Carboxylic acids Barbier reaction

The nature and amount of the amine used for acid deprotonation determines the reaction yield. In most cases, dienediolates of unsaturated carboxylic acids can be generated, without Barbier s reduction or Michael adduct formation, by deprotonation of the corresponding acid with butyllithium in the presence of a catalytic amount of amine198. This renders dienediolates compatible with a large number of functional groups, as happens with nitriles where self-condensation is minimized under these conditions. Unfortunately, this cannot be considered a general rule and it is convenient to optimize the amine and its amount for each acid and nitrile. 

A fairly straightforward scheme, called the Barbier-Wieland degradation, was at that time used for determining the number of carbon atoms in an ahphatic acid fragment. This involves first converting the carboxylic acid 11-1 to the corresponding ester 11-2 (Scheme 1.11). Reaction of the ester with phenylmagnesium bromide leads to carbinol 11-3. Treatment with acid leads to dehydration and formation of the olefin 11-4. Oxidation by one of several methods cleaves... 

Perfluoroalkane carboxylic and sulfonic acids and their derivatives have been synthesized by Zn-Barbier reactions using iodoperfluoroalkanes in dimethyl-sulfoxide (DMSO) as solvent [71]. A Zn/Cu (100 1) couple was used for most of the reactions but other couples such as Zn-Pb, Zn-Cd or Zn-Hg led to the same results ... 

In the Barbier-Wieland degradation, the alpha-methylene group in an aliphatic carboxylic acid is removed in a sequence of reaction steps, effectively a chainshortening. The inverse procedure is the Amdt-Eistert synthesis, where an acid is converted into acyl halide and reacts with diazomethane to give the highest homolog. 

Usually, in situ preparation in Barbier-type carbonyl additions are carried out with the bromides or chlorides even sterically blocked carboxylates, such as 2,4,6-trimethylbenzoic acid esters, can be used successfully15. The reactions are accelerated by ultrasound16,17. 

An interesting aspect of the Bi-mediated Barbier-type allylation is that the reaction can be conducted in aqueous media. When the reaction is carried out using metallic bismuth powder in water, addition of an equimolar amount of potassium fluoride improves the yield of homoallyl alcohol (Equation (40)).74 The reaction is also compatible with hydroxyl and carboxyl groups of the carbonyl substrates. When succinaldehydic acid, 4-oxopentanoic acid,... 

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