Estudo computacional do mecanismo de acoplamento cruzado C-C via dupla ativação das ligações C-O de éteres catalisado por complexo de níquel

Abstract

C−O activation is an excellent strategy to promote cross-coupling reactions of oxygenated electrophiles 1 . A new methodology for ether deoxygenation catalyzed by Ni(dppb), in the presence of zinc dust and B 2 pin 2 as likely reducing agent and oxygen acceptor, respectively, was developed by Shi and Cao 1 . The relevance of this methodology lies on the fact that both C−O bonds are activated, resulting in the union of both ether carbon chains, granting a good atom economy to the system. Thereby, in this study, the molecular mechanism of the ether deoxygenation reaction was characterized, via electronic structure calculations. The calculations were performed in DFT/PBE-D3 level. Several mechanistic pathways were considered in the present work and it was concluded that in the absence of bis(pinacolato) diboron in the reaction medium, the kinetically favored cycle occurs through the steps of i) 1st oxidative addition, which is associated with the breaking of an ether C-O bond with concomitant connection of its fragments to the nickel of the catalyst; ii) reduction of the Ni(II) complex generated to Ni(I), via abstraction of its alkoxide group by metallic zinc; iii) formation of an alkyl radical through the reaction of the Ni(I) intermediate with a new ether molecule, again, only one of the substrate C-O bonds is cleaved; iv) further reduction of the nickel complex to Ni(I); v) addition of the radical formed in step (iii) to the Ni(I) complex and v) reductive elimination, which leads to C-C coupling between the carbon fragments of the two consumed ethers. The formation of the alkyl radical was identified as the ratedetermining event of this catalytic cycle with ∆G ‡ = 31.0 kcal/mol. When B 2 pin 2 is present in the reaction medium, it reacts with an alkoxide group anchored to the zinc surface and not used in the previously discussed cycle. This reaction promotes the breakage of the 2nd C-O bond of the ether and forms an alkyl radical consisting of its entire carbonic fragment that binds to the Ni(I) complex, and the most energetic barrier is associated with the desorption of the radical from the metallic surface, followed by its connection to the nickel complex with ∆G ‡ = 31.5 kcal/mol. As the barriers differ by only 0.5 kcal/mol, it is concluded that both cycles are equally competitive and that (bis)pinacolato diboron increases the experimental yield significantly, as it transforms the reactional stoichiometry from 2R→1P to 1R→1P.