Diastereoselective Cycloreductions and Cycloadditions Catalyzed by Co(dpm)₂-Silane (dpm = 2,2,6,6-tetramethylheptane-3,5-dionate):  Mechanism and Partitioning of Hydrometallative versus Anion Radical Pathways

In the presence of phenylsilane and 5 mol % cobalt(II) bis(2,2,6,6-tetramethylheptane-3,5-dionate), aryl-substituted monoenone monoaldehydes and bis(enones) undergo reductive cyclization to afford syn-aldol and anti-Michael products, respectively. For both aldol and Michael cycloreductions, five- and six-membered ring formation occurs in good yield with high levels of diastereoselectivity. Cycloreduction of monoenone monoaldehyde 1a in the presence of d³-phenylsilane reveals incorporation of a single deuterium at the enone β-position as an equimolar mixture of epimers, inferring rapid isomerization of the kinetically formed cobalt enolate prior to cyclization. The deuterated product was characterized by single-crystal neutron diffraction analysis. For bis(enone) substrates, modulation of the silane source enables partitioning of the competitive Michael cycloreduction and [2 + 2] cycloaddition manifolds. A study of para-substituted acetophenone-derived bis(enones) reveals that substrate electronic features also direct partitioning of cycloreduction and cycloaddition manifolds. Further mechanistic insight is obtained through examination of the effects of enone geometry on product stereochemistry and electrochemical studies involving cathodic reduction of bis(enone) substrates. The collective experiments reveal competitive enone reduction pathways. Enone hydrometalation produces metallo-enolates en route to aldol and Michael cycloreduction products, that is, products derived from coupling at the α-position of the enone. Electron-transfer-mediated enone reduction produces metallo-oxy-π-allyls en route to [2 + 2] cycloadducts and, under Ni catalysis, homoaldol cycloreduction products, that is, products derived from coupling at the β-position of the enone. The convergent outcome of the metal-catalyzed and electrochemically induced transformations suggests the proposed oxy-π-allyl intermediates embody character consistent with the mesomeric metal-complexed anion radicals.