Organic Chemistry - Prof. Gooßen

Carboxylic acids are easily converted in situ to the mixed anhydrides by treatment dialkyl dicarbonates. These compounds were found to undergo facile decarboxylate in the presence of mild Lewis acids such as Mg(ClO₄)₂ providing a high-yielding synthesis of the corresponding esters.

Particular advantages of this esterification method are its compatibility with many functional groups along with the fact that solely volatile byproducts are formed.

The low reactivity of tertiary alcohols allowed the use of di-t-butyl dicarbonate as activating agent for conversion of carboxylic acids to the esters of primary or secondary alcohols in the presence of catalytic amount of DMAP.

The esters of the sterically less hindered alcohols were formed selectively, while none of the t-butyl esters were detected. In contrast to the traditional process using DCC as the coupling reagent, only volatile byproducts are formed, thus significantly simplifying the work-up.

The methylenecarboxyl group is an important structural motif often found in biologically active compounds and commercially available drugs, e.g. diclofenac, aclofenac and camostat. We have developed a convenient new synthesis of arylacetic acid derivatives from boronic acid and a-bromoacetic acid derivatives.

The palladium catalyst is generated in situ from palladium acetate and tri-1-naphthylphosphine. With this sterically demanding, moderately electron donating ligand, excellent selectivities towards the cross-coupling reaction are observed. With most other ligands, oxidative coupling of the boronic acids yielding biaryls is predominant. The reaction proceeds at room temperature in wet THF in the presence of an excess of a mild base such as potassium carbonate. Thus, a plethora of functional groups are tolerated including even base sensitive ester and keto groups.

The aryltrimethysilyl group is a key functionality in several biologically active compounds including the fungicide "Latitude". We have developed a new synthetic procedure in which aryl bromides are directly converted into the aryltrimethylsilanes by reaction with hexamethyldisilane in the presence of a mild base and a palladium catalyst.

The palladium catalyst has to be chosen with according to the electronic properties of the aryl bromide. Unlike other procedures, the new process no longer requires high-pressure equipment, since a reaction temperature of 100 °C, well below the boiling point of the substrates, is sufficient. A variety of different aryltrimethylsilanes were synthesized demonstrating the wide scope of the new transformation.