Ammonium phenoxide

Silyl enolates are useful carbon nucleophiles in the asymmetric tandem Michael addition and lactonization (Scheme 3.3). Mukaiyama recently reported that cinchona-derived ammonium phenoxides act as activators (nucleophilic catalysis), to give highly stereocontrolled products [18-20]. In a typical PTC manner, most of the... 

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]. 

Cinchonidine-derived quaternary ammonium phenoxides (e.g., 296) have been shown to catalyze vinylogous aldol-type reaction between benzaldehyde and 4-methyl-2-(trimethylsilyloxy)furan, leading to the formation of a 5-substituted butenolide in good yield and good ee% as can be seen in Equation (181) <2007CL8>. 

Since it has been demonstrated by eonductimetry that both K" " and BU4N phen-oxides are in the form of ion pairs in dioxane and are largely dissociated in acetonitrile [33], the inereased reaetivity of ammonium phenoxide in dioxane can be ascribed to the greater interionie distanee. 

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,... 

The first observation made was of a chemical reaction between the epoxy and the tertiaiy amine. Sorokin and Shode observed the formation of a quaternary ammonium phenoxide in stoichiometric concentrations of epoxy and amine, which was due to the reaction of the epoxy with the tertiary amine. No product of the epoxyphenol reaction was noted ... 

Elemental analysis of extraction residue was used to identify reaction products. Nearly all of the tertiaiy amine was converted into the quaternaiy ammonium phenoxide in 90-95% yield (based on the amine) at amine concentrations lower than or equal to the epojqr concentration. The product of the reaction between epoxy and phenol, l,3-diphenojq -2-propanol, was formed only when the initial amine concentration was less than the epojqr concentration. The yield of l,3-dipheno3Q -2-propanol was dictated by the difference between the initial epojqr and amine concentrations. Thus, their results indicate that the reaction of epoxy with phenol in the presence of tertiaiy amines must initially go through the stage in which the... 

It is interesting to note that the very widely used Makosza catalyst , benzyl triethyl ammonium chloride, does not show high efficiency in this study. 4) Phosphonium ions are somewhat more effective and thermally stable than the corresponding ammonium catalysts and both are better than arsonium systems. 5) Substitution of the quaternary ion by alkyl rather than aryl groups yields more effective catalysts. 6) Reaction rates are generally greater in orf/io-dichlorobenzene (and presumably in other chlorocarbon media) than in benzene, and botli are better than heptane. In connection with this latter point, Ugelstad and coworkers have studied the reactions of quaternary ammonium phenoxide ions with alkyl halides in a variety of media and concluded that the... 

Cinchona alkaloid-derived ammonium phenoxides as Lewis base catalysts have been appUed to asymmetric vinylogous Mukaiyama-type aldol reactions (Scheme 14.8) [30]. In the first step of this reaction, silyl compound 14 reacts with ammonium phenoxide to produce ammonium dienolate 15 with generation of trimethyl(phenoxy) silane. The latter part of this reachon mechanism is basically simQar to the reaction mechanism of ammonium fluoride-catalyzed reactions with silyl nucleophiles as shown in Scheme 14.7. This reaction system was also appUed to other asymmetric transformations [6a, 31]. 

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. 

Trimethylsilyl)acetonitrile generates cyanomethyl anionic speceis in the presence of a nucleophilic mediator such as fluoride, lithium acetate,and ammonium phenoxides and reacts with aldehydes and imines to give /9-hydroxy- and y9-aminoalkanitriles (Schemes 3-134 and 3-135). 

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