Multipoint Recognition of Molecular Conformations with Organocatalysts for Asymmetric Synthetic Reactions

Abstract

Abstract Organocatalysts activate substrates through mild noncovalent and covalent interactions, and their cooperative actions at multiple catalytic sites are essential even in intrinsically rapid organic reactions such as intramolecular cyclizations. The enzyme-like catalytic system is effective for recognizing specific molecular conformations of substrates, which continually change under reaction conditions, through multipoint interactions, thereby leading to high stereoselectivity. On the basis of this concept, we developed a range of organocatalytic asymmetric synthetic reactions, which are challenging using other categories of catalysts. The proposed catalysis was applied to various manners of asymmetric induction including those accompanied by not only facial selectivity but also by kinetic resolution (KR), dynamic kinetic resolution (DKR), desymmetrization, and dynamic kinetic asymmetric transformation (DYKAT). They enabled various asymmetric transformations through intramolecular hetero-Michael addition, construction of axial chirality, and α,β-unsaturated acylammonium catalysis, which advanced the methods for asymmetric heterocycle synthesis, construction of tetrasubstituted chiral carbons, enantioselective synthesis of axially chiral compounds, and asymmetric library synthesis of pharmaceutically potential compounds. This study also expanded the chemistry of bifunctional organocatalysis. This review provides a comprehensive account of our achievements regarding multipoint recognition of molecular conformations with organocatalysts for asymmetric synthetic reactions.