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An iron-catalyzed coupling reaction of difluoroenol silyl ethers and cyclobutanone oxime esters is described. This protocol provides a convenient access to various previously unknown and potentially useful gem-difluoromethylenated ketonitriles inmoderate to good yields. The transformations of resulting products to other fluorinecontaining products is also documented.

An iron-catalyzed strategy for the rapid synthesis of indolo[2,3- c ]quinolines has been developed. This cascade reaction involving alcohol oxidation, nitro reduction, and oxidative annulation was achieved in a one-pot. The present protocol was started from mono-functionalized indoles and readily available benzylic alcohols/aldehydes, affording a variety of functionalized indolo[2,3- c ]quinolines in satisfactory yields.

An efficient and convenient method for the synthesis of amidines bearing a β-naphthalenone moiety catalyzed by cheap iron(ii) chloride is presented by employing oxadiazolones as the nitrene precursors.

Iron-catalyzed oxidative amination of benzylic C(sp3)-H bonds with anilines bearing electron-withdrawing groups (EWGs) or electron-donating groups (EDGs) is realized based on simple variations of N-substituents on imidazolium cations in novel ionic Fe(III) complexes. The structural modification of the imidazolium cation resulted in regulation of the redox potential and the catalytic performance of the iron metal center. Using DTBP as oxidant, [HItBu][FeBr4] showed the highest catalytic activity for anilines bearing EWGs, while [HIPym][FeBr4] was more efficient for EDG-substituted anilines. This work provides alternative access to benzylamines with the advantages of both a wide substrate scope and iron catalysis.

Succinimide derivatives are valuable compounds in synthesis of natural products and pharmaceuticals. A catalytic hydroaminocarbonylation reaction was developed for the synthesis of succinimides from alkynes, CO and NH4HCO3. The novel transformation proceeds in the presence of Fe3(CO)12 without the need for expensive ligands or additives. Various substituted alkynes are selectively transformed into corresponding succinimides in good yields. Preliminary mechanistic studies suggest that NH4HCO3 plays an important role in the formation and stabilization of iron catalyst.

A novel iron-catalyzed ring opening of cyclopropanols and their 1,6-conjugate addition to p-quinone methides for accessing substituted phenols is disclosed. In this protocol, various cyclopropanols are converted to alkyl radicals and undergo 1,6-conjugate addition to p-quinone methides toward C-C bond formation. The salient features of this methodology include operationally simple and mild reaction conditions, environmentally benign protocol, high efficiency, inexpensive catalyst, good to excellent yield, and a wide range of substrate scope.

We report a general photocatalytic protocol for the remote C(sp3)-H bond amination of free aliphatic alcohols. The electron transfer between the abundant and inexpensive catalyst FeCl3 and simple alkanols under blue LED irradiation enables the alkoxy radical formation under mild redox-neutral conditions, with no need for additional oxidant and prefunctionalization. The subsequent selective 1,5-hydrogen atom transfer (HAT) and amination provide a simple and efficient way to access molecular complexity from readily available and bulk alcohols.

We have developed an efficient iron-catalyzed one-pot reaction of tryptamines, ynones and nitroolefins, affording indole-tethered tetrasubstituted pyrroles in acceptable to good yields. Other aromatic and aliphatic amines can also be utilized in this process, delivering the corresponding highly functionalized tetrasubstituted pyrroles. Indolizino[8,7-b]indole derivatives could be obtained through TFA-, TfOH- or Fe(OTf)3-mediated cyclizations via dearomatization of indole. Unexpected dibrominated products, 7,9-dibromo-6,11-dihydro-5H-indolizino[8,7-b]indoles, were formed when trimethylphenylammonium tribromide (PTAP) was employed as electrophilic cyclization promoter.

A new method of FeCl2-catalyzed [4+2] annulation of α,β-unsaturated ketoxime acetates with N-acetyl enamides in batch and flow is reported. The current strategy features low-cost catalytic system, use of electron-rich olefins, operational simplicity, and broad substrate scope, thus providing a facile and efficient access to substituted pyridines in moderate to good yields.

Ironing on hydroxyls Although iron-dependent enzymes efficiently hydroxylate aryl rings, this activity has proven hard to replicate with synthetic catalysts. Cheng et al . report that a disulfide ligand activates iron to catalyze carbon–hydrogen hydroxylation of a wide variety of arenes using hydrogen peroxide. The protocol can also cleanly functionalize phenols with an additional hydroxyl group, although unfunctionalized arenes react more rapidly, in contrast to conventional oxidative selectivity patterns. The authors showcase this complementary selectivity through hydroxylation of pharmaceuticals with complex substitution patterns. —JSY

Herein, we describe an iron-catalyzed borylation and silylation of unactivated alkyl chlorides, delivering the tertiary, secondary, and primary alkylboronic esters, and secondary, primary alkylsila...

