Multiselective Diels–Alder Reaction Induced by Chiral
Supramolecular Lewis Acid Catalysts
Nagoya University, Japan
The control of multiple selectivities is still a challenging subject in modern organic chemistry. In this regard, the Diels–Alder (DA) reaction is a significant tool for the total synthesis of complex organic molecules. When used in the DA reaction, conventional chiral catalysts can discriminate the prochiral enantio-face (i.e., re/si-face) of a dienophile regardless of the diene (two-dimensional discrimination). However, they cannot control the diastereo- (i.e., endo/exo-), regio-, site-, or substrate-selectivity, since this would require the three-dimensional discrimination of isomeric transition-state structures. In general, huge enzymes in vivo can realize such multi-selectivity by using a chiral cavity, which provides a three-dimensional space that includes an active site. The cavities of enzymes are conformationally flexible to catch substrates and release products (induced fit function). To overcome the limited selectivity due to the small cavity and conformational rigidity of conventional chiral Lewis acid catalysts, supramolecular catalysts, which are prepared in situfrom small components by coordinating bonds, have been considered. Indeed, there are a few examples of the use of supramolecular O-shaped catalysts that induce anomalous site-selectivity in DA reactions. However, their catalytic activities are not adequate due to their conformational rigidity. In contrast, Prof. Ishihara et al.envisioned that chiral supramolecular U-shaped catalysts, which are more conformationally flexible than O-shaped catalysts, could induce high catalytic activity with multi-selectivity. In this lecture, Prof. Ishihara presents that an asymmetric DA reaction of propargyl aldehyde with cyclopentadiene can be controlled so as to provide high enantio-, endo/exo-, regio-, and substrate-selectivities by using chiral supramolecular U-shaped catalysts.