Retro-Claisen fragmentation

Compound 403 is readily reduced with sodium borohydride at -78°C and yields the monoalcohol 405 (115). It also reacts with potassium t -butyl hydroperoxide at -20°C and gives the cis-enone-perester carbonate 406 in high yield (116). This last transformation can be explained by retro-Claisen fragmentation of intermediate 407 followed by the elimination of methoxide ion from 408. It is also possible that 407 undergoes a direct stereoelectronically controlled Grob type fragmentation to compound 406. 

It should be noted that the cyano group is lost by a retro-Claisen-type fragmentation 6->7 which gives automatically the pyrrocorphin 7 on the hexahydro oxidation level rather than by a /i-elimination-type process which would give a tetrahydroporphyrin. A similar fragmentation process has been observed in the total syntheses of chlorophyll a (sec Section 1.2.1.) and of a tolyporphin model (see Section 1.3). 

Ozonolysis of diketone carbonate 417 in methanol afforded an almost quantitative yield of the bicyclic diene triketone hydroxy-ester 418 (119). This remarkable transformation can also be readily explained. Ozonolysis of 417 produces the tetraketone intermediate 419 followed by methanol addition to produce the hemi-ketal 420 which undergoes a retro-Claisen reaction to 421. Then, loss of carbon dioxide from 421 yields 418. Again, 420 could also undergo a Grob type fragmentation to yield 418 directly. 

Competitive experiments with 2H-, 13C- and 180-labelled chorismate derivatives and three different chorismate mutase enzymes have shown that in all catalysed and non-catalysed Claisen rearrangements a non-synchronous, concerted, pericyclic transition state is involved, with C-O bond cleavage considerably in advance of C-C bond formation. Some evidence has suggested that the ionic active site of the enzymes may polarize the transition state more than occurs in solution. Similar findings apply to the retro-ene fragmentation of chorismate to 4-hydroxybenzoate.17... 

When o-phcnylenediamine reacts with aliphatic or aliphatic-aromatic ketones the initially formed benzimidazolines can be thermally decomposed, losing a hydrocarbon fragment to yield 2-substituted benzimidazoles [81, 131]. While this method does not appear to have major synthetic importance, the analogous reaction with a, 6-diketonc has some application [132]. Presumably it involves an acid-catalysed retro-Claisen condensation of the S-dicarbonyl compound. When acetylacetonc is used, acetone is formed. The process, then, offers an unambiguous approach to compounds such as 2-methyl-4-nitrobenzimidazoles (not available by direct nitration). Neither the numbers of substituents on the arylenediamine nor their natures appear to affect yields or reaction times significantly. 

FuithermoFe, there is a class of reactions (retroaldol, retro-Claisen, etc.) which are similar to the fragmentations, but they are not to be considered as such. Here, the electron acceptor group X is double bonded to the atom d, and therefore two fragments rather than three are formed (equation 4). 

A copper-catalyzed deacylative arylation of 1,3-diketones was reported (Eq. (6.11)) [27]. The potential intermediate 52 did not undergo deacylation, which excludes the pathway based on retro-Claisen-type fragmentation of 52. 

The Baeyer-Villiger oxidation of 7-oxabicyclo[2.2.1]heptan-2-ones is the most used reaction to cleave a C-C bond of the 7-oxabicyclo[2.2.1]heptanes. Other routes have used retro-Claisen, retro-Diekmann, and Grob fragmentations. They have been reviewed elsewhere [11]. Enoxysilanes derived from 7-oxanorboman-2-ones can be ozonolyzed into 2,5-anhydrouronic acid derivatives, precursors for C-nucleosides [225]. 

Ten years later, Lubineau et al. reported the direct reaction of unprotected carbohydrates with acetylacetone in aqueous alkali media [11]. By application of this method, an access to different mixtures of furanoid and pyranoid structures of a- and P-configured C-glycosides [12] was obtained. The ratio of the products depends on the conditions of execution for this reaction and the carbohydrates deployed (Eq. 2, Scheme 2.1). This Knoevenagel/Michael/retro-Claisen-aldol cascade is carried out at high temperature (60-90°C) and is associated with the loss of a C2 fragment of the starting 1,3-dicarbonyl component (when used with acetylacetone). 

These results differ considerably from those obtained by Lubineau reactions. In the Lubineau series, a Knoevenagel condensation followed by an oxa-Michael/intermolecular retro-Claisen process is proposed. As a result of the Lubineau sequence, the loss of an acetate-fragment occurs in reactions with acetylacetone. 

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