Nickel‐Catalyzed Cross‐Electrophile Coupling of Aryl Bromides with Pyrimidin‐2‐yl Tosylates

A new protocol for the NiCl₂ ‐catalyzed cross‐electrophile coupling of aryl bromides with pyrimidin‐2‐yl tosylates to give the corresponding C2 ‐arylation pyrimidine derivatives has been developed. This study provides an improvement over previous methods by using pyrimidin‐2‐yl tosylates instead of halides as coupling partners that are stable and easily available.     

Cross‐Electrophile Coupling of Vinyl Halides with Alkyl Halides

An improved method for the reductive coupling of aryl and vinyl bromides with alkyl halides that gave high yields for a variety of substrates at room temperature with a low (2.5 to 0.5 mol %) catalyst loading is presented. Under the optimized conditions, difficult substrates, such as unhindered alkenyl bromides, can be coupled to give the desired olefins with minimal diene formation and good stereoretention. These improved conditions also worked well for aryl bromides. For example, a gram‐scale reaction was demonstrated with 0.5 mol % catalyst loading, whereas reactions at 10 mol % catalyst loading completed in as little as 20 minutes. Finally, a low‐cost single‐component pre‐catalyst, (bpy)NiI₂ (bpy=2,2′‐bipyridine) that is both air‐ and moisture‐stable over a period of months was introduced.     

Ligand‐Promoted Oxidative Cross‐Coupling of Aryl Boronic Acids and Aryl Silanes by Palladium Catalysis

The first cross‐coupling reaction between aryl silanes and aryl boronic acids is described. This transformation represents one of the very few examples of coupling reactions between two nucleophilic organometallic reagents and provides a new method for the formation of biaryl compounds. The successful development of this reaction was enabled by the use of commercially available 2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl (BINAP) as the ligand. A small amount of BINAP (3 mol %) was sufficient to suppress the formation of the homocoupling products, and the reaction yielded the cross‐coupling products with high selectivity under mild conditions, even when the ratio of the two coupling partners was 1:1.     

Ligand‐Assisted Gold‐Catalyzed Cross‐Coupling with Aryldiazonium Salts: Redox Gold Catalysis without an External Oxidant

Gold‐catalyzed C(sp)–C(sp²) and C(sp²)–C(sp²) cross‐coupling reactions are accomplished with aryldiazonium salts as the coupling partner. With the assistance of bpy ligand, gold(I) species were oxidized to gold(III) by diazonium without any external oxidants. Monitoring the reaction with NMR and ESI‐MS provided strong evidence for the nitrogen extrusion followed by Au^III reductive elimination as the key step.     

Gold‐Catalyzed Homogeneous Oxidative Cross‐Coupling Reactions

Oxidizing gold? A gold(I)/gold(III) catalytic cycle is essential for the first oxidative cross‐coupling reaction in gold catalysis. By using Selectfluor for gold(I) oxidation, this chemistry reveals the synthetic potential of incorporating gold(I)/gold(III) catalytic cycles into contemporary gold chemistry and promises a new area of gold research by merging powerful gold catalysis and oxidative metal‐catalyzed cross‐coupling reactions.

     

Double Heck Cross‐Coupling Reactions of Dibrominated Pyridines

Double Heck cross‐coupling reactions of 2,3‐ and 3,5‐dibromopyridine with various alkenes afforded the corresponding novel di(alkenyl)pyridines. The Heck reaction of 2,5‐dibromopyridine unexpectedly afforded 5,5′‐di(alkenyl)‐2,2′‐bipyridines by palladium‐catalyzed dimerization to give 5,5′‐dibromo‐2,2′‐bipyridine and subsequent twofold Heck reaction.     

A Highly Efficient and Selective Aerobic Cross‐Dehydrogenative‐Coupling Reaction Photocatalyzed by a Platinum(II) Terpyridyl Complex

Thanks to the superior redox potential of platinum(II) complex compared with that of Ru(bpy)₃²⁺ in the excited state, an efficient and selective visible‐light‐induced CDC reaction has been developed by using a catalytic amount (0.25 %) of 1 . With the aid of FeSO₄ (2 equiv), the corresponding amide could not be detected under visible‐light irradiation (λ=450 nm), but the desired cross‐coupling product was exclusively obtained under ambient air conditions. A spectroscopic study and product analysis revealed that the CDC reaction is initiated by photoinduced electron‐transfer from N‐phenyltetrahydroisoquinoline to the complex. An EPR (electron paramagnetic resonance) experiment provides direct evidence on the generation of superoxide radical anion (O₂^{? .} ) rather than singlet oxygen (¹O₂) under irradiation of the reaction system, in contrast to that reported in the literature. Combined, the photoinduced electron‐transfer and subsequent formation of superoxide radical anion (O₂^{? .} ) results in a clean and facile transformation.     

