Highly diastereoselective four-component synthesis of polysubstituted 1,4,5,6-tetrahydropyridines

A novel four-component diastereoselective synthesis of polysubstituted tetrahydropyridines is reported. The Michael addition - Mannich reaction - cyclization - dehydration cascade of benzylidenemalononitriles, esters of 3-oxocarboxylic acids, aromatic aldehydes, and ammonium acetate in methanol provides convenient access to 2-substituted alkyl (4SR,6RS)-4,6-diaryl-5,5-dicyano-1,4,5,6-tetrahydropyridine-3-carboxylates with two stereocenters in 66-92% yields. The formation of products was highly stereoselective, with only one diastereomer formed. Ammonium acetate plays dual role acting as a base and as a nitrogen source. Structures of the synthesized compounds were confirmed by H-1, C-13 NMR, IR, and mass spectral studies. The formation of single diastereomer was confirmed by singe crystal X-ray diffraction studies.

Automated summary

A novel four-component diastereoselective synthesis of polysubstituted tetrahydropyridines was reported, with high yields and strong stereoselectivity, confirmed by structural analysis of the synthesized compounds.