A Pd-catalyzed/N-heterocycle-directed C(sp³)−H olefination has been developed. The monoprotected amino acid ligand (MPAA) is found to significantly promote Pd-catalyzed C(sp³)−H olefination for the first time. Cu(OAc)₂ instead of Ag⁺ salts are used as the terminal oxidant. This reaction provides a useful method for the synthesis of alkylated pyrazoles.

A quinoline-based ligand effectively promotes the palladium-catalyzed borylation of C(sp³)H bonds. Primary β-C(sp³)H bonds in carboxylic acid derivatives as well as secondary C(sp³)H bonds in a variety of carbocyclic rings, including cyclopropanes, cyclobutanes, cyclopentanes, cyclohexanes, and cycloheptanes, can thus be borylated. This directed borylation method complements existing iridium(I)- and rhodium(I)-catalyzed CH borylation reactions in terms of scope and operational conditions.

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.

Pd^II-catalyzed arylation of γ-C(sp³)−H bonds of aliphatic acid-derived amides was developed by using quinoline-based ligands. Various γ-aryl-α-amino acids were prepared from natural amino acids using this method. The influence of ligand structure on reactivity was also systematically investigated.

A quinoline-based ligand effectively promotes the palladium-catalyzed borylation of C(sp³)H bonds. Primary β-C(sp³)H bonds in carboxylic acid derivatives as well as secondary C(sp³)H bonds in a variety of carbocyclic rings, including cyclopropanes, cyclobutanes, cyclopentanes, cyclohexanes, and cycloheptanes, can thus be borylated. This directed borylation method complements existing iridium(I)- and rhodium(I)-catalyzed CH borylation reactions in terms of scope and operational conditions.

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.

Pd^II-catalyzed arylation of γ-C(sp³)−H bonds of aliphatic acid-derived amides was developed by using quinoline-based ligands. Various γ-aryl-α-amino acids were prepared from natural amino acids using this method. The influence of ligand structure on reactivity was also systematically investigated.

meta-CH olefination of phenylacetic acid derivatives has been achieved using a commercially available nitrile-containing template. The identification of N-formyl-protected glycine as the ligand (Formyl-Gly-OH) was crucial for the development of this reaction. Versatility of the template approach in accommodating macrocyclopalladation processes with different ring sizes is demonstrated.

The commonly used para-nitrobenzenesulfonyl (nosyl) protecting group is employed to direct the CH activation of amines for the first time. An enantioselective ortho-CH cross-coupling between nosyl-protected diarylmethylamines and arylboronic acid pinacol esters has been achieved utilizing chiral mono-N-protected amino acid (MPAA) ligands as a promoter.

2,4,6-Trimethoxypyridine is identified as an efficient ligand for promoting a Pd-catalyzed ortho-CH amination of both benzamides and triflyl-protected benzylamines. This finding provides guidance for the development of ligands that can improve or enable Pd^II-catalyzed CH activation reactions directed by weakly coordinating functional groups.

An intermolecular C(sp³)H amination using a Pd⁰/PAr₃ catalyst was developed. The reaction begins with oxidative addition of R₂NOBz to a Pd⁰/PAr₃ catalyst and subsequent cleavage of a C(sp³)H bond by the generated PdNR₂ intermediate. The catalytic cycle proceeds without the need for external oxidants in a similar manner to the extensively studied palladium(0)-catalyzed CH arylation reactions. The electron-deficient triarylphosphine ligand is crucial for this C(sp³)H amination reaction to occur.

The commonly used para-nitrobenzenesulfonyl (nosyl) protecting group is employed to direct the CH activation of amines for the first time. An enantioselective ortho-CH cross-coupling between nosyl-protected diarylmethylamines and arylboronic acid pinacol esters has been achieved utilizing chiral mono-N-protected amino acid (MPAA) ligands as a promoter.

meta-CH olefination of phenylacetic acid derivatives has been achieved using a commercially available nitrile-containing template. The identification of N-formyl-protected glycine as the ligand (Formyl-Gly-OH) was crucial for the development of this reaction. Versatility of the template approach in accommodating macrocyclopalladation processes with different ring sizes is demonstrated.

An intermolecular C(sp³)H amination using a Pd⁰/PAr₃ catalyst was developed. The reaction begins with oxidative addition of R₂NOBz to a Pd⁰/PAr₃ catalyst and subsequent cleavage of a C(sp³)H bond by the generated PdNR₂ intermediate. The catalytic cycle proceeds without the need for external oxidants in a similar manner to the extensively studied palladium(0)-catalyzed CH arylation reactions. The electron-deficient triarylphosphine ligand is crucial for this C(sp³)H amination reaction to occur.

2,4,6-Trimethoxypyridine is identified as an efficient ligand for promoting a Pd-catalyzed ortho-CH amination of both benzamides and triflyl-protected benzylamines. This finding provides guidance for the development of ligands that can improve or enable Pd^II-catalyzed CH activation reactions directed by weakly coordinating functional groups.

Diverse 4-aryl-2-quinolinones are prepared from propionamides in one pot by ligand-promoted triple sequential CH activation reactions and a stereospecific Heck reaction. In these cascade reactions, three new CC bonds and one CN bond are formed to rapidly build molecular complexity from propionic acid.

The direct ortho-trifluoromethylation of arenes, including heteroarenes, with TMSCF₃ has been accomplished by a copper(II)-promoted CH activation reaction which completes within 30 minutes. Mechanistic investigations are consistent with the involvement of CH activation, rather than a simple electrophilic aromatic substitution (S_EAr), as the key step.

