engleski

Organocatalytic Stereoselective Arylation Of Isoindolinone Derivatives

Enantiomerically pure 3, 3-disubstituted isoindolinones are represented as highly valuable structural motifs found in a numerous of natural products and biologically active compounds. Their biological activities are greatly influenced by the type of substituents and absolute configuration on this position. A broad range of methodologies for the synthesis of chiral isoindolinone derivatives has already been developed, including additions of heterocylces, heteroatoms and non-aromatic carbon nucleophiles. On the other hand, there are still no reports on organocatalytic protocols for the enantioselective construction of the third phenyl ring on the isoindolinone C3 position. Herein, we report a chiral phosphoric acid-catalyzed (CPA) stereoselective reaction between diaryl ketimines and phenols for the construction of triarily substituted quaternary stereogenic center. The success of this transformation lies in the in situ generation of the reactive N-acil ketiminium spices from 3-hydroxysubstituted isoindolinones, making them susceptible for a reaction with phenols.The reaction proceeds with high regioselectivity and enantioselectivity, and is tolerant of various functionalities on isoindolinone alcohol, as well as on phenol. Stereochemical induction model was investigated with density functional theory calculations. The calculation showed that Re face attack of phenols is more favorable.

organocatalysis ; stereoselective arylation ; isoindolinone derivatives ; quaternary stereogenic center

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