Iron-Catalyzed Directed C(sp²)–H and C(sp³)–H Functionalization with Trimethylaluminum

Conversion of a C­(sp²)–H or C­(sp³)–H bond to the corresponding C–Me bond can be achieved by using AlMe₃ or its air-stable diamine complex in the presence of catalytic amounts of an inorganic iron­(III) salt and a diphosphine along with 2,3-dichlorobutane as a stoichiometric oxidant. The reaction is applicable to a variety of amide substrates bearing a picolinoyl or 8-aminoquinolyl directing group, enabling methylation of a variety of (hetero)­aryl, alkenyl, and alkyl amides. The use of the mild aluminum reagent prevents undesired reduction of iron and allows the reaction to proceed with catalyst turnover numbers as high as 6500

Iron-Catalyzed C–H Activation for Heterocoupling and Copolymerization of Thiophenes with Enamines

C–H/C–H coupling via C–H activation provides straightforward synthetic access to the construction of complex π-conjugated organic molecules. The palladium-catalyzed Fujiwara–Moritani (FM) coupling between an arene and an electron-deficient olefin presents an early example but is not applicable to enamines such as N-vinylcarbazoles and N-vinylindoles. We report herein iron-catalyzed C–H/C–H heterocoupling between enamines and thiophenes and its application to copolymerization of bisenamine and bisthiophene using diethyl oxalate as an oxidant and AlMe3 as a base, as a result of our realization that synthetic limitations in oxidative C–H/C–H couplings imposed by the high redox potential of the Pd(II)/Pd(0) catalytic cycle can be circumvented by the use of iron, which has a lower Fe(III)/Fe(I) redox potential. The trisphosphine ligand provides a coordination environment for iron to achieve the reaction’s regio-, stereo-, and chemoselectivity. The reaction includes C–H activation of thiophene via σ-bond metathesis and subsequent enamine C–H cleavage triggered by nucleophilic enamine addition to the Fe(III) center, thereby differing from the FM reaction in mechanism and synthetic scope. The copolymers synthesized by the new reaction possess a new type of enamine-incorporated polymer backbone

Iron-Catalyzed Directed C(sp²)–H and C(sp³)–H Functionalization with Trimethylaluminum

Conversion of a C­(sp²)–H or C­(sp³)–H bond to the corresponding C–Me bond can be achieved by using AlMe₃ or its air-stable diamine complex in the presence of catalytic amounts of an inorganic iron­(III) salt and a diphosphine along with 2,3-dichlorobutane as a stoichiometric oxidant. The reaction is applicable to a variety of amide substrates bearing a picolinoyl or 8-aminoquinolyl directing group, enabling methylation of a variety of (hetero)­aryl, alkenyl, and alkyl amides. The use of the mild aluminum reagent prevents undesired reduction of iron and allows the reaction to proceed with catalyst turnover numbers as high as 6500

Iron-Catalyzed <i>Ortho</i> C–H Methylation of Aromatics Bearing a Simple Carbonyl Group with Methylaluminum and Tridentate Phosphine Ligand

Iron-catalyzed C–H functionalization of aromatics has attracted widespread attention from chemists in recent years, while the requirement of an elaborate directing group on the substrate has so far hampered the use of simple aromatic carbonyl compounds such as benzoic acid and ketones, much reducing its synthetic utility. We describe here a combination of a mildly reactive methylaluminum reagent and a new tridentate phosphine ligand for metal catalysis, 4-(bis­(2-(diphenyl­phosphanyl)­phenyl)­phosphanyl)-<i>N</i>,<i>N</i>-dimethyl­aniline (Me₂N-TP), that allows us to convert an <i>ortho</i> C–H bond to a C–CH₃ bond in aromatics and heteroaromatics bearing simple carbonyl groups under mild oxidative conditions. The reaction is powerful enough to methylate all four <i>ortho</i> C–H bonds in benzophenone. The reaction tolerates a variety of functional groups, such as boronic ester, halide, sulfide, heterocycles, and enolizable ketones

Photoredox/Brønsted Acid Co-Catalysis Enabling Decarboxylative Coupling of Amino Acid and Peptide Redox-Active Esters with N‑Heteroarenes

