ECHC - XXIX European Colloquium on HETEROCYCLIC CHEMISTRY,virtual edition

The pressing need to reduce the environmental footprint of chemical processes is driving the scientific community towards the design of new approaches aim at avoiding the use of scarce precious metals, using cheap organic promoters of low toxicity, high stability to air and moisture, and able to work under mild and less hazardous reaction conditions. The one-pot and tandem methodologies are highly attractive considering their advantages in minimizing waste production while avoiding purification or separation of intermediates. Over the years, our group has been focusing on the development of organocatalytic one-pot methodologies for the stereoselective synthesis of differently functionalized heterocyclic scaffolds, such as benzothiazepines, epoxides, tetrahydrothiophenes, piperazinones and γ-butyrolactones. In particular, considering the prominent role played by nitrogen-containing heterocycles in the fields of natural products, market drugs, agrochemicals, dyes, to cite only a few, we recently paid attention to the design of one-pot and cascade processes to easily access new libraries of highly functionalized 2-pyrrolines, amidines and dihydroacridines. These heterocycles represent important 3D structural scaffolds of significant interest in the area of medicinal chemistry endowed with antivirus, antibacterial, anthelmintic, anticancer activities or are effective in the treatment of Alzheimer’s disease. We developed simple one-pot approaches to novel N-unprotected-tetrasubstituted trans-2-pyrrolines and amidines bearing, for the first time, three contiguous stereocenters, starting from commercially available reagents and exploiting fundamental consecutive organic reactions (5 or 4 steps) using benign solvents. Both methodologies share the advantages to be conveniently promoted by a commercially available organic base, embodying a minimum number of operations despite the number of transformations involved. The same approach has been designed to set up the first stereoselective cascade synthesis of dihydroacridines via a Michal/aldol/dehydration cascade sequence catalyzed by a synergistic combination of a simple commercially available metal Lewis acid and a chiral secondary amine