Chiral Guanidines

The chiral auxiliary 1, developed by Ishikawa and co-workers, is a monocyclic chiral guanidine. The chiral guanidines have been used in various studies of asymmetric synthesis.¹⁾ For example, in the Michael reaction of iminoacetic acid derivatives with methyl vinyl ketone in THF, 1b was used as catalyst to prepare 3a with high enantioselectivity. When ethyl acrylate was used as Michael acceptor, the reaction produced 3b without any solvent. The reason for the high enantioselectivity, as proposed by Ishikawa and his group, is the presence of a transition state where the chiral guanidine derivative and the iminoacetic acid derivatives are bound together at 3-points by either hydrogen bonding or aromatic-aromatic interaction.²⁾ Efforts to synthesize various chiral guanidine compounds from reactions between imidazolinium compound 2 and chiral amines are being made continuously in the quest to develop novel chiral auxiliaries.³⁾