Anion–π Catalysis of Enolate Chemistry: Rigidified Leonard Turns as a General Motif to Run Reactions on Aromatic Surfaces

Abstract

To integrate anion-π, cation-π, and ion pair-π interactions in catalysis, the fundamental challenge is to run reactions reliably on aromatic surfaces. Addressing a specific question concerning enolate addition to nitroolefins, this study elaborates on Leonard turns to tackle this problem in a general manner. Increasingly refined turns are constructed to position malonate half thioesters as close as possible on π-acidic surfaces. The resulting preorganization of reactive intermediates is shown to support the disfavored addition to enolate acceptors to an absolutely unexpected extent. This decisive impact on anion-π catalysis increases with the rigidity of the turns. The new, rigidified Leonard turns are most effective with weak anion-π interactions, whereas stronger interactions do not require such ideal substrate positioning to operate well. The stunning simplicity of the motif and its surprisingly strong relevance for function should render the introduced approach generally useful.

Exploiting non-covalent π interactions for catalyst design

“…7b) 76,79 . The addition of malonic acid half thioester (MAHT) 7.3 to β-nitrostyrene proceeded in low yields when catalysed by triethylamine owing to competitive decarboxylation (addition/decarboxylation = 0.6).…”

Asymmetric Anion−π Catalysis of Iminium/Nitroaldol Cascades To Form Cyclohexane Rings with Five Stereogenic Centers Directly on π-Acidic Surfaces

“…duced as powerful tools to run reactions on aromatic surfaces and enable also weak aromatic interactions to contribute to catalysis. 14 Contrary to enamine chemistry, 16 cationic iminium chemistry 13,17 should be destabilized rather than stabilized on π-acidic surfaces. In 4−10, a proline is positioned quite far from the π-acidic surface to avoid such cation−π repulsion.…”

Anion–π catalysis: bicyclic products with four contiguous stereogenic centers from otherwise elusive diastereospecific domino reactions on π-acidic surfaces

“…2–8 In anion–π catalyst 4 , this π surface was connected to a tertiary amine catalyst via a fixed Leonard turn. 4 These turns have been introduced to assure that the reactions really occur on the π surfaces and benefit best from anion–π interactions, even when they are not particularly strong. 4 The imide on the other side of the π-acidic surface continues with a simple solubilizing group.…”