LongLarf

Defluorinative functionalization of readily accessible trifluoromethyl groups constitutes an economical route to partially fluorinated molecules. However, the controllable replacement of one or two fluorine atoms while maintaining high chemoselectivity remains a formidable challenge. Here we describe a general strategy for sequential carbon-fluorine (C–F) bond functionalizations of trifluoroacetamides and trifluoroacetates. The reaction begins with the activation of a carbonyl oxygen atom by a 4-dimethylaminopyridine-boryl radical, followed by a spin-center shift to trigger the C–F bond scission. A chemoselectivity-controllable two-stage process enables sequential generation of difluoro- and monofluoroalkyl radicals, which are selectively functionalized with different radical traps to afford diverse fluorinated products. The reaction mechanism and the origin of chemoselectivity were established by experimental and computational approaches.

The synthesis of the first homoleptic nickel carbonyl cation [Ni(CO)₄]^.+ and the nickel tricarbonyl-nitrosyl cation [Ni(CO)₃(NO)]⁺ in the condensed phase is reported. They were obtained by oxidation of nickel metal in CO atmosphere and stabilized with a suitable weakly coordinating anion.

Abstract

130 years after Mond discovered the first homoleptic carbonyl complex Ni(CO)₄, we report on a [Ni(CO)₄]^.+ salt as the first synthesis of any homoleptic nickel carbonyl cation in the condensed phase. It was prepared by oxidation of nickel metal with the synergistic oxidant Ag[F{Al(OR^F)₃}₂]/0.5 I₂ (R^F=C(CF₃)₃) in CO atmosphere. This D_2d-symmetric metalloradical represents the last missing entry among the structurally characterized homoleptic carbonyl cations of Groups 6 to 11. Additionally, the nickel tricarbonyl-nitrosyl cation [Ni(CO)₃(NO)]⁺ was obtained by usage of NO[F{Al(OR^F)₃}₂] and all products were fully characterized by means of IR, Raman, NMR/EPR, single crystal and powder XRD.

Coupling runs across water and DES: Scalable Pd‐catalyzed Negishi cross‐couplings between (hetero)aryl bromides and organozinc halides have been developed either by using bulk water, or the choline chloride/urea eutectic mixture as a reaction medium. These processes proceed under mild conditions, short reaction times in air, in the absence of additional ligands, with high chemoselectivity and a broad substrate scope.

Abstract

Pd‐catalyzed Negishi cross‐coupling reactions between organozinc compounds and (hetero)aryl bromides have been reported when using bulk water as the reaction medium in the presence of NaCl or the biodegradable choline chloride/urea eutectic mixture. Both C(sp³)‐C(sp²) and C(sp²)‐C(sp²) couplings have been found to proceed smoothly, with high chemoselectivity, under mild conditions (room temperature or 60 °C) in air, and in competition with protonolysis. Additional benefits include very short reaction times (20 s), good to excellent yields (up to 98 %), wide substrate scope, and the tolerance of a variety of functional groups. The proposed novel protocol is scalable, and the practicability of the method is further highlighted by an easy recycling of both the catalyst and the eutectic mixture or water.

An approach to selectively transform C_γ−H bonds of alicyclic amines to C_γ(sp³)−halogen, oxygen, nitrogen, boron, and sulfur bonds is described. This method is enabled via the pre‐complexation of the amine substrate with palladium followed by the addition of oxidant to yield bioactive motifs functionalized at the γ‐position.

Abstract

This paper describes a new method for the transannular functionalization of the γ‐C−H bonds in alicyclic amines to install C(sp³)−halogen, oxygen, nitrogen, boron, and sulfur bonds. The key challenge for this transformation is controlling the relative rate of C_γ−H versus C_α−H functionalization. We demonstrate that this selectivity can be achieved by pre‐complexation of the substrate with Pd prior to the addition of oxidant. This approach enables the use of diverse oxidants that ultimately install various heteroatom functional groups at the γ‐position with high site‐ and diastereoselectivity.

To expand the current portfolio of saturated, fluorinated carbocycles for drug discovery, a main-group catalysis-based synthesis of novel, trifluorinated tetralins is disclosed. Isosteric replacement of [CH₂−CH₂] by [CF₂−CHF] removes the conformational degeneracy intrinsic to the parent tetralin, since the CH−F bond occupies a pseudo-axial orientation (σ_C−H→σ_C−F*). This provides pre-organised module for contemporary medicinal chemistry.

