Diastereoselective Aldolization of α-Aminonitriles. Diastereoselective Synthesis of β-Amino Alcohols and β,γ-Diamino Alcohols

Aldolization performed by addition of lithiated N-benzyl-N-tert-butylaminoacetonitrile to aldehydes provides diastereomerically pure anti-β-hydroxy-α-aminonitriles. They are transformed into syn,anti-protected β,γ-diamino alcohols by a two-step procedure, involving addition of a Grignard reagent and reduction. The cleavage of the N-tert-butyl group is achieved by a simple acidic treatment. The application of this methodology to chiral, nonracemic aldehydes is studied. Starting from d-isopropylideneglyceraldehyde, an anti, anti, syn, anti-(2R,3S,4S,5R,6R)-diaminotriol is prepared in acceptable yield and with a good level of diastereoselectivity.