Indole Synthesis through Sequential Electrophilic N−H and C−H Bond Activation Using Iodine(III) Reactivity

An intramolecular approach towards the regioselective construction of 2,3‐diarylated indoles is reported. The reaction follows an intramolecular electrophilic N?H and C?H bond functionalization between the aniline and acetylene. This methodology employs the concept of a traceless tether to provide access to the free 2,3‐diarylated indole products comprising a total of 18 examples. Hypervalent iodine reagents were identified as suitable promoters and four different protocols are provided, including stoichiometric and catalytic transformations.     

Sterically Congested 2,6‐Disubstituted Anilines from Direct C−N Bond Formation at an Iodine(III) Center

2,6‐Disubstituted anilines are readily prepared from the direct reaction between amides and diaryliodonium salts. As demonstrated for 24 different examples, the reaction is of unusually broad scope with respect to the sterically congested arene and the nitrogen source, occurs without the requirement for any additional promoter, and proceeds through a direct reductive elimination at the iodine(III) center. The efficiency of the coupling procedure is further demonstrated within the short synthesis of a chemerin binding inhibitor.     

Hypervalent‐Iodine(III)‐Mediated Oxidative Methodology for the Synthesis of Fused Triazoles

The organic chemistry of hypervalent organoiodine compounds has been an area of unprecedented development. This surge in interest in the use of hypervalent iodine compounds has mainly been owing to their highly selective oxidizing properties, environmentally benign character and commercial availability. Hypervalent iodine reagents have also been used as an alternative to toxic heavy metals, owing to their low toxicity and ease of handling. Hypervalent organoiodine(III) reagents are versatile oxidants that have been successfully employed to extend the scope of selective oxidative transformations of complex organic molecules in synthetic chemistry. This Focus Review concerns the tandem in situ generation and 1,5‐electrocyclization of N‐heteroaryl nitrilimines into fused triazoles. We describe the importance of recently developed hypervalent‐organoiodine(III)‐catalyzed oxidative cyclization reactions, building towards the conclusion that hypervalent iodine chemistry is a promising frontier for oxidative cyclization, in particular of hydrazones, for the synthesis of fused triazoles.     

Metal‐Free CH Bond Activation of Branched Aldehydes with a Hypervalent Iodine(III) Catalyst under Visible‐Light Photolysis: Successful Trapping with Electron‐Deficient Olefins

Direct acyl radical formation of linear aldehydes (RCH₂‐CHO) and subsequent hydroacylation with electron‐deficient olefins can be effected with various types of metal and nonmetal catalysts/reagents. In marked contrast, however, no successful reports on the use of branched aldehydes have been made thus far because of their strong tendency of generating alkyl radicals through the facile decarbonylation of acyl radicals. Here, use of a hypervalent iodine(III) catalyst under visible light photolysis allows a mild way of generating acyl radicals from various branched aldehydes, thereby giving the corresponding hydroacylated products almost exclusively. Another characteristic feature of this approach is the catalytic use of hypervalent iodine(III) reagent, which is a rare example on the generation of radicals in hypervalent iodine chemistry.     

A Selective C−H Deprotonation Strategy to Access Functionalized Arynes by Using Hypervalent Iodine

Described here is an efficient method to access highly functionalized arynes from unsymmetrical aryl(mesityl)iodonium tosylate salts. The iodonium salts are prepared in a single pot from either commercially available aryl iodides or arylboronic acids. The aryne intermediates are generated by ortho‐C?H deprotonation of aryl(mesityl)iodonium salt with a commercially available amide base and trapped in a cycloaddition reaction with furan in moderate to good yields. Coupling partners for the aryne intermediates beyond furan are also described, including benzyl azide and alicyclic amine nucleophiles. The regio‐ and chemoselectivity of this reaction is discussed and evidence for the spectator aryl ligand of the iodonium salt as a critical control element in selectivity is presented.     

Ruthenium(II)‐Catalyzed Traceless C−H Functionalization Using an N−N Bond as an Internal Oxidant

A previously elusive Ru^II‐catalyzed N?N bond‐based traceless C?H functionalization strategy is reported. An N‐amino (i.e., hydrazine) group is used for the directed C?H functionalization with either an alkyne or an alkene, affording an indole derivative or olefination product. The synthesis features a broad substrate scope, superior atom and step economy, as well as mild reaction conditions.     

Photoinduced Cobalt(III)−Trifluoromethyl Bond Activation Enables Arene C−H Trifluoromethylation

Visible‐light capture activates a thermodynamically inert Co^III−CF₃ bond for direct C−H trifluoromethylation of arenes and heteroarenes. New trifluoromethylcobalt(III) complexes supported by a redox‐active [OCO] pincer ligand were prepared. Coordinating solvents, such as MeCN, afford green, quasi‐octahedral [(^SOCO)Co^III(CF₃)(MeCN)₂] ( 2 ), but in non‐coordinating solvents the complex is red, square pyramidal [(^SOCO)Co^III(CF₃)(MeCN)] ( 3 ). Both are thermally stable, and 2 is stable in light. But exposure of 3 to low‐energy light results in facile homolysis of the Co^III−CF₃ bond, releasing ^.CF₃ radical, which is efficiently trapped by TEMPO^. or (hetero)arenes. The homolytic aromatic substitution reactions do not require a sacrificial or substrate‐derived oxidant because the Co^II by‐product of Co^III−CF₃ homolysis produces H₂. The photophysical properties of 2 and 3 provide a rationale for the disparate light stability.