Overriding Intrinsic Reactivity in Aliphatic C−H Oxidation: Preferential C3/C4 Oxidation of Aliphatic Ammonium Substrates

The site‐selective C?H oxidation of unactivated positions in aliphatic ammonium chains poses a tremendous synthetic challenge, for which a solution has not yet been found. Here, we report the preferential oxidation of the strongly deactivated C3/C4 positions of aliphatic ammonium substrates by employing a novel supramolecular catalyst. This chimeric catalyst was synthesized by linking the well‐explored catalytic moiety Fe(pdp) to an alkyl ammonium binding molecular tweezer. The results highlight the vast potential of overriding the intrinsic reactivity in chemical reactions by guiding catalysis using supramolecular host structures that enable a precise orientation of the substrates.     

Supramolecular Recognition Allows Remote,Site‐Selective C−H Oxidation of Methylenic Sites in Linear Amines

Site‐selective C−H functionalization of aliphatic alkyl chains is a longstanding challenge in oxidation catalysis, given the comparable relative reactivity of the different methylenes. A supramolecular, bioinspired approach is described to address this challenge. A Mn complex able to catalyze C(sp³)‐H hydroxylation with H₂O₂ is equipped with 18‐benzocrown‐6 ether receptors that bind ammonium substrates via hydrogen bonding. Reversible pre‐association of protonated primary aliphatic amines with the crown ether selectively exposes remote positions (C8 and C9) to the oxidizing unit, resulting in a site‐selective oxidation. Remarkably, such control of selectivity retains its efficiency for a whole series of linear amines, overriding the intrinsic reactivity of C−H bonds, no matter the chain length.     

Bio‐inspired Nonheme Iron Oxidation Catalysis: Involvement of Oxoiron(V) Oxidants in Cleaving Strong C−H Bonds

Nonheme iron enzymes generate powerful and versatile oxidants that perform a wide range of oxidation reactions, including the functionalization of inert C?H bonds, which is a major challenge for chemists. The oxidative abilities of these enzymes have inspired bioinorganic chemists to design synthetic models to mimic their ability to perform some of the most difficult oxidation reactions and study the mechanisms of such transformations. Iron‐oxygen intermediates like iron(III)‐hydroperoxo and high‐valent iron‐oxo species have been trapped and identified in investigations of these bio‐inspired catalytic systems, with the latter proposed to be the active oxidant for most of these systems. In this Review, we highlight the recent spectroscopic and mechanistic advances that have shed light on the various pathways that can be accessed by bio‐inspired nonheme iron systems to form the high‐valent iron‐oxo intermediates.     

Iron and Manganese Catalysts for the Selective Functionalization of Arene C(sp2)−H Bonds by Carbene Insertion

The first examples of the direct functionalization of non‐activated aryl sp² C?H bonds with ethyl diazoacetate (N₂CHCO₂Et) catalyzed by Mn‐ or Fe‐based complexes in a completely selective manner are reported, with no formation of the frequently observed cycloheptatriene derivatives through competing Buchner reaction. The best catalysts are Fe^II or Mn^II complexes bearing the tetradentate pytacn ligand (pytacn= 1‐(2‐pyridylmethyl)‐4,7‐dimethyl‐1,4,7‐triazacyclononane). When using alkylbenzenes, the alkylic C(sp³)?H bonds of the substituents remained unmodified, thus the reaction being also selective toward functionalization of sp² C?H bonds.     

Biologically Inspired C−H and C=C Oxidations with Hydrogen Peroxide Catalyzed by Iron Coordination Complexes

The development of catalysts for the selective oxidation of readily available hydrocarbons or organic precursors into oxygenated products is a long‐standing goal in organic synthesis. In the last decade, some iron coordination complexes have shown the potential to fit this role. These catalysts can mimic the O?O activation mode of far more sophisticated iron oxygenase enzymes, generating powerful yet selective oxidants. In this review, we report state‐of‐the‐art C?H and C=C oxidations catalyzed by non‐heme iron complexes and H₂O₂ as the oxidant. Finally, we briefly describe some novel oxidative reactivity and the perspectives of this chemistry.     

