Photoarylation of Iodocarboranes with Unactivated (Hetero)Arenes: Facile Synthesis of 1,2-[(Hetero)Aryl]n-o-Carboranes (n=1,2) and o-Carborane-Fused Cyclics

Photoarylation of iodocarboranes with unactivated arenes/heteroarenes at room temperature has been achieved, for the first time, thus leading to the facile synthesis of a large variety of cage carbon mono(hetero)arylated and di(hetero)arylated o-carboranes. This work represents a clean, efficient, transition-metal-free, and cheap synthesis of functionalized carboranes, which has significant advantages over the known methods.     

Cu‐Mediated Amination of (Hetero)Aryl C−H bonds with NH Azaheterocycles

Direct synthesis of N‐(hetero)arylated heteroarenes has been realized through Cu‐mediated C?N coupling of NH azaheterocycles with aryl C?H bonds under aerobic conditions. This method features a broad scope of both heterocyclic arenes (pyridine, quinoline, pyrazole, imidazole, furan, thiophene, benzofuran, and indole) and NH azaheterocycles (imidazole, pyrazole, indole, azindole, purine, indazole, benzimidazole, pyridone, carbazole), providing a versatile method for the synthesis of pharmaceutically important N‐(hetero)arylated heteroarenes. The versatility of this reaction was further demonstrated through late‐stage modification of marketed drugs and the synthesis of a key intermediate for accessing a class of angiotensin II receptor 1 antagonists.     

Visible‐Light‐Promoted Photocatalytic B−C Coupling via a Boron‐Centered Carboranyl Radical: Facile Synthesis of B(3)‐Arylated o‐Carboranes

A visible‐light‐mediated in situ generation of a boron‐centered carboranyl radical (o‐C₂B₁₀H₁₁ ^. ) has been described. With eosin Y as a photoredox catalyst, 3‐diazonium‐o‐carborane tetrafluoroborate [3‐N₂‐o‐C₂B₁₀H₁₁][BF₄] was converted into the corresponding boron‐centered carboranyl radical intermediate, which can undergo efficient electrophilic substitution reaction with a wide range of (hetero)arenes. This general and simple procedure provides a metal‐free alternative for the synthesis of 3‐(hetero)arylated‐o‐carboranes.     

Palladium‐Catalyzed Synthesis of (Hetero)Aryl Alkyl Sulfones from (Hetero)Aryl Boronic Acids,Unactivated Alkyl Halides,and Potassium Metabisulfite

A palladium‐catalyzed one‐step synthesis of (hetero)aryl alkyl sulfones from (hetero)arylboronic acids, potassium metabisulfite, and unactivated or activated alkylhalides is described. This transformation is of broad scope, occurs under mild conditions, and employs readily available reactants. A stoichiometric experiment has led to the isolation of a catalytically active dimeric palladium sulfinate complex, which was characterized by X‐ray diffraction analysis.     

Palladium‐Catalyzed Synthesis of (Hetero)Aryl Alkyl Sulfones from (Hetero)Aryl Boronic Acids,Unactivated Alkyl Halides,and Potassium Metabisulfite

A palladium‐catalyzed one‐step synthesis of (hetero)aryl alkyl sulfones from (hetero)arylboronic acids, potassium metabisulfite, and unactivated or activated alkylhalides is described. This transformation is of broad scope, occurs under mild conditions, and employs readily available reactants. A stoichiometric experiment has led to the isolation of a catalytically active dimeric palladium sulfinate complex, which was characterized by X‐ray diffraction analysis.     

Nickel‐Catalyzed Cross‐Coupling Reactions of o‐Carboranyl with Aryl Iodides: Facile Synthesis of 1‐Aryl‐o‐Carboranes and 1,2‐Diaryl‐o‐Carboranes

A nickel‐catalyzed arylation at the carbon center of o‐carborane cages has been developed, thus leading to the preparation of a series of 1‐aryl‐o‐carboranes and 1,2‐diaryl‐o‐carboranes in high yields upon isolation. This method represents the first example of transition metal catalyzed C,C′‐diarylation by cross‐coupling reactions of o‐carboranyl with aryl iodides.     

