2‐Acetylbenzonitriles have been conveniently synthesized by the oxidation of the respective 2‐ethylbenzonitriles, combining in a one‐pot procedure radical bromination and hydrolysis reactions. The obtained ketones reacted under very mild conditions with carbon and hetero nucleophiles to give a wide range of 3,3‐disubstituted isoindolinones in yields of 80–99 % by a tandem process consisting of an addition step and a subsequent Dimroth‐type rearrangement. Among the tested nucleophiles, the addition of water in the presence of a catalytic amount of KOH allowed a convenient access to an unprecedented variety of novel 3‐hydroxy‐3‐methylisoindolinones.

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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.

A new carboxylating reagent ((-)CH(2)CN/CO(2)) was obtained by bubbling CO(2) in a CH(3)CN-TEAP (tetraethylammonium perchlorate) solution previously electrolyzed under galvanostatic control. Organic carbamates were isolated from these solutions after addition of amines and an alkylating agent. In this paper, we describe the optimized conditions for the electrochemical synthesis of carbamates from amines and CO(2), in mild and safe conditions, without any addition of bases, probases, or catalysts. Carbamates were isolated from primary and secondary aliphatic amines in high to excellent yields and from aromatic amines in moderate yields (dependent on the nucleophilicity of the nitrogen atom).

Herein we describe the first asymmetric organocatalytic synthesis of 3-substituted isoindolinones in a convenient aldolcyclization- rearrangement tandem reaction of malonates with 2- 15 cyanobenzaldehyde. Bifunctional thiourea-cinchona catalysts proved to be particularly effective, giving the title compounds in high yields and moderate to good enantiomeric excesses. Moreover an efficient process of reverse crystallization led to a further enrichment up to >99% ee