On the relative rate of hydrolysis of a series of ketals and their proton affinities

Abstract

The relative rates of hydrolysis of a series of cyclic and acyclic ketals was studied. Their reactivity toward acid hydrolysis is explained by considering the ease of protonation and the cleavage of the C-O bond. The experimental work and the theoretical calculations of the proton affinities of the ketals suggest that the ratelimiting step of hydrolysis of ketals is a concerted protonation and cleavage of the C-O bond. The relative proton affinity is considered to be a direct consequence of the ease of proper lone pair orbital alignment on the oxygen atoms of the various ketals.

Reactions of Aldehydes and Ketones and their Derivatives

“…105 A catalytic enantioselective Henry reaction of nitromethane with α-keto esters uses a chiral bisoxazoline-copper(II) catalyst: the product α-hydroxy-β-nitro esters are useful in themselves, but particularly so as a step towards the corresponding β-amino compounds. 106 3,7,7,8,quinolin-5(6H )-ones (43), linear tricyclic enaminones, can be prepared in one pot from 5-amino-3methylpyrazole, dimedone, and an aldehyde (RCHO). When R = H, the product dehydrogenates to the corresponding pyrazolpyridine.…”

“…Threo-and erythro-alcohols, (8t) and (8e), have been prepared by ring opening of a cyclic ketene ortho-ester (7) with a range of aldehydes. 5 Enantioselectivities range from 45 to 99%, with de values of up to 96%.…”

“…6 A stereoelectronic correlation of the relative rates of hydrolysis of ketone-derived acetals with their proton affinities considers both cyclic and acyclic cases. 7 Terminal isopropylidene acetals have been chemoselectively hydrolysed to the corresponding 1,2-diols using Yb(OTf) 3 •H 2 O. 8 Similar functional groups, even isopropylidene acetals elsewhere in the substrate, are left untouched.…”

Synthesis of Enantiopure Triols from Racemic Baylis–Hillman Adducts Using a Diastereoselective Peroxidation Reaction

“…This destabilizing effect may be stereoelectronic in origin, considering that the hydrolysis of 1,3-dioxanes has been shown to be about 40 times faster than the hydrolysis of 1,3dioxolanes due to improved orbital alignment during the protonation/elimination step. 46 The stereoselective addition and rearrangement reaction was general for the other substrates. In each case, the major product of the allylations of dioxanes 26 and 38−41 shared the same overall structure as the product shown in Scheme 4 (28 and 43−46, Scheme 7).…”

“…This rearrangement revealed that not only 1,3-diaxial interactions contribute to the tendency for these substrates to undergo ring contraction. This destabilizing effect may be stereoelectronic in origin, considering that the hydrolysis of 1,3-dioxanes has been shown to be about 40 times faster than the hydrolysis of 1,3-dioxolanes due to improved orbital alignment during the protonation/elimination step …”