Asymmetric organocatalytic Strecker-type reactions of aliphatic N,N-dialkylhydrazones.

The enantioselective organocatalytic Strecker-type reaction of aliphatic N,N-dialkylhydrazones is presented. Using trimethylsilyl cyanide (TMSCN) as the cyanide source, the reaction can be efficiently catalyzed by a tert-leucine-derived bifunctional thiourea to afford the corresponding hydrazino nitriles in good to excellent yields (50-96%) and moderate to good enantioselectivities, up to 86% ee. Further transformations of the nitrile functionality allow access to useful protected hydrazino acids and imidazolidinones. Interestingly, some of the hydrazino nitriles and their derivatives could be recrystallized in high recovery, yielding essentially pure enantiomers.

Organocatalytic kinetic resolution cascade reactions: new mechanistic and stereochemical manifold in diphenyl prolinol silyl ether catalysis.

A new cascade reaction involving an iminium-catalyzed intramolecular oxa-Michael addition followed by an enamine-catalyzed intermolecular Michael addition is reported herein. This cascade reaction generates enantiopure, highly functionalized tetrahydropyrans and tetrahydrofurans in a one-pot reaction and in up to 89 % combined yield and up to 99 % ee. This cascade reaction is catalyzed by diaryl prolinol silyl ethers, which are a privileged class of catalysts. The stereochemical outcome of these cascade reactions is unprecedented. Computational studies indicate that this stereochemical outcome arises from nonclassical hydrogen-bonding interactions between the electrophile and the substrate, and from entropic considerations of preorganization. The unprecedented configurations of the cascade products, combined with the computational models, reveal for the first time that asymmetric induction by diaryl prolinol silyl ether catalysts is not always exclusively reagent controlled. The stereochemical outcome also arises from a kinetic resolution or dynamic kinetic resolution of the ß-stereocenter through an enamine-catalyzed intermolecular reaction. This unprecedented organocascade reaction mechanism may be adaptable to diaryl prolinol silyl ether-catalyzed cascade reactions, in which both the iminium- and enamine-catalyzed steps are intermolecular, an underdeveloped type of cascade reaction.