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.