Cycloaddition, Regio-reversed

Cycloaddition of the cyclic nitrone derived from proline benzyl ester with alkenes proceeds readily to give isoxazolidines with good regio-and stereoselectivity (Eq. 8.47).68 The reaction favors exo-mode addition. However, certain cycloadditions are reversible and therefore the product distribution may reflect thermodynamic rather than kinetic control. 

Chiral 1,2-dihydropyridine complex 78 has been shown to undergo Lewis acid-initiated [5+2] cycloadditions with electron-deficient alkenes, such as methyl acrylate, to give, after demetalation using ceric ammonium nitrate, functionalized tropanes 80 (Scheme 22) <20000L3909, 1999JA5811>. Short reaction times and substoichiometric amounts of Lewis acid are sufficient to ensure regio- and enantioselectivity. It is thought that excess Lewis acid mediates a slow reversal... 

In 1970 Bauslaugh22 proposed that the regioselectivity of enone cycloadditions can be explained by a diradical mechanism without invoking exciplexes. In this approach, the regio-chemical outcome is regarded as a consequence of the competition between cyclization and reversion from 1,4-diradicals. It is assumed that the more stable biradicals must return at a faster rate to the ground state starting molecules and therefore lead to less product. 

Mechanism of Ozonolysis (Criegee mechanism) The initial step of the reaction involves a 1,3-dipolar cycloaddition of ozone to the alkene leading to the formation of the primary ozonide (molozonide or 1,2,3-trioxolane), which decomposes to give a carbonyl oxide and a carbonyl compound. The carbonyl oxides are similar to ozone in being 1,3-dipolar compounds and undergo 1,3-dipolar cycloaddition to the carbonyl compound with the reverse regio-chemistry, leading to a relatively stable secondary ozonide (1,2,4-trioxolane) (Scheme 5.47). 

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