Efficient Electrocatalysis for the Preparation of (Hetero)aryl Chlorides and Vinyl Chloride with 1,2‐Dichloroethane

Although the application of 1,2‐dichloroethane (DCE) as a chlorinating reagent in organic synthesis with the concomitant release of vinyl chloride as a useful byproduct is a fantastic idea, it still presents a tremendous challenge and has not yet been achieved because of the harsh dehydrochlorination conditions and the sluggish C?H chlorination process. Here we report a bifunctional electrocatalysis strategy for the catalytic dehydrochlorination of DCE at the cathode simultaneously with anodic oxidative aromatic chlorination using the released HCl as the chloride source for the efficient synthesis of value‐added (hetero)aryl chlorides. The mildness and practicality of the protocol was further demonstrated by the efficient late‐stage chlorination of bioactive molecules.     

Pd‐Catalyzed Csp2H Functionalization of Heteroarenes via Isocyanide Insertion: Concise Synthesis of Di‐(Hetero)Aryl Ketones and Di‐(Hetero)Aryl Alkylamines

We report herein an efficient Pd‐catalyzed direct C?H bond functionalization of heteroarenes via an isocyanide insertion strategy for the synthesis of di‐(hetero)aryl ketones and di‐(hetero)aryl alkylamines. The methodology involves a three component reaction between an azole, a haloarene and an isocyanide resulting in the formation of an imine, which in turn is either hydrolyzed or reduced to get the desired product.     

Light‐Induced CH Arylation of (Hetero)arenes by In Situ Generated Diazo Anhydrides

Diazo anhydrides (Ar?N?N?O?N?N?Ar) have been known since 1896 but have rarely been used in synthesis. This communication describes the development of a photochemical catalyst‐free C?H arylation methodology for the preparation of bi(hetero)aryls by the one‐pot reaction of anilines with tert‐butyl nitrite and (hetero)arenes under neutral conditions. The key step in this procedure is the in situ formation and subsequent photochemical (>300 nm) homolytic cleavage of a transient diazo anhydride intermediate. The generated aryl radical then efficiently reacts with a (hetero)arene to form the desired bi(hetero)aryls producing only nitrogen, water, and tert‐butanol as byproducts. The scope of the reaction for several substituted anilines and (hetero)arenes was investigated. A continuous‐flow protocol increasing selectivity and safety has been developed enabling the experimentally straightforward preparation of a variety of substituted bi(hetero)aryls within 45 min of reaction time.     

Gold(I)‐catalyzed Benzylation of (Hetero)aryl Boronic Acids with (Hetero)benzyl Bromides by the Strategy of a SN2‐type Reaction

Herein, the first example of gold‐catalyzed benzylation of (hetero)aryl boronic acids with (hetero)benzyl bromides to give the corresponding cross‐coupling products in moderate to good yields is reported. The reaction proceeds through a possible intermolecular S_N2‐type reaction pathway to give a wide variety of di(hetero)arylmethanes as the desired products. An intriguing reaction mechanism has been proposed on the basis of control experiments, ³¹P‐NMR spectroscopic detection and DFT calculations.     

PhPAd‐DalPhos: Ligand‐Enabled,Nickel‐Catalyzed Cross‐Coupling of (Hetero)aryl Electrophiles with Bulky Primary Alkylamines

The base metal‐catalyzed C?N cross‐coupling of bulky α,α,α‐trisubstituted primary alkylamines with (hetero)aryl electrophiles represents a challenging and under‐developed class of transformations that is of significant potential utility, including in the synthesis of lipophilic active pharmaceutical ingredients. Herein, we report that a new, air‐stable Ni(II) pre‐catalyst incorporating the optimized ancillary ligand PhPAd‐DalPhos enables such transformations of (hetero)aryl chloride, bromide, and tosylate electrophiles to be carried out for the first time with substrate scope rivalling that achieved using state‐of‐the‐art Pd catalysts, including room temperature cross‐couplings of (hetero)aryl chlorides that are unprecedented for any catalyst (Pd, Ni, or other).     

