Enantioselective construction of a tetrasubstituted stereocenter in isoindolinones via an organocatalyzed reaction between ketones and 3-hydroxyisoindolinones.

An efficient enantioselective reaction between ketones and 3-hydroxyisoindolinones is described. In a reaction catalyzed by a chiral phosphoric acid, a broad range of ketones and in situ generated ketimines afforded isoindolinone derivatives comprising a tetrasubstituted stereocenter in high yields and enantioselectivities. The developed methodology is also suitable for the construction of compounds with vicinal stereogenic centers.

Enantioselective and Diastereodivergent Synthesis of Spiroindolenines via Chiral Phosphoric Acid-Catalyzed Cycloaddition.

A diastereodivergent and enantioselective synthesis of chiral spirocyclohexyl-indolenines with four contiguous stereogenic centers is achieved by a chiral phosphoric acid-catalyzed cycloaddition of 2-susbtituted 3-indolylmethanols with 1,3-dienecarbamates. Modular access to two different diastereoisomers with high enantioselectivities was obtained by careful choice of reaction conditions. Their functional group manipulation provides an efficient access to enantioenriched spirocyclohexyl-indolines and -oxindoles. The origins of this stereocontrol have been identified using DFT calculations, which reveal an unexpected mechanism compared to our previous work dealing with enecarbamates.