An iridium photoredox catalyst in combination with a phosphoric acid catalyzes the decarboxylative α-aminoalkylation of natural and unnatural α-amino acid-derived redox-active esters (<i>N</i>-hydroxyphthalimide esters) with a broad substrate scope of N-heteroarenes at room temperature under irradiation. Dipeptide- and tripeptide-derived redox-active esters are also amenable substrates to achieve decarboxylative insertion of a N-heterocycle at the C-terminal of peptides, yielding molecules that have potential medicinal applications. The key factors for the success of this reaction are the following: use of a photoredox catalyst of suitable redox potential to controllably generate α-aminoalkyl radicals, without overoxidation, and an acid cocatalyst to increase the electron deficiency of N-heteroarenes

Irradiation-Induced Palladium-Catalyzed Decarboxylative Heck Reaction of Aliphatic <i>N</i>‑(Acyloxy)­phthalimides at Room Temperature

It is reported that Pd­(PPh₃)₂Cl₂ in combination with 4,5-bis­(diphenyl­phosphino)-9,9-dimethyl­xanthene (Xantphos) under irradiation of blue LEDs efficiently catalyzes a decarboxylative Heck reaction of vinyl arenes and vinyl heteroarenes with aliphatic <i>N</i>-(acyloxy)­phthalimides at room temperature. A broad scope of secondary, tertiary, and quaternary carboxylates, including α-amino acid derived esters, can be applied as amenable substrates with high stereoselectivity. The experimental observation was explained by excitation-state reactivity of the palladium complex under irradiation to induce single-electron transfer to activate <i>N</i>-(acyloxy)­phthalimides, and to suppress undesired β-hydride elimination of alkyl palladium intermediates

β‑Arylation of Carboxamides via Iron-Catalyzed C(sp³)–H Bond Activation

A 2,2-disubstituted propionamide bearing an 8-aminoquinolinyl group as the amide moiety can be arylated at the β-methyl position with an organozinc reagent in the presence of an organic oxidant, a catalytic amount of an iron salt, and a biphosphine ligand at 50 °C. Various features of selectivity and reactivity suggest the formation of an organometallic intermediate via rate-determining C–H bond cleavage rather than a free-radical-type reaction pathway

Iron-Catalyzed C(sp²)–H Bond Functionalization with Organoboron Compounds

We report here that an iron-catalyzed directed C–H functionalization reaction allows the coupling of a variety of aromatic, heteroaromatic, and olefinic substrates with alkenyl and aryl boron compounds under mild oxidative conditions. We rationalize these results by the involvement of an organoiron­(III) reactive intermediate that is responsible for the C–H bond-activation process. A zinc salt is crucial to promote the transfer of the organic group from the boron atom to the iron­(III) atom

Iron/Zinc-Co-catalyzed Directed Arylation and Alkenylation of C(sp³)–H Bonds with Organoborates

An iron­(III) salt, (<i>Z</i>)-1,2-bis­(diphenylphosphino)­ethene or its electron-rich congener, (<i>Z</i>)-1,2-bis­[bis­(4-methoxyphenyl)­phosphine]­ethene, and a zinc­(II) salt catalyze the arylation, heteroarylation, and alkenylation of propionamides possessing an 8-quinolylamide group with organoborate reagents in the presence of 1,2-dichlorobutane as oxidant at 70 °C. Stoichiometric experiments provided evidence for the involvement of an organoiron­(III) species as a key intermediate for C–H activation and C–C bond formation

Iron-Catalyzed 5‑Endo-Dig Synthetic Approach to Indenes and Its Bidirectional Extension to Narrow Bandgap π‑Systems

The indene skeleton is a key structure in a variety of compounds, with applications in medicinal and materials science. Traditional syntheses often require harsh conditions or reactive intermediates due to the temporary disruption of the aromaticity of the developing indene ring. To circumvent this problem, we have investigated iron-catalyzed 5-endo-dig cyclization for the construction of the five-membered carbocycle component of indene, which does not interrupt the benzene ring’s aromaticity. A reduced iron reactive species generated by the reduction of FeCl2 with metallic magnesium is a key reactive species that effectively cleaves the C–O bond in the starting material to generate a dormant radical-stabilized iron, which smoothly undergoes the 5-endo-dig closure of an indene ring. The synthetic conditions are so mild that we synthesized a high highest occupied molecular orbital (HOMO), narrow bandgap conjugated compound that has a HOMO level as high as −4.59 eV and an optical bandgap of 1.50 eV; hence, it is unstable even under air