PhPAd‐DalPhos: Ligand‐Enabled,Nickel‐Catalyzed Cross‐Coupling of (Hetero)aryl Electrophiles with Bulky Primary Alkylamines

The base metal‐catalyzed C?N cross‐coupling of bulky α,α,α‐trisubstituted primary alkylamines with (hetero)aryl electrophiles represents a challenging and under‐developed class of transformations that is of significant potential utility, including in the synthesis of lipophilic active pharmaceutical ingredients. Herein, we report that a new, air‐stable Ni(II) pre‐catalyst incorporating the optimized ancillary ligand PhPAd‐DalPhos enables such transformations of (hetero)aryl chloride, bromide, and tosylate electrophiles to be carried out for the first time with substrate scope rivalling that achieved using state‐of‐the‐art Pd catalysts, including room temperature cross‐couplings of (hetero)aryl chlorides that are unprecedented for any catalyst (Pd, Ni, or other).     

Exceptionally Long C−C Single Bonds in Diamino‐o‐carborane as Induced by Negative Hyperconjugation

The synthesis of a series of 1,2‐diamino‐o‐carboranes ( 1 – 4 ) is reported. The molecular structures of these diamino‐o‐carboranes are remarkable as the inner‐cluster C?C bonds are all ultra‐long (162.7–193.1 pm) and vary substantially with small variations in the substituents. The results of quantum mechanical investigations suggest that the origin of the bond elongation is significant in‐plane negative hyperconjugation of lone pairs of the nitrogen substituents with the σ* orbitals of the C?C bonds in o‐carboranes.     

Palladium‐Catalyzed Trifluoromethylation of (Hetero)Arenes with CF3Br

The CF₃ group is an omnipresent motif found in many pharmaceuticals, agrochemicals, catalysts, materials, and industrial chemicals. Despite well‐established trifluoromethylation methodologies, the straightforward and selective introduction of such groups into (hetero)arenes using available and less expensive sources is still a major challenge. In this regard, the selective synthesis of various trifluoromethyl‐substituted (hetero)arenes by palladium‐catalyzed C?H functionalization is herein reported. This novel methodology proceeds under comparably mild reaction conditions with good regio‐ and chemoselectivity. As examples, trifluoromethylations of biologically important molecules, such as melatonin, theophylline, caffeine, and pentoxifylline, are showcased.     

Palladium-catalyzed direct (hetero)arylation of ethyl oxazole-4-carboxylate: an efficient access to (hetero)aryloxazoles

A straightforward route toward 2-(hetero)arylated and 2,5-di(hetero)arylated oxazoles through regiocontrolled palladium-catalyzed direct (hetero)arylation of ethyl oxazole-4-carboxylate with iodo-, bromo-, and chloro(hetero)aromatics followed by a two-step hydrolysis/decarboxylation sequence was described. The method was applied here to a neat synthesis of two 2,5-di(hetero)aryloxazole natural products, balsoxin and texaline.     

General Access to Aminobenzyl‐o‐carboranes as a New Class of Carborane Derivatives: Entry to Enantiopure Carborane–Amine Combinations

The convenient synthesis of original aminobenzyl‐o‐carboranes, which represent a new class of nitrogenated carborane derivatives, is described. These novel compounds have been efficiently prepared starting from commercially available aromatic aldehydes and monosubstituted o‐carboranes via carboranyl alcohols and chlorides as intermediates. The key step of this methodology is a selective nucleophilic amination under mild conditions that allows the formation of the expected amines while limiting the partial deboronation of the carborane cluster. This general strategy has been applied to the preparation of a wide variety of aminobenzyl‐o‐carboranes. The extension of this pathway to the synthesis of enantiopure carborane–amine combinations is also described.     