NHC‐Stabilized Iridium Nanoparticles as Catalysts in Hydrogen Isotope Exchange Reactions of Anilines

The preparation of N‐heterocyclic carbene‐stabilized iridium nanoparticles and their application in hydrogen isotope exchange reactions is reported. These air‐stable and easy‐to‐handle iridium nanoparticles showed a unique catalytic activity, allowing selective and efficient hydrogen isotope incorporation on anilines using D₂ or T₂ as isotopic source. The usefulness of this transformation has been demonstrated by the deuterium and tritium labeling of diverse complex pharmaceuticals.     

Oxidation of Alkanes by Periodate Using a MnV Nitrido Complex as Catalyst

The design of catalytic systems that can selectively oxidize unactivated C?H bonds under mild conditions is a challenge to chemists. We report here that the manganese(V) nitrido complex [Mn^V(N)(CN)₄]^2? is a highly efficient catalyst for the oxidation of alkanes by periodate (IO₄^?) at ambient conditions. Excellent yields of alcohols and ketones (>95 %) are obtained with a maximum turnover number (TON) of 3000.     

A Planar‐Chiral Rhodium(III) Catalyst with a Sterically Demanding Cyclopentadienyl Ligand and Its Application in the Enantioselective Synthesis of Dihydroisoquinolones

The rapid development of enantioselective C?H activation reactions has created a demand for new types of catalysts. Herein, we report the synthesis of a novel planar‐chiral rhodium catalyst [(C₅H₂^tBu₂CH₂^tBu)RhI₂]₂ in two steps from commercially available [(cod)RhCl]₂ and tert‐butylacetylene. Pure enantiomers of the catalyst were obtained through separation of its diastereomeric adducts with natural (S)‐proline. The catalyst promoted enantioselective reactions of aryl hydroxamic acids with strained alkenes to give dihydroisoquinolones in high yields (up to 97 %) and with good stereoselectivity (up to 95 % ee).     

C(sp3)−H Functionalizations Promoted by the Gold Carbene Generated from Vinylidenecyclopropanes

The gold carbene generated from vinylidenecyclopropanes (VDCPs) can smoothly perform a C(sp³)?H bond insertion reaction, stereoselectively affording the intramolecular C(sp³)?H bond functionalized product, benzoxepine, with syn‐configuration in moderate to good yields under mild conditions. The KIE investigation on this bond functionalization partially revealed that the carbene insertion step might be rate‐determining. Using a chiral gold(I) catalyst, the first example on the asymmetric variant of gold carbene insertion into C(sp³)?H bond has been disclosed, giving the desired products with excellent results.     

Mononuclear Nonheme High‐Spin (S=2) versus Intermediate‐Spin (S=1) Iron(IV)–Oxo Complexes in Oxidation Reactions

Mononuclear nonheme high‐spin (S=2) iron(IV)–oxo species have been identified as the key intermediates responsible for the C?H bond activation of organic substrates in nonheme iron enzymatic reactions. Herein we report that the C?H bond activation of hydrocarbons by a synthetic mononuclear nonheme high‐spin (S=2) iron(IV)–oxo complex occurs through an oxygen non‐rebound mechanism, as previously demonstrated in the C?H bond activation by nonheme intermediate (S=1) iron(IV)–oxo complexes. We also report that C?H bond activation is preferred over C=C epoxidation in the oxidation of cyclohexene by the nonheme high‐spin (HS) and intermediate‐spin (IS) iron(IV)–oxo complexes, whereas the C=C double bond epoxidation becomes a preferred pathway in the oxidation of deuterated cyclohexene by the nonheme HS and IS iron(IV)–oxo complexes. In the epoxidation of styrene derivatives, the HS and IS iron(IV) oxo complexes are found to have similar electrophilic characters.     

