Understanding the Reactivity and Selectivity of Fluxional Chiral DMAP‐Catalyzed Kinetic Resolutions of Axially Chiral Biaryls

Abstract

Fluxional chiral DMAP‐catalyzed kinetic resolutions of axially chiral biaryls were examined using density functional theory. Computational analyses lead to a revised understanding of this reaction in which the interplay of numerous non‐covalent interactions control the conformation and flexibility of the active catalyst, the preferred mechanism, and the stereoselectivity. Notably, while the DMAP catalyst itself is confirmed to be highly fluxional, electrostatically driven π⋅⋅⋅π+ interactions render the active, acylated form of the catalyst highly rigid, explaining its pronounced stereoselectivity.

The Size‐Accelerated Kinetic Resolution of Secondary Alcohols

“…Geometry optimizations and frequency analyses were performed at SMD(Et 2 O)/B3LYP‐D3/6‐31+G(d) [28] level of theory, followed by single point calculations at the DLPNO‐CCSD(T)/def2‐TZVPP level [15, 29] . In accordance with recent results of Wheeler et al [30] . the energy profile of the reaction (see SI) implies that loading of the catalyst 3 through a first transition state TS1 is rate limiting, followed by the selectivity‐determining acylation of alcohol 1 b through transition state TS2 .…”

Homologation of the Fischer Indolization: A Quinoline Synthesis via Homo‐Diaza‐Cope Rearrangement

“…Furthermore, our effort to quantify CH-O interaction using AIM [15] indicates the difference is largely electrostatic in nature. [16] Notably all these additional non-covalent stabilizations also contribute significantly to the 20 kcal mol À1 reduction of the activation barrier as compared to the uncatalyzed reaction.…”

Die größenbeschleunigte kinetische Racematspaltung sekundärer Alkohole

“…Die Geometrieoptimierungen und Frequenzanalysen wurde dabei auf dem SMD(Et 2 O)/B3LYP‐D3/6‐31+G(d) [28] ‐Theorieniveau durchgeführt und durch Einzelpunkt‐Rechnungen auf dem DLPNO‐CCSD(T)/def2‐TZVPP‐Niveau [15, 29] ergänzt. In Übereinstimmung mit Ergebnissen von Wheeler et al [30] . deutet das Energieprofil der Reaktion (vgl.…”

“…Die Konformationen von (S) ‐TS2 lassen sich am besten als “Dreifach‐Sandwich”‐Strukturen des aromatischen Rests am Alkohol sowie des Pyridiniumkerns und der aromatischen Seitenkette des Katalysators beschreiben. Ähnliche Konformationen wurden von Wheeler et al [30] . für die kinetische Racematspaltung von Biarylsubstraten mit Katalysator 3 gefunden.…”