Chemodivergent 1,3-Dipolar Cycloadditions of C,N-Cyclic Azomethine Imines with γ-Sulfonamido-α,β-Unsaturated Ketones to Synthesize Tricyclic Dinitrogen-Fused Heterocycles

Abstract

1,3-Dipolar cycloadditions of C,N-cyclic azomethine imines with γ-NHTs-α,β-unsaturated ketones were developed to synthesize tricyclic dinitrogen-fused heterocycles. Highly functionalized tricyclic tetrahydroisoquinolines were readily obtained in good to high yields in the [3 + 2]-cycloaddition reaction of N-Bz-protected C,N-cyclic azomethine imines with γ-NHTs-α,βunsaturated ketones under mild reaction conditions. Moreover, DABCO-catalyzed cycloaddition of N-Ts-protected C,N-cyclic azomethine imines with γ-NHTs-α,β-unsaturated ketones followed by cleavage of the tosyl group is a convenient route to synthesize tetrahydropyrazolo [5,1-a]isoquinolines in good yields with excellent diastereoselectivities.

Synthesis of 5,6-Dihydropyrazolo[5,1-a]isoquinolines through Tandem Reaction of C,N-Cyclic Azomethine Imines with α,β-Unsaturated Ketones

“…Recently, we published a study on the DABCO-catalyzed cycloaddition of N-Tprotected C,N-cyclic azomethine imines with γ-NHTs-α,β-unsaturated ketones followed by a cleavage of the tosyl group, resulting in the efficient synthesis of tetrahydropyrazolo [5,1a]isoquinolines (19 examples) with high yields (up to 87% yield) and excellent diastereoselectivity (up to >30:1 dr) [24]. The reaction of N-T-protected C,N-cyclic azomethine imine 1a with γ-NHTs-α,β-unsaturated ketone 2a in the presence of the DABCO catalyst provided by tetrahydropyrazolo [5,1-a]isoquinoline 3aa in an 87% yield with >30:1 dr (Scheme 2(1)).…”