Lactones tetrahedral intermediate formation

Few relevant data are available. Both equilibrium and rate constants have been measured for very few reaction series in solution, but comparisons are possible for lactone and thiolactone formation, and for a few anhydrideforming reactions (Tables 4 and 5). For lactone formation (Table 4) the EM for the rate process is of the same order of magnitude as that derived from the equilibrium constant data, and in some cases actually exceeds it (though only in one case by an amount clearly greater than the estimated uncertainty which is nominally a factor of 4 for these ratios). Lactonization generally involves rate-limiting breakdown of the tetrahedral intermediate, and the transition state is expected to be late and thus close in structure to the conjugate acid of the lactone. 

In a cyclic orthoester such as 55 (Fig. 5) when the two alkoxy groups are different, there is the possibility of forming three different hemi-orthoesters (56, 57, and 58) which can lead to three different esters, the two hydroxy-esters 59 and 60 and the lactone 6K Thus, there is a possibility that some specific hemi-orthoesters will be generated which will lead to the preferential formation of one of the ester products. The mild acid hydrolysis of orthoesters is therefore a potential method to test the principle of stereoelectronic control in the formation and cleavage of hemi-orthoester tetrahedral intermediates. 

The results obtained with compounds 72 and 73 show that in orthoesters which are conformationally labile, the hydroxy-ester is still the major product but the formation of lactone can occur to some extent. Thus, it can be concluded that whenever a tetrahedral intermediate can exist as a mixture of conformers 66-71, the formation of an E ester (from 69, 70, or 71) will be able to compete (due to an entropy factor) to some extent with the formation of Z ester (from 66 or 69). 

The preferred formation of lactone 73 was explained by the orientation of the non-bonded electron pairs of the hydroxyl group in the corresponding tetrahedral intermediate and by assuming that the migrating C —C bond must be antiperiplanar to the RC00 - 0 bond. They have also assumed that the per-acid reacts on the least hindered face of the carbonyl group in 72. 

Diisobutylaluminum hydride (DIBAL) is a reliable reagent for the reduction of lactone 29 to the corresponding lactol 67. This is due to the formation of stable tetrahedral intermediate 66, which prevents further reduction (via hydroxyaldehyde 68 to the diol) and decomposes during aqueous workup to provide the desired lactol 67. 

Extensive DFT calculations have revealed the mechanism and factors affecting the reaction rate for the intramolecular acid-catalysed hydrolysis of a series of seven iV-methylmaleamic acids (107 R, R = H, H H, Me H, Et Me, Me H, Pr -( 112)3- -(012)4-). The results confirm the three-step pathway formulated from the classical experimental work of Kirby and coworkers in which following a proton transfer from the CO2H group of (107) to the adjacent C=0 group, an intramolecular attack by the carboxylate group of zwitterion (108) yielded a tetrahedral intermediate (109), which after an H-transfer from OH to NHMe to give (110) broke down to a lactone (111) and methylamine (Scheme 35). In the gas phase, the rds was the formation of the tetrahedral intermediate (109), but in solution it was its breakdown. ... 

Catalytic antibodies have been produced to catalyze an impressive variety of chemical reactions. For instance, stable phosphonic esters (or lactones, respectively) have been used as transition state mimics for the hydrolysis of esters and amides [555-557], acyl transfer [558] and lactonization [559] reactions, which all proceed via a tetrahedral carbanionic intermediate. In some instances, the reactions proved to be enantiospecific [560]. Elimination reactions [561, 562], reductions [563], formation and breakage of C-C bonds [564,565] and even photochemical reactions [566] can be catalyzed. The cleavage of an ether [567] and cis-trans isomerization of alkenes have been reported [568]. 

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