Practical catalytic enantioselective synthesis of 2,3-dihydroquin-azolinones by chiral bronsted acid catalysis

Herein, we report on the highly efficient and practical synthesis of 2,3-dihydroquinazolinones directly from diverse aldehydes with excellent yields and enantioselectivity. Particularly, this protocol affords better enantiocontrol for aliphatic aldehydes (up to 99% yield, 97% ee), which always gave unsatisfactory results in the previous studies. Moreover, this catalytic system shows wide tolerance to different functional groups such as alkenyl, nitro and halogens. Most importantly, its practicability is well elucidated via the gram-scale synthesis of different types of products at 0.1 mol% catalyst loading and the simplified work-up procedure. To better understand the reaction pathway and origin of the enantioselectivity, DFT calculations were also performed.

Automated summary

This study presents a highly efficient and practical method for the direct synthesis of 2,3-dihydroquinazolinones from diverse aldehydes with excellent yields and enantioselectivity. The method shows improved enantioselectivity for aliphatic aldehydes and wide tolerance to different functional groups. Gram-scale synthesis and simplified work-up procedure demonstrate the practicality of this method.