Significant Enhancement in the Efficiency and Selectivity of Iron‐Catalyzed Oxidative Cross‐Coupling of Phenols by Fluoroalcohols

Significant enhancement of both the rate and the chemoselectivity of iron‐catalyzed oxidative coupling of phenols can be achieved in fluorinated solvents, such as 1,1,1,3,3,3‐hexafluoropropan‐2‐ol (HFIP), 2,2,2‐trifluoroethanol (TFE), and 1‐phenyl‐2,2,2‐trifluoroethanol. The generality of this effect was examined for the cross‐coupling of phenols with arenes and polycyclic aromatic hydrocarbons (PAHs) and of phenol with β‐dicarbonyl compounds. The new conditions were utilized in the synthesis of 2′′′‐dehydroxycalodenin B in only four synthetic steps.     

Single‐Electron Transmetalation: Synthesis of 1,1‐Diaryl‐2,2,2‐trifluoroethanes by Photoredox/Nickel Dual Catalytic Cross‐Coupling

Novel methods for the incorporation of fluorinated subunits into organic frameworks are important in pharmaceutical, agrochemical, and materials science applications. Herein, the first method for the cross‐coupling of benzylic α‐trifluoromethylated alkylboron reagents with (hetero)aryl bromides is achieved through application of a photoredox/nickel dual catalytic system. The harsh conditions and high temperatures required by conventional Suzuki‐coupling protocols are avoided by exploitation of an odd‐electron pathway that permits room temperature transmetalation of these recalcitrant reagents. This method represents the first direct and general route for the synthesis of unsymmetrical 1,1‐diaryl‐2,2,2‐trifluoroethanes, thereby providing efficient access to a previously unexplored chemical space.     

Gold(I)‐Catalyzed Diazo Cross‐Coupling: A Selective and Ligand‐Controlled Denitrogenation/Cyclization Cascade

An unprecedented gold‐catalyzed ligand‐controlled cross‐coupling of diazo compounds by sequential selective denitrogenation and cyclization affords N‐substituted pyrazoles in a position‐switchable mode. This novel transformation features selective decomposition of one diazo moiety and simultaneous preservation of the other one from two substrates. Notably, the choice of the ancillary ligand to the gold complex plays a pivotal role on the chemo‐ and regioselectivity of the reactions.     

Coupling of Heteroaryl Halides with Chlorodifluoroacetamides and Chlorodifluoroacetate by Nickel Catalysis

A nickel-catalyzed cross-coupling of heteroaryl halides with chlorodifluoroacetamides and chlorodifluoroacetate has been developed. The combination of NiCl₂ ⋅ DME with 4,4′-diNon-bpy, co-ligand PPh₃, and additive LiCl renders the catalytic system efficient for the synthesis of medicinal interest heteroaryldifluoroacetamides. The application of the method leads to short and highly efficient synthesis of biologically active molecules, providing a facile route for applications in medicinal chemistry and agrochemistry.     

Addressing Challenges in Palladium‐Catalyzed Cross‐Coupling Reactions Through Ligand Design

The development of palladium‐catalyzed cross‐coupling reactions has revolutionized the synthesis of organic molecules on both bench‐top and industrial scales. While significant research effort has been directed toward evaluating how modifying various reaction parameters can influence the outcome of a given cross‐coupling reaction, the design and implementation of novel ancillary ligand frameworks has played a particularly important role in advancing the state‐of‐the‐art. This Review seeks to highlight notable examples from the recent chemical literature, in which newly developed ancillary ligands have enabled more challenging substrate transformations to be addressed with greater selectivity and/or under increasingly mild conditions. Throughout, the importance and subtlety of ligand effects in palladium‐catalyzed cross‐coupling reactions are described, in an effort to inspire further development and understanding within the field of ancillary ligand design.     

The Selective Cross‐Coupling of Secondary Alkyl Zinc Reagents to Five‐Membered‐Ring Heterocycles Using Pd‐PEPPSI‐IHeptCl

The ability to cross‐couple secondary alkyl centers is fraught with a number of problems, including difficult reductive elimination, which often leads to β‐hydride elimination. Whereas catalysts have been reported that provide decent selectivity for the expected (non‐rearranged) cross‐coupled product with aryl or heteroaryl oxidative‐addition partners, none have shown reliable selectivity with five‐membered‐ring heterocycles. In this report, a new, rationally designed catalyst, Pd‐PEPPSI‐IHept^Cl, is demonstrated to be effective in selective cross‐coupling reactions with secondary alkyl reagents across an impressive variety of furans, thiophenes, and benzo‐fused derivatives (e.g., indoles, benzofurans), in most instances producing clean products with minimal, if any, migratory insertion for the first time.     

Expedient Synthesis of Chiral α‐Amino Acids through Nickel‐Catalyzed Reductive Cross‐Coupling

A novel method for the synthesis of non‐natural L ‐ and D ‐amino acids by a Ni‐catalyzed reductive cross‐coupling reaction is described. This strategy enables the racemization‐free cross‐coupling of serine/homoserine‐ derived iodides with aryl/acyl/alkyl halides. It provides convenient access to varieties of enantiopure and functionalized amino acids, which are important building blocks in bioactive compounds and pharmaceuticals.     

Enantioselective Construction of Tertiary Boronic Esters by Conjunctive Cross‐Coupling

Catalytic enantioselective conjunctive cross‐coupling has been developed to construct tertiary alkylboronic esters. These reactions occur with good yield and enantioselectivity for a range of substrates. Mechanistic experiments reveal aspects of the catalytic cycle that allow hindered substrates to react without significant complicating side reactions.