Synthesis of α‐(Fluorophenyl)pyridine by Palladium‐Catalyzed Cross‐Coupling Reaction

A series of α‐(fluoro‐substituted phenyl)pyridines have been synthesized by means of a palladium‐catalyzed cross‐coupling reaction between fluoro‐substituted phenylboronic acid and 2‐bromopyridine or its derivatives. The reactivities of the phenylboronic acids containing di‐ and tri‐fluoro substituents with α‐pyridyl bromide were investigated in different catalyst systems. Unsuccessful results were observed in the Pd/C and PPh₃ catalyst system due to phenylboronic acid containing electron‐withdrawing F atom(s). For the catalyst system of Pd(OAc)₂/PPh₃, the reactions gave moderate yields of 55% –80%, meanwhile, affording 10% –20% of dimerisation (self‐coupling) by‐products, but trace products were obtained in coupling with 2,4‐difluorophenylboronic acids because of steric hinderance. Pd(PPh₃)₄ was more reactive for boronic acids with sterically hindering F atom(s), and the coupling reactions gave good yields of 90% and 91% without any self‐coupling by‐product.     

Palladium‐Catalyzed Chlorocarbonylation of Aryl (Pseudo)Halides Through In Situ Generation of Carbon Monoxide

An efficient palladium‐catalyzed chlorocarbonylation of aryl (pseudo)halides that gives access to a wide range of carboxylic acid derivatives has been developed. The use of butyryl chloride as a combined CO and Cl source eludes the need for toxic, gaseous carbon monoxide, thus facilitating the synthesis of high‐value products from readily available aryl (pseudo)halides. The combination of palladium(0), Xantphos, and an amine base is essential to promote this broadly applicable catalytic reaction. Overall, this reaction provides access to a great variety of carbonyl‐containing products through in situ transformation of the generated aroyl chloride. Combined experimental and computational studies support a reaction mechanism involving in situ generation of CO.     

Visible‐Light‐Induced Palladium‐Catalyzed Generation of Aryl Radicals from Aryl Triflates

A mild visible‐light‐induced Pd‐catalyzed intramolecular C?H arylation of amides is reported. The method operates by cleavage of a C(sp²)?O bond, leading to hybrid aryl Pd‐radical intermediates. The following 1,5‐hydrogen atom translocation, intramolecular cyclization, and rearomatization steps lead to valuable oxindole and isoindoline‐1‐one motifs. Notably, this method provides access to products with readily enolizable functional groups that are incompatible with traditional Pd‐catalyzed conditions.     

Phosphine‐Free Palladium‐Catalyzed Allene Carbopalladation/Allylic Alkylation Domino Sequence: A New Route to 4‐(α‐Styryl) γ‐Lactams

Free to decide : Various 4‐(α‐styryl) γ‐lactams are synthesized in 61–88 % yield by a phosphine‐free palladium‐catalyzed carbopalladation/allylic alkylation domino sequence (see scheme). The cyclization is totally regio‐ and diastereoselective in favor of the 3,4‐trans‐disubstituted γ‐lactam. The process is successfully applied to the synthesis of a new aza analogue of the naturally occurring lignan (+)‐oxo‐parabenzlactone.

     

Synergistic N‐Heterocyclic Carbene/Palladium‐Catalyzed Umpolung 1,4‐Addition of Aryl Iodides to Enals

An umpolung 1,4‐addition of aryl iodides to enals promoted by cooperative (terpy)Pd/NHC catalysis was developed that generates various bioactive β,β‐diaryl propanoate derivatives. This system is not only the first reported palladium‐catalyzed arylation of NHC‐bound homoenolates but also expands the scope of NHC‐induced umpolung transformations. A diverse array of functional groups such as esters, nitriles, alcohols, and heterocycles are tolerated under the mild conditions. This method also circumvents the use of moisture‐sensitive organometallic reagents.     

