Experimental and Theoretical Studies in Hydrogen-Bonding Organocatalysis

Chiral thioureas and squaramides are among the most prominent hydrogen-bond bifunctional organocatalysts now extensively used for various transformations, including aldol, Michael, Mannich and Diels-Alder reactions. More importantly, the experimental and computational study of the mode of activation has begun to attract considerable attention. Various experimental, spectroscopic and calculation methods are now frequently used, often as an integrated approach, to establish the reaction mechanism, the mode of activation or explain the stereochemical outcome of the reaction. This article comprises several case studies, sorted according to the method used in their study. The aim of this review is to give the investigators an overview of the methods currently utilized for mechanistic investigations in hydrogen-bonding organocatalysis

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

Chiral derivatives of γ-aminobutyric acid are widely used as medicines and can be obtained by organocatalytic Michael additions. We show here the stereoselective synthesis of 4-methylpregabalin stereoisomers using a Michael addition of dimethyl malonate to a racemic nitroalkene. The key step of the synthesis operates as a kinetic resolution with a chiral squaramide catalyst. Furthermore, specific organocatalysts can provide respective stereoisomers of the key Michael adduct in up to 99:1 er

CCDC 1937210: Experimental Crystal Structure Determination

Related Article: Denisa Vargová, Juana M. Pérez, Syuzanna R. Harutyunyan, Radovan Šebesta|2019|Chem.Commun.|55|11766|doi:10.1039/C9CC05041

[5]Ferrocenophane based ligands for stereoselective Rh-catalyzed hydrogenation and Cu-catalyzed Michael addition

A series of homochiral [5]ferrocenophane based N/P, N/S, N/Se, Se/P and P/P ligands was prepared from (R)-N,N-dimethylamino[5]ferrocenophane. These ligands were tested in the Rh-catalyzed hydrogenation of dimethyl itaconate and in Cu-catalyzed Michael addition of Et2Zn to cyclohex-2-enone. The best results in terms of conversion and enantioselectivity in the Rh-catalyzed hydrogenation provided bis(diphenylphosphine) ligand (100% conversion and 95% ee) and aminophosphine in the Cu-catalyzed conjugate addition (100% conversion 84% ee). The enantioselectivity of the Rh-catalyzed hydrogenation of methyl 2-acetamidoacrylate was lower (41% ee).

Catalytic enantioselective conjugate addition of dialkylzinc reagents to N-substituted-2,3-dehydro-4-piperidones

The first, highly enantioselective, copper/phosphoramidite-catalyzed conjugate addition of dialkylzinc reagents to N-substituted 2,3-dehydro-4-piperidones is described.

Synthesis of β-damascone from 2,6-dimethylcyclohexanone

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