The project explores the reduction of 2-substituted-1-nitroarenes, furnishing either nitroso or nitrene intermediates, followed by further reactions ultimately leading to nitrogen-containing heterocycles. Five objectives will be pursued: a) reductive N-heteroannulation of 2-nitro-1- alkenylarenes to give either N-oxygenated indoles or indoles, b) reductive N-heteroannulation of heterocyclic 2-nitro-1-alkenylarenes to give heterocyclic [4.3.0]- and [3.3.0]-ring systems all containing a 2,3-fused pyrrole unit, c) reductive N-heteroannulation of 2-nitro-1-alkenylarenes, 2-nitro-1-iminoarenes, or 2-nitroazobenzenes in the presence of an electrophiles to give a new six-membered ring containing 1-3 nitrogen atoms, d) N-heteroannulation of 2-nitro-1-alkenylarenes involving a carbanion intermediate to give polycyclic N-oxygenated indoles or indoles, and e) reductive N-heteroannulations of enamines derived from 2-nitro-1-aminoarenes affording 2,3-fused pyrazines.
Heterocycles, cyclic compounds containing elements other than carbon within the cyclic framework, form the basis of the majority of current pharmaceutical agents, and the development of new methods for their synthesis, as well as methods for the synthesis of new types of heterocycles, is essential in the quest for new and effective drugs. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Bjorn C. Soderberg, of the Department of Chemistry at West Virginia University. Professor Soderberg and his students are developing general and flexible methodologies for the synthesis of a variety of complex nitrogen-containing heterocycles. The aim is to develop methodologies that will allow both for the preparation of a variety of isomeric compounds of a given heterocycle by varying the substrate and for the preparation of different heterocycles from the same substrate by varying the reaction conditions. A particularly powerful feature of the proposed research is the complementary approach starting from the same starting material and by small variations in conditions and additives generating a number of isomeric compounds.
