Acid-catalyzed ring strain

The relation between strain and reactivity may be illustrated with electrophilic reactions of cyclopropane and cyclobutane (218). The decrease in strain is essentially equal in both compounds, but cyclopropane is highly reactive, whereas cyclobutane is essentially inert. Acid-catalyzed ring opening, for example, is controlled by the basicity of the two cycloalkanes. The latter are only slightly deformed by protonation and little strain is therefore released. 

This method was also used to construct the strained oxetane 22 from the gibberellin derivative 20. Acid-catalyzed ring opening of 22 yields the C-ll hydroxylated gibberellin 23, in which nucleophilic attack has occurred stereospecifically with inversion at C-867. 

Trifluoroacetic acid is a sufficiently strong acid to react with olefins under relatively mild conditions. The addition is regiospecific in the direction predicted by Markownikoff s rule. The reaction is catalyzed by sulfuric acid, and ring strain... 

Another skeletal rearrangement involving the strained cyclobutane ring was recently reported 93). The formic acid catalyzed reaction converted the compound (273)... 

The driving force for rearrangement is relief of steric strain between the isopropyl group and one of its adjacent methyl groups. Isomerization is acid-catalyzed. Protonation of the ring generates the necessary carbocation intermediate and rearomatization occurs by loss of a proton. 

In general, bicyclic acetals are highly reactive toward acid-catalyzed hydrolysis. For example, the hydrolysis of 2,7-dioxabicyclo[2.2.1]heptane (2) in aqueous acetone containing dichloroacetic acid was 2.5 x 104 times faster than that of an acyclic reference compound, dimethyl acetal. [77] 2,6-Dioxabicyclo[Z2.1]heptane (79) is more reactive, and hydrolyzed 6.9 x 10s times faster than dimethyl acetal. [78] These rate accelerations for bicyclic acetals arise from a partial liberation of the ring strain on hydrolysis, and have been correlated to the reactivities of bicyclic acetals in the cationic ring-opening polymerization. [5]... 

Epoxides are much more reactive than common dialkyl ethers because of the large strain energy (about 105 kJ/mol or 25 kcal/mol) associated with the three-membered ring. Unlike other ethers, epoxides react under both acidic and basic conditions. The products of acid-catalyzed opening depend primarily on the solvent used. 

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