Acyclic acetal, ring-closure

The formation and the hydrolysis of acyclic and cyclic acetals have been studied in rather great detail [91]. Several reviews on this topic are available [92] and some comments have been made [13] concerning the carbohydrate series. We have shown in Schemes 1,2, and 3 that a common feature of this reaction seems to be the intermediacy of an oxocarbenium ion. However, the cyclization of such an intermediate has been questioned more recently [93] in the light of the Baldwin s rules for ring closure [94]. At least for the five-membered ring, an SN2-type displacement mechanism far the protonated form (B) of die hemiacetal (A) (favorable 5-exo-tet cyclization) has been proposed rather than the unfavorable 5-endo-trig cyclization of the oxocarbenium ion (C) (Scheme 5). Except when the formation of the enol ether (D) is structurally impossible, the intermediacy of such a compound remains feasible. 

Nucleophilic participation by the hydroxyl group has been noted in acid-catalyzed studies of systems other than carboxyl groups. In dilute aqueous acid solution, methyl furanosides [e.g., (248)] were formed by ring closure during hydrolysis of the acetal bonds of the acyclic dimethyl acetals of glucose (247) and galactose.It was estimated that the rates of these cyclizations were faster than the expected unassisted rates of hydrolysis. 

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