An unprecedented highly efficient Lewis acid catalyzed one-pot cascade has been demonstrated as a general catalytic system for the synthesis of diversely substituted isoindolinones and tetrahydroisoquinolines. The cascade effects one C-C and two C-N bond-forming events in one pot. Several interesting transformations of the products into valuable synthetic intermediates are featured with the successful total synthesis of (±)-crispine A.

An organocatalytic direct Mannich-lactamization sequence for the syntheses of pharmacologically important enantioenriched isoindolinones is reported. The method utilizes simple α-amino acids to deliver syn- and anti- selective isoindolinones with remarkably high enantioselectivity (up to >99% ee) in good to excellent yields and diastereomeric ratios. The overall sequence involves one C-C and two C-N bond forming events in one pot starting from inexpensive starting material.

An efficient route to pharmacologically interesting isoindolinone-based α-amino phosphonates is described via asymmetric hydrophosphonylation of in situ generated ketimines catalyzed by BINOL-derived phosphoric acid. The reaction proceeds smoothly at ambient temperature affording a variety of α-amino phosphonates with a quaternary stereogenic center embedded in isoindolinone motif in high yields with excellent enantiomeric ratios (up to 98.5:1.5 er). Several interesting transformations of the products into valuable synthetic intermediates are also depicted.

Chiral Brønsted acid catalyzed enantioselective syntheses of isoindolinones and phthalides have been accomplished via tandem Mannich-lactamization and aldol-lactonization reactions, respectively. A variety of enantioenriched isoindolinones (up to 99% ee) and phthalides (up to 85% ee) containing α-diazoesters were afforded in excellent yields. Furthermore, a concise synthesis of (S)-PD 172938 has been demonstrated by using this protocol.

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A chiral phosphoric acid-catalyzed asymmetric Mannich-type reaction of α-diazo esters with in situ generated N-acyl ketimines, derived from 3-hydroxyisoindolinones has been demonstrated in this communication. A variety of isoindolinone-based α-amino diazo esters bearing a quaternary stereogenic center were afforded in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee). Furthermore, the synthetic utility of the products has been depicted by the hydrogenation of the diazo moiety of adducts.

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Catalytic enantioselective direct vinylogous Michael addition of α,α-dicyanoalkenes to 2-enoylpyridine N-oxides with a bifunctional organocatalyst is described. The methodology offers an efficient way to install an asymmetric carbon-carbon bond at the γ-position of α,α-dicyanoalkenes in excellent regio-, diastereo-, and enantioselectivity. Further, application in desymmetrization of achiral α,α-dicyanoalkene to access highly functionalized enantioenriched cyclohexylidenemalononitrile derivatives has been demonstrated.