The role of the C(2) configuration and methyl substitution on the catalytic activity of novel 2,3,3‐ and 2,7,7‐trimethyl‐substituted γ‐aminonorbornan‐2‐ols

Abstract

A new set of optically active 2,3,3- and 2,7,7-trimethyl-substituted gamma-aminonorbornan-2-ols have been obtained from 2-methylenenorbornane-1-carbonitriles derived from (+)-camphor and (-)-fenchone and probed as chiral ligands for the enantioselective addition of diethylzinc to benzaldehyde. This has allowed the study of the structural factors influencing the chirality transfer, such as variation of the relative configuration at C(2) and steric hindrance at C(2), C(3), and C(7) positions of norbornane, which result in the observance of the important role played by the gem-dimethyl position in gamma-aminonorbornan-2-exo-ols. An empirical rationalization of the obtained experimental results has been realized on the basis of energetically-favored diastereomeric Noyori-like transition states.

Deciphering the mechanism behind efficient enantioselective ethylation with thiazolidine‐based amino alcohols

“…The coordination of the aldehyde to either face of the zinc atom leads to a completely different set of arrangements. These two types of configurations that have been previously reported [ 35,41,44,51,93–95 ] and that are schematically represented in Figure 1 were also considered in the TSS search. In order to simplify the nomenclature of the target species, the terms ‘normal’ ( n ) and ‘inverted’ ( i ) (Figure 1, green and blue arrows, respectively) were used to designate the configurations assumed when the aldehyde coordinates to Zn(1).…”