N-Heterocyclic Carbene-Catalyzed Enantioselective Synthesis of C-O Axially Chiral Diaryl Ethers, Tricyclic Lactones and Lactams

Abstract

N-heterocyclic carbene (NHC)-catalyzed transformations with distinctive activation modes allow the facile synthesis of atropoisomers. In this context, we have demonstrated the NHC-catalyzed synthesis of axially chiral diaryl ethers via atroposelective esterification of dialdehyde-containing diaryl ethers. Additionally, we have developed a dynamic kinetic resolution approach towards the NHC-catalyzed synthesis of C-O axially chiral benzonitrile derivatives. NHCs are also well-known to catalyze cascade process to synthesize various carbocycles and heterocycles. In this regard, we have disclosed the NHC-catalyzed desymmetrization of cyclic-1,3-diketones allowing the enantioselective construction of tricyclic β-lactones with five contiguous stereocenters, including two quaternary stereocenters. Furthermore, we have described an aza-Michael-Mannich-lactamization cascade for NHC-catalyzed synthesis of functionalized pyrazoloquinolin-3-ones. In addition to the non-umpolung (normal) reactivity, we have also explored umpolung reactivity of NHCs where NHC-homoenolate intermediate undergo an efficient Michael-isomerization-lactonization cascade sequence to produce the dihydrocoumarin scaffolds.