Darzen’s reaction

The ammonium catalyst can also influence the reaction path and higher yields of the desired product may result, as the side reactions are eliminated. In some cases, the structure of the quaternary ammonium cation may control the product ratio with potentially tautomeric systems as, for example, with the alkylation of 2-naph-thol under basic conditions. The use of tetramethylammonium bromide leads to predominant C-alkylation at the 1-position, as a result of the strong ion-pair binding of the hard quaternary ammonium cation with the hard oxy anion, whereas with the more bulky tetra-n-butylammonium bromide O-alkylation occurs, as the binding between the cation and the oxygen centre is weaker [11], Similar effects have been observed in the alkylation of methylene ketones [e.g. 12, 13]. The stereochemistry of the Darzen s reaction and of the base-initiated formation of cyclopropanes under two-phase conditions is influenced by the presence or absence of quaternary ammonium salts [e.g. 14], whereas chiral quaternary ammonium salts are capable of influencing the enantioselectivity of several nucleophilic reactions (Chapter 12). 

Stereochemical control of Darzen s reaction of a-chlorophenylacetonitrile with benzaldehyde by phase-transfer catalysts... 

Asymmetric induction using catalytic amounts of quininium or A-methyl-ephedrinium salts for the Darzen s reaction of aldehydes and ketones with phenacyl halides and chloromethylsulphones produces oxiranes of low optical purity [3, 24, 25]. The chiral catalyst appears to have little more effect than non-chiral catalysts (Section 12.1). Similarly, the catalysed reaction of sodium cyanide with a-bromo-ketones produces epoxynitriles of only low optical purity [3]. The claimed 67% ee for the phenyloxirane derived from the reaction of benzaldehyde with trimethylsul-phonium iodide under basic conditions [26] in the presence of A,A-dimethyle-phedrinium chloride was later retracted [27] the product was contaminated with the 2-methyl-3-phenyloxirane from the degradation of the catalyst. 

Darzen s reaction org chem Condensation of aldehydes and ketones with a-haloesters to produce glycidic esters. dar-zonz re.ak-shon ... 

A modified variant of the Darzen s reaction has been described for the production of new derivatives by conjugate addition of nucleophiles to haloolefins (Eqs. 82 and 83). ... 

Since the discovery of phosphomycin, interest has turned to phosphorus-containing oxiranes. The Darzen s reaction of a-halomethylphosphorus compounds with carbonyl compounds leads to such oxiranes (Eq. 84). 

Shibata, I., Yamasaki, H., Baba, A., Matsuda, H. Stereoselective synthesis of a,P-epoxy ketones by the Darzen s reaction with methyl N-ethyl-N-(tributylstannyl)carbamate. Syrr/etf 1990, 490-492. 

Piozzi et al. (219) have confirmed 317 as the structure of japonine by synthesis (Scheme 27). Application of Darzen s reaction to 2-nitro-5-methoxybenzaldehyde furnished epoxide 314. This was converted with hydrogen chloride and hydroquinone into 315, which was reduced to the 3-hydroxy-4-quinolone 316 methylation then afforded japonine as the major product. 

The usual Darzen s reaction consists of the reaction of aldehydes or ketones with a-haloester or a-halonitriles in presence of a base like potassium tertiarybutoxide to give glycidic esters or nitriles, respectively (Scheme 20). 

The intense heat and mass transfer environment that can be established within the liquid film flowing over the disc allows high selectivities and conversions to be achieved when fast liquid-phase reactions are performed. Very encouraging results were achieved in an industrial study of a phase-transfer-catalysed (p-t-c) Darzen s reaction to produce a drug intermediate, as described below. 

Polymer-supported podands appear to be more commonly used in solid-liquid systems. A variety of chemical transformations including nucleophilic substitutions at saturated carbon atoms [214,215], esterifications [214], sodium bo-rohydride reduction [214], fluoride-catalyzed Michael addition [214], phenacyl ester synthesis, Darzen s reaction, Wittig alkenylation, and dichlorocarbene reactions can be carried out under these conditions [214],... 

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