Rhodium‐Catalyzed Enantioselective Silylation of Cyclopropyl C−H Bonds

Hydrosilyl ethers, generated in situ by the dehydrogenative silylation of cyclopropylmethanols with diethylsilane, undergo asymmetric, intramolecular silylation of cyclopropyl C?H bonds in high yields and with high enantiomeric excesses in the presence of a rhodium catalyst derived from a rhodium precursor and the bisphosphine (S)‐DTBM‐SEGPHOS. The resulting enantioenriched oxasilolanes are suitable substrates for the Tamao–Fleming oxidation to form cyclopropanols with conservation of the ee value from the C?H silylation. Preliminary mechanistic data suggest that C?H cleavage is likely to be the turnover‐limiting and enantioselectivity‐determining step.     

Photochemistry of Methane on Pd/Al2O3 Model Catalysts: Control of Photochemistry on Transition Metal Surfaces

The mean size of the Pd clusters deposited on an Al₂O₃ thin film influences the efficiency of photodissociation of CD₄ into CD₃ and D as well as the photodesorpion upon irradiation with 193-nm laser light. The picture shows the degree of desorption on Pd clusters of various sizes (as well as on a Pd(111) single-crystal surface) as a function of temperature; the values given refer to the average thickness of the evaporated metal layer.     

Enantioselective Copper(I)/Chiral Phosphoric Acid Catalyzed Intramolecular Amination of Allylic and Benzylic C−H Bonds

Radical‐involved enantioselective oxidative C?H bond functionalization by a hydrogen‐atom transfer (HAT) process has emerged as a promising method for accessing functionally diverse enantioenriched products, while asymmetric C(sp³)?H bond amination remains a formidable challenge. To address this problem, described herein is a dual Cu^I/chiral phosphoric acid (CPA) catalytic system for radical‐involved enantioselective intramolecular C(sp³)?H amination of not only allylic positions but also benzylic positions with broad substrate scope. The use of 4‐methoxy‐NHPI (NHPI=N‐hydroxyphthalimide) as a stable and chemoselective HAT mediator precursor is crucial for the fulfillment of this transformation. Preliminary mechanistic studies indicate that a crucial allylic or benzylic radical intermediate resulting from a HAT process is involved.     

Cu/Fe Catalyzed Intermolecular Oxidative Amination of Benzylic C−H Bonds

We report a Cu/Fe co‐catalyzed Ritter‐type C?H activation/amination reaction that allows efficient and selective intermolecular functionalization of benzylic C?H bonds. This new reaction is featured by simple reaction conditions, readily available reagents and general substrate scope, allowing facile synthesis of biologically interesting nitrogen containing heterocycles. The Cu and Fe salts were found to play distinct roles in this cooperative catalysis.     

Aromatic Aminocatalysis

Aromatic aminocatalysis refers to transformations that employ aromatic amines, such as anilines or aminopyridines, as catalysts. Owing to the conjugation of the amine moiety with the aromatic ring, aromatic amines demonstrate distinctive features in aminocatalysis compared with their aliphatic counterparts. For example, aromatic aminocatalysis typically proceeds with slower turnover, but is more active and conformationally rigid as a result of the stabilized aromatic imine or iminium species. In fact, the advent of aromatic aminocatalysis can be traced back to before the renaissance of organocatalysis in the early 2000s. So far, aromatic aminocatalysis has been widely applied in bioconjugation reactions through transamination; in asymmetric organocatalysis through imine/enamine tautomerization; and in cooperative catalysis with transition metals through C?H/C?C activation and functionalization. This Focus Review summarizes the advent of and major advances in the use of aromatic aminocatalysis in bioconjugation reactions and organic synthesis.     

Enantioselective Access to 1H‐Isoindoles with Quaternary Stereogenic Centers by Palladium(0)‐Catalyzed C−H Functionalization

A catalytic enantioselective method for the synthesis of chiral 1H‐isoindoles bearing quaternary stereogenic centers is reported. Powered by readily accessible phosphordiamidite ligands, the presented palladium(0)‐catalyzed C?H functionalization uses trifluoroacetimidoyl chlorides as electrophilic components. It delivers previously inaccessible perfluoroalkylated 1H‐isoindoles in high yields and enantioselectivities. The subsequent diastereoselective addition of nucleophiles provides access to densely substituted and sterically hindered isoindolines.