Palladium‐Catalyzed Synthesis of Ammonium Sulfinates from Aryl Halides and a Sulfur Dioxide Surrogate: A Gas‐ and Reductant‐Free Process

Sulfonyl‐derived functional groups populate a broad range of useful molecules and materials, and despite a variety of preparative methods being available, processes which introduce the most basic sulfonyl building block, sulfur dioxide, using catalytic methods, are rare. Described herein is a simple reaction system consisting of the sulfur dioxide surrogate DABSO, triethylamine, and a palladium(0) catalyst for effective convertion of a broad range of aryl and heteroaryl halides into the corresponding ammonium sulfinates. Key features of this gas‐ and reductant‐free reaction include the low loadings of palladium (1 mol %) and ligand (1.5 mol %) which can be employed, and the use of isopropyl alcohol as both a solvent and formal reductant. The ammonium sulfinate products are converted in situ into a variety of sulfonyl‐containing functional groups, including sulfones, sulfonyl chlorides, and sulfonamides.     

Transfer of Aryl Halide to Alkyl Halide: Reductive Elimination of Alkylhalide from Alkylpalladium Halides Containing syn‐β‐Hydrogen Atoms

β‐Hydride abstraction is a well‐accepted elementary step for catalytic cycles in organometallic chemistry. It is usually anticipated that alkylpalladium halides containing syn‐β‐hydrogen atoms will undergo β‐hydride abstraction to afford the Heck‐type products. However, this study discloses that the above general knowledge is only conditionally correct. Our experimental results demonstrate that the reductive elimination of alkylhalides from alkylpalladium halides containing syn‐β‐hydrogen atoms may surpass the β‐hydride abstraction or even become exclusive in certain cases.     

Single‐Flask Multicomponent Palladium‐Catalyzed α,γ‐Coupling of Ketone Enolates: Facile Preparation of Complex Carbon Scaffolds

A three‐component palladium‐catalyzed reaction sequence has been developed in which γ‐substituted α,β‐unsaturated products are obtained in a single flask by an α‐alkenylation with either a subsequent γ‐alkenylation or γ‐arylation of a ketone enolate. Coupling of a variety of electronically and structurally different components was achieved in the presence of a Pd/Q‐Phos catalyst (2 mol %), usually at 22 °C with yields of up to 85 %. Most importantly, access to these products is obtained in one simple operation in place of employing multiple reactions.     

Direct Access to α,α‐Difluoroacylated Arenes by Palladium‐Catalyzed Carbonylation of (Hetero)Aryl Boronic Acid Derivatives

A palladium‐catalyzed carbonylative coupling of (hetero)aryl boronates or boronic acid salts with carbon monoxide and α‐bromo‐α,α‐difluoroamides and bromo‐α,α‐difluoroesters is described herein. The method is useful for the synthesis of a diverse selection of (hetero)aryl α,α‐difluoro‐β‐ketoamides and α,α‐difluoro‐β‐ketoesters, which are useful building blocks for the generation of functionalized difluoroacylated and difluoroalkyl arenes. The method could be further extended to a one‐pot protocol for the formation of difluoroacetophenones.     

Palladium‐Catalyzed C−H Silylation through Palladacycles Generated from Aryl Halides

A highly efficient palladium‐catalyzed disilylation reaction of aryl halides through C?H activation has been developed for the first time. The reaction has broad substrate scope. A variety of aryl halides can be disilylated by three types of C?H activation, including C(sp²)?H, C(sp³)?H, and remote C?H activation. In particular, the reactions are also unusually efficient. The yields are essentially quantitative in many cases, even in the presence of less than 1 mol % catalyst and 1 equivalent of the silylating reagent under relatively mild conditions. The disilylated biphenyls can be converted into disiloxane‐bridged biphenyls.     

Palladium‐Catalyzed Direct Cross‐Coupling of Carboranyllithium with (Hetero)Aryl Halides

A palladium‐catalyzed direct C‐arylation reaction of readily available cage carboranyllithium reagents with aryl halides has been developed for the first time. This method is applicable to a wide range of aryl halide substrates including aryl iodides, aryl bromides, and heteroaromatic halides.     

1‐Bromo‐2‐(cyclopropylidenemethyl)benzene: A Useful Building Block in the Palladium‐Catalyzed Reaction of 2‐Alkynylbenzenamine

A novel palladium‐catalyzed domino reaction of 1‐bromo‐2‐(cyclopropylidenemethyl)benzene and 2‐alkynylbenzenamine is reported, which generates 2‐(naphthalen‐2‐yl)benzenamines and 5H‐indeno[1,2‐c]quinolines via 6‐endo and 5‐exo cyclization, respectively. The regioselectivity for the final outcome can be affected by phosphine and N‐heterocyclic carbene ligands.