The products of hydrolysis of 2,2-dimethoxy- and 2,2-diethoxy-tetrahydropyran

The products of hydrolysis of cyclic orthoesters as a function of pH and the theory of stereoelectronic control

“…The product ratio observed at pH = 4 and 5 in orthoester 2 (R = C2H5) is identical to the value that we originally obtained (3) by vpc analysis., ' The product ratio observed at pH 5 3 for orthoesters 2 (R = CH, and C2H5) corresponds to the value observed by Capon and Grieve (8 our results (3) and those of Capon and Grieve (8) can now be explained. In our original work, the hydrolysis must have taken place at pH higher than 3.…”

“…Due to the fact that (a) part of our results are not concordant with those of Capon and Grieve (8), and (b) product ratio varies ' Analysis of the reaction products was carried out by two different methods: (a) "C nmr spectroscopy of the reaction mixture, which showed less than 1% of lactone, and (b) vpc analysis of the reaction mixture (after treatment with acetic anhydride and pyridine), which gave a -5:95 ratio of lactone and the acetate derivative of the hydroxy-ester. Method (a) was believed to be more accurate, and it was concluded that the amount of lactone produced was negligible (5 1%).…”

“…Capon and Grieve (8) have recently reported that part of the above results were erroneou~.~ They have studied 2,2-diethoxytetrahydropyran (2, R = C2HS) and found that under our reported conditions, 20-30% of 8-valerolactone was observed by 'H and I3C nmr spectroscopy. They have also investigated the mild acid hydrolysis of 2,2-dimethoxytetrahydropyran (2, R = CH,) under a variety of solvents and, again, they found 30-40% of 8-valerolactone. In the meantime, McClelland and Alibhai (9) reported (in 1981) the observation that the hydroxy-ester/lactone product ratio of 10 and 9 varies as a function of pH in the course of the acid hydrolysis of the phthalide orthoester 7.…”

Stereoelectronic effects in biomolecules

“…A major difficulty with the stereoelectronic effect explanation for a portion of the rate acceleration was the observation of significant exocyclic cleavage in the product-determining step of the reaction.98,99 As shown in Schemes VI and VII, hydrolysis of 77 (MEP) yielded not only the expected product of stereoelectronic control, the endocyclic cleavage product, methyl 2hydroxyethyl phosphate (79), but as much as 1-50% of an exocyclic product, 2-hydroxyethyl phosphate (83),…”

On the antiperiplanar lone pair hypothesis and its application to catalysis by glycosidases

“…There are a number of experimental difficulties with ALPH; results with cyclic orthoesters were originally rationalized on the assumption that the lifetime of a hemiorthoester was short compared with the time of rotation about C-0 bonds. With the direct detection of such intermediates (Capon et al, 1981;McClelland & Santry, 1983) this assumption has become untenable; moreover, some of the original experiments were shown to be wrong (Capon & Grieve, 1982). Nonetheless, it has proved possible to rationalize the correct experimental data (on mild acid hydrolysis, conformationally labile cyclic orthoesters such as I give a mixture of lactone and hydroxyester but conformationally rigid ones such as II give hydroxyester exclusively) by invoking a 'secondary stereoelectronic effect' as well as a primary one (Deslongchamps, 1983, pp.…”