N-Heterocyclic Carbene-Catalyzed Atroposelective Synthesis of N–N Axially Chiral 3-Amino Quinazolinones
Kuruva Balanna, Soumen Barik, Shilpa Barik, Sayan Shee, Niket Manoj, Rajesh G. Gonnade, Akkattu T. Biju
Abstract
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.