Noncovalent interaction with a spirobipyridine ligand enables efficient iridium-catalyzed C-H activation.

Exploitation of noncovalent interactions for recognition of an organic substrate has received much attention for the design of metal catalysts in organic synthesis. The CH-π interaction is especially of interest for molecular recognition because both the C-H bonds and the π electrons are fundamental properties of organic molecules. However, because of their weak nature, these interactions have been less utilized for the control of organic reactions.

Molybdenum-Quinone-Catalyzed Deoxygenative Coupling of Aromatic Carbonyl Compounds.

In the presence of triphenylphosphine as a mild reductant, the use of catalytic amounts of Mo(CO) and an -quinone ligand enables the intermolecular reductive coupling of aromatic aldehydes and the intramolecular coupling of aromatic ketones to produce functionalized alkenes. Diaryl- and diheteroaryl alkenes are synthesized with high ()-selectivity and a tolerance toward bromide, iodide, and steric hindrance. Intramolecular coupling of dicarbonyl compounds under similar conditions affords mono- and disubstituted phenanthrenes.

Remote steric control for undirected -selective C-H activation of arenes.

Regioselective functionalization of arenes remains a challenging problem in organic synthesis. Steric interactions are often used to block sites adjacent to a given substituent, but they do not distinguish the remaining remote sites. We report a strategy based on remote steric control, whereby a roof-like ligand protects the distant site in addition to the sites, and thereby enables selective activation of carbon-hydrogen (C-H) bonds in the absence of or substituents.

Halogen-sodium exchange enables efficient access to organosodium compounds.

With sodium being the most abundant alkali metal on Earth, organosodium compounds are an attractive choice for sustainable chemical synthesis. However, organosodium compounds are rarely used-and are overshadowed by organolithium compounds-because of a lack of convenient and efficient preparation methods. Here we report a halogen-sodium exchange method to prepare a large variety of (hetero)aryl- and alkenylsodium compounds including tri- and tetrasodioarenes, many of them previously inaccessible by other methods.

Chromium(III)-Catalyzed C(sp)-H Alkynylation, Allylation, and Naphthalenation of Secondary Amides with Trimethylaluminum as Base.

Among base metals used for C-H activation reactions, chromium(III) is rather unexplored despite its natural abundance and low toxicity. We report herein chromium(III)-catalyzed C(sp)-H functionalization of an -position of aromatic and α,β-unsaturated secondary amides using readily available AlMe as a base and using bromoalkynes, allyl bromide, and 1,4-dihydro-1,4-epoxynaphthalene as electrophiles. This redox-neutral reaction taking place at 70-90 °C, requires as low as 1-2 mol % of CrCl or Cr(acac) as a catalyst without any added ligand, and tolerates functional groups such as aryl iodide, boronate, and thiophene groups.

Silylation of Aryl Halides with Monoorganosilanes Activated by Lithium Alkoxide.

Lithium alkoxide activates a monoorganosilane to generate a transient LiH/alkoxysilane complex, which quickly reacts with aryl and alkenyl halides at 25 °C to deliver a diorganosilane product. Experimental and theoretical studies suggest that the reaction includes nucleophilic attack of LiH on the halogen atom of the organic halide to generate a transient organolithium/alkoxysilane intermediate, which undergoes quick carbon-silicon bond formation within the complex.

Manganese-Catalyzed Directed Methylation of C(sp)-H Bonds at 25 °C with High Catalytic Turnover.

We report here a manganese-catalyzed C-H methylation reaction of considerable substrate scope, using MeMgBr, a catalytic amount of MnCl·2LiCl, and an organic dihalide oxidant. The reaction features ambient temperature, low catalyst loading, typically 1%, high catalytic turnover reaching 5.9 × 10, and no need for an extraneous ligand and illustrates a unique catalytic use of simple manganese salts for C-H activation, which so far has relied on catalysis by manganese carbonyls.

Iron-Catalyzed C-H Bond Activation.

Catalytic C-H bond activation, which was an elusive subject of chemical research until the 1990s, has now become a standard synthetic method for the formation of new C-C and C-heteroatom bonds. The synthetic potential of C-H activation was first described for ruthenium catalysis and is now widely exploited by the use of various precious metals. Driven by the increasing interest in chemical utilization of ubiquitous metals that are abundant and nontoxic, iron catalysis has become a rapidly growing area of research, and iron-catalyzed C-H activation has been most actively explored in recent years.

Indole Synthesis via Cyclative Formation of 2,3-Dizincioindoles and Regioselective Electrophilic Trapping.

Upon zincation of two acidic protons attached to the nitrogen and the sp-carbon atoms, a N-protected 2-ethynylaniline cyclizes to a 2,3-dizincioindole at 120 °C. Driven by the energy gain due to formation of two C-Zn bonds, this reaction occurs smoothly without side reactions, although this transformation is intrinsically endothermic in its bare anionic form. The resulting dizinc intermediate can be functionalized with one or two different electrophiles either inter- or intramolecularly on either C or C selectively, depending on the choice of catalyst and the electrophiles.

Iron-Catalyzed Ortho 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)-N,N-dimethylaniline (Me2N-TP), that allows us to convert an ortho 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 ortho C-H bonds in benzophenone.

Oxidative C-H Activation Approach to Pyridone and Isoquinolone through an Iron-Catalyzed Coupling of Amides with Alkynes.

An iron catalyst combined with a mild organic oxidant promotes both C-H bond cleavage and C-N bond formation, and forms 2-pyridones and isoquinolones from an alkene- or arylamide and an internal alkyne, respectively. An unsymmetrical alkyne gives the pyridone derivative with high regioselectivity, this could be due to the sensitivity of the reaction to steric effects because of the compact size of iron.

