Synthesis of Benzofuranones via Malonates Desymmetrization: Yield Increase by the Portion-wise Addition of Quinones.

The organocatalyzed addition of several malonates to 1,4-benzoquinones affords benzofuranones bearing a quaternary stereocenter with good enantioselectivity. This reaction is an intramolecular desymmetrization since it proceeds through the formation of an arylated achiral malonate that cyclizes to give the reaction product. The addition rate of the quinone dramatically affects the reaction yield which was originally low. The yield was considerably increased, in some cases, from less than 20 % to over 95 %, by adding the quinone in portions rather than at once, keeping similar enantioselectivity. A possible rationalization for the preferential formation of the indicated enantiomer has been investigated by DFT calculations.

Enantioselective aza-Michael addition of imides by using an integrated strategy involving the synthesis of a family of multifunctional catalysts, usage of multiple catalysis, and rational design of experiment.

A challenging asymmetric reaction (aza-Michael addition of imides to enones) has been optimized through an integrated approach involving the synthesis of a family of organocatalysts, multiple catalysis (usage of additives), and finally with rational exploration of the chemical space by the application of the experiment design.