SummaryNew bifunctional chiral ammonium salts were investigated in an asymmetric cascade synthesis of a key building block for a variety of biologically relevant isoindolinones. With this chiral compound in hand, the development of further transformations allowed for the synthesis of diverse derivatives of high pharmaceutical value, such as the Belliotti (S)-PD172938 and arylated analogues with hypnotic sedative activity, obtained in good overall total yield (50%) and high enantiomeric purity (95% ee). The synthetic routes developed herein are particularly convenient in comparison with the current methods available in literature and are particularly promising for large scale applications.

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New heterocyclic hybrids were synthesized in an aldol initiated organocascade reaction of nucleophilic\ud isoindolinones with 2-formyl benzonitriles (2-cyano benzaldehydes). Excellent diastereo- and\ud enantioselectivities and good yields were obtained in the presence of bifunctional organocatalysts. In\ud addition, a new application of the Staudinger reaction has been proposed for the synthesis of substituted\ud nucleophilic isoindolinone

Readily available chiral ammonium salts derived from cinchona alkaloids have proven to be effective phase transfer catalysts in the asymmetric Michael reaction of 3-substituted isoindolinones. This protocol provides a convenient method for the construction of valuable asymmetric 3,3-disubstituted isoindolinones in high yields and  moderate to good enantioselectivity. Diastereoselectivity was also investigated in the construction of contiguous tertiary and quaternary stereocenters. The use of acrolein as Michael acceptor led to an interesting tricyclic derivative, a pyrroloisoindolinone analogue, via a tandem conjugated addition/cyclization reaction.

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