N-Heterocyclic Carbene-Catalyzed Atroposelective Synthesis of N–N Axially Chiral 3-Amino Quinazolinones

Although the atroposelective synthesis of biaryls and related compounds bearing axially chiral C-C bonds is well-known, the synthesis of axially chiral C-N bond-containing compounds is relatively less explored, and the construction of axially chiral N-N bonds has received only scant attention. Demonstrated herein is the N-heterocyclic carbene (NHC)-catalyzed selective amidation reaction, leading to the atroposelective synthesis of N-N axially chiral 3-amino quinazolinones. The NHC-catalyzed reaction of quinazolinones containing a free N-H moiety with α,β-unsaturated aldehydes under oxidative conditions furnished the atropisomeric quinazolinone derivatives under mild conditions and broad scope. Preliminary studies on experimental and density functional theory-based N-N rotational barrier determination are also presented.