Second generation protocol for multicomponent coupling reactions of aldehydes, amides and dienophiles

An improved one-pot procedure for the three-component coupling reaction of aldehydes, amides and dienophiles (AAD reaction) has been developed. Compared to known protocols for this type of reaction, the use of aromatic solvents in the presence of dehydrating reagents allows an efficient synthesis of previously not accessible products. Condensation of ubiquitous available aldehydes and amides and subsequent Diels-Alder reactions with dienophiles furnishes endo-selective amino-functionalized hexahydroisoindole-1,3-dione and tetrahydrophthalic acid derivatives in good yield.