Diaryliodoniums by Rhodium(III)‐Catalyzed CH Activation: Mild Synthesis and Diversified Functionalizations

Diaryliodonium salts play an increasingly important role as an aryl source. Reported is the first synthesis of diaryliodoniums by rhodium(III)‐catalyzed C? H hyperiodination of electron‐poor arenes under chelation assistance. This C? I coupling reaction occurred at room temperature with high regio‐selectivity and functional‐group compatibility. Subsequent diversified nucleophilic functionalization of a diaryliodonium allowed facile construction of C? C, C? N, C? O, C? S, C? P and C? Br bonds, and in all cases the initial functionalization occurred at the arene containing the chelating‐group.     

Rhodium(III)‐Catalyzed CC and CO Coupling of Quinoline N‐Oxides with Alkynes: Combination of CH Activation with O‐Atom Transfer

[Cp*Rh^III]‐catalyzed C? H activation of arenes assisted by an oxidizing N? O or N? N directing group has allowed the construction of a number of hetercycles. In contrast, a polar N? O bond is well‐known to undergo O‐atom transfer (OAT) to alkynes. Despite the liability of N? O bonds in both C? H activation and OAT, these two important areas evolved separately. In this report, [Cp*Rh^III] catalysts integrate both areas in an efficient redox‐neutral coupling of quinoline N‐oxides with alkynes to afford α‐(8‐quinolyl)acetophenones. In this process the N? O bond acts as both a directing group for C? H activation and as an O‐atom donor.     

Rhodium(III)‐Catalyzed Alkenylation Reactions of 8‐Methylquinolines with Alkynes by C(sp3)H Activation

The alkenylation reactions of 8‐methylquinolines with alkynes, catalyzed by [{Cp*RhCl₂}₂], proceeds efficiently to give 8‐allylquinolines in good yields by C(sp³)? H bond activation. These reactions are highly regio‐ and stereoselective. A catalytically competent five‐membered rhodacycle has been structurally characterized, thus revealing a key intermediate in the catalytic cycle.     

Rhodium(III)‐Catalyzed Transannulation of Cyclopropenes with N‐Phenoxyacetamides through CH Activation

An efficient rhodium(III)‐catalyzed synthesis of 2H‐chromene from N‐phenoxyacetamides and cyclopropenes has been developed. The reaction represents the first example of using cyclopropenes as a three‐carbon unit in rhodium(III)‐catalyzed C(sp²)? H activations.     

Palladium‐Catalyzed CH Activation and Intermolecular Annulation with Allenes

A new and efficient Pd^II‐catalyzed intermolecular annulation of N‐benzoylsulfonamide with allenes for the synthesis of 3,4‐dihydroisoquinolin‐1(2H)‐ones is reported. This C?H functionalization is compatible with ambient air and moisture, and it can be applied to terminal or internal allenes with di?erent synthetically attractive functional groups. Control experiments and a kinetic isotope effect study are conducted and a plausible mechanism is proposed.     

Rhodium(III)‐Catalyzed Three‐Component Reaction of Imines,Alkynes, and Aldehydes through CH Activation

An efficient rhodium(III)‐catalyzed tandem three‐component reaction of imines, alkynes and aldehydes through C?H activation has been developed. High stereo‐ and regioselectivity, as well as good yields were obtained in most cases. The simple and atom‐economical approach offers a broad scope of substrates, providing polycyclic skeletons with potential biological properties.     

Cobalt(III)‐Catalyzed Dehydrative [4+2] Annulation of Oxime with Alkyne by CH and NOH Activation

Efficient, scalable cobalt‐catalyzed redox‐neutral [4+2] annulation of readily available oximes and alkyne is reported. The developed synthetic methodology is widely applicable and tolerates various functional groups including heterocycles. A stable Cp*Co^III neutral complex is employed as the catalyst for this redox‐neutral [4+2] annulation reaction, which progresses smoothly by way of a reversible cyclometallation without any external oxidizing agent, and produces only water as the side product.     

Asymmetric Synthesis of Isoindolones by Chiral Cyclopentadienyl‐Rhodium(III)‐Catalyzed CH Functionalizations

Directed Cp*Rh^III‐catalyzed carbon–hydrogen (C? H) bond functionalizations have evolved as a powerful strategy for the construction of heterocycles. Despite their high value, the development of related asymmetric reactions is largely lagging behind due to a limited availability of robust and tunable chiral cyclopentadienyl ligands. Rhodium complexes comprising a chiral Cp ligand with an atropchiral biaryl backbone enables an asymmetric synthesis of isoindolones from arylhydroxamates and weakly alkyl donor/acceptor diazo derivatives as one‐carbon component under mild conditions. The complex guides the substrates with a high double facial selectivity yielding the chiral isoindolones in good yields and excellent enantioselectivities.     

