Allylic Acetals as Acrolein Oxonium Precursors in Tandem C-H Allylation and [3+2] Dipolar Cycloaddition

Abstract

The ruthenium(II)-catalyzed C-H functionalization of (hetero)aryl azomethine imines with allylic acetals is described. The initial formation of allylidene(methyl)oxoniums from allylic acetals could trigger C(sp² )-H allylation, and subsequent endo-type [3+2] dipolar cycloaddition of polar azomethine fragments to deliver valuable indenopyrazolopyrazolones. The utility of this method is showcased by the late-stage functionalization of bioactive molecules such as estrone and celecoxib. Combined experimental and computational investigations elucidate a plausible mechanism of this new tandem reaction. Notably, the reductive transformation of synthesized compounds into biologically relevant diazocine frameworks highlights the importance of the developed methodology.

Keywords: C−H functionalization; allylic acetal; dipolar cycloaddition; indenopyrazolopyrazolone; tandem reaction.