Multicomponent Reaction for the Synthesis of 5,6-Dihydropyrrolo[2,1-<i>a</i>]isoquinolines

Abstract

A multicomponent reaction between isatin, tetrahydroisoquinoline, and terminal alkyne in the presence of benzoic acid for the synthesis of <i>N</i>-(substituted-2-(2-phenyl-5,6-dihydropyrrolo[2,1-<i>a</i>]isoquinolin-3-yl)phenyl)-3,4-dihydroisoquinoline-2(1<i>H</i>)-carboxamides is described. This three-component reaction proceeds via sequential formation of spirooxindole, generation of isocyanate functionality via cleavage of the C2-C3 bond in the isatin subunit of spirooxindole, and addition of the second molecule of tetrahydroisoquinoline to the isocyanate group to offer title compounds. Expansion of the protocol to four-component by including an additional primary amine affords 1-substituted-3-(2-(2-phenyl-5,6-dihydropyrrolo[2,1-<i>a</i>]isoquinolin-3-yl)phenyl)urea in low to moderate yields. However, the reaction of intermediate spirooxindole with tetrahydroisoquinoline or any primary or secondary amine produced the title compound in excellent yields.