Mechanistic Insight into Catalytic Redox-Neutral C–H Bond Activation Involving Manganese(I) Carbonyls: Catalyst Activation, Turnover, and Deactivation Pathways Reveal an Intricate Network of Steps

Manganese­(I) carbonyl-catalyzed C–H bond functionalization of 2-phenylpyridine and related compounds containing suitable metal directing groups has recently emerged as a potentially useful synthetic methodology for the introduction of various groups to the ortho position of a benzene ring. Preliminary mechanistic studies have highlighted that these reactions could proceed via numerous different species and steps and, moreover, potentially different catalytic cycles. The primary requirement for typically 10 mol % catalyst, oftentimes the ubiquitous precursor catalyst, BrMn­(CO)₅, has not yet been questioned nor significantly improved upon, suggesting catalytic deactivation may be a serious issue to be understood and resolved. Several critical questions are further raised by the species responsible for providing a source of protons in the protonation of vinyl–manganese­(I) carbonyl intermediates. In this study, using a combination of experimental and theoretical methods, we provide comprehensive answers to the key mechanistic questions concerning the Mn­(I) carbonyl-catalyzed C–H bond functionalization of 2-phenylpyridine and related compounds. Our results enable the explanation of alkyne substrate dependencies, i.e., internal versus terminal alkynes. We found that there are different catalyst activation pathways for BrMn­(CO)₅, e.g., terminal alkynes lead to the generation of Mn^I–acetylide species, whose formation is reminiscent of Cu^I–acetylide species proposed to be of critical importance in Sonogashira cross-coupling processes. We have unequivocally established that alkyne, 2-phenylpyridine, and water can facilitate hydrogen transfer in the protonation step, leading to the liberation of protonated alkene products.