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.     

Rhodium(III)‐Catalyzed Redox‐Neutral Coupling of α‐Trifluoromethylacrylic Acid with Benzamides through Directed C−H Bond Cleavage

A rhodium(III)‐catalyzed redox‐neutral coupling of α‐trifluoromethylacrylic acid with bezamides proceeds smoothly accompanied by amide‐directed C?H bond cleavage to produce β‐[2‐(aminocarbonyl)phenyl]‐α‐trifluoromethylpropanoic acid derivatives. One of the products can be transformed to a trifluoromethyl substituted heterocyclic compound. In addition, the redox‐neutral coupling of α‐trifluoromethylacrylic acid with related aromatic substrates possessing a nitrogen‐containing directing group can also be conducted under similar conditions.     

Rhodium‐Catalyzed Remote C(sp3)−H Borylation of Silyl Enol Ethers

A rhodium‐catalyzed remote C(sp³)?H borylation of silyl enol ethers (SEEs, E/Z mixtures) by alkene isomerization and hydroboration is reported. The reaction exhibits mild reaction conditions and excellent functional‐group tolerance. This method is compatible with an array of SEEs, including linear and branched SEEs derived from aldehydes and ketones, and provides direct access to a broad range of structurally diverse 1,n‐borylethers in excellent regioselectivities and good yields. These compounds are precursors to various valuable chemicals, such as 1,n‐diols and aminoalcohols.     

Rhodium‐Catalyzed Electrooxidative C−H Olefination of Benzamides

Metal‐catalyzed chelation‐assisted C?H olefinations have emerged as powerful tools for the construction of functionalized alkenes. Herein, we describe the rhoda‐electrocatalyzed C?H activation/alkenylation of arenes. The olefinations of challenging electron‐poor benzamides were thus accomplished in a fully dehydrogenative fashion under electrochemical conditions, avoiding stoichiometric chemical oxidants, and with H₂ as the only byproduct. This versatile alkenylation reaction also features broad substrate scope and used electricity as a green oxidant.     

Rhodium‐Catalyzed C(sp2)‐ or C(sp3)−H Bond Functionalization Assisted by Removable Directing Groups

In recent years, transition‐metal‐catalyzed C?H activation has become a key strategy in the field of organic synthesis. Rhodium complexes are widely used as catalysts in a variety of C?H functionalization reactions because of their high reactivity and selectivity. The availability of a number of rhodium complexes in various oxidation states enables diverse reaction patterns to be obtained. Regioselectivity, an important issue in C?H activation chemistry, can be accomplished by using a directing group to assist the reaction. However, to obtain the target functionalized compounds, it is also necessary to use a directing group that can be easily removed. A wide range of directed C?H functionalization reactions catalyzed by rhodium complexes have been reported to date. In this Review, we discuss Rh‐catalyzed C?H functionalization reactions that are aided by the use of a removable directing group such as phenol, amine, aldehyde, ketones, ester, acid, sulfonic acid, and N‐heteroaromatic derivatives.     

Cobalt‐Catalyzed Coupling of Benzoic Acid C−H Bonds with Alkynes,Styrenes, and 1,3‐Dienes

A method for cobalt‐catalyzed, carboxylate‐directed functionalization of arene C?H bonds is reported. Alkynes, styrenes, and 1,3‐dienes can be coupled with benzoic acids to provide cyclic products in good yields. The reactions proceed in the presence of a cobalt(II) hexafluoroacetylacetonate catalyst, (TMS)₂NH base, Ce(SO₄)₂ cooxidant, and oxygen oxidant.     

Cobalt‐Catalyzed Tandem C−H Activation/C−C Cleavage/C−H Cyclization of Aromatic Amides with Alkylidenecyclopropanes

A cobalt‐catalyzed chelation‐assisted tandem C?H activation/C?C cleavage/C?H cyclization of aromatic amides with alkylidenecyclopropanes is reported. This process allows the sequential formation of two C?C bonds, which is in sharp contrast to previous reports on using rhodium catalysts for the formation of C?N bonds. Here the inexpensive catalyst system exhibits good functional‐group compatibility and relatively broad substrate scope. The desired products can be easily transformed into polycyclic lactones with m‐CPBA. Mechanistic studies revealed that the tandem reaction proceeds through a C?H cobaltation, β‐carbon elimination, and intramolecular C?H cobaltation sequence.     

