Iron Catalysis in Organic Synthesis

Research and industrial interest in radical C–H activation/radical cross-coupling chemistry has continuously grown over the past few decades. These reactions offer fascinating and unconventional approaches toward connecting molecular fragments with high atom- and step-economy that are often complementary to traditional methods. Success in this area of research was made possible through the development of photocatalysis and first-row transition metal catalysis along with the use of peroxides as radical initiators. This Review provides a brief and concise overview of the current status and latest methodologies using radicals or radical cations as key intermediates produced via radical C–H activation. This Review includes radical addition, radical cascade cyclization, radical/radical cross-coupling, coupling of radicals with M–R groups, and coupling of radical cations with nucleophiles (Nu).

Recent Advances in Radical C-H Activation/Radical Cross-Coupling.

This Perspective illustrates the defining characteristics of free radical chemistry, beginning with its rich and storied history. Studies from our laboratory are discussed along with recent developments emanating from others in this burgeoning area. The practicality and chemoselectivity of radical reactions enable rapid access to molecules of relevance to drug discovery, agrochemistry, material science, and other disciplines. Thus, these reactive intermediates possess inherent translational potential, as they can be widely used to expedite scientific endeavors for the betterment of humankind.

Radicals: Reactive Intermediates with Translational Potential

Recent Advances in Radical Difunctionalization of Simple Alkenes

Carbo- and heterocycles are widely found in natural products, biologically active structures, medicinally relevant compounds, and in many other fine chemicals. The development of novel, general and efficient methods for their construction has therefore gained great interest in synthetic organic chemistry. Recently, radical chemistry has become a heavily investigated research field (a renaissance!). Along these lines, radical cascade cyclization of 1,n-enynes and diynes has emerged as a powerful strategy for the preparation of carbo- and heterocycles. In this review, we highlight recent advances in this rapidly growing area also focusing on reaction mechanisms.

Radical cascade cyclization of 1,n-enynes and diynes for the synthesis of carbocycles and heterocycles

Benzannulation of Indoles to Carbazoles and Its Applications for Syntheses of Carbazole Alkaloids

Cross-dehydrogenative coupling (CDC), which enables the formation of carbon–carbon (C–C) and C–heteroatom bonds from the direct coupling of two C–H bonds or C–H/X–H bonds, represents a new state of the art in the field of organic chemistry. Iron, a prominent metal, has already shown its versatile application in chemical synthesis. This review attempts to provide a comprehensive understanding of the evolution of cross-dehydrogenative coupling via iron catalysis, as well as its application in synthetic chemistry.

Fe-Catalyzed Cross-Dehydrogenative Coupling Reactions

Biologically significant clavilactones A, B, and the previously proposed D have been synthesized through iron-catalyzed carbonylation–peroxidation of a 1,5-diene. Three steps from aldehydes, alkenes, and tert-butylhydroperoxide build up α,β-epoxy-γ-butyrolactone skeleton as a key building block for synthesis of clavilactone family and its derivatives. Based on our results, the structure of the proposed clavilactone D is not correct and requires revision.

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Total synthesis of (±)-clavilactones A, B, and proposed D through iron-catalyzed carbonylation-peroxidation of olefin.

Iron-catalyzed acylation-oxygenation of terminal alkenes is reported. Acyl radicals generated by the oxidation of aldehydes add to terminal alkenes and followed by intramolecular oxygenation give functionalized 2,3-dihydrofuran derivatives bearing a quaternary carbon.

Leiyang Lv

Papers

Benzannulation of Indoles to Carbazoles and Its Applications for Syntheses of Carbazole Alkaloids

Fe-Catalyzed Cross-Dehydrogenative Coupling Reactions

Total synthesis of (±)-clavilactones A, B, and proposed D through iron-catalyzed carbonylation-peroxidation of olefin.

Iron-Catalyzed Acylation-Oxygenation of Terminal Alkenes for the Synthesis of Dihydrofurans Bearing a Quaternary Carbon

Iron-Catalyzed Radical [2 + 2 + 2] Annulation of Benzene-Linked 1,7-Enynes with Aldehydes: Fused Pyran Compounds