Enantioselective Metal-Catalyzed Passerini Reaction

In sharp contrast to the importance acquired by asymmetric catalysis in the last decades, and although asymmetric induction has been achieved in Passerini reaction through diastereoselective approaches by using chiral substrates and/or chiral auxiliaries [33], the number of catalytic asymmetric procedures reported is still limited for this reaction and it remains as a significant challenge [34], Several drawbacks exist that make this task particularly difficult to 

FIGURE 8.3 Scope of the [(salen)Al Cl] 41-catalyzed enantioselective Passerini reaction. 

The addition of the isocyanide to the active complex A gives the nitrilium ion B, which is further trapped by HN3 42 delivering tetrazole 44 as final product. Simultaneously, reaction of B with HCl could provide the chloroimidate C. 

FIGURE 8.4 General structure of norstatines 46 [44], cw-constrained norstatine analogues 47 [40a], benzimidazole analogues 48 [45], and peptidic kinase inhibitors 49 [46]. 

This intennediate, in the presence of water, can be converted into the a-hydroxyamide 45. It is worth noting that in this case the anthors use HN3 42 as the acid instead of the usual carboxylic acid component. 

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