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Complex N-Heterocycle Synthesis via Iron-Catalyzed, Direct C–H Bond Amination

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Science  03 May 2013:
Vol. 340, Issue 6132, pp. 591-595
DOI: 10.1126/science.1233701

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Closing the Cycle

Cyclic hydrocarbons that incorporate nitrogen in the ring are among the most heavily investigated compounds in medicinal chemistry. Hennessy and Betley (p. 591) demonstrate an iron catalyst that forms a range of such cyclic compounds by inducing linear alkyl azides to curl back on themselves, inserting the nitrogen at one end into a carbon-hydrogen bond further down the chain. The reaction furthers a trend of C-H bond activation chemistry that forms elaborate products from relatively simple precursors, without the need to install activating groups at unreactive sites.

Abstract

The manipulation of traditionally unreactive functional groups is of paramount importance in modern chemical synthesis. We have developed an iron-dipyrrinato catalyst that leverages the reactivity of iron-borne metal-ligand multiple bonds to promote the direct amination of aliphatic C–H bonds. Exposure of organic azides to the iron dipyrrinato catalyst furnishes saturated, cyclic amine products (N-heterocycles) bearing complex core-substitution patterns. This study highlights the development of C–H bond functionalization chemistry for the formation of saturated, cyclic amine products and should find broad application in the context of both pharmaceuticals and natural product synthesis.

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