Palladium-Catalyzed Atroposelective Coupling-Cyclization of 2-Isocyanobenzamides to Construct Axially Chiral 2-Aryl- and 2,3-Diarylquinazolinones

A palladium-catalyzed imidoylative cycloamidation of N-alkyl-2-isocyanobenzamides with 2,6-disubstituted aryl iodides, affording unprecedented axially chiral 2-arylquinazolinones, has been developed with good yields and atroposelectivities. In this coupling-cyclization process, the biaryl linkage and the heteroaromatic ring are formed sequentially in one step. When N-(2,4dimethoxyphenyl)-2-isocyanobenzamide is applied as a substrate, 2,3-diarylquinazolinones containing two stereogenic axes are produced with moderate diastereoselectivity and good enantioselectivities.

Automated summary

A palladium-catalyzed imidoylative cycloamidation of N-alkyl-2-isocyanobenzamides with 2,6-disubstituted aryl iodides has been developed to afford unprecedented axially chiral 2-arylquinazolinones with good yields and atroposelectivities. The coupling-cyclization process allows for the sequential formation of the biaryl linkage and the heteroaromatic ring in one step. When N-(2,4dimethoxyphenyl)-2-isocyanobenzamide is used as a substrate, 2,3-diarylquinazolinones containing two stereogenic axes are produced with moderate diastereoselectivity and good enantioselectivities.