Enantioselective organocatalytic approach to the synthesis of alpha,alpha-disubstituted cyanosulfones.

Optically pure cyano tert-alkyl sulfones have been obtained by organocatalytic enantioselective Michael addition of alpha-substituted cyanosulfones to vinyl ketones using cinchona alkaloids as catalysts. The best results were obtained for p-trifluorophenylsulfones by using VIII as catalyst in toluene at -40 degrees C. Reactions proved to be applicable for a variety of alpha,beta-unsaturated ketones, affording alpha,alpha-disubstituted cyanosulfones in excellent yields with er's up to 90:10.

Intriguing behavior of cinchona alkaloids in the enantioselective organocatalytic hydroxyamination of alpha-substituted-alpha-cyanoacetates.

The cinchona alkaloid quinine promotes the enantioselective nitroso-aldol reaction between alpha-aryl-alpha-cyanoacetates and nitrosobenzene to give the hydroxyamination products with total chemoselectivity. Treatment of the reaction mixture with Zn/AcOH affords the corresponding amines in high yield and moderate enantioselectivity. An unusual effect on the enantioselectivity was observed with the catalyst loading and solvent.

Organocatalytic asymmetric 1,6-additions of beta-ketoesters and glycine imine.

The first organocatalytic enantioselective 1,6-addition of beta-ketoesters and benzophenone imine to electron-poor delta-unsubstituted dienes using cinchona alkaloids under phase-transfer conditions is demonstrated. The scope of the reaction for the beta-ketoesters is outlined for reactions with different delta-unsubstituted dienes having ketones, esters, and sulfones as electron-withdrawing substituents giving the corresponding optically active products in good yields and enantioselectivities in the range of 90-99% ee. The 1,6-addition also proceeds with a number of cyclic beta-ketoesters having different ring sizes, ring systems and substituents in high yields and enantioselectivities.

Asymmetric aza-Henry reactions from N-p-tolylsulfinylimines.

[reaction: see text] N-Sulfinylimines derived from aromatic or aliphatic aldehydes and ketones react with nitromethane and NaOH in a highly diastereoselective manner under mild conditions. In the presence of TBAF, the reaction rates are strongly increased and the stereoselectivity is inverted. This method provides enantiomerically pure beta-nitroamines derived from enolizable aldimines and ketimines, which so far are hardly accessible by aza-Henry reactions.