A cheap iron-catalyzed C-C bond cleavage/thiolation and selenylation of cycloalkyl hydroperoxides are presented. This redox-neutral protocol provides efficient access to diverse distal keto-functionalized thioethers and selenium compounds. Remarkably, only some amounts of disulfides are required for this transformation.

Here, we reported for the first time an iron-catalyzed highly enantioselective hydrogenation of minimally functionalized 1,1-disubstituted alkenes to access chiral alkanes with full conversion and excellent ee. A novel chiral 8-oxazoline iminoquinoline ligand and its iron complex have been designed and synthesized. This protocol is operationally simple by using 1 atm of hydrogen gas and shows good functional group tolerance. A primary mechanism has been proposed by the deuterium-labeling experiments.

Iron catalyzed coupling of β-amino alcohols with allylic alcohols for the synthesis of 3,4-dihydro-2H-pyrrole derivatives has been developed. Mechanistic studies suggest that the reaction involves iron catalyzed dehydrogenative coupling and C–C bond cleavage processes.

Azidation of alkenes is an efficient protocol to synthesize organic azides which are important structural motifs in organic synthesis. Enantioselective radical azidation, as a useful strategy to install a C-N3 bond, remains challenging due to the inherently instability and unique structure of radicals. Here, we disclose an efficient enantioselective radical carboazidation and diazidation of α,β-unsaturated ketones and amides catalyzed by chiral N,N'-dioxide/Fe(OTf)2 complexes. An array of substituted alkenes was transformed to the corresponding α-azido carbonyl derivatives in good to excellent enantioselectivities, benefiting the preparation of chiral α-amino ketones, vicinal amino alcohols, and vicinal diamines. Control experiments and mechanistic studies proved the radical pathway in the reaction process. The DFT calculations showed that the azido transferred to the radical intermediate via an intramolecular five-membered transition state with the internal nitrogen of the Fe-N3 species.

Pyrrole derivatives and their related five membered azacycles are a class of important five-membered aromatic nitrogen heterocyclic compounds and their synthesis attracted much attention of organic chemists. Iron catalysis has been widely used in various organic transformations due to the benefits of their excellent catalytic activity, their environmentally benign character, their easy accessibility and their low price. Over the past decades, a variety of facile and effective synthesis of pyrrole derivatives and related five membered azacycles based on iron catalysis has been reported. In this review, a comprehensive coverage of the development of iron-catalyzed synthesis of pyrrole derivatives and their related five membered azacycles was summerized, which covered the literatures up to March 2021.

Herein, we report the first example of iron-catalyzed defluoroborylation of unactivated gem-difluoroalkenes, gem-dichloroalkenes, and gem-dibromoalkenes, providing the 1,2-bis(boryl)alkanes in moderate to good yield. This transformation has high regioselectivity, wide substrate scope, and excellent functional group compatibility. Preliminary mechanistic studies indicate that double β-F elimination is involved in the catalytic cycle, and the 1,1-diborylated alkenes might be intermediates in this iron-catalyzed 1,2-diborylation reaction.

The use of iron catalysts in carbon–carbon bond forming reactions is of interest as an alternative to precious metal catalysts, offering reduced cost, lower toxicity, and different reactivity. While well-defined ligands such as N-heterocyclic carbenes (NHCs) and phosphines can be highly effective in these reactions, additional additives such as N-methylpyrrolidone (NMP), N,N,N′,N′-tetramethylethylenediamine (TMEDA), and iron salts that alter speciation can also be employed to achieve high product yields. However, in contrast to well-defined iron ligands, the roles of these additives are often ambiguous, and molecular-level insights into how they achieve effective catalysis are not well-defined. Using a unique physical–inorganic in situ spectroscopic approach, detailed insights into the effect of additives on iron speciation, mechanism, and catalysis can inform further reaction development. In this Perspective, recent advances will be discussed as well as ongoing challenges and potential opportunities in iron-catalyzed reactions.

Herein we disclose an iron-catalyzed method to access skeletal rearrangement reactions akin to the Dowd-Beckwith ring expansion from unactivated C(sp(3))-H bonds. Photoinduced ligand-to-metal charge transfer at the iron center generates a chlorine radical, which abstracts electron-rich C(sp(3))–H bonds. The resulting unstable alkyl radicals can undergo rearrangement in the presence of suitable functionality. Addition to an electron deficient olefin, recombination with a photoreduced iron complex, and subsequent protodemetallation allows for redox-neutral alkylation of the resulting radical. Simple adjustments to the reaction conditions enable the selective synthesis of the directly alkylated or the rearranged-alkylated products. As a radical clock, these rearrangements also enable the measurement of rate constants of addition into various electron deficient olefins in the Giese reaction.

