In situ generated cobalt(i) catalyst for the efficient synthesis of novel pyridines: revisiting the mechanism of [2 + 2 + 2] cycloadditions†

Abstract

The [2 + 2 + 2] cycloaddition of alkynes and nitriles is an efficient and atom-economic method for the synthesis of pyridines. However, most of the examples so far reported entail the use of diynes, which circumvents selectivity issues but limits the scope of the reaction—with examples of discrete alkynes being scarce. Moreover, the most widely used catalysts are Co(i) complexes featuring Cp or Cp* ligands, which are either too unstable to store or require harsh conditions to promote the cycloaddition reaction. This work describes a mild method for the preparation of a wide range of pyridines employing a Co(i) active species generated in situ from a well-defined, air-stable Co(iii) complex—namely, [CoCp*(CH₃CN)()][BF₄]₂—upon treatment with NaBEt₃H. This complex, which contains a hemilabile ligand, has been found to be substantially more active than complexes featuring monodentate or bidentate phosphanes. This behavior has been ascribed to the inadequate stabilization of the resulting Co(i) species for the former, or overstabilization of the Co(iii) complex in the case of the latter. A comprehensive DFT study has been conducted to elucidate the experimentally observed chemo- and regioselectivity by examining the competitive pathways following the oxidative coupling of CoCp*(bisalkyne) complex, taking under account the participation of triplet states and intersystem crossing points.