C-H Functionalization via Iron-Catalyzed Carbene-Transfer Reactions

Abstract

The direct C-H functionalization reaction is one of the most efficient strategies by which to introduce new functional groups into small organic molecules. Over time, iron complexes have emerged as versatile catalysts for carbine-transfer reactions with diazoalkanes under mild and sustainable reaction conditions. In this review, we discuss the advances that have been made using iron catalysts to perform C-H functionalization reactions with diazoalkanes. We give an overview of early examples employing stoichiometric iron carbene complexes and continue with recent advances in the C-H functionalization of C(sp2)-H and C(sp3)-H bonds, concluding with the latest developments in enzymatic C-H functionalization reactions using iron-heme-containing enzymes.

Iron catalysts with N-ligands for carbene transfer of diazo reagents

“…In view of the importance of applying non-noble metals in more sustainable processes, extensive efforts have been made to replace the rhodium-based catalysts with iron-containing systems, which are now widely recognized as very active catalysts in mediating carbene insertions. 11,13,[155][156][157] In this section, the most recent published data on the iron-mediated C-H and X-H functionalization are discussed by taking into account the influence of the catalyst environment and the electronic/steric nature of the employed diazo reagent on the reaction mechanism. The analysis of the high number of reported studies has allowed the identification of some general mechanisms and among them, two pathways were proposed passing through the formation of a carbene intermediate (Scheme 47).…”

The Power of Iron Catalysis in Diazo Chemistry

“…A metal carbene can then be used for a wide variety of reactions, notably cyclopropanation and insertion reactions. [7][8][9][10][11][12][13][14] Since their initial discovery until the present day, diazo compounds have been the subject of constant research where numerous advancements have been made in this field. The most commonly employed transition metal catalysts with diazo compounds are Rh and Cu, which have been highly efficient in mediating carbene reactions with high selectivities and at low loadings.…”

“…The most commonly employed transition metal catalysts with diazo compounds are Rh and Cu, which have been highly efficient in mediating carbene reactions with high selectivities and at low loadings. [7][8][9][10][11][12][13]15 However, these precious and toxic metals have shown equal, if not less, efficiency compared to iron catalysts in certain transformations with diazo compounds. The first iron-catalyzed reaction with diazo compounds was reported in 1994 for the cyclopropanation of olefins.…”

“…Iron-catalyzed C-H insertion and cyclopropanation reactions are well known and described as main routes for C-H functionalization with many key developments in the field over the past decade. [10][11][12][13][14] Insertion reactions into C-H bonds catalyzed by iron complexes are highly appreciated for their efficiency, selectivity, and sustainability when compared to alternative methods to functionalize activated and non-activated C-H bonds. 12 In addition, cyclopropanation reactions of diazo compounds have been significantly studied using iron catalysts as better alternatives to precious metal catalysts.…”

Iron‐Catalyzed Intermolecular Functionalization of Non‐Activated Aliphatic C−H Bonds via Carbene Transfer

“…[2,3] Because of sustainability considerations, iron is an appealing option to add to this list due to its inherent low toxicity and high earthabundancy. [4] However, the iron catalyzed reaction has been developed only to a modest extent and reports are scarce. [5][6][7][8][9][10] Seminal studies started with the intramolecular functionalization of CÀ H bonds using stoichiometric amounts of a preformed iron-carbene compound.…”