Experimental and Theoretical Conformational Analysis of 5‐Benzylimidazolidin‐4‐one Derivatives – a ‘Playground’ for Studying Dispersion Interactions and a ‘Windshield‐Wiper’ Effect in Organocatalysis

Abstract

The PF 6 salts of 5-benzyl-1-isopropylidene-and 5-benzyl-1-cinnamylidene-3-methylimidazolidin-4-ones 1 (Scheme) with various substituents in the 2-position have been prepared, and single crystals suitable for X-ray structure determination have been obtained of 14 such compounds, i.e., 2 -10 and 12 -16 (Figs. 2 -5). In nine of the structures, the Ph ring of the benzyl group resides above the heterocycle, in contact with the cis-substituent at C(2) (staggered conformation A; Figs. 1 -3); in three structures, the Ph ring lies above the iminium p-plane (staggered conformation B; Figs. 1 and 4); in two structures, the benzylic CÀC bond has an eclipsing conformation (C; Figs. 1 and 5) which places the Ph ring simultaneously at a maximum distance with its neighbors, the CO group, the N¼C-p-system, and the cissubstituent at C(2) of the heterocycle. It is suggested by a qualitative conformational analysis (Fig. 6) that the three staggered conformations of the benzylic CÀC bond are all subject to unfavorable steric interactions, so that the eclipsing conformation may be a kind of escape . State-of-the-art quantumchemical methods, with large AO basic sets (near the limit) for the single-point calculations, were used to compute the structures of seven of the 14 iminium ions, i.e., 3, 4/12, 5 -7, 13, and 16 (Table) in the two staggered conformations, A and B, with the benzylic Ph group above the ring and above the iminium psystem, respectively. In all cases, the more stable computed conformer ( isolated-molecule structure) corresponds to the one present in the crystal (overlay in Fig. 7). The energy differences are small ( 2 kcal/mol) which, together with the result of a potential-curve calculation for the rotation around the benzylic CÀC bond of one of the structures, 16 (Fig. 8), suggests that the benzyl group is more or less freely rotating at ambident temperatures. The importance of intramolecular London dispersion (benzene ring in contact with the cis-substituent in conformation A) for DFT and other quantum-chemical computations is demonstrated; the benzyl-imidazolidinones 1 appear to be ideal systems for detecting dispersion contributions between a benzene ring and alkyl or aryl CH groups. Enylidene ions of the type studied herein are the reactive intermediates of enantioselective organocatalytic conjugate additions, Diels -Alder reactions, and many other transformations involving a,b-unsaturated carbonyl compounds. Our experimental and theoretical results are discussed in view of the performance of 5-benzylimidazolidinones as enantioselective catalysts.

Double-hybrid density functionals: merging wavefunction and density approaches to get the best of both worlds

“…Other recent applications, the (necessarily limited and biased) following selection tries only to show the wide and rich range of systems being currently afforded, include the modelling of ionic liquids [175], gas adsorption in metalorganic frameworks [176,177], isomerism in monosaccharides [178], conformational analysis [179,180], nonlinear optical responses [181], magnetic couplings in organometallics [182], enzymatic catalysis [183,184], electron paramagnetic resonance hyperfine coupling tensors [185], inclusion complexes and nanoencapsulation [186], electronic circular dichroism [187], organometallic complexes of graphene [188], interfacial chemistry [189], photosynthetic water oxidation [190], hyperpolarizability of pushpull systems [191], lightharvesting complexes [192], adsorbate-zeolite interactions [193], or harmonic and anharmonic vibrational frequency calculations [194], among others. • Figure 1.…”

Large Molecules - Small Energies: Challenges for Contemporary Quantum Chemistry

“…36 This correspondence between gas phase and solid state indicates that the conformers are stabilized by dominating intramolecular interactions. For the imidazolidinones these are mainly of polarization and dispersion origin.…”

“…35 In a subsequent study the number of derivatives was increased to a representative amount which allowed for an investigation into the origin of their enantioselective catalytic properties. 36 The latter study was supported by a thorough theoretical investigation. The system was previously studied at the B3LYP/6-31G* level in the group of K. Houk.…”

London’sche Dispersionswechselwirkungen in der Molekülchemie – eine Neubetrachtung sterischer Effekte

“…[196] Dieses Konzept wird unterstützt vom Erfolg der Disalenliganden mit Indium als Metallzentrum und R = R' = tert-Butyl bei der Lactidpolymerisierung. [197] Die Bedeutung intramolekularer LD für enantioselektive organokatalytische Reaktionen wurde kürzlich demonstriert, [198] und es wurde gezeigt, dass es sogar in kurzen Peptiden mit vielen polaren Bindungen für ionische Wechselwirkungen und Wasserstoffbrücken immer noch einen signifikanten Effekt der LD gibt, entweder durch die Bildung einer bestimmten Katalysatorstruktur oder durch deren Beitrag zur Substraterkennung. [199] Dieser Ansatz war wichtig bei der Nutzung unpolarer Reaktanten für organokatalytische Reaktionssequenzen, [200] die in Gegenwart kleiner PeptidMultikatalysatoren als Modelle für kleine Enzyme zu enantiomerenreinen Produkten führen.…”

“…[213] Bemerkenswert ist, dass sich die Dispersionskorrekturen der Übergangszustände auf [36][37][38][39] [215] In ähnlicher Weise wurde das Selektivitätsmodell für die MacMillanschen Imidazolidinon-Katalysatormotive [216] zunächst ohne, [217] dann unter Einbeziehung der LD untersucht. [198] Eine kritische Studie,d ie sich experimentell auf 19 Kristallstrukturen und rechnerisch auf hochwertige computerchemische Studien mit und ohne Berücksichtigung von Dispersionswechselwirkungen stützt, kommt zu dem Schluss, dass der energetische Unterschied für die "ScheibenwischerKonformere" (À)-sc und (+ +)-sc im Bereich von nur AE 2kcal mol À1 liegt, sodass die Berücksichtigung der LD entscheidend ist. Tatsächlich ist das (+ +)-sc-Konformer für den ursprüngli-chen MacMillan-Katalysator mit zwei geminalen Methylgruppen durch eine günstige s-p-Wechselwirkung zwischen der Benzylgruppe des Katalysators und der cis-Methylgruppe des Moleküls bevorzugt (Abbildung 15).…”