Fluoro- or trifluoromethyl-substituted benzyl and phenethyl alcohols: Substrates for metal-mediated site-selective functionalization

It was possible to functionalize the three fluorobenzyl alcs. and the three 2-(fluorophenyl)ethanols by metalation and subsequent carboxylation, the prototype electrophilic trapping reaction. Triisopropylsilyl (TIPS) outperformed methoxymethyl (MOM) as an O-protective group making seven new fluorobenzoic acids, including I and II, accessible in 63% av. yield. The TIPS group tolerates weakly basic and acidic media and may facilitate further structural elaboration. The unprotected alcs. reacted more sluggishly and were unable to provide two of the targeted products. The yield averaged only 46% in the five other cases. The direct metalation of fluorinated benzyl and phenethyl alcs. remains nevertheless an attractive option because of its operational simplicity. All three (trifluoromethyl)benzyl alcs. and two of the three (trifluoromethyl)phenethyl alc. isomers were successfully submitted to the metalation/functionalization sequence. These five starting materials gave rise to a total nine new benzoic acids or lactones, e.g. III. Despite the poor yields (31% on av.), the employed organometallic methods are extremely regioselective, economical and easy to perform. [on SciFinder (R)]