A bimetallic Rh^II catalyst promoted the CH alkenylation of simple arenes at 1.0 equivalent without the use of a directing group. A phosphine ligand as well as cooperative reoxidation of Rh^II with Cu(TFA)₂ and V₂O₅ proved essential in providing monoalkenylated products in good yields and selectivities, especially with di- and trisubstituted arenes.

We disclose a protocol for the palladium-catalyzed ortho-selective CH deuteration of arenes. Phenylacetic acids and benzoic acids are suitable substrates for this reaction. This reaction offers a catalytic route to ortho-deuterated phenylacetic acids and benzoic acids and demonstrates the sharp difference in reactivity of palladacycle intermediates held together by weak and strong coordination.

A bimetallic Rh^II catalyst promoted the CH alkenylation of simple arenes at 1.0 equivalent without the use of a directing group. A phosphine ligand as well as cooperative reoxidation of Rh^II with Cu(TFA)₂ and V₂O₅ proved essential in providing monoalkenylated products in good yields and selectivities, especially with di- and trisubstituted arenes.

Diverse 4-aryl-2-quinolinones are prepared from propionamides in one pot by ligand-promoted triple sequential CH activation reactions and a stereospecific Heck reaction. In these cascade reactions, three new CC bonds and one CN bond are formed to rapidly build molecular complexity from propionic acid.

We disclose a protocol for the palladium-catalyzed ortho-selective CH deuteration of arenes. Phenylacetic acids and benzoic acids are suitable substrates for this reaction. This reaction offers a catalytic route to ortho-deuterated phenylacetic acids and benzoic acids and demonstrates the sharp difference in reactivity of palladacycle intermediates held together by weak and strong coordination.

Reductive elimination from partially or completely oxidized metal centers is a vital step in a myriad of carbon–carbon and carbon–heteroatom bond-forming reactions. One strategy for promoting otherwise challenging reductive elimination reactions is to oxidize the metal center using a two-electron oxidant (that is, from M⁽ⁿ⁾ to M⁽ⁿ⁺²⁾). However, many of the commonly used oxidants for this type of transformation contain oxygen, nitrogen, or halogen moieties that are subsequently capable of participating in reductive elimination, thus leading to a mixture of products. In this Minireview, we examine the use of bystanding F⁺ oxidants for addressing this widespread problem in organometallic chemistry and describe recent applications in Pd^II/Pd^IV and Au^I/Au^III catalysis. We then briefly discuss a rare example in which one-electron oxidants have been shown to promote selective reductive elimination in palladium(II)-catalyzed CH functionalization, which we view as a promising future direction in the field.

Die reduktive Eliminierung teils oder vollständig oxidierter Metallzentren ist ein wichtiger Schritt in einer Unzahl von C-C- und C-Heteroatom-Bindungsbildungen. Eine Möglichkeit, anspruchsvolle reduktive Eliminierungen zu erleichtern, besteht in der Oxidation der Metallzentren durch Zwei-Elektronen-Oxidationsmittel (also von Mⁿ zu Mⁿ⁺²). Viele der für diese Umwandlung typischen Oxidationsmittel enthalten allerdings Sauerstoff-, Stickstoff- oder Halogenatome — die sich anschließend an der reduktiven Eliminierung beteiligen könnten —, sodass ein Produktgemisch entstehen würde. In diesem Kurzaufsatz beschreiben wir die Untersuchungen zu einem neuartigen Lösungsansatz für dieses verbreitete Problem in der metallorganischen Chemie: die Verwendung von passiven F⁺-Oxidationsmitteln sowie die jüngsten Anwendungen in Pd^II/Pd^IV- und Au^I/Au^III-Katalysen. Außerdem besprechen wir kurz ein seltenes Beispiel, in dem die Verwendung eines Ein-Elektronen-Oxidationsmittels zur Begünstigung einer selektiven reduktiven Eliminierung bei Palladium(II)-katalysierten C-H-Funktionalisierungen gezeigt werden konnte; dies sehen wir als eine vielversprechende Richtung für zukünftige Anwendungen auf diesem Gebiet an.

Palladium-catalyzed C–H activation/C–C bond-forming reactions have emerged as a promising class of synthetic tools in organic chemistry. Among the many different means of forging C–C bonds using Pd-mediated C–H activation, a new horizon in this field is Pd(II)-catalyzed cross-coupling of C–H bonds with organometallic reagents via a Pd(II)/Pd(0) catalytic cycle. While this type of reaction has proven to be effective for the selective functionalization of aryl C(sp²)–H bonds, the focus of this review is on Pd(II)-catalyzed C(sp³)–H activation/C–C cross-coupling, a topic of particular importance because reactions of this type enable fundamentally new methods for bond construction. Since our laboratory’s initial report on cross-coupling of C–H bonds in 2006, this area has expanded rapidly, and the unique ability of Pd(II) catalysts to cleave and functionalize alkyl C(sp³)–H bonds has been exploited to develop protocols for forming an array of C(sp³)–C(sp²) and C(sp³)–C(sp³) bonds. Furthermore, enantioselective C(sp³)–H activation/C–C cross-coupling has been achieved through the use of chiral amino acid-derived ligands, offering a novel technique for producing enantioenriched molecules. Although this nascent field remains at an early stage of development, further investigations hold the potential to revolutionalize the way in which chiral molecules are synthesized in industrial and academic laboratories.