Cycloadditions with electron-deficient triple bond

The cycloaddition of azides to multiple -ir-bonds is an old and widely used reaction. Organic azides are well known to behave as 1,3-dipoles in thermal cycloaddition reactions.178 The first example of this reaction was observed by Michael in 1893.179 Since then the addition of azide to carbon-carbon double and triple bonds has become the most important synthetic route to 1,2,3-triazoles, -triazolines and their derivatives.180-184 The cycloadditions of simple organic azides with electron-rich dipolarophiles are LUMO controlled.3 Since the larger terminal coefficients are on the unsubstituted nitrogen in the azide and unsubstituted terminus in the dipolarophiles, the 5-substituted A2-triazolines are favored, in agreement with experiment.185-187 Reactions with electron-deficient dipolarophiles are HOMO controlled, and... 

The Diels-Alder reaction with inverse electron demand has been one of the most intensively studied reactions of 1,2,4-triazines. In this reaction 1,2,4-triazines behave as electron-deficient dienes and react with electron-rich dienophiles to give, generally, pyridines (see Houben-Weyl, Vol. E7b, p 471 ff). [4 + 2] Cycloadditions of 1,2,4-triazines have been observed with alkenes, alkynes, strained double bonds, electron-rich double and triple bonds, but in a few cases also with electron-deficient alkynes C—N double and triple bonds can also be used as dienophiles. In addition to intermolecular Diels-Alder reactions, intramolecular [4 + 2] cycloaddition reactions of 1,2,4-triazines have also been studied and used for the synthesis of condensed heterocyclic systems. A review on the intermolecular Diels-Alder reaction was published by Boger and Weinreb 14 Sauer published a review on his studies in 1992,381 and E. C. Taylor published a summary of his own work on intramolecular Diels-Alder reactions in 1988.382... 

In 2009, de Meijere s group reported on the formal cycloaddition of a-metallated methyl isocyanides onto the triple bond of electron-deficient acetylenes, giving oligosubstituted pyrroles. The reaction showed broad scope (24 examples, 25-97% yield). In addition, a related novel Cu(l)-mediated synthesis of 2,3-disubstituted pyrroles by the reaction of copper acetylides derived from unactivated terminal alkynes with substituted methyl isocyanides was reported (11 examples, 5-88% yield) [99,100]. 

Despite the great achievements that have been made in catalytic asymmetric 1,3-dipolar cycloadditions, electron-deficient carbon-carbon triple bonds had never been used as dipolarophiles until Shi et al. treated them with aldehydes 3 and amino esters 49 in the promotion of phosphoric add 5e (Scheme 2.18). This reaction provides an unprecedented approach to accessing 2,5-dihydropyrrole skeletons 63 in perfect enantioselectivities of up to >99% ee [29]. 

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