Infoscience

Journal article

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)]

    Keywords: Carboxylic acids Role: SPN (Synthetic preparation) ; PREP (Preparation) (arom.; prepn. of fluoro- and trifluoromethyl(hydroxyalkyl)benzoic acids via regioselective lithiation-carboxylation of fluoro- and trifluoromethylphenyl alkanols); Carboxylation (pr ; hydroxymethylfluorobenzoic acid regioselective prepn; benzoic acid hydroxyethyltrifluoromethyl regioselective prepn; hydroxyethylfluorobenzoic acid regioselective prepn; trifluoromethylhydroxymethylbenzoic acid regioselective prepn; fluorohydroxymethylb

    Note:

    CAN 138:73053 25-17 Benzene, Its Derivatives, and Condensed Benzenoid Compounds Section de Chimie et genie chimique, EPF BCh,Lausanne,Switz. Journal 1434-193X written in English. 481075-44-9 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of fluoro- and trifluoromethyl(hydroxyalkyl)benzoic acids and lactones via regioselective lithiation-carboxylation of fluoro- and trifluoromethylphenyl alkanols); 64372-57-2P; 481075-45-0P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of fluoro- and trifluoromethyl(hydroxyalkyl)benzoic acids and lactones via regioselective lithiation-carboxylation of fluoro- and trifluoromethylphenyl alkanols); 346-06-5 (2-(Trifluoromethyl)benzyl alcohol); 349-75-7 (3-(Trifluoromethyl)benzyl alcohol); 349-95-1 (4-(Trifluoromethyl)benzyl alcohol); 446-51-5 (2-Fluorobenzyl alcohol); 455-01-6; 456-47-3 (3-Fluorobenzyl alcohol); 459-56-3 (4-Fluorobenzyl alcohol); 2932-58-3 (2-(2-Fluorophenyl)ethanol); 2968-93-6; 7589-27-7 (2-(4-Fluorophenyl)ethanol); 13154-24-0 (Chlorotriisopropylsilane); 481075-39-2; 481075-40-5; 481075-41-6; 481075-42-7; 481075-52-9; 481075-53-0; 481075-54-1 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of fluoro- and trifluoromethyl(hydroxyalkyl)benzoic acids via regioselective lithiation-carboxylation of fluoro- and trifluoromethylphenyl alkanols); 328-67-6P; 52059-53-7P (2-(3-Fluorophenyl)ethanol); 104620-55-5P; 481075-26-7P; 481075-27-8P; 481075-28-9P; 481075-29-0P; 481075-30-3P; 481075-31-4P; 481075-32-5P; 481075-33-6P; 481075-34-7P; 481075-35-8P; 481075-36-9P; 481075-58-5P; 481075-59-6P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of fluoro- and trifluoromethyl(hydroxyalkyl)benzoic acids via regioselective lithiation-carboxylation of fluoro- and trifluoromethylphenyl alkanols); 2211-82-7P (7-Fluorophthalide); 214554-18-4P; 481075-37-0P; 481075-38-1P; 481075-43-8P; 481075-46-1P; 481075-47-2P; 481075-48-3P; 481075-49-4P; 481075-50-7P; 481075-51-8P; 481075-55-2P; 481075-56-3P; 481075-57-4P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of fluoro- and trifluoromethyl(hydroxyalkyl)benzoic acids via regioselective lithiation-carboxylation of fluoro- and trifluoromethylphenyl alkanols); 1073-06-9 (1-Bromo-3-fluorobenzene) Role: RCT (Reactant), RACT (Reactant or reagent) (prereactant, hydroxyethylation; prepn. of fluoro- and trifluoromethyl(hydroxyalkyl)benzoic acids via regioselective lithiation-carboxylation of fluoro- and trifluoromethylphenyl alkanols); 401-78-5 (1-Bromo-3-(trifluoromethyl)benzene) Role: RCT (Reactant), RACT (Reactant or reagent) (prereactant, iodination; prepn. of fluoro- and trifluoromethyl(hydroxyalkyl)benzoic acids via regioselective lithiation-carboxylation of fluoro- and trifluoromethylphenyl alkanols)

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    Record created on 2006-03-03, modified on 2016-08-08

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