Synthesis of dienes from pyrrolidines using skeletal modification

Abstract

Saturated N-heterocyclic pyrrolidines are common in natural products, medicinal compounds and agrochemicals. However, reconstruction of their skeletal structures creating new chemical space is a challenging task, and limited methods exist for this purpose. In this study, we report a skeletal modification strategy for conversion of polar cyclic pyrrolidines into nonpolar linear dienes through a N-atom removal and deconstruction process. This involves N-sulfonylazidonation followed by rearrangement of the resulting sulfamoyl azide intermediates. This can be an energetically unfavorable process, which involves the formation of active C–C π bonds, the consumption of inert C–N and C–C σ bonds and the destruction of stable five-membered rings, but we have used it here to produce versatile conjugated and nonconjugated dienes with links of varying lengths. We also studied the application of this method in late-stage skeletal modification of bioactive compounds, formal traceless C(sp ²)–H functionalization and formal N-atom deletion.

Abstract

Saturated N-heterocyclic pyrrolidines are common in natural products and medicinal compounds, but reconstruction of their skeletal structures to access new chemical space is a challenging. Here, the authors report a skeletal modification strategy for conversion of polar cyclic pyrrolidines into nonpolar linear dienes through a N-atom removal and deconstruction process.