Research: New catalytic transformations for organic synthesis
Decarboxylative esterification
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.
Esterifications with (BOC)2O as activating
agent
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.
Synthesis of arylacetic acids
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.
Synthesis of aryltrimethylsilanes
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.
