Selective Mono-Defluorinative Cross-Coupling of Trifluoromethyl arenes via Multiphoton Photoredox Catalysis.

A new cross-coupling of trifluoromethyl arenes has been realized via multiphoton photoredox catalysis. Trifluoromethyl arenes were demonstrated to undergo selective mono-defluorinative alkylation under mild reaction conditions providing access to a series of valuable α,α-difluorobenzylic compounds. The reaction shows broad substrate scope and general functional group tolerance. In addition to the electron-deficient trifluoromethyl arenes that are easily reduced to the corresponding radical anion, more challenging electron-rich substrates were also successfully applied. Steady-State Stern-Volmer quenching studies indicated that the trifluoromethyl arenes were reduced by the multiphoton excited Ir-based photocatalyst.

Aza-Ortho-Quinone Methides as Reactive Intermediates: Generation and Utility in Contemporary Asymmetric Synthesis.

The aza-ortho-quinone methide (aza-o-QM) chemistry has overwhelmingly progressed in the past few decades. This review aims to integrate various transition metal-catalyzed and organocatalytic strategies in taming aza-o-QM intermediates, including the aza-ortho-vinylidene quinone methide (aza-o-VQM), aza-ortho-alkynyl quinone methide (aza-o-AQM), aza-para-quinone methide (aza-p-QM), and indole-based aza-o-QM analog. These transient species are often utilized for the direct and enantioselective synthesis of complex (hetero)polycyclic or fused-ring molecular scaffolds such as tetrahydroquinoline and indoline, among others, which are abundant in many natural products, bioactive compounds, and pharmaceuticals.

Desulfurative Ni-Catalyzed Reductive Cross-Coupling of Benzyl Mercaptans/Mercaptoacetates with Aryl Halides.

The C-S activation and sulfur removal from native thiols is challenging, which limits their application as feedstock materials in organic synthesis despite their natural abundance. Herein, we introduce a per-/polyfluoroaryl moiety, which serves as a redox-active scaffold, into sp3-hybridized thiols to activate the C-S bond. Using a Ni catalyst with MgBr2 as an additive, the S group can be removed to yield an aliphatic radical that can react with an aryl halide in a reductive cross-coupling.

Reductive Cross-Coupling of α-Oxy Halides Enabled by Thermal Catalysis, Photocatalysis, Electrocatalysis, or Mechanochemistry.

Herein, we report a reductive cross-coupling reaction of α-oxy halides, simply generated from aldehydes, with a series of C(sp2 )- and C(sp)-electrophiles. A wide range of aryl and heteroatom aryl halides, vinyl bromides, alkynyl bromides, and acyl chlorides react with unhindered and hindered aldehyde-derived α-oxy halides by providing protected alcohols as well as α-hydroxy ketones. Noteworthy, the reductive couplings are achieved not only through thermal catalysis with the use of metal reductants but also by photocatalysis, electrochemistry, and mechanochemistry. The unrestricted interchange of the four strategies indicates their underlying mechanistic similarities. The generation of NiI intermediate is proposed to be the key point for ketyl radical formation via a single-electron transfer (SET) event, which was rationalized by an array of control experiments and density functional theory (DFT) calculations.

Nickel-Catalyzed C-S Bond Formation via Decarbonylative Thioetherification of Esters, Amides and Intramolecular Recombination Fragment Coupling of Thioesters.

A nickel catalyzed cross-coupling protocol for the straightforward C-S bond formation has been developed. Various mercaptans and a wide range of ester and amide substrates bearing various substituents were tolerated in this process which afforded products in good to excellent yields. Furthermore, an intramolecular protocol for the synthesis of thioethers starting from thioesters has been developed. The utility of this protocol has been demonstrated in a new synthetic protocol of benzothiophene.

Selective Reductive Removal of Ester and Amide Groups from Arenes and Heteroarenes through Nickel-Catalyzed C-O and C-N Bond Activation.

An inexpensive nickel(II) catalyst and a hydrosilane were used for the efficient reductive defunctionalization of aryl and heteroaryl esters through a decarbonylative pathway. This versatile method could be used for the removal of ester and amide functional groups from various organic molecules. Moreover, a scale-up experiment and a synthetic application based on the use of a removable carboxylic acid directing group highlight the usefulness of this reaction.

Nickel-catalyzed C(sp2)-C(sp3) coupling via photoactive electron donor-acceptor complexes.

We have developed a novel Ni-catalyzed reductive cross-coupling reaction of aryl bromides and alkyl iodides via a photoactive electron donor-acceptor (EDA) complex. This photo-induced process enables the efficient construction of C(sp2)-C(sp3) bonds in the absence of an external photocatalyst. Electronically and structurally diverse aryl bromides, as well as secondary and primary alkyl iodides could undergo this transformation smoothly. Natural product derivatives were employed successfully, and UV-vis spectroscopy was utilized to gain mechanistic insight.

FluoroFusion: NHC-Catalyzed Nucleophilic Aromatic Substitution Reaction Unveils Functional Perfluorinated Diarylmethanones.

A mild, facile, and metal-free approach via the N-heterocyclic carbene-catalyzed SNAr reaction between aryl aldehydes with perfluoroarenes to obtain the coveted functional perfluorinated diarylmethanones is disclosed. This method accommodates a diverse substrate range and exhibits notable tolerance toward various functional groups. Our success in modifying biologically relevant molecules, crafting a fully fluorinated bioisosteric analogue of drug candidate D1, and highlighting the potential of these ketones as valuable electrolyte additives for lithium-ion batteries (LIBs) underscores the versatility of our methodology.

A protocol for the gram-scale synthesis of polyfluoroaryl sulfides via an SNAr step.

Polyfluoroaryl sulfide is one of the prevalent motifs ubiquitous in materials and pharmaceutical chemistry. We herein describe a simple yet efficient procedure for their synthesis from readily available thiols and polyfluoroarenes via an SNAr step. We detail specific steps for a gram-scale preparation of 2-((perfluoropyridin-4-yl)thio)benzo[d]thiazole 3 from mercaptobenzothiazole 1 and pentafluoropyridine 2. For complete details on the use and execution of this protocol, please refer to Liao et al. (2022).1.

Aromatization as an Impetus to Harness Ketones for Metallaphotoredox-Catalyzed Benzoylation/Benzylation of (Hetero)arenes.

Herein we report ketones as feedstock materials in radical cross-coupling reactions under Ni/photoredox dual catalysis. In this approach, simple condensation first converts ketones into prearomatic intermediates that then act as activated radical sources for cross-coupling with aryl halides. Our strategy enables the direct benzylation/benzoylation of (hetero)arenes under mild reaction conditions with high functional group tolerance.

Nickel-catalyzed exo-selective hydroacylation/Suzuki cross-coupling reaction.

The first nickel-catalyzed intramolecular hydroacylation/Suzuki cross coupling cascade of o-allylbenzaldehydes with a broad range of phenylboronic acid neopentyl glycol esters has been developed. This strategy shows high regioselectivity and step economy in the construction of two C-C bonds via aldehyde C-H bond activation, affording valuable indanones with high efficiency.

Nickel-Catalyzed C-CN Bond Formation via Decarbonylative Cyanation of Esters, Amides, and Intramolecular Recombination Fragment Coupling of Acyl Cyanides.

An efficient nickel-catalyzed decarbonylative cyanation reaction which allows the direct functional-group interconversion of readily available esters into the corresponding nitriles was developed. This reaction successfully offers access to structurally diverse nitriles with high efficiency and excellent functional-group tolerance and provides a good alternative to classical synthetic pathways from diazonium salts or organic halide compounds.