BETA-KETONITRILE-DERIVED PROTECTING GROUPS OF THE AMINO FUNCTION - SYNTHESIS OF AMINO-ALCOHOLS

The amino group of natural L-amino acid esters is protected by condensation with 2-oxocyclopentanenitrile (1) or 2-formyl-2-phenylacetonitrile (10). Only the ester group of the formed cyanoeanmino esters 2 and 11 reacts with nucleophilic reagents such as organometallics (RMgX, RLi), borohydrides, or metal amides, whereas the cyanoenamino group is unchanged (Schemes 1 and 2). Cyanoenamino alcohols obtained by reduction of cyanoenamino esters 2 are hydrolyzed under acidic conditions to amino alcohols with retention of the configuration of the starting amino acid. This sequence of reactions allows to prepare derivatives of L-tyrosinol from (-)-L-tyrosine (see, e.g., Scheme 4). Cyanoenamino esters 11 are readily methylated at the N-atom to give N-methylated cyanoenamino esters (Scheme 3). This property is exploited on the way of a multistep procedure to obtain N-methylated amino alcohols homologous to natural (-)-(1R,2S)-ephedrine.