Konformative Fluoreffekte in der Organokatalyse: eine neuartige Strategie zum molekularen Design

Abstract

Strategien zum molekularen Design, die von den intrinsischen stereoelektronischen und elektrostatischen Effekten fluorierter organischer Moleküle profitieren, sind bisher hauptsächlich auf die bioorganische Chemie beschränkt. Bei vielen konformativen Fluoreffekten handelt es sich zwar um akademische Kuriositäten ohne unmittelbare Anwendung, die Renaissance der Organokatalyse bietet allerdings die Möglichkeit zur Erforschung vieler dieser ausführlich beschriebenen Phänomene zur molekularen Präorganisation. In diesem Kurzaufsatz werden Beispiele zur Verbesserung von Katalysatoren durch die Einführung einer aliphatischen C‐F‐Bindung erläutert, die als eine chemisch inerte dirigierende Gruppe zur Steuerung der Konformation dient.

Long‐Lived Trifluoromethanide Anion: A Key Intermediate in Nucleophilic Trifluoromethylations

“…Because of the potential applications of fluorinated compounds in chemistry, biology, and materials science, [1][2][3][4][5] fluorine substitution of organic compounds has become a vibrant research area in synthetic organic chemistry. [6][7][8][9][10] Among various fluorinated substituents, the trifluoromethyl group (CF 3 ) stands out not only because of its role as the parent of other fluoroalkyl moieties, but also owing to its remarkable potential for modulating chemical, physical, and biochemical properties of molecules.…”

Phosphine‐Catalyzed Asymmetric Umpolung Addition of Trifluoromethyl Ketimines to Morita–Baylis–Hillman Carbonates

“…the asymmetric umpolung addition of trifluoromethyl ketimines to electrophiles has been documented so far. [6] Very recently, Deng and co-workers successfully applied this umpolung strategy to the synthesis of optically active trifluoromethyl amines, with a chiral tertiary stereocenter, from readily available trifluoromethyl ketimines (1) and enals by the employing a chiral phase-transfer catalyst (PTC; Scheme 1 b). Inspired by Dengs work and our continual interest in asymmetric phosphine catalysis, [7,8] we envisaged that the Morita-Baylis-Hillman (MBH) carbonates 2, another very readily available and widely used compounds in organocatalytic reactions, [9] would generate the chiral quaternary phosphonium salts 3 in the presence of chiral phosphine catalyst (Scheme 1 c).…”

“…[1] Among fluorinated compounds, chiral trifluoromethyl amines were widely found as the key structural subunits in many biologically interesting compounds, and were recognized to improve lipophilicity and metabolic stability over that of the corresponding methyl amines (Figure 1). [2] In light of their importance, various powerful strategies for the synthesis of chiral trifluoromethyl amines have been developed in the past years.…”

Stereoselective Fluorination Alters the Geometry of a Cyclic Peptide: Exploration of Backbone‐Fluorinated Analogues of Unguisin A

“…Overall, it is striking that the syn-difluoro analogues (4, 5) have very different conformations, while the anti-difluoro analogues (6,7) are very similar to one another. This seems to parallel the results of a previous GABA receptor binding study [18] involving the free amino acids 1 and 2 ( Figure 1): the syn isomers (1 and ent-1) displayed opposite pharmacology at the GABA C receptor, whereas the anti isomers (2 and ent-2) displayed identical activity at the GABA A receptor.…”

“…Also, C À F bonds prefer to align antiparallel to adjacent carbonyl groups, which can be rationalized in terms of dipolar repulsion. [2,6] This concept has been exploited to enhance the properties of a variety of functional molecules including organocatalysts, [7] liquid crystals, [8] enzyme inhibitors, [9] biological receptor ligands, [10] fatty acids, [11] and peptides. [2,6] This concept has been exploited to enhance the properties of a variety of functional molecules including organocatalysts, [7] liquid crystals, [8] enzyme inhibitors, [9] biological receptor ligands, [10] fatty acids, [11] and peptides.…”