Iron-Catalyzed Directed C(sp(2))-H and C(sp(3))-H Functionalization with Trimethylaluminum.

Conversion of a C(sp(2))-H or C(sp(3))-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(sp(2))-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-catalyzed directed alkylation of aromatic and olefinic carboxamides with primary and secondary alkyl tosylates, mesylates, and halides.

Alkenes, arenes, and heteroarenes possessing an 8-quinolylamide group as the directing group are alkylated with primary and secondary alkyl tosylates, mesylate, and halides in the presence of Fe(acac)3/diphosphine as a catalyst and ArZnBr as a base. The reaction proceeds stereospecifically for alkene substrates and takes place without loss of regiochemical integrity of the starting secondary tosylate, but with loss of the stereochemistry of the chiral center.

Synthesis of anthranilic acid derivatives through iron-catalyzed ortho amination of aromatic carboxamides with N-chloroamines.

Arenes possessing an 8-quinolinylamide group as a directing group are ortho aminated with N-chloroamines and N-benzoyloxyamines in the presence of an iron/diphosphine catalyst and an organometallic base to produce anthranilic acid derivatives in high yield. The reaction proceeds via iron-catalyzed C-H activation, followed by the reaction of the resulting iron intermediate with N-chloroamine. The choice of the directing group and diphosphine ligand is crucial for obtaining the anthranilic acid derivative with high yield and product selectivity.

Iron-catalyzed ortho-allylation of aromatic carboxamides with allyl ethers.

Arenes possessing an N-(quinolin-8-yl)amide directing group are ortho-allylated with allyl phenyl ether in the presence of an iron/diphosphine catalyst and an organometallic base at 50-70 °C. The reaction proceeds via fast iron-catalyzed C-H activation, followed by reaction of the resulting iron intermediate with the allyl ether in γ-selective fashion.

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 allylic arylation of olefins via C(sp3)-H activation under mild conditions.

An aryl Grignard reagent in the presence of mesityl iodide converts an allylic C-H bond of a cycloalkene or an allylbenzene derivative into a C-C bond in the presence of a catalytic amount of Fe(acac)(3) and a diphosphine ligand at 0 °C. The stereo- and regioselectivity of the reaction, together with deuterium labeling experiments, suggest that C-H bond activation is the slow step in the catalytic cycle preceding the formation of an allyliron intermediate.

Nickel-catalyzed synthesis of diarylamines via oxidatively induced C-N bond formation at room temperature.

A nickel-catalyzed oxidative coupling of zinc amides with organomagnesium compounds selectively produces diarylamines under mild reaction conditions, with tolerance for chloride, bromide, hydroxyl, ester, and ketone groups. A diamine is bis-monoarylated. A bromoaniline undergoes N-arylation followed by Kumada-Tamao-Corriu coupling in one pot.

Iron-catalyzed chemo- and stereoselective hydromagnesiation of diarylalkynes and diynes.

Diarylalkynes are chemo- and stereoselectively hydromagnesiated in high yields at room temperature with an iron species generated in situ from FeCl(2)and EtMgBr. Functional groups such as bromide, iodide, amine, phenoxide, and alkene are well tolerated. Under similar conditions, diynes are chemo-, regio-, and stereoselectively hydromagnesiated.

Nickel-catalyzed monosubstitution of polyfluoroarenes with organozinc reagents using alkoxydiphosphine ligand.

A new diphosphine (POP) ligand bearing an alkoxide group allows us to synthesize partially fluorinated arenes. A nickel-catalyzed cross-coupling between a polyfluoroarene and an organozinc reagent in the presence of POP selectively produces a monosubstitution product. Aryl and alkylzinc reagents smoothly take part in the reaction.

Iron-catalyzed regio- and stereoselective chlorosulfonylation of terminal alkynes with aromatic sulfonyl chlorides.

Terminal alkynes react with aromatic sulfonyl chlorides in the presence of an iron(II) catalyst and a phosphine ligand to give (E)-β-chlorovinylsulfones with 100% regio- and stereoselectivity. Various functional groups, such as chloride, bromide, iodide, nitro, ketone, and aldehyde, are tolerated under the reaction conditions. Addition of tosyl chloride to a 1,6-enyne followed by radical 5-exo-trig cyclization gave an exocyclic alkenylsulfone.

Iron-catalyzed oxidative monoarylation of primary amines with organozinc reagents.

The reaction of a primary zinc amide with a diorganozinc reagent gives a secondary amine in the presence of Fe(acac)(3) as a catalyst and 1,2-dichloroisobutane (DCIB) as an oxidant. Halogen groups such as F, Cl, Br, and I are tolerated well. The dichloride oxidant and heat are essential to achieve the C-N bond formation presumably from a catalytic iron intermediate species bearing aryl and amido groups.

Synthesis of functionalized 1H-indenes via copper-catalyzed arylative cyclization of arylalkynes with aromatic sulfonyl chlorides.

A variety of polysubstituted 1H-indenes can be prepared through the copper-catalyzed arylative cyclization of simple arylalkynes with commercially available aromatic sulfonyl chlorides that function as an aryl group donor. The reaction tolerates a broad range of functional groups, including bromide and iodide, nitrile, ketone, and nitro groups. The reaction allowed the synthesis of polycyclic aromatic hydrocarbons, such as a bis(indene), indacene, and fused polyarene derivatives, some of them showing strong fluorescence in solution and the solid state.

Iron-catalyzed C-H bond activation for the ortho-arylation of aryl pyridines and imines with Grignard reagents.

Direct arylation of the ortho-C-H bond of an aryl pyridine or an aryl imine with an aryl Grignard reagent has been achieved by using an iron-diamine catalyst and a dichloroalkane as an oxidant in a short reaction time (e.g., 5 min) under mild conditions (0 °C).