Enamine Catalysis for the Direct Asymmetric Hydroxyamination

Significance

The direct enantioselective hydroxyamination is a potentially powerful method to provide α-amino aldehydes as interesting synthetic building blocks. Here, the authors describe a method employing the chiral secondary amine organocatalyst 1 to give N-hydroxy-β-amino alcohols 5 from nitrosobenzene (2) and different aldehydes 3 in good yields (70-90%) and excellent enantioselectivities (96-99%) after reduction of the hydroxyamination product 4. When using p-methoxynitrosobenzene it was possible to isolate either β-amino alcohol 6 or fully protected 1,2-diamine 7, both in high enantioselectivity (95%). Catalyst tuning is easily possible, but an alcohol moiety in the 3,3′-substituent of the catalyst is required in terms of conversion. Aminooxylated products were observed in less than 1% yield.