3-arylphthalides 3 were obtained via metallation [n-BuLi] of benzanilides 1 and subsequent treatment of the generated bis-lithiated anilides 2 with aromatic aldehydes. Next, the 3-arylphthalides 3 were reduced [LiBH4] to phthalanes 5 and then, via reductive metallation [Li/C10H8] and reaction of the generated bis-lithiated species 6 with dimethylformamide, 3-hydroxy-4-arylisochromans 7 were produced. In the final step the isochromans 7 were treated with 1-methoxy-1-trimethylsilyloxyethene in the presence of titanium tetrachloride and furnished 4-arylisochromans-3-acetic acid methyl esters 8 as trans stereoisomers (Ψ-e/e).