N-Heterocyclic Carbene-Catalyzed Synthesis of C–N Atropisomers and Heteroatom Chiral Molecules

Abstract

Asymmetric catalysis has received worldwide interest due to the increasing demand for optically pure compounds in pharmaceuticals, agrochemicals, natural products, and materials science. Traditionally, research in this area has been dominated by chirality on the carbon, where a stereogenic carbon atom bears distinct substituents. In recent years, attention has broadened to encompass other stereochemical architectures such as axial, planar, helical, and stereogenic heteroatoms. In this context, N-heterocyclic carbene (NHC)-catalyzed transformations with distinctive activation modes allow the facile synthesis of such stereochemical architectures. The objective of this thesis is to develop NHC-catalyzed routes to C-N axially chiral and heteroatom chiral molecules. In this context, we have developed the NHC-catalyzed desymmetrization of N-aryl maleimides to access C-N axially chiral succinimides. The strategy followed Stetter-aldol-oxidation cascade to deliver the C-N axially chiral succinimides with high enantiopurity, however with poor control over multiple stereogenecity. We have addressed this issue via kinetic resolution of N-aryl maleimides to access C-N axially chiral dihydropyridinones with point chirality with good diastereoselectivity and excellent enantioselectivity. Moreover, we have demonstrated the first organocatalytic atroposelective synthesis of N-aryl phthalimides via the traditional N-CC=O disconnection under mild conditions. In another phase of the work, given the diverse applications of heteroatom stereogenic compounds, we have realized the precise control over heteroatom stereogenecity using NHC organocatalysis. In this context, the first NHC-catalyzed enantioselective synthesis of cyclic sulfonimidamides (SIAs) bearing S(VI) stereogenic center has been demonstrated. Moreover, the NHC-catalyzed highly diastereo- and enantioselective synthesis of P(V)-stereogenic phosphacycles will also be presented.