FeCl3-Promoted Facile Synthesis of Multiply Arylated Nicotinonitriles

Abstract

Many biologically active nicotinonitriles have been reported to date. Consequently, the development of synthetic methods for multiply arylated/alkylated nicotinonitriles remains a sought-after field of research. In the present work, a new synthetic strategy for multi-substituted nicotinonitriles was provided. A FeCl3-promoted condensation-cyclization reaction of an enamino nitrile and α,β-unsaturated ketones efficiently proceeded with a wide range of substrates. It is noteworthy that this method facilitated the access to fully- and differently substituted nicotinonitriles including tetra-arylated nicotinonitriles in only three steps. Using the functionality of the cyano group, the copper-catalyzed annulation reaction of the nicotinonitrile was achieved to yield benzo[c][2,7]naphthyridin-5(6H)-one.

Synthesis of Substituted Pyridines via Formal (3+3) Cycloaddition of Enamines with Unsaturated Aldehydes and Ketones

“…On the basis of these observations, we hypothesized that preinstallation of the putative pyridyl nitrogen within one of the reactants would simplify the transformation and could improve the reaction efficiency. β-Enaminonitriles have been long known as versatile building blocks in heterocyclic synthesis, [30][31][32][33]40 which prompted us to investigate β-enaminonitrile 6a as an alternative building block to 3, potentially providing direct access to 2a via formal (3+3) cycloaddition with 4 (Scheme 2). β-Enaminonitrile 6a can be quantitatively prepared by an nbutyllithium-mediated heterodimerization of two different nitriles under cryogenic conditions and purified by vacuum distillation as a stereoisomeric mixture (i.e., Z:E = 3:1).…”