Chloral acid cleavage

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. 

Organo-silanes and -stannanes possessing sp caibon-metal bonds also add to carbonyls in the presence of Lewis acids. Alkynylation with silyl- and stannyl-alkynes is promoted by AlCb or Z11CI2 (equations 9 and lO). " Notably, the reaction of l,3-bis(trimethylsilyl)-l-prcq>yne with chloral affords ynic alcohol instead of allenylic alcohol, showing the preferential cleavage of sp C—Si bonds (equation 11). ... 

However, mixtures of 16 and chloral, in any proportion, give only the 2 1 adduct 20 which can be isolated in 83% yield.1 Obviously the immediate product 19 reacts with chloral at least as fast as does 16. Fortunately the synthesis can be rescued by acid-catalysed cleavage of 20 with HC1 which gives a good yield of the target 17. 

The process from the FMC company involves as the pivotal step an intramolecular stereoselective [2 + 1 [-cycloaddition. In a Prins reaction [94] of chloral and isobutene, followed by an isomerisation, a racemic, trichloromethyl-substituted aUyl alcohol is obtained. Reaction with the isocyanate from (R)-naphthylethyl-amine enables separation ofthe diastereomers by crystallisation. The carbamate is cleaved by trichlorosilane/triethylamine, thus permitting the recycling of the chiral auxiliary. The optically pure (R)-aUyl alcohol is reacted with diketene, to produce the / -keto-ester. After diazo transfer and basic cleavage, the diazoacetate is obtained catalysed by a copper salt, this is converted in a [2 + 1 ]-cyclo-addition into a bicyclic lactone. The Boord reaction (discovered by Cecil E. Boord in 1930) [95] finally gives (IR)-cis-permethric acid. [96]... 

Optically active a-branched proline derivative III-47 was obtained by a one-pot procedure (Scheme 4.25) [121]. Proline/chloral precursor III-45 was exposed to sodium methoxide, resulting in rapid conversion to the A-formyl ester at room temperature. Cleavage of the A-formyl group was efficient performed by heating with hydrochloric acid Thus, the desired / -allyl prolinate hydrochloride salt III-47 was obtained reproducibility in a multigram scale. °... 

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