Rhodium‐Catalyzed CH Annulation of Nitrones with Alkynes: A Regiospecific Route to Unsymmetrical 2,3‐Diaryl‐Substituted Indoles

The direct C? H annulation of anilines or related compounds with internal alkynes provides straightforward access to 2,3‐disubstituted indole products. However, this transformation proceeds with poor regioselectivity in the synthesis of unsymmetrically 2,3‐diaryl substituted indoles. Herein, we report the rhodium(III)‐catalyzed C? H annulation of nitrones with symmetrical diaryl alkynes as an alternative method to prepare 2,3‐diaryl‐substituted N‐unprotected indoles with two different aryl groups. One of the aryl substituents is derived from N?C‐aryl ring of the nitrone and the other from the alkyne substrate, thus providing the indole products with exclusive regioselectivity.     

Rhodium(III)‐Catalyzed CH Activation and Indole Synthesis With Hydrazone as an Auto‐Formed and Auto‐Cleavable Directing Group

An efficient, practical, and external‐oxidant‐free indole synthesis from readily available aryl hydrazines was developed, by using hydrazone as a directing group for Rh^III‐catalyzed C?H activation and alkyne annulation. The hydrazone group was formed by in situ condensation of hydrazines and C?O source, whereas its N?N bond was served as an internal oxidant, for which we termed it as an auto‐formed and auto‐cleavable directing group (DG^auto). This method needs no step for pre‐installation and post‐cleavage of the directing group, making it a quite easily scalable approach to access unprotected indoles with high step economy. The DG^auto strategy was also applicable for isoquinoline synthesis. In addition, synthetic utilities of this chemistry for rapid assembly of π‐extended nitrogen‐doped polyheterocycles and bioactive molecules were demonstrated.     

Highly Enantioselective Rhodium(I)‐Catalyzed Carbonyl Carboacylations Initiated by CC Bond Activation

The lactone motif is ubiquitous in natural products and pharmaceuticals. The Tishchenko disproportionation of two aldehydes, a carbonyl hydroacylation, is an efficient and atom‐economic access to lactones. However, these reaction types are limited to the transfer of a hydride to the accepting carbonyl group. The transfer of alkyl groups enabling the formation of C? C bonds during the ester formation would be of significant interest. Reported herein is such asymmetric carbonyl carboacylation of aldehydes and ketones, thus affording complex bicyclic lactones in excellent enantioselectivities. The rhodium(I)‐catalyzed transformation is induced by an enantiotopic C? C bond activation of a cyclobutanone and the formed rhodacyclic intermediate reacts with aldehyde or ketone groups to give highly functionalized lactones.     

Highly Enantioselective Rhodium(I)‐Catalyzed Activation of Enantiotopic Cyclobutanone CC Bonds

The selective functionalization of carbon–carbon σ bonds is a synthetic strategy that offers uncommon retrosynthetic disconnections. Despite progress in C? C activation and its great importance, the development of asymmetric reactions lags behind. Rhodium(I)‐catalyzed selective oxidative additions into enantiotopic C? C bonds in cyclobutanones are reported. Even operating at a reaction temperature of 130 °C, the process is characterized by outstanding enantioselectivity with the e.r. generally greater than 99.5:0.5. The intermediate rhodacycle is shown to react with a wide variety of tethered olefins to deliver complex bicyclic ketones in high yields.     

Manganese‐Catalyzed Dehydrogenative [4+2] Annulation of NH Imines and Alkynes by CH/NH Activation

Described herein is a manganese‐catalyzed dehydrogenative [4+2] annulation of N? H imines and alkynes, a reaction providing highly atom‐economical access to diverse isoquinolines. This transformation represents the first example of manganese‐catalyzed C? H activation of imines; the stoichiometric variant of the cyclomanganation was reported in 1971. The redox neutral reaction produces H₂ as the major byproduct and eliminates the need for any oxidants, external ligands, or additives, thus standing out from known isoquinoline synthesis by transition‐metal‐catalyzed C? H activation. Mechanistic studies revealed the five‐membered manganacycle and manganese hydride species as key reaction intermediates in the catalytic cycle.     