Divergent and Stereoselective Synthesis of β‐Silyl‐α‐Amino Acids through Palladium‐Catalyzed Intermolecular Silylation of Unactivated Primary and Secondary C−H Bonds

A general and practical Pd^II‐catalyzed intermolecular silylation of primary and secondary C?H bonds of α‐amino acids and simple aliphatic acids is reported. This method provides divergent and stereoselective access to a variety of optical pure β‐silyl‐α‐amino acids, which are useful for genetic technologies and proteomics. It can also be readily performed on a gram scale and the auxiliary can be easily removed with retention of configuration. The synthetic importance of this method is further demonstrated by the late‐stage functionalization of biological small molecules, such as (?)‐santonin and β‐cholic acid. Moreover, several key palladacycles were successfully isolated and characterized to elucidate the mechanism of this β?C(sp³)‐H silylation process.     

Electrooxidative Rhodium‐Catalyzed C−H/C−H Activation: Electricity as Oxidant for Cross‐Dehydrogenative Alkenylation

Rhodium(III) catalysis has enabled a plethora of oxidative C?H functionalizations, which predominantly employ stoichiometric amounts of toxic and/or expensive metal oxidants. In contrast, we herein describe the first electrochemical rhodium‐catalyzed C?H activation that avoids hazardous chemical oxidants. Environmentally benign twofold C?H/C?H functionalizations were accomplished with weakly coordinating benzoic acids and benzamides, employing electricity as the terminal oxidant and generating H₂ as the sole byproduct.     

Rhodium(III)‐Catalyzed Annulation of 2‐Alkenyl Anilides with Alkynes through C−H Activation: Direct Access to 2‐Substituted Indolines

A Rh^III complex featuring an electron‐deficient η⁵‐cyclopentadienyl ligand catalyzed an unusual annulation between alkynes and 2‐alkenyl anilides to form synthetically appealing 2‐substituted indolines. Formally, the process can be viewed as an allylic amination with concomitant hydrocarbonation of the alkyne. Mechanistic experiments indicate that this transformation involves an unusual rhodium migration with a concomitant 1,5‐H shift.     

Rhodium‐Catalyzed Intramolecular C−H Silylation by Silacyclobutanes

Silacyclobutane was discovered to be an efficient C?H bond silylation reagent. Under the catalysis of Rh^I/TMS‐segphos, silacyclobutane undergoes sequential C?Si/C?H bond activations, affording a series of π‐conjugated siloles in high yields and regioselectivities. The catalytic cycle was proposed to involve a rarely documented endocyclic β‐hydride elimination of five‐membered metallacycles, which after reductive elimination gave rise to a Si?Rh^I species that is capable of C?H activation.     

Manganese‐Catalyzed Redox‐Neutral C−H Olefination of Ketones with Unactivated Alkenes

Since 1987, stoichiometric cyclomanganation of ketones and subsequent reactions with olefins in the presence of either palladium salts or trimethylamine N‐oxide (Me₃N⁺O^?) have been reported, but the catalytic versions remain untouched so far. Herein, the first manganese‐catalyzed redox‐neutral C?H olefination of ketones with unactivated alkenes is described, and shows a distinct reactivity with its parent stoichimetric reactions. Remarkably, mechanistic experiments and DFT calculations uncovers a unique concerted bis‐metalation deprotonation (CBMD) mechanism of the Mn‐Zn‐enabled C?H bond activation.     

Enantioselective C−H Olefination of α‐Hydroxy and α‐Amino Phenylacetic Acids by Kinetic Resolution

Significant progress has been made in the past decade regarding the development of enantioselective C?H activation reactions by desymmetrization. However, the requirement for the presence of two chemically identical prochiral C?H bonds represents an inherent limitation in scope. Reported is the first example of kinetic resolution by a palladium(II)‐catalyzed enantioselective C?H activation and C?C bond formation, thus significantly expanding the scope of enantioselective C?H activation reactions.     

