A mechanistic study on the regioselective Ni-catalyzed methylation-alkenylation of alkyne with AlMe3 and allylic alcohol

The recently reported Ni-catalyzed methylation-allylation of alkynes with allylic alcohols and AlMe3 reagents delivers valuable tetrasubstituted alkene units in a highly regioselective fashion. Motivated by the experimental significance and the mechanistic ambiguity (e.g. the details of C-O bond activation, the function of the Lewis acid AlMe3, etc.), we conducted a detailed mechanistic study using density functional theory (DFT) calculations. The reaction was found to occur via the C-O bond activation of allylic alcohol, allylation of alkyne, transmetalation, reductive elimination and catalyst regeneration steps. AlMe3 could easily react with the allylic alcohol to form a cyclodialuminoxane species bearing two groups of Lewis acid-base interactions. In this regard, the C(allyl)-O bond is remarkably activated, resulting in a relatively facile C-O activation (compared to the typical Lewis-acid mediated reactions). In addition, the Al-Me interaction is a double-edged sword to the methylation step: the cyclodialuminoxane group functions as the methyl resource, while the full dissociation of the Al-Me interaction (via a cis-to-trans isomerization) is a requisite to fully release the methyl group. In this context, the Me-relay pathway involving the [Ni]-Me intermediate is found to be more plausible than all other mechanistic possibilities (such as the typical concerted Me-transfer mechanism in previous studies).

Automated summary

This study revealed the detailed mechanism of Ni-catalyzed methylation-allylation reaction using density functional theory calculations, including C-O bond activation, allylation, transmetalation, reductive elimination, and catalyst regeneration steps. AlMe3 reacts with allylic alcohols to form cyclodialuminoxane species, activating the C(allyl)-O bond. The Al-Me interaction serves as both the methyl resource and is necessary for the full release of the methyl group through isomerization.