Endocyclic cleavage

For a number of reactions of cyclic di- and triesters of phosphoric acid, there are exchange data which can be rationalized on the assumption of trigonal bipyrami-dal intermediates which readily interconvert by pseudorotation. This constitutes a strong argument that at least these cyclic esters react by an associative mechanism and is suggestive evidence that simple trialkyl phosphates also react by this mechanism. The pH dependence of exocyclic versus endocyclic cleavage of methyl ethylene phosphate is readily interpreted in terms of the effect of ionization of the intermediate on the pseudorotation of these pentacoordinate intermediates. ... 

Substituent effects on the endocyclic cleavage of glycosides by trimethylaluminium have been explained in terms of a cyclic C-H O hydrogen-bonded intermediate. ... 

Regioselective endocyclic cleavage of the ortho ester cw-2-methoxy-4-methy 1-1,3 -dioxane by Grignard reagents, involving rupture of the less congested C(2)—0(1) bond remote from the 4-methyl substituent, has been discussed.115... 

Conversion to the Acid. Hydroxide and peroxide agents saponify acyl imides in excellent yields however, with ster-ically hindered acyl groups endocyclic cleavage may predominate upon treatment with Lithium Hydroxide. Lithium Hydroperoxide, however, is highly selective for the exocyclic carbonyl moiety. 

Conversion to the Aldehyde. This transformation is accomplished through a two-step procedure. One such variant requires reduction to the alcohol (e.g. LiAllTt, H2O) and subsequent oxidation (e.g. Swem conditions). Alternatively, Wein-reb transamination " followed by Diisobutylaluminum Hydride or conversion to the thioester (see below) and subsequent Triethylsilane reduction, afford the desired aldehyde in excellent yields. Weinreb transamination proceeds with minimal endocyclic cleavage when there is a p-hydroxy moiety free for internal direction of the aluminum species. 

Reactions of Phosphoric Acids and Their Derivatives. - Numerous investigations of phosphate ester hydrolysis continue to be reported. The hydrolysis between 1.5 < pH < 4 of five- and six-membered cyclic phosphoramides (71) has been followed by UV and NMR spectroscopy. Small differences in hydrolysis reactivity for n = 5 and n = 6 constitutes evidence for syn lone pair catalysis. The product ratios from the hydrolysis shows that in the five-membered rings the main product is the one produced by endocyclic cleavage meanwhile, in the six- membered cyclic phosphoramide the kinetic product is the one produced by exocyclic cleavage. The syn orientation of two electron pairs on nitrogen stabilizes the transition state of water approach to the phosphoramides by ca. 3 kcal/moN when compared to the orthogonal attack. (Scheme 12). ... 

Liras, J. L. and Anslyn, E. V. (1994) Exocyclic and Endocyclic Cleavage of Pyranosides in Both Methanol and Water Detected by a Novel Probe, J. Am. Chem. Soc. 116, 2645-2646. 

Figure 3.11 Exocyclic and endocyclic cleavage during the hydrolysis of glycosides.

There is, of course, no a priori reason why aldopyranosides with a sufficiently strained ring should not react by endocyclic cleavage and such a system has been constructed (Figure 3.12). °... 

Figure 3.13 (a) ALPH favours endocyclic cleavage in acid-catalysed hydrolysis... 

When this 6-isomer was added to the reaction product of 1,2,6-hexanetriol and acetic acid, the 11.62 peak was enhanced. Thus, the 10.98 and 11.24 peaks in chromatogram 31a are the 1 and 2-isomers. Because the sensitivity of the gas chromatographic assay is such that as little as 0.01% of the 6-isomer can be detected, hydrolysis of this particular polymer proceeds exclusively by the exocyclic cleavage path shown in Scheme 20. This is in very good agreement with a reported hydrolysis study of the closely related model compounds 2-methoxy-l,3-dioxalane (1) and 2-phenyl, 2-methoxy-l,3-dioxalane (2) which have been reported to undergo respectively about 2.5% and less than 0.1% endocyclic cleavage [52]. 

On this basis, Gorenstein and coworkers predicted a stereoelectronic acceleration in the hydrolysis of methyl ethylene phosphate via endocyclic cleavage (Gorenstein et al., 1977a,b, 1979). As we have seen, studies on methyl ethylene phosphate and related systems formed a foundation for the development of Westheimer s guidelines (Westheimer, 1968). 

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