Mechanistic Study on Rh‐Catalyzed Stereoselective CC/CH Activation of tert‐Cyclobutanols

A mechanistic study was performed on the Rh‐catalyzed stereoselective C?C/C?H activation of tert‐cyclobutanols. The present study corroborated the previous proposal that the reaction occurs by metalation, β‐C elimination, 1,4‐Rh transfer, C?O insertion, and a final catalyst‐regeneration step. The rate‐determining step was found to be the 1,4‐Rh transfer step, whereas the stereoselectivity‐determining step did not correspond to any of the aforementioned steps. It was found that both the thermodynamic stability of the product of the β‐C elimination and the kinetic feasibility of the 1,4‐Rh transfer and C?O insertion steps made important contributions. In other words, three steps (i.e., β‐C elimination, 1,4‐Rh transfer, and C?O insertion) were found to be important in determining the configurations of the two quaternary stereocenters.     

Catalytic 1,4‐Rhodium(III) Migration Enables 1,3‐Enynes to Function as One‐Carbon Oxidative Annulation Partners in CH Functionalizations

1,3‐Enynes containing allylic hydrogens cis to the alkyne are shown to act as one‐carbon partners, rather than two‐carbon partners, in various rhodium‐catalyzed oxidative annulations. The mechanism of these unexpected transformations is proposed to occur through double C? H activation, involving a hitherto rare example of the 1,4‐migration of a Rh^III species. This phenomenon is general across a variety of substrates, and provides a diverse range of heterocyclic products.     

Rhodium(III)‐Catalyzed Selective ortho‐Olefinations of N‐Acyl and N‐Aroyl Sulfoximines by CH Bond Activation

Two new rhodium‐catalyzed oxidative couplings between sulfoximine derivatives and alkenes by regioselective C?H activation, affording ortho‐olefinated (Heck‐type) products, are reported. A synthetic application of the ortho‐alkenylated products into the corresponding cyclic derivatives has been demonstrated, and a mechanistic rational for the rhodium catalysis is presented.     

Carboxylic Acids as Traceless Directing Groups for the Rhodium(III)‐Catalyzed Decarboxylative CH Arylation of Thiophenes

A rhodium(III)‐catalyzed carboxylic acid directed decarboxylative C? H/C? H cross‐coupling of carboxylic acids with thiophenes has been developed. With a slight adjustment of the reaction conditions based on the nature of the substrates, aryl carboxylic acids with a variety of substituents could serve as suitable coupling partners, and a broad variety of functional groups were tolerated. This method provides straightforward access to biaryl scaffolds with diverse substitution patterns, many of which have conventionally been synthesized through lengthy synthetic sequences. An illustrative example is the one‐step gram‐scale synthesis of a biologically active 3,5‐substituted 2‐arylthiophene by way of the current method.     

Synthesis of Silaphenalenes by Ruthenium‐Catalyzed Annulation between 1‐Naphthylsilanes and Internal Alkynes through CH Bond Cleavage

Ruthenium‐catalyzed annulation of 1‐naphthylsilanes with internal alkynes afforded silaphenalenes through cleavage of the C?H bond at the 8‐position of the naphthalene. [RuH₂(CO){P(p‐FC₆H₄)₃}₃] efficiently catalyzed the reaction. The use of 1‐naphthyldiphenylsilane as a substrate resulted in a better yield of the annulation product compared to the use of silanes with alkyl groups on the silicon atom. Internal alkynes with both aryl and alkyl groups were tolerated in this reaction.     

Amidines for Versatile Ruthenium(II)‐Catalyzed Oxidative CH Activations with Internal Alkynes and Acrylates

Cationic ruthenium complexes derived from KPF₆ or AgOAc enabled efficient oxidative C?H functionalizations on aryl and heteroaryl amidines. Thus, oxidative annulations of diversely decorated internal alkynes provided expedient access to 1‐aminoisoquinolines, while catalyzed C?H activations with substituted acrylates gave rise to structurally novel 1‐iminoisoindolines. The powerful ruthenium(II) catalysts displayed a remarkably high site‐, regio‐ and, chemoselectivity. Therefore, the catalytic system proved tolerant of a variety of important electrophilic functional groups. Detailed mechanistic studies provided strong support for the cationic ruthenium(II) catalysts to operate by a facile, reversible C?H activation.     

Rhodium(I)‐Catalyzed Cycloisomerization of Benzylallene‐Alkynes through CH Activation

The efficient Rh^I‐catalyzed cycloisomerization of benzylallene‐alkynes produced the tricyclo[9.4.0.0^3,8]pentadecapentaene skeleton through a C? H bond activation in good yields. A plausible reaction mechanism proceeds via oxidative addition of the acetylenic C? H bond to Rh^I, an ene‐type cyclization to the vinylidenecarbene–Rh^I intermediate, and an electrophilic aromatic substitution with the vinylidenecarbene species. It was proposed based on deuteration and competition experiments.