Designing Fluorinated Cinchona Alkaloids for Enantioselective Catalysis: Controlling Internal Rotation by a Fluorine‐Ammonium Ion gauche Effect (φ_NCCF)

Abstract

The C9 position of cinchona alkaloids functions as a molecular hinge, with internal rotations around the C8-C9 (τ(1)) and C9-C4' (τ(2)) bonds giving rise to four low energy conformers (1; anti-closed, anti-open, syn-closed, and syn-open). By substituting the C9 carbinol centre by a configurationally defined fluorine substituent, a fluorine-ammonium ion gauche effect (σ(C-H) → σ(C-F)*; F(δ-)⋅⋅⋅N(+)) encodes for two out of the four possible conformers (2). This constitutes a partial solution to the long-standing problem of governing internal rotations in cinchonium-based catalysts relying solely on a fluorine conformational effect.

Dekonstruktion kovalenter Organokatalyse

“…B. 12-17)g eführt, darunter Cinchoniumsalze, [55] Acylpyridiniumsalze (16) [56] und deren protonierte Analoga. [57] Intermediate kçnnen wichtig für eine effektive Katalyse sein, als Brücke auf dem Wegzusekundären katalytischen Spezies fungieren oder als Zuschauer oder Katalysatorreservoir wirken.…”

Chemistry without Bo(a)rders

“…With the goal of exploiting the similar fluorineammonium ion gauche effect, a configurationally defined fluorine was installed at the C9 carbinol center of cinchona alkaloids (Figure 7, right). [16,17] This class of ligands has found widespread application as phase transfer catalysts. However, the C9 position functions as a molecular hinge with internal rotations around the C8-C9 (τ1) and C9-C4′ (τ2) bonds, giving rise to four low energy conformers.…”

“…The merit of this approach was displayed in the application of this novel class of chiral, fluorinated cinchonium salts for the enantioselective, electrophilic fluorination of β-ketoesters (up to 81% ee). [17] Furthermore, X-ray crystallography and solution phase conformational analysis were successfully undertaken to gain insight into the catalysts mode of enantioinduction. [17] Also, working in a newly established laboratory makes for a very special atmosphere and some especially close bonding.…”

“…[17] Furthermore, X-ray crystallography and solution phase conformational analysis were successfully undertaken to gain insight into the catalysts mode of enantioinduction. [17] Also, working in a newly established laboratory makes for a very special atmosphere and some especially close bonding. A few of my best memories come from our annual group trips (I guess it is hard to forget your Professor riding on a pony or almost capsizing a canoe with your terrified lab partner inside) (Figure 8).…”

Neue Entwicklungen bei asymmetrischen Phasentransferreaktionen

“…[173] Die gleiche Reaktion wurde auch mit dem 9-fluorierten, von Chinidin abgeleiteten Katalysator 1 E untersucht (Schema 136). [174] [175] Das Reaktionssystem wurde auch auf die hoch enantioselektive Fluorierung von Enamiden wie 212 angewendet (Schema 137). [176] 13.…”