The synthesis and evaluation of structure-activity relationships of saturated nitrogen heterocycles is the focal point of various pharmaceutical companies owing to the high biological activity of previously isolated azaheterocycles. Here, we describe our progress toward the development of an operationally simple and highly efficient approach to macrocyclic lactams bearing vicinal stereocenters and a challenging cycloalkyne motif. A newly discovered [4 + 2] cycloaddition reaction between N-iodoarylated-1,3-azadienes and cyclic anhydrides, the interception of the cycloadducts in cross-coupling manifolds (e.g., Sonogashira coupling), concomitant lithiation-cyclization of the tethered alkyne are some of the reactivity modes explored in these studies. It is anticipated that the synthesis of these novel N-containing macrocycles would lead to new pharmacophores with profound medicinal value.

Expedient access to highly functionalized iodoarylated allyic lactams: Application to the synthesis of macrocyclic enamidynes

253rd National Meeting (2017)

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