Facial Synthesis of o‐Carborane‐Substituted Alkenes and Allenes by a Regioselective Ene Reaction of 1,3‐Dehydro‐o‐carborane

1,3‐Dehydro‐o‐carborane is a useful synthon for selective cage boron functionalization of o‐carboranes. It reacts readily with alkenes or alkynes to give a variety of cage B(3)‐alkenyl/allenyl o‐carboranes by ene reactions in very high yields and excellent regioselectivity. This can be ascribed to the highly polarized cage C?B multiple bond, which lowers the activation barriers of the ene reaction.     

A Cascade Synthesis of Hetero‐arylated Triarylmethanes Through a Double 5‐endo‐dig Cyclization Sequence

A sequential two‐step method for the synthesis of hetero‐arylated triarylmethanes through a Ag‐catalyzed sequential double cyclization–nucleophilic addition cascade is described. This methodology basically involves an initial 5‐endo‐dig cyclization of o‐alkynyl anilines to provide 2‐substituted indole derivatives, which then react with 2‐(2‐enynyl)‐pyridines to afford indolizine‐containing unsymmetrical triarylmethanes through another 5‐endo‐dig cyclization.     

Rhodium(III)‐Catalyzed ortho CH Heteroarylation of (Hetero)aromatic Carboxylic Acids: A Rapid and Concise Access to π‐Conjugated Poly‐heterocycles

Rh^III‐catalyzed oxidative C? H/C? H cross‐coupling between (hetero)aromatic carboxylic acids and various heteroarenes has been accomplished to construct highly functionalized ortho‐carboxy‐substituted bi(hetero)aryls. The use of a carboxy group as the directing group obviates tedious steps for installation and removal of extra directing groups, and enables a facile one‐step synthesis of ortho‐carboxy bi(hetero)aryls. The method provides opportunities for rapid assembly of a library of important fluorene and coumarin‐type poly‐heterocycles through intramolecular electrophilic substitution or oxidative lactonization. As illustrative examples, the strategy developed herein greatly streamlines accesses to a variety of appealing polyheterocycles such as DTPO (5H‐dithieno[3,2‐b:2′,3′‐d]pyran‐5‐one), CPDTO (cyclopentadithiophen‐4‐one), and indenothiophenes.     

Integrative Self‐Sorting: One‐Pot Synthesis of a Hetero[4]rotaxane from a Daisy‐Chain‐Containing Hetero[4]pseudorotaxane

The structural complexity of mechanically interlocked molecules are very attractive to chemists owing to the challenges they present. In this article, novel mechanically interlocked molecules with a daisy‐chain‐containing hetero[4]rotaxane motif were efficiently synthesized. In addition, a novel integrative self‐sorting strategy is demonstrated, involving an ABB‐type (A for host, dibenzo‐24‐crown‐8 (DB24C8), and B for guest, ammonium salt sites) monomer and a macrocycle host, benzo‐21‐crown‐7 (B21C7), in which the assembled species in hydrogen‐bonding‐supported solvent only includes a novel daisy‐chain‐containing hetero[4]pseudorotaxane. The found self‐sorting process involves the integrative recognition between B21C7 macrocycles and carefully designed components simultaneously containing two types of secondary ammonium ions and a host molecule, DB24C8 crown ether. The self‐sorting strategy is integrative to undertake self‐recognition behavior to form one single species of pseudorotaxane compared with the previous report. This self‐sorting system can be used for the efficient one‐pot synthesis of a daisy‐chain‐containing hetero[4]rotaxane in a good yield. The structure of hetero[4]rotaxane was confirmed by ¹H NMR spectroscopy and high‐resolution electrospray ionization (HR‐ESI) mass spectrometry.