Bifunctional Catalysis and Apparent Stereoelectronic Control in Hydrolysis of Cyclic Imidatonium Ions

Abstract

To test stereoelectronic control in cleavage of tetrahedral intermediates, cyclic imidatonium ions were hydrolyzed in buffered aqueous media. In carbonate buffer >97% amino ester was observed, as previously reported. However, in borate buffers 65−91% hydroxy amide was observed from five-membered-ring imidatonium ions, except for a highly alkylated one. Selectivity is attributed to leaving-group ability. Stereoelectronic control does operate in six-membered rings but provides only 2 kcal/mol toward rate acceleration. Production of amino ester in carbonate buffers is due to the bifunctional nature of bicarbonate ion and thus cannot be used to support a large stereoelectronic contribution. The geometrical requirements for bifunctional catalysis further imply the intermediacy of conformations counter to stereoelectronic control.

7 Reaction mechanisms. Part (i) Polar reactions

“…107 The observation of a preference for C-N cleavage in a previous investigation of the alkaline hydrolysis of five-membered ring cyclic imidatonium (oxazolinium) ions 129 (R 2 = H) was shown to be due to bifunctional catalysis by bicarbonate ion and not due to stereoelectronic control as originally proposed. 108 In the absence of bicarbonate ion, C-O cleavage was predominant which was consistent with results for non-cyclic imidates where selectivity was governed by leaving group abilities. The observation of only C-N cleavage in the alkaline hydrolysis of imidatonium ion 129 (R 2 = CH 3 ), even in the absence of bicarbonate ion, was attributed to steric hindrance between the C-4 methyl and the C-2 hydroxy groups of the tetrahedral intermediate, which is Scheme 44 relieved upon cleavage of the C-N bond.…”

Hyperconjugation

“…Donation of electron density from filled π‐orbitals or lone pairs into σ*‐orbitals (negative hyperconjugation) is important not only in anions, but also in many neutral molecules. In particular, it is implicated in the anomeric effect (and its spectroscopic counterparts—the Bohlman88 and the Perrin effects,89–92 see Figure 7) and as a provider of covalent character and directionality of H‐bonding. Negative hyperconjugation that involves nonbonding orbitals is isovalent (Figure 6) and the one that involves π‐orbitals is sacrificial (Figure 5).…”

The Construction of Anhydro Monosaccharides

“…It has been proposed that the cleavage of the β‐glycosidic bond proceeds through a boat‐like conformer such as the 1,4 B conformer of pyranoside in which the cleaved glycosidic bond was in an antiperiplanar orientation to the doubly occupied non‐bonding orbital of the endocyclic oxygen atom . In addition, one of the hypothetical mechanism to explain the function of uridine 5‐diphosphate (UDP)‐galactosemutase, a flavoenzyme catalyzing the isomerization of UDP‐galactopyranose into UDP‐galactofuranose, is that the ring contraction process goes through a putative 1,4‐anhydro galactopyranose with bicyclic 1,4 B boat conformation as an intermediate in the reaction .…”