Computational molecular refinement to enhance enantioselectivity by reinforcing hydrogen bonding interactions in major reaction pathway

Abstract

Computational analyses have revealed that the distortion of the catalyst and the substrates and their interactions are key to determining the stability of the transition state. Hence, two strategies “distortion...

Intermolecular exo-selective Diels–Alder reaction catalysed by dual-functional Brønsted acid: conformational restriction of transition states by hydrogen bonds as the key interaction

“…In our previous work, we thoroughly searched several functions of the DFT calculation and confirmed that B3LYP-D3 is one of the reliable ones for the transition state analysis in the present reaction system (see, ref. 20 ). 21,22 In the model calculations, vinylquinoline 1b and dienylcarbamate 2a were employed and all possible conformations, relative orientations, and enantiotopic faces of these substrates were considered because of using chiral phosphoric acid ( R )-4 as the model catalyst ( Fig.…”

“…In our previous work, we thoroughly searched several functions of the DFT calculation and confirmed that B3LYP-D3 is one of the reliable ones for the transition state analysis in the present reaction system (see, ref. 20 ).…”

“…To verify this hypothesis, we devised a model reaction, that is, the DA reaction of vinylquinolines 1 with dienylcarbamates 2 catalysed by phosphoric acid, which we had previously reported as an endo -selective reaction. 20 Computational analysis of this reaction revealed that the dual-functional nature of the phosphoric acid catalyst strictly restricts the relative orientation of the diene and the dienophile. Extraction of factors necessary for the exo -selectivity from this reaction system by computational studies and their experimental verification are expected to offer new insights into the control of the endo -/ exo -selectivity in the DA reactions.…”