23 September 2008
Prof. Shu Kobayashi (University of Tokyo, Japan)
Toward Truly Efficient and Powerful Organic Synthesis - New Dimension of Acid and Base Catalysis
Recent advances in acid and base catalysis will be discussed. Catalytic asymmetric 1,4-addition and [3+2] cycloaddition reactions using chiral calcium complexes prepared from calcium isopropoxide and chiral bisoxazoline ligands have been developed. Glycine Schiff bases reacted with acrylic esters to afford 1,4-addition products, glutamic acid derivatives, in high yields with high enantioselectivities. During the investigation of the 1,4-addition reactions, we unexpectedly found that a [3+2] cycloaddition occurred in the reactions with crotonate derivatives affording substituted pyrrolidine derivatives in high yields with high enantioselectivities. Based on this finding, we investigated asymmetric [3+2] cycloadditions, and it was revealed that several kinds of optically active substituted pyrrolidine derivatives containing contiguous stereogenic tertiary and quaternary carbon centers were obtained with high diastereo- and enantioselectivities. NMR spectroscopic analysis and observation of non-amplification of enantioselectivity in non-linear effect experiments suggested that a monomeric calcium complex with an anionic ligand was formed. A stepwise mechanism of the [3+2] cycloaddition, consisting of 1,4-addition and successive intramolecular Mannich-type reaction was suggested. Furthermore, modification of the Schiff base structure resulted in a modification of the reaction course from a [3+2] cycloaddition to a 1,4-addition affording 3-substituted glutamic acid derivatives with high diasterero- and enantioselectivities.