Asymmetric Catalytic Synthesis of Hexahydropyrrolo-isoquinolines via Three-Component 1,3-Dipolar-Cycloaddition

An asymmetric three-component 1,3-dipolar cycloaddition of 3,4-dihydroisoquinolines, bromoacetates and alpha,beta-unsaturated pyrazole amide is realized by using a chiral N,N'-dioxide-Y(OTf)(3) complex as the catalyst. The process includes a base-promoted formation of dihydroisoquinolium ylides in situ, and a chiral Lewis acid-catalyzed asymmetric [3+2] cycloaddition with alpha,beta-unsaturated pyrazole amides. A series of hexahydropyrrolo-isoquinolines are obtained in moderate to good yields with excellent diastereo- and enantioselectivities.

Automated summary

An asymmetric three-component 1,3-dipolar cycloaddition has been achieved using a chiral catalyst, resulting in a series of hexahydropyrrolo-isoquinolines with excellent diastereo- and enantioselectivities.