Diversity-oriented Synthesis of Bicyclic Heterocycles from Levulinic Acid through a Fast and Operationally Simple Multicomponent Approach

Levulinic acid, which is one of the most important renewable building blocks derived from lignocellulosic biomass, has been converted, in a diversity-oriented manner, into two families of drug-like bicyclic nitrogen heterocycles. The methodology, endowed with high step economy and operational simplicity, is based on an Ugi multicomponent reaction, which employs aminoalcohols as components, followed by a SN2 cyclization. Worth of noting is the successful synthesis of hexahydro pyrrolodiazepinediones, since the cyclization of the isocyanide-derived secondary amide onto an alcohol to give a seven-membered ring was unprecedented. Also enantiopure products have been prepared using chiral aminoalcohols.