1 -Amino-2-imino-1,2-dihydropyridines

In 2007, AntiUa and coworkers disclosed the first asymmetric organocatalytic reduction of acyclic a-imino esters (Scheme 23) [39], Chiral VAPOL phosphate (5)-16 (5 mol%) served as a catalyst for the transfer hydrogenation of the latter (62) employing commercially available dihydropyridine 44a to give both aromatic and aliphatic a-amino esters 63 in very high yields (85-98%) and enantioselectivities (94-99% ee). 

Schmidpeter et al. [37] developed an alternative method for the synthesis of 24 involving condensation of l-amino-2-imino-l,2-dihydropyridines (25) with P(NMe2)3 (Scheme 7). 

The mechanism of the amination starts with the formation of an imine from the black amino group and the green carbonyl. Removal of the now very acidic proton between the protonated pyridine and the conjugated imino-carboxylic acid gives a dihydropyridine, which rearomatizes by protonation next to the carboxylic acid. This step is enantioselective, with the proton being delivered from the enzyme. Finally, hydrolysis of the new imine gives pyridoxal and a single enantiomer of the amino acid. 

In 2014, Odom and coworkers reported a titanium-catalyzed synthesis of 2-amino-3-cyanopyridines (Scheme 3.41) [89]. The reactions were performed in a one-pot manner with two manipulation steps. Firstly, titanium-catalyzed alkyne iminoamination and generation tautomers of 1,3-diimines. Then, 2-amino-3-cyanopyridines were formed in good to modest yields after treatment with base (DBU) and malononitrile. A Dimroth rearrangement mechanism for 2-aminopyridine formation was proposed based on the isolation of a 2-imino-l,2-dihydropyridine intermediate which undergoes rearrangement under the reaction conditions. 

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