Organocatalytic Syntheses of Bioactive Natural Products
129
Scheme 3. Kinetic resolution of rac-4a
observed a kinetic resolution process in the NMR tube. In solution, quinine (like a shift reagent) and the enantiomers of 4a form diastereomeric
ion pairs, which lead to isolated resonances (H a , H b and H c ) indicative
of the reaction progress. As shown in Scheme 3, (–)-4a cyclizes faster
than its enantiomer to form the enantiomerically enriched lactone 10.
The enantiomeric ratio of the carboxylic acids and the conversion can
be easily determined by integration of the respective resonances. It is
important to note that this system is suited to contribute to the understanding of cinchona alkaloid-catalyzed processes, since solvent effects,
catalyst performance and kinetics are directly observable.
Recently, Blackmond (Klussmann et al. 2006) and Hayashi (Hayashi
et al. 2006) investigated the solid–liquid equilibrium of scalemic amino
acids in different solvents and the consequences for catalysis. The most
striking example, serine, has its eutectic at >99% ee, with the practical consequence that an almost racemic sample can provide an almost
enantiopure solution in the solid–liquid equilibrium. It is also known
that trituration can influence enantiomeric and diastereomeric compo-
129
Scheme 3. Kinetic resolution of rac-4a
observed a kinetic resolution process in the NMR tube. In solution, quinine (like a shift reagent) and the enantiomers of 4a form diastereomeric
ion pairs, which lead to isolated resonances (H a , H b and H c ) indicative
of the reaction progress. As shown in Scheme 3, (–)-4a cyclizes faster
than its enantiomer to form the enantiomerically enriched lactone 10.
The enantiomeric ratio of the carboxylic acids and the conversion can
be easily determined by integration of the respective resonances. It is
important to note that this system is suited to contribute to the understanding of cinchona alkaloid-catalyzed processes, since solvent effects,
catalyst performance and kinetics are directly observable.
Recently, Blackmond (Klussmann et al. 2006) and Hayashi (Hayashi
et al. 2006) investigated the solid–liquid equilibrium of scalemic amino
acids in different solvents and the consequences for catalysis. The most
striking example, serine, has its eutectic at >99% ee, with the practical consequence that an almost racemic sample can provide an almost
enantiopure solution in the solid–liquid equilibrium. It is also known
that trituration can influence enantiomeric and diastereomeric compo-