Chloral, cycloaddition with ketene

The cycloaddition of aldehydes and ketones with ketene under the influence of quinine or quinidine produce chiral 2-oxetanones [46,47]. Solvolytic cleavage of the oxetanone, derived from chloral, and further solvolysis of the trichloromethyl group leads to (5)- and (R)-malic acids with a 98% ee [46] (the chirality of the product depends on the configuration of the catalyst at C-8 and, unlike other alkaloid-induced reactions, it is apparently independent of the presence of the hydroxyl group). No attempts have been made to catalyse the reaction with chiral ammonium salts. 

The synthesis of 1,3-disubstituted-4-trichloromethyl azetidin-2-ones by the Staudinger cycloaddition of ketenes with imines derived from chloral has been described to occur with high stereoselectivity [91], The civ-isomer was obtained almost always as the major or the single product. 

Polymer-supported organocatalysts have been used for cycloaddition of ketene, 127, to chloral, 128 [141]. Use of homo-acrylate polymers of cinchona alkaloids led to formation of the desired /Mactone (S)-130 with enantioselectivity up to... 

The cycloaddition of ketene with chloral in the presence of catalytic quantities of quinidine or quinine leads to the oxetanones in high optical and chemical yield (Scheme 26.22). This reaction is practiced on an industrial scale with the chiral building blocks malic and citramalic acids being formed by hydrolysis.492... 

Cinchona alkaloids are the effective asymmetric catalysts in the [2+2] cycloaddition reaction of ketenes and aldehydes [47]. That is, the reaction between ketenes and chloral proceeds with a catalytic amount (2.5 mol %) of quinidine in toluene at -50 °C to provide the P-propionolactone (-)-18 in quantitative yield with 98% ee (Scheme 17). 

The 2 4-2 cycloaddition of ketene to chloral in toluene at —50 °C in the presence of 4 mol% of cinchonine results in the formation of j -lactone 886 in high yield with 84% ee. Recrystallization from methylcyclohexane furnishes optically pure (R)-lactone. Mild acid hydrolysis of the lactone to the trichloromethyl hydroxy acid 887 followed by careful basic hydrolysis gives optically pure (R)-malic acid (885) in 79% overall yield [196]. 

A more complicated example arises from the strange reactions used to make malic acid from chloral and ketene. An initial [2 + 2] cycloaddition (Chapter 35) is followed by acid treatment and then treatment with an excess of aqueous NaOH. Neutralization gives malic acid, an acid found naturally in apples (Malus spp.). 

Chiral Catalysis. Brucine has been utilized as chiral catalyst in a variety of reactions. For example, its incorporation into a polymer support provides a chiral catalyst for performing enan-tioselective benzoin condensations. It has also been used as a chiral catalyst in the asymmetric synthesis of (I )-malic acid via the corresponding p-lactone, which results from the asymmetric cycloaddition of chloral and ketene (eq 12). Though brucine yields malic acid with 68% ee, quinidine was found to be a more selective catalyst (98% ee). 

A Russian group has described two types of [2+2]-cycloadditions of N-sulfonyl imines. It was found that both ketene and trimethylsilyl ketene react with chloral-derived N-sulfonyl imine 233 to afford -lactams 234 in excellent yields [81] [Eq. (57)]. Although the compound produced from trimethylsilyl ketene appears to be a single isomer, the stereochemistry was not elucidated. 

In the cycloaddition reaction of mono substituted ketenes (R = Cl, Me, i-Pr and PhO) with chloral, mixtures of cis- 223 and fra 5-2-oxetanones 224 are obtained in about equal... 

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