Alkyne Hydrofunctionalization Mechanism Including an Off-Cycle Alkoxycarbene Deactivation Complex

The cooperative [Ru­(Cp)­(P2CyN2Ph)­(MeCN)]­[PF6] (Ru2) complex was utilized for additive-free hydroalkoxylation of 2-ethynylbenzyl alcohol (1a) to generate isochromene. The phenyl-substituted pendent amine of the supporting ligand effectively mediated proton-transfer steps and mitigated a vinyl ammonium deactivation pathway that was previously favored with a more nucleophilic N-benzyl substituent. A select set of substrates were cyclized to uncover mechanistic opportunities and limitations of Ru2 and related catalysts. Isotopic labeling and kinetic studies, using the variable time normalization analysis (VTNA) method, were utilized to identify vinylidene formation as the most likely rate-limiting step of catalysis. Attempted cyclization of 3-butyn-1-ol afforded an isolable alkoxycarbene complex, the stability of which was investigated both computationally and through stoichiometric reactions. This compound is identified as an off-cycle catalytic species, and it reveals a critical competing proton-transfer pathway for this family of cooperative catalysts.