Chiral ammonium phenoxide

Scheme 3.3 Tandem Michael addition and lactonization using chiral ammonium phenoxide.

Diastereo- and enantio-selective cascade of Michael addition and lactonization between various silyl enolates derived from phenyl carboxylates and -unsaturated ketones were successfully carried out by using an efficient organic catalyst, a cinchoni- dine-derived chiral quaternary ammonium phenoxide. In this asymmetric domino reaction, the corresponding tnms-3,4-dihydropyran-2-oncs were obtained in high yields with almost complete diastereoselectivities and good to excellent enantioselectivities.161... 

Homogeneous Catalysis with Chiral Quaternary Ammonium Phenoxides... 

Recently, Mukaiyama and co-workers prepared cinchona alkaloid-derived chiral quaternary ammonium phenoxide-phenol complex 23 and used it as an efficient organocatalyst for the tandem Michael addition and lactonization between oc,f-unsaturated ketones and a ketene silyl acetal 24 derived from phenyl isobutyrate. This approach permits the highly enantioselective synthesis of a series of 3,4-dihydropyran-2-ones (25), as shown in Scheme 4.11 [17]. 

In a paper that described a detailed preparation of air-stable cinchona alkaloid-derived chiral quaternary ammonium phenoxides, the Mukaiyama group also used these to enantioselectively prepare 3,4-dihydropyran-2-ones 160 [85]. A low loading of organocatalyst 159 at low temperatures, in a series of solvents, resulted in the formation of the optically active lactone products in high yields with excellent control of enantio- and diastereoselectivity. This process was proposed to go through a phenoxide-ion-catalyzed domino Michael addition and lactonization catalytic cycle as illustrated below. Many variations of the ketene silyl acetals and a, -unsaturated ketones were combined in this domino process (Scheme 7.32). Earlier,... 

An ammonium betaine of type (R)-16 could be considered as an intramolecular version of ammonium phenoxide. The potential of chiral ammonium betaine (R)-16 as Brpnsted base catalyst has been demonstrated in asymmetric Mamiich reactions (Scheme 14.9) [6b, 32]. The basic phenoxide anion is responsible for abstraction of the active methine proton of a nucleophile 18 and thus gives the corresponding chiral ammonium enolate. Subsequent stereoselective bond formation with imine 17 afforded ammonium amide that can be rapidly protonated by the in situ formed phenolic hydrogen to regenerate the ammonium betaine (R)-16. 

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