An efficient aerobic iron-catalyzed annulation of unsaturated carboxylic acids with disulfides has been developed. This procedure proceeds using FeCl3 as the catalyst and KI as an iodine source under an air atmosphere, which provides practical access to a wide range of substituted γ-lactone derivatives. The disclosed method is quite simple, highly atom-economic, environmentally friendly, and tolerates a broad substrate scope.

The iron-catalyzed δ-C(sp3)-H bond difluoromethylthiolation and difluoromethylselenation of aliphatic amides with high site selectivity are reported. Essential to the success is the employment of an amide radical formed in situ to activate the inert C(sp3)-H bond and the utilization of the easily handled PhSO2SCF2H and PhSO2SeCF2H as coupling reagents under mild conditions. This scalable protocol exhibits a broad substrate scope bearing versatile functional groups. Mechanistic studies indicate that the reaction proceeds through -SCF2H and -SeCF2H radical transfer.

Stereoselective synthesis of sarmentine has been achieved via iron-catalyzed cross-coupling of pentylmagnesium bromide with ethyl (2E,4E)-5-chloropenta-2,4-dienoate obtained by one-pot oxidation–olefination of readily available (2E)-3-chloroprop-2-en-1-ol.

We present herein an efficient synthetic protocol involving iron-catalyzed cross-coupling of organolithium compounds with vinyl halides as key coupling partners. More than 30 examples were obtained with moderate to good yields and high stereoselectivities. The practicality of this method is evidenced by a gram-scale synthesis. In addition, a preliminary mechanistic investigation was also performed.

The iron-catalyzed alkyl-aryl coupling reaction between sulfones and arylboron compounds has remained a challenge. We report the first iron-catalyzed radical difluoroalkylation of arylborates with N-heteroaryl sulfones. The coordination between the iron catalyst and the nitrogen atom of N-heteroaryl sulfones was identified to be important in overcoming the reduction potential limitation of sulfones in the intermolecular single-electron-transfer process, which enables both fluoroalkyl N-heteroaryl sulfones (with relatively high reduction potentials) and nonfluorinated alkyl N-heteroaryl sulfones (with low reduction potentials) to serve as powerful alkylation reagents.

An iron-catalyzed allyation of isoquinoline with potassium allyltrifluoroborate is described. The operation of this reaction is very simple and highly practical. The diastereoisomer having two adjacent chiral centers were obtained in single anti-configuration.

The development of pyrimidine-based analogues of the well-known pyridinediimine (PDI) iron complexes enables access to a functional-group-tolerant methodology for the catalytic trimerization of ter...

A FeCl2·4H2O-catalyzed oxidative alkoxycarbonylation of activated alkenes with carbazates toward alkoxycarbonylated benzimidazo[2,1-a]isoquinolin-6(5H)-ones has been established. The reaction proceeded smoothly to furnish a series of structurally diverse benzimidazo[2,1-a]isoquinolin-6(5H)-one frameworks in moderate to good yield.

An iron-catalyzed C(sp3)–H cyanoalkylation of glycine derivatives with cyclobutanone oxime esters was established for the incorporation of a cyano group into amino acids and peptides. In this react...

We report here a C–H homoallylation reaction of aromatic ketones with methylenecyclopropanes (MCPs) only using a catalytic amount of Fe(PMe3)4. A variety of aromatic ketones and MCPs are applicable...

The significant progress made in the context of iron-catalyzed cross-coupling reactions in the past several years has boosted competition with well-known nickel and palladium catalyst systems. Iron...

Strecker reaction is widely applied for the synthesis of amino acids from aldehydes, amines and cyanides. Herein, we report the FeI2-catalyzed reductive Strecker type reaction of formamides instead of aldehydes to produce amino acetonitriles. The challenging capture of carbinolamine intermediates by CN− was achieved via Fe catalysis. This approach afforded better yields than the use of Ir- or Rh-catalysts. The application ability of this methodology is demonstrated by 1) one-pot construction of (13C labeled) complex molecules from CO2 via amino acetonitrile intermediates and 2) convenient production of homologated carboxylic acids from aldehydes.

This Account summarizes our work in the area of organoiron chemistry during the last two decades, with special emphasis on iron catalyzed C-C-bond formation. Specifically, it is shown that iron cat...

The iron-catalyzed direct arylation of a variety of N-heteroarenes, quinones, and hydroquinones with arylboronic acids is investigated under microwave heating. The reaction proceeds at 70 °C under air using K2S2O8 as an oxidant and FeSO4 as a catalyst. Under microwave heating, reaction times decreased 14- to 115-fold. Reaction scope with N-heteroarenes and quinones is comparable with or slightly expanded when compared with previous reports, but the scope of arylboronic acid utility was slightly limited due to previously unobserved arylboronic acid hydroxydeboronation.