Imines, reaction with pyruvic acid

Similarly, the Doebner reactionl >i b condenses aromatic amines and aldehydes and pyruvic acid derivatives. Reaction of p-toluidine with pyruvic acid (266) gave the aminopyruvic acid (267) in situ and subsequent cyclization and air oxidation under Friedel-Crafts conditions generated the 4-carboalkoxy-quinoline (268).Presumably, the reaction proceeds via initial imine formation (via reaction with benz-aldehyde) followed by condensation with pyruvate (in its enol form).l l Similar cyclization occurs with imines and pyruvate derivatives. ... 

Yet a third method for the synthesis of a-amino acids is by reductive amination of an a-keto acid with ammonia and a reducing agent. Alanine, for instance, is prepared by treatment of pyruvic acid with ammonia in the presence of NaBH As described in Section 24.6, the reaction proceeds through formation of an intermediate imine that is then reduced. 

The oxidative deamination of amines to ketones, via oxaziridines, was reported as a model for the process found in oxidative deamination of a-amino-acids to pyruvic acids in biochemical systems." The primary amine, such as (58) or (59) with pyridine-2-carboxaldehyde, was converted into the imine (60) which was oxidized with m-chloroperbenzoic acid to the oxaziridine (61). Ring opening of (61) was effected with KOH in MeOH or in DMF (Scheme 8). Acetone was added to trap regenerated pyridine-2-carboxaldehyde. When other bases were used a competing reaction resulting in (62) occurred. 

Despite the importance of this reaction for the synthesis of chiral amines and amino acids, no effective solid catalyst is yet available [3]. There are two instances where 26 % ee was achieved (Fig. 9), but results with silk-supported Pd are difficult to reproduce, and in the hydrogenation of acetophenone oxime and pyruvic acid oxime stoichiometric amounts of chiral auxiliary were used [21,49]. The latter reaction was also extremely slow - only 15 % yield of alanine was obtained in 45 h. Efficient enantioselective hydrogenation of imines and oximes apparently remains a challenge for future development. 

---