5 - Max-Planck-Institut für Kohlenforschung

50
O
R O
Synthetic Organic Chemistry – L. J. Gooßen
H 2
O
Ru, L* R O
*
> 85 % ee
Scheme 4. Asymmetric reduction of enol esters
In reductions of the type shown in the general Scheme 4, ee values of more than 95 %
were achieved, a new record for this substrate class. Thus, a synthetic sequence
consisting of the addition of a carboxylic acid to an alkyne, followed by an asymmetric
hydrogenation of the enol ester, appears to be a valuable alternative to the asymmetric
reduction of dialkyl ketones (i.e. methyl ethyl ketone) followed by esterification.
Furthermore, new processes were developed for the esterification of carboxylic acids,
which is one of the most widely used transformations in organic chemistry. The
carboxylic acids were converted in situ to the mixed anhydrides with dialkyl
dicarbonates, which then decarboxylate in the presence of suitable catalysts (Scheme 5).
Mild Lewis acids, such as Mg(ClO4)2, proved to be significantly more active and
selective catalysts than the previously employed DMAP.
O
R OH
+
R O
O
O
O
OR - CO2 - R1 1 1
Mg(ClO4 ) 2
OH
R
O
OR
Scheme 5. Decarboxylative esterification
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 was used in the conversion of carboxylic acids to
the esters of primary or secondary alcohols in the presence of (BOC)2O and a catalytic
amount of DMAP (Scheme 6).
O
R OH
+
1
R OH
O O
tBuO O OtBu
cat. DMAP
- CO 2
- tBuOH
Scheme 6. Esterification in the presence of (BOC)2O
O
1
R OR
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.
1