Research Projects

Heterocycles are crucial in the medicinal chemistry domain, as they are found in numerous bioactive molecules. The Morita-Baylis-Hillman (MBH) reaction is a fascinating carbon-carbon bond-forming transformation that has been explored for its potential in building nitrogen-containing heterocyclic scaffolds. The proposal aims to use the chemistry of the Baylis-Hillman reaction to create diverse heterocyclic scaffolds, including hexahydroimidazopyridines, dihydropyrazoles, and tetrahydroquinolines. The scientific objectives include synthesizing hexahydroimidazo[1,2-a]pyridines, gaining deeper insight into the retro-Mannich reaction, exploring a unique base-dependent reactivity switch, conducting photophysical studies of selected dihydropyrazoles, attempting the total synthesis of deoxy-Atazanavir, and accessing tetrahydroquinolines and phenothiazines using a nucleophile-electrophile cascade annulation strategy. Main experiments include synthesizing MBH adducts and their oxidation to access substrates, reacting on MBH ketones derived from cyclic precursors with diamines to access hexahydroimidazo[1,2-a]pyridines, reacting MBH ketones with substituted hydrazines in the absence of a base for the generation of dihydropyrazoles, oxidizing dihydropyrazoles to pyrazoles, inserting hydrazine into MBH ketone using specific substrates relevant to Atazanavir structure, and further steps toward the total synthesis of deoxy-Atazanavir. The proposal also explores cascade annulation of MBH ketones with o-aminobenzaldehydes for the synthesis of tetrahydroqyuinolines bearing a tetrasubstituted center, and oxidative cyclization of 2-aminothiophenols with MBH ketones derived from cyclic precursors for accessing the phenothiazine scaffold.