Abstract

Saturated, fluorinated carbocycles are emerging as important modules for contemporary drug discovery. To expand the current portfolio, the synthesis of novel trifluorinated tetralins has been achieved. Fluorinated methyleneindanes serve as convenient precursors and undergo efficient difluorinative ring expansion with in situ generated p-TolIF₂ (>20 examples, up to >95 %). A range of diverse substituents are tolerated under standard catalysis conditions and this is interrogated by Hammett analysis. X-ray analysis indicates a preference for the CH−F bond to occupy a pseudo-axial orientation, consistent with stabilising σ_C−H→σ_C−F* interactions. The replacement of the symmetric [CH₂−CH₂] motif by [CF₂−CHF] removes the conformational degeneracy intrinsic to the parent tetralin scaffold leading to a predictable half-chair. The conformational behavior of this novel structural balance has been investigated by computational analysis and is consistent with stereoelectronic theory.

The C(sp²−H)‐trifluoromethylation of aromatic aldehyde N‐aminomorpholine hydrazones has been achieved under free‐radical conditions through Cu(II) catalysis using the cost‐effective Langlois reagent (sodium trifluoromethanesulfinate). The reaction tolerates a series of electron‐releasing as well as electron‐withdrawing substituents on the aromatic ring.

Abstract

The C(sp²−H)‐trifluoromethylation of hydrazones would give access to the α‐trifluoromethylated hydrazones that can serve as intermediates in the synthesis of pharmaceutically interesting fluorinated compounds. Herein, we demonstrate the Cu‐catalyzed C(sp²−H)‐trifluoromethylation of the aldehyde hydrazones using the readily available and cost effective Langlois reagent (sodium trifluoromethanesulfinate). This reaction is broadly applicable to a series of aromatic aldehyde N‐aminomorpholine hydrazones to give the corresponding C(sp²)‐trifluoromethyl hydrazones in moderate to high yields. The reaction generally tolerates a series of electron‐releasing as well as electron‐withdrawing substituents on the aromatic ring.

Here we report that attempted preparation of low-valent Ca^I complexes in the form of LCa-CaL (where L is a bulky β-diketiminate ligand) under dinitrogen (N₂) atmosphere led to isolation of LCa(N₂)CaL, which was characterized crystallographically. The N₂² anion in this complex reacted in most cases as a very potent two-electron donor. Therefore, LCa(N₂)CaL acts as a synthon for the low-valent Ca^I complex LCa-CaL, which was the target of our studies. The N₂² anion could also be protonated to diazene (N₂H₂) that disproportionated to hydrazine and N₂. The role of Ca d orbitals for N₂ activation is discussed.

Data Sharing: The German NFDI initiative (National Research Data Infrastructure) aims to create a unique research data infrastructure covering all scientific disciplines. One of the firstly funded consortia, NFDI4Cat (NFDI for Catalysis-related Sciences), proposes a concept that serves all aspects and fields of catalysis research.

Abstract

Modern research methods produce large amounts of scientifically valuable data. Tools to process and analyze such data have advanced rapidly. Yet, access to large amounts of high-quality data remains limited in many fields, including catalysis research. Implementing the concept of FAIR data (Findable, Accessible, Interoperable, Reusable) in the catalysis community would improve this situation dramatically. The German NFDI initiative (National Research Data Infrastructure) aims to create a unique research data infrastructure covering all scientific disciplines. One of the consortia, NFDI4Cat, proposes a concept that serves all aspects and fields of catalysis research. We present a perspective on the challenging path ahead. Starting out from the current state, research needs are identified. A vision for a integrating all research data along the catalysis value chain, from molecule to chemical process, is developed. Respective core development topics are discussed, including ontologies, metadata, required infrastructure, IP, and the embedding into research community. This Concept paper aims to inspire not only researchers in the catalysis field, but to spark similar efforts also in other disciplines and on an international level.

A study on CuH‐ and CuBpin‐catalyzed borylative methylation of alkyl iodides with CO as the C1 source is reported. Various one carbon prolongated alkyl boranes (RCH₂Bpin and RCH(Bpin)₂) were produced in moderate to good yields from the corresponding alkyl iodides (RI). In this cooperative system, CuH reacts with alkyl iodide faster than CuBpin.

Abstract

CuH and CuBpin are versatile catalysts and intermediates in organic chemistry. However, studies that involve both CuH and CuBpin in the same reaction is still rarely reported due to their high reactivity. Now, a study on CuH‐ and CuBpin‐catalyzed borylative methylation of alkyl iodides with CO as the C1 source is reported. Various one carbon prolongated alkyl boranes (RCH₂Bpin and RCH(Bpin)₂) were produced in moderate to good yields from the corresponding alkyl iodides (RI). In this cooperative system, CuH reacts with alkyl iodide faster than CuBpin.

Abstract

Several manganese-PNP pincer catalysts for the formal hydroamination of allylic alcohols are presented. The resulting γ-amino alcohols are selectively obtained in high yields applying Mn-1 in a tandem process under mild conditions.