Crown Darzens-reaction

Early work on the use of chiral phase-transfer catalysis in asymmetric Darzens reactions was conducted independently by the groups of Wynberg [38] and Co-lonna [39], but the observed asymmetric induction was low. More recently Toke s group has used catalytic chiral aza crown ethers in Darzens reactions [40-42], but again only low to moderate enantioselectivities resulted. 

The Darzens reaction can also proceed in the presence of a chiral catalyst. When chloroacetophenone and benzaldehyde are subjected to asymmetric Darzens reaction, product 89 with 64% ee is obtained if chiral crown ether 88 is used as a phase transfer catalyst (Scheme 8-30).69... 

Makosza and co-workers have reported the preparation of epoxides from a-halo carbanions and ketones, according to the Darzens reaction, under PT conditions, using TEBA72,73 or dibenzo-18-crown-6.74 The ratio of isomers depends on the reaction conditions.75,76 Asymmetric induction has been reported in the Darzens reaction using chiral catalysts.77,78 The use of several chloro carbanions as well as K2C03 and Na2C03 in the solid state has also been studied. 

Besides of these main types of the chiral TAA salts, numerous other chiral TAA salts and crown ethers acting as moderately enantioselective PT catalysts were reported. Chiral PTC was mostly used for enantioselective formation of chiral carbon centers via alkylation of carbanions (enolates), Michael addition, the Darzens reaction and other reactions of carbanions. There are also numerous examples of enantioselective PTC epoxidation of electron deficient alkenes (for review, see Ref 105). 

Anhydrous sodium or potassium carbonates have been shown to act as efficient strong bases in solid-organic liquid two-phase systems in the presence of crown ethers this by-passes the requirement for concentrated aqueous hydroxide solutions in the equivalent liquid-liquid techniques. Among the reactions possible with this new method are the alkylation of active methylene compounds, the Williamson ether synthesis, and the Darzens reaction. 

P. Bako, A. Szolloy, P. Bombicz, L. Toke, Asymmetric C-C Bond Forming Reactions by Chiral Crown Catalysts Darzens Condensation and Nitroalkane Addition to the Double Bond , Synlett 1997, 291-292. 

Promising examples of the catalytic asymmetric Darzens condensation, which yields an epoxide product via carbon-carbon and carbon-oxygen bond formation, have been reported recently by two groups (Scheme 10.11). Toke and co-workers used crown ether 24 in the reaction to form the a,P-unsaturated ketone 78 [38b] with 64% ee, whereas the Shioiri group used the cinchona-derived salt 3a [52], which resulted in 78 with 69% ee. The latter authors propose a catalytic cycle involving generation of a chiral enolate in situ from an achiral inorganic base... 

Akabari, S., Ohtomi, N., and Yatabe, S., Two-phase Darzene condensation reaction with octopus compounds as catalysts. Bull. Soc. Chem. Japan, 53, 1463, 1980. Dehmlow, E. W, and Lissel, H., Alkyne synthesis using tert-BuOH-18C6 crown ether-petroleum ether as catalytic system, Liebigs Ann., 1980, 1. 

Wittig reactions (Equation 3) in non-polar media can be initiated by solid-liquid phase transfer of potassium carbonate or t-butoxide with 18-crown-6. Typical salt-free product distributions (Z-disubstituted alkene predominant) are observed with non-stabilized ylidcs in THF, but they are surprisingly reversed in dichloro-methane solution. -Alkenes usually predominate in both solvents when stabilized ylides are involved. Two-phase Wittig-Horner syntheses of ajS-unsaturated sulphides etc. (Equation 5) are also crown-catalysed, as is the Darzens-type process (Equation 14). ... 

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