From Mechanistic Study to Chiral Catalyst Optimization: Theoretical Insight into Binaphthophosphepine-catalyzed Asymmetric Intramolecular [3 + 2] Cycloaddition

Abstract

Density functional M11 was used to study the mechanism and enantioselectivity of a binaphthophosphepine-catalyzed intramolecular [3 + 2] cycloaddition reaction. The computational results revealed that this reaction proceeds through nucleophilic addition of the phosphine catalyst to the allene, which yields a zwitterionic phosphonium intermediate. The subsequent stepwise [3 + 2] annulation process, which starts with the intramolecular nucleophilic addition of the allenoate moiety to the electron-deficient olefin group, determines the enantioselectivity of the reaction. This step is followed by a ring-closing reaction and water-assisted proton-transfer process to afford the final product with concomitant regeneration of the phosphine catalyst. Theoretical predictions of the enantioselectivity for various phosphine catalysts were consistent with experimental observations, and 2D contour maps played an important role in explaining the origin of the enantioselectivity. Moreover, on the basis of our theoretical study, new binaphthophosphepine catalysts were designed and that are expecting to afford higher enantioselectivity in this cycloaddition reaction.

Mechanism of Phosphine‐Catalyzed Allene Coupling Reactions: Advances in Theoretical Investigations

“…Moreover, our group investigated the binaphthophosphepine‐catalyzed asymmetric intramolecular [3+2] cycloaddition (Figure c). We found that nucleophilic addition of binaphthophosphepine 13 to the β position of γ‐alkyl‐substituted 14 takes place via the transition state 15‐ts with a free energy barrier of 22.9 kcal mol −1 . The barrier of this step with the γ‐alkyl‐substituted allenoate is close to that with the α‐substituted allenoate, therefore, steric hindrance at the γ position of the allenoate plays a similar role to that at the α position.…”

“…To exclude the possibility of a concerted pathway, we performed a theoretical calculation for the binaphthophosphepine‐catalyzed intramolecular [3+2] cycloaddition of allene. As shown in Figure , the two‐dimensional potential‐energy surface was calculated by the B3LYP density functional, for which the reaction pathway is labeled . The C1 and C2 atoms close first.…”

Toward a Predictive Understanding of Phosphine-Catalyzed [3 + 2] Annulation of Allenoates with Acrylate or Imine

“…Harmonic vibrational frequency calculations were performed with the same method for all stationary points to confirm them as a local minima or transition structures and to derive the thermochemical corrections for the enthalpies and free energies. Recent works from our group showed that the M11 functional, recently proposed by the Truhlar group, could give more accurate energetic information. Here we used the M11 functional with the larger basis set 6-311+G­(d) to derive single-point energies on B3LYP/6-31G­(d) optimized geometries.…”

Automated approaches, reaction parameterisation, and data science in organometallic chemistry and catalysis: towards improving synthetic chemistry and accelerating mechanistic understanding

“…These proton affinities have been used to describe the binding behaviour of ligands to metal centres. 205,206 In a related parameter, the lone pair energy of the phosphine has also been used as a metric of electronic donation strength from the ligand to the metal centre. 207 The electronic character of a molecule can be expressed by considering the charge localised on each atom.…”