Clean and molecularly programmable protocol for preparation of bis-heterobiarylic systems via a domino pseudocyclic reaction as a valuable alternative for TM-catalyzed cross-couplings

Abstract

The domino sequence of pseudocyclic reactions involving 4-methoxybenzonitrile N-oxide and trans-2-phenyl-1-cyano-1-nitroethene proceeding in mild (r.t.; atm. pressure) non-catalytic (without participation of palladium or other transition metals (TM)) conditions yielded a bis-heterobiarylic molecular system containing an oxadiazole moiety with an almost 40% yield. The presented methodology represents therefore an evident contrast to the existing methods of preparation of bis-heterobiarylic systems, which require the presence of TMs. This reaction should be considered stereochemically “clean” and contains a stage of cycloaddition to the CN bond. It should be underlined that this is the first case of non-catalyzed [3 + 2] cycloaddition involving the nitrile CN bond. Our comprehensive study shows that the described protocol can be applied as a general methodology for preparation of a wide group of bis-heterobiarylic molecules. The self-adjusted cascade of transformations, which is unique and valuable from the practical point of view, leads to formation of a single isomeric product (from many possible) as a consequence of three pseudocyclic tandem reactions performed in agreement with the fundamental principles of green chemistry and sustainable development with a maximal level of atom economy and good overall yields. A self-adjustment phenomenon observed in the studied smart technology leading to production of a material with special properties was explained by it deep quantum nature confirmed undoubtedly by the modern Molecular Electron Density Theory.