Research: Catalytic addition reactions
Ru-catalyzed addition of amides to alkynes
The enamide moiety is an
important substructure often encountered in biologically active compounds and
synthetic drugs. Furthermore, enamides and their derivatives are versatile
synthetic intermediates for the preparation of chiral amines, amino acids and
various heterocyclic compounds. Traditional syntheses of this important
substrate class involve rather harsh reaction conditions such as high
temperatures and/or the use of strong acids and bases.
We have now developed a
broadly applicable protocol for the synthesis of enamides, N-alkenyl
carbamates,
N-alkenyl ureas, and N-alkenyl lactames via a novel,
waste-free, catalytic addition of N-nucleophiles to terminal alkynes.
The choice of ligands and additives determines the regiochemical outcome so that with two complementary catalyst systems, both the (E)-anti-Markovnikov products and the (Z)-anti-Markovnikov products can be synthesized highly regio- and stereoselectively.
Ru-catalyzed addition of carboxylic acids to alkynes
We also developed new
ruthenium catalysts for the addition of carboxylic acids to alkynes. These allow
a preparatively simple, highly regioselective access to either the alk-1-en-2-yl
esters or the (Z)-alk-1-en-1-yl esters.
Asymmetric reduction of enol esters
In a cooperation with Prof.
Reetz, we investigated the synthetic utility of alk-1-en-2-ylesters. In this
context, we found that they can be reduced in a highly enantioselective fashion
in the presence of a ruthenium catalyst bearing novel sugar-based chiral
phosphite ligands.
In reductions of the type
shown, e.e. 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.
