A rational approach to catalyst design via enantiomeric studies of chiral alkylation

A novel approach to a rational catalyst design was proposed. The electronic effect of different aromatic substituted groups on the chiral alkylation of 2-propyl-1-indanones with a chiral phase transfer cinchona alkaloid catalyst was investigated. The information gathered from this study allowed for the rational design of this type of catalyst.;Indanones were fitted with different groups on the aromatic ring to increase and decrease the electron density in the aromatic ring. The indanones were alkylated with 1,3-dichloro-2-butene in the presence of the chiral phase transfer catalyst and the enantiomeric excess was determined by hydrolyzing the vinyl chloride to a methyl ketone then making a chiral cyclic ketal. Combinations of indanones were allowed to compete for the active site of the phase transfer catalyst. The degree of enantiomeric excess and the preference of the phase transfer catalyst for one indanone over the other provided valuable information about the geometric and electronic factors responsible for the selectivity. This information can be used to rationally design a cinchona alkaloid catalyst by electronically "tuning" the quinoline moiety with electron withdrawing or donating groups.