Atom-Efficient Carbon−Oxygen Bond Formation Processes. DFT Analysis of the Intramolecular Hydroalkoxylation/Cyclization of Alkynyl Alcohols Mediated by Lanthanide Catalysts

This contribution focuses on organolanthanide-mediated hydroalkoxylation processes and investigates the hydroalkoxylation/cyclization of a prototypical alkynyl alcohol, HO(CH2)3CCR, (R = H, CH3, TMS) catalyzed by the homoleptic La[N(SiMe3)2]3 amido complex using density functional theory. The reaction is found to occur in two steps, namely, cyclization with concerted Ln−C and C−O bond formation and subsequent Ln−C protonolysis. Calculations are carried out for: (i) insertion of the alkynyl moiety into the La−O bond via a four-center transition state and (ii) protonolysis by a second substrate molecule. The cyclized ether then dissociates, restoring the active catalyst. Analysis is also carried out on the effects of other Ln3+ ions and alkyne R substituents on the reaction energetics in comparison to the analogous organolanthanide-mediated aminoalkyne and aminoolefin hydroamination processes. DFT energetic profiles are computed for the turnover-limiting insertion of the alkynyl alcohol CC triple bond into the La−O bond, and the geometries and stabilities of reactants, intermediates, and products are analyzed. The picture that emerges involves a concerted, rate-limiting insertion of the alkyne fragment into the La−O bond via a highly organized transition state (ΔH ‡ calcd = 15.3 kcal/mol, ΔS ‡ calcd = −6.5 cal/(mol K)). The resulting cyclopentylmethylene complex then undergoes exothermic protonolysis to regenerate the active catalyst. Thermodynamic and kinetic estimates are in excellent agreement with experimental data.