CYCLOADDITION REACTIONS OF ENAMINES

Department of Chemistry Valparaiso University Valparaiso, Indiana 

Most of the reactions described in this chapter would fall under Huisgen s definition of a cycloaddition reaction (/, la). However some of the reactions described would not be considered cycloaddition reactions according to this restrictive definition. Therefore, the more liberal definition given by Baldwin will be used as a guideline, namely, Cycloadditions are chemical transformations giving at least one product having at least two new bonds as 

The types of cycloadditions discovered for enamines range through a regular sequence starting with divalent addition to form a cyclopropane ring, followed by 1,2 addition (i) of an alkene or an alkyne to form a cyclo-cyclobutane or a cyclobutene, then 1,3-dipolar addition with the enamine the dipolarophile 4), and finally a Diels-Alder type of reaction (5) with the enamine the dienophile. 

The reactions of electrophilic alkenes (alkenes attached to electron-withdrawing groups) with enamines produce one or more of the following products simple alkylation (2), 1,2 cycloaddition (3), and 1,4 cycloaddition (4). Competition with C alkylation by N alkylation is inconsequential and therefore will be largely ignored (5,7). A stepwise ionic mechanism leading to these products necessarily involves the formation of a zwitterion intermediate (1) as the first step, which is then followed either by one of the 

The first reported cyclization involving an enamine was the 1,4 cycloaddition of methyl vinyl ketone with the enamine of cyclohexanone to give. 

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For a review of cycloaddition reactions of enamines, see Cook, in Cook Enamines, 2nd ed. Marcel Dekker New York, 1988, pp. 347-440. 

Diphenylcyclopropenone is the first stable molecule prepared which has a carbonyl group in a three-membered ring. In a very real sense the compound has aromatic character and is fairly stable.4 An interesting cycloaddition reaction of enamines with diphenylcyclopropenone has been reported.7... 

Four-membered carbocyclic ring systems are commonly formed by cycloaddition of electrophilic alkenes, ketenes and arynes to enamines. Since cycloaddition reactions of enamines are dealt with in Chapter 18 these reactions will only be mentioned briefly here. 

The present chapter is dedicated to the cycloaddition reactions of enamines, which include transformations that, independently of the mechanism, create a new ring1. The cycloadditions may proceed via a concerted mechanism (following Woodward-Hoff-mann rules) or a two-step mechanism which may involve zwitterionic or diradical intermediates. Due to their low ionization potentials and asymmetric molecular orbital... 

Inevitably there is some overlap between the present chapter and that on Cycloaddition reactions of enamines because many such reactions result in the formation of heterocycles. The criterion for inclusion in this chapter is isolation of, or evidence for, discrete acyclic intermediates. Often the mechanism of the reaction is not known the mere suspicion that the cycloaddition proceeds in a stepwise manner was thought sufficient justification for mentioning it here. 

The AgC03-catalysed 3 + 2-cycloaddition of isocyanides with unactivated terminal and internal alkynes produced 2,3-disubstituted and 2,3,4-trisubstituted pyrroles under base- and ligand-free conditions. The reactions are regioselective and the products are obtained in high yields (71-96%). The secondary amine-catalysed inverse-electron-demand 3 + 2-cycloaddition reaction of enamines with diazoacetates yielded polysub-stituted pyrazoles in good to excellent yields and high regioselectivities under mild conditions. ... 

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