Asymmetric Catalytic Ketimine Mannich Reactions and Related Transformations

The catalytic enantioselective ketimine Mannich and its related reactions provide direct access to chiral building blocks bearing an α-tertiary amine stereogenic center, a ubiquitous structural motif in nature. Although ketimines are often viewed as challenging electrophiles, various approaches/strategies to circumvent or overcome the adverse properties of ketimines have been developed for these transformations. This review showcases the selected examples that highlight the benefits and utilities of various ketimines and remaining challenges associated with them in the context of Mannich, allylation, and aza-Morita–Baylis–Hillman reactions as well as their variants.

Synthesis, crystal and molecular structure, vibrational spectroscopic, DFT study and activity evaluation of 4-(2-chlorobenzyl)-1-(4-hydroxy -3-((4-hydroxypiperidin-1-yl)methyl-5-methoxyphenyl)-[1,2,4] triazolo[4,3-a]quinazolin-5(4H)-one

In current work, we have firstly synthesized 4-(2-chlorobenzyl)-1-(4-hydroxy-3- ((4-hydroxypiperidin-1-yl)methyl)-5-methoxyphenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one (1) by ring-opening, cyclization, substitution, doamine condensation and Mannich reactions. The structural properties of the title compound 1 were explored using spectroscopy (1H NMR, 13C NMR, MS and FT-IR) and X-ray crystallography method. The single-crystal structure confirmed by X-ray diffraction was consistent with the molecular structure optimized by density functional theory (DFT) calculation at B3LYP/6-311G (2d, p) level of theory. The geometrical parameters, molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) analysis were performed by DFT using the B3LYP/6-311G (2d, p) method. Molecular docking has shown favorable interaction between the title compound 1 and SHP2 protein. The inhibitory activity of target compound 1 on SHP2 protein at 10 μM is better than the reference compound (SHP244).