A series of pyrrolidine-camphor-derived organocatalysts (1-4) were designed and synthesised. These organocatalysts were used for direct α-amination of aldehydes with dialkyl azodicarboxylates to give the desired α-aminated products in high chemical yields (up to 92%) and with high to excellent levels of stereoselectivity (up to >99% ee). The reactions proceeded rapidly (within 5 min) with low catalyst loading (5 mol-%) at ambient temperature. Enantioselective aminations of asymmetric α,α-disubstituted aldehydes in the catalytic system were studied, with reasonable to high stereoselectivities (up to 75% ee) being obtained. The utility of this methodology was demonstrated with the synthesis of derivatives of β-amino-γ-butyrolactone and a tetrasubstitutedcyclohexane-derived amino alcohol with high stereoselectivities. Transition models were proposed for the asymmetric α-amination reactions; they involve hydrogen-bond interactions between the nucleophilic enamine formed in situ and the nitrogen source. A highly efficient method for the α-amination of aldehydes with the aid of pyrrolidine-camphor-derived organocatalysts 1-4 has been developed. The α-aminated products were obtained in high chemical yieldsand with excellent enantioselectivities (up to >99% ee). The synthetic utility was demonstrated by the synthesis of derivatives of β-amino-γ- butyrolactone and a highly substituted cyclohexane.
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Organic Chemistry