Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles

Abstract

SummaryA highly diastereo- and enantioselective Mannich-type reaction of 3-aryloxindoles with N-Boc aldimines was achieved under the catalysis of axially chiral ammonium betaines. This catalytic method provides a new tool for the construction of consecutive quaternary and tertiary stereogenic carbon centers on biologically intriguing molecular frameworks with high fidelity.

Chemistry of Ammonium Betaines: Application to Ion-Pair Catalysis for Selective Organic Transformations

“…A betaine catalyst is also effective for controlling the stereochemistry of the Mannich type reaction of 3 aryl oxindoles (Scheme 4). 13 Despite the importance of 3 quaternary chiral oxindoles in the synthesis of biologically relevant molecules, examples of catalytic asymmetric Mannich type reactions of oxindoles are rare and 3 aryl oxindoles are regarded as a particularly problematic substrate. 14,15 We solved this problem by utilizing bifunctional organic base catalysis of betaine 1.…”

Enantioselective Mannich Reaction Promoted by Chiral Phosphinoyl-Aziridines

“…The organocatalyzed enantioselective Mannich reaction [9] constitutes one of the ways of constructing nitrogen-containing chiral systems. Apart from simple, common molecules like proline, more sophisticated systems have been tested in this transformation, for example, chiral ammonium betaine [10], D-glucosamine derivatives [11], metal-based complexes [12], or protease [13]. The Mannich reaction can serve for the formation of natural products [14] exhibiting various biological activities [15], for the formation of the quaternary carbon stereogenic centers [16,17], or for the synthesis of other β-amino ketones [18].…”

Acridinium Betaine as a Single-Electron-Transfer Catalyst: Design and Application to Dimerization of Oxindoles

“…In conjunction with our continuing program of chiral ammonium betaine catalysis, − we sought to design an intramolecular ion-pairing electron-transfer catalyst, namely, an acridinium phenoxide. We hypothesized that PCET would occur within a hydrogen-bonding complex of the basic catalyst possessing a redox-active site and an acidic substrate and that the resulting radical species could engage in a downstream bond formation.…”