Synthesis and Organocatalytic Activity of Imidazolidinone Organocatalysts

A series of cis-5-arylmethyl-2-alkyl-3-methylimidazolidin-4-ones, prepared from arylmethyl-substituted α-amino acids, and a series of trans- and cis-2-(fluoromethyl)-2,3-dimethylimidazolidin-4-ones, derived from L-valine and L-leucine, were synthesized and fully characterized. Their catalytic activity was evaluated in the addition of 1-methylindole to cinnamaldehyde. Using the cis-5-arylmethyl-2-alkyl-3-methylimidazolidin-4-one catalysts, enantioselectivities of up to 78% ee (S) were achieved. Notably, with the L-valine-derived cis-imidazolidinone organocatalyst, the highest reversal of stereoselectivity to date (92% ee, (R) at –43 °C) was observed.