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 are well-known, the synthesis of axially chiral C-N bond-containing compounds are 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 -unsaturated aldehydes under oxidative conditions furnished the atropisomeric quinazolinone derivatives under mild conditions and broad scope. Preliminary studies on experimental and DFT-based N-N rotational barrier determination is also presented.