N-Heterocyclic Carbene-Catalyzed Synthesis of Oxazolones, e-Lactones and N-N Axially Chiral Molecules

Abstract

The diverse reactivity of N-heterocyclic carbenes (NHCs) in organocatalysis is due to the possibility of different modes of action. Although NHC-bound enolates and dienolates were well-known, the NHC-bound cross-conjugated aza-trienolates were undisclosed. We have demonstrated the synthesis of pyrrolooxazolones via NHC-bound azatrienolate intermediates. In the same fashion, involvement of chiral alpha-carbon center (proximal reaction centre) in dynamic kinetic resolution (DKR) via NHC-bound enolates were known. However, the gamma, gamma-disubstituted chiral carbon center (remote reaction centre) involving in DKR via NHC-bound dienolates were unknown. We have recently demonstrated the DKR of gamma,gamma-disubstituted indole 2-carboxaldehydes via NHC-Lewis acid cooperative catalysis for the synthesis of tetracyclic epsilon-lactones. Additionally, NHC-catalyzed atroposelective synthesis of C-C and C-N axially chiral molecules were known, and the asymmetric synthesis of axially chiral N-N molecules remains unknown in carbene catalysis. We have demonstrated the N-heterocyclic carbene (NHC)-catalyzed selective amidation reaction leading to the atroposelective synthesis of N-N axially chiral 3-amino quinazolinones.