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

Although the atroposelective synthesisof biaryls and related compoundsbearing axially chiral C-C bonds is well-known, the synthesisof axially chiral C-N bond-containing compounds is relativelyless explored, and the construction of axially chiral N-N bondshas received only scant attention. Demonstrated herein is the N-heterocycliccarbene (NHC)-catalyzed selective amidation reaction, leading to theatroposelective synthesis of N-N axially chiral 3-amino quinazolinones.The NHC-catalyzed reaction of quinazolinones containing a free N-Hmoiety with & alpha;,& beta;-unsaturated aldehydes under oxidativeconditions furnished the atropisomeric quinazolinone derivatives undermild conditions and broad scope. Preliminary studies on experimentaland density functional theory-based N-N rotational barrierdetermination are also presented.

Automated summary

While the selective synthesis of biaryls with axially chiral C-C bonds is well-known, the synthesis of compounds containing axially chiral C-N bonds is less explored, and the construction of axially chiral N-N bonds has received little attention. This study demonstrates the selective amidation reaction catalyzed by N-heterocyclic carbenes (NHCs), leading to the atroposelective synthesis of N-N axially chiral 3-amino quinazolinones. The NHC-catalyzed reaction of quinazolinones with a free N-H group and α,β-unsaturated aldehydes under oxidative conditions provides the atropisomeric quinazolinone derivatives under mild conditions and with a broad scope. Preliminary studies on experimental and density functional theory-based determination of N-N rotational barrier are also presented.