Further studies on Ni/Zr-mediated one-pot ketone synthesis: Use of a mixture of Ni^I- And Ni^II-catalysts greatly improves the molar ratio of coupling partners

A new Ni/Zr-mediated one-pot ketone synthesis is developed, with use of a mixture of (Me)₃tpy·Ni^II- and py-(Me)imid·Ni^IICl₂-catalysts. The Ni^I-catalyst selectively activates iodides, whereas the Ni^II-catalyst activates thio-pyridine esters. An adjustment of a relative loading of the two catalysts allows to tune the relative rate of the two activations and trap a short-lived radical intermediate(s) efficiently. Thus, the new method makes one-pot ketone synthesis highly effective even with a 1:1 mixture of the coupling partners. The synthetic value of the new method is demonstrated with the C-C bond formation at the final stage of a convergent halichondrin-synthesis.