Assessing the Recyclability of Supramolecularly Assembled Organocatalytic Species: A Theoretical Insight

Abstract

Asymmetric organocatalytic synthesis is a powerful tool in organic chemistry to achieve desired stereoisomers in high purity via mild catalytic routes. The immobilization of homogeneous catalytic species onto heterogeneous phases embodies the evolution of asymmetric catalysis, since it allows the recycling of the catalyst for several runs until degradation. Previously reported non-covalent immobilization of proline-based catalysts for aldol reaction onto magnetic nanoparticles functionalized with β-cyclodextrin (MNP-β-CB) demonstrated the viability of the methodology. This paper proposes two new catalyst recycling strategies based on Cucurbit[7]uril (CB[7]) for the aldol reaction and the Robinson annulation. These recycling methodologies are conceptually different. The former relies on the homogeneous encapsulation of the catalyst in cucurbituril, CB [7] · Cat, and its recycling in the aqueous phase by extraction of the aldol product with organic solvents. The latter relies on the heterogeneous encapsulation of the catalyst as MNP-CB[7] · Cat2 system and its recycling by magnetic harvesting. Density functional theory (DFT) calculations have been employed to rationalize the thermodynamics of experimental results, and to suggest caveats and plausible improvements in view of a future catalytic design.

Separating Enthalpic, Configurational, and Solvation Entropic Components in Host–Guest Binding: Application to Cucurbit[7]uril Complexes through a Full In Silico Approach via Water Nanodroplets

“…71 In this work, the combination BLYP-D3/def2-TZVPP//BLYP-D3/def2-SVP has been chosen following the work published by Hostašand co-workers 48 and our recent work. 71 We also briefly tested other GGA and meta-GGA functionals to provide a straight comparison with BLYP-D3 data. B97D3 and LC-ωPBE provided the closest results, in moderate agreement with the experimental thermodynamics (i.e., 5−6 kcal•mol −1 error).…”

“…In any case, as anticipated from previous results, the introduction of diffuse functions via def2-TZVPPD is not advantageous in terms of computational cost/improvement ratio. 48,71 Host−Guest Calculations Based on Implicit Solvation. Implicit solvation treats the solvent as a continuum envelope around the solute 76 and is the simplest way to introduce the effects of a dielectric medium at an affordable computational cost.…”

“…In such a case, DFT calculations may represent a reliable alternative to force fields (faster, but dependent on a heavy parametrization in most of the cases) and may be used efficiently to obtain good predictions on catalytic design involving CB[7]. 71 QTAIM Analysis. Different reports in the literature claim the presence of several interactions between negatively charged portal(s) of the CB[7] and the guest (ion−dipole interactions): the negative charge of the oxygens in the portals arises from the strong polarization of the carbonyl groups.…”

“…56 We recently used QTAIM to devise structural improvements in organocatalysts for aldol reactions reversibly supported by CB[7]. 71 Figure 4 shows a comprehensive study of the topological aspects of ρ in three representative complexes in the present study: HG1 (top) featuring a hydroxyl site, HG2 (middle) featuring a primary ammonium site and HG10 (bottom) featuring two quaternary ammonium sites. Top views of the complexes on the left-hand side of Figure 4 combine the overlay of critical points, molecular graphs, and reduced density gradient maps.…”

“…Previous models for the study of CB­[ n ] complexation behavior include statistical, force field, molecular dynamics, and quantum mechanical approaches. ,,,,− In a previous study in our laboratory, a theoretical investigation was performed on the reversible binding between CB[7] and catalytically active guests for aldol reaction and Robinson annulations . In this work, the combination BLYP-D3/def2-TZVPP//BLYP-D3/def2-SVP has been chosen following the work published by Hostaš and co-workers and our recent work .…”