Palladium‐Catalyzed C−H Functionalization of Phenyl 2‐Pyridylsulfonates

An efficient palladium(II)‐catalyzed intermolecular direct ortho ‐alkenylation and acetoxylation of phenols has been developed. The reaction proceeded via a seven‐membered cyclopalladated intermediate and showed complete regio‐ and diastereoselectivity. The approach also provided an efficient route for the synthesis of coumarins and benzofurans.     

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.     

Origin of the Ability of α‐Fe2O3 Mesopores to Activate C−H Bonds in Methane

Methane is a most abundant and inexpensive hydrocarbon feedstock for the production of chemicals and fuels. However, it is extremely difficult to directly convert methane to higher hydrocarbons because the C?H bonds in methane are the most stable C?H bonds of all hydrocarbons. The activation of the C?H bonds in methane by using an efficient and mild route remains a daunting challenge. Here, we show that the inner surface structures of the pore walls in mesoporous α‐Fe₂O₃ possess excellent catalytic performance for methane activation and convert C?H bonds into the C?O bonds in an O₂ atmosphere at 140 °C. We found that such unusual structures are mainly comprised of turbostratic ribbons and K crystal faces and have higher catalytic activity than the (110) plane. These results are without precedent in the history of catalysis chemistry and will provide a new pathway for designing and preparing highly efficient catalytic materials.     

Ligand‐Enabled β‐Methylene C(sp3)−H Arylation of Masked Aliphatic Alcohols

Despite recent advances, reactivity and site‐selectivity remain significant obstacles for the practical application of C(sp³)?H bond functionalization methods. Here, we describe a system that combines a salicylic‐aldehyde‐derived L,X‐type directing group with an electron‐deficient 2‐pyridone ligand to enable the β‐methylene C(sp³)?H arylation of aliphatic alcohols, which has not been possible previously. Notably, this protocol is compatible with heterocycles embedded in both alcohol substrates and aryl coupling partners. A site‐ and stereo‐specific annulation of dihydrocholesterol and the synthesis of a key intermediate of englitazone illustrate the practicality of this method.     

Rhodium‐Catalyzed Regioselective Hydroxylation of Cage B−H Bonds of o‐Carboranes with O2 or Air

A rhodium‐catalyzed hydroxylation of a cage B4?H bond in o‐carboranes with either O₂ or air as the oxygen source is described, and serves as a new methodology for the regioselective generation of a series of 4‐OH‐o‐carboranes in a one‐pot process. The use of either O₂ or air as both the oxidant and the oxygen source makes this protocol very environmentally friendly and practical.     

Intermolecular Amination of Unactivated C(sp3)−H Bonds with Cyclic Alkylamines: Formation of C(sp3)−N Bonds through Copper/Oxygen‐Mediated C(sp3)−H/N−H Activation

The first example of intermolecular amination of unactivated C(sp³)?H bonds by cyclic alkylamines mediated by Cu(OAc)₂/O₂ is reported. This method avoids the use of benzoyloxyamines as the aminating reagent, which are normally prepared from alkylamines in extra steps. A variety of unnatural β^{2, 2}‐amino acid analogues are synthesized by this simple and efficient procedure. This approach offers a solution to the previous unmet challenge of C(sp³)?H/N?H activation for the formation of C(sp³)?N bonds.     

Chiral Carboxylic Acid Enabled Achiral Rhodium(III)‐Catalyzed Enantioselective C−H Functionalization

Reported is an achiral Cp^xRh^III/chiral carboxylic acid catalyzed asymmetric C?H alkylation of diarylmethanamines with a diazomalonate, followed by cyclization and decarboxylation to afford 1,4‐dihydroisoquinolin‐3(2H)‐one. Secondary alkylamines as well as nonprotected primary alkylamines underwent the transformation with high enantioselectivities (up to 98.5:1.5 e.r.) by using a newly developed chiral carboxylic acid as the sole source of chirality to achieve enantioselective C?H cleavage by a concerted metalation‐deprotonation mechanism.