Splitting a Substrate into Three Parts: Gold‐Catalyzed Nitrogenation of Alkynes by CC and CC Bond Cleavage

A gold‐catalyzed nitrogenation of alkynes for the synthesis of carbamides and amino tetrazoles through C? C and C?C bond cleavages is described. A diverse set of functionalized carbamide and amino tetrazole derivatives were selectively constructed under mild conditions. The chemoselectivity can be easily switched by the selection of the acid additives. The reaction is characterized by its broad substrate scope, direct construction of high value products, easy operation under air, and mild conditions at room temperature. This chemistry provides a way to transform alkynes by splitting the substrate into three parts.     

Copper‐Catalyzed Aerobic Oxidative Inert CC and CN Bond Cleavage: A New Strategy for the Synthesis of Tertiary Amides

A copper‐catalyzed aerobic oxidative amidation reaction of inert C?C bonds with tertiary amines has been developed for the synthesis of tertiary amides, which are significant units in many natural products, pharmaceuticals, and fine chemicals. This method combines C?C bond activation, C?N bond cleavage, and C?H bond oxygenation in a one‐pot protocol, using molecular oxygen as the sole oxidant without any additional ligands.     

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.     

Lewis Acid Mediated Tandem Reaction of Propargylic Alcohols to Tetrazoles Involving CO‐ and CC‐Bond Cleavage Reactions and a CN‐Bond Formation

A novel and direct synthesis of 1‐aryl‐5‐arylvinyl‐tetrazoles from easily prepared propargylic alcohols and TMSN₃ is developed in the presence of TMSCl under mild conditions (TMS=trimethylsilyl). The process involves an allenylazide intermediate, followed by a C?C‐bond cleavage and C?N‐bond formation to afford the desired products. Moreover, this method offers a good functional‐group applicability and can be scaled‐up to grams (yield up to 85 %).     

The Mechanism of NO Bond Cleavage in Rhodium‐Catalyzed CH Bond Functionalization of Quinoline N‐oxides with Alkynes: A Computational Study

Metal‐catalyzed C?H activation not only offers important strategies to construct new bonds, it also allows the merge of important research areas. When quinoline N‐oxide is used as an arene source in C?H activation studies, the N?O bond can act as a directing group as well as an O‐atom donor. The newly reported density functional theory method, M11L, has been used to elucidate the mechanistic details of the coupling between quinoline N?O bond and alkynes, which results in C?H activation and O‐atom transfer. The computational results indicated that the most favorable pathway involves an electrophilic deprotonation, an insertion of an acetylene group into a Rh?C bond, a reductive elimination to form an oxazinoquinolinium‐coordinated Rh^I intermediate, an oxidative addition to break the N?O bond, and a protonation reaction to regenerate the active catalyst. The regioselectivity of the reaction has also been studied by using prop‐1‐yn‐1‐ylbenzene as a model unsymmetrical substrate. Theoretical calculations suggested that 1‐phenyl‐2‐quinolinylpropanone would be the major product because of better conjugation between the phenyl group and enolate moiety in the corresponding transition state of the regioselectivity‐determining step. These calculated data are consistent with the experimental observations.     

Manganese‐Catalyzed Oxidative Azidation of Cyclobutanols: Regiospecific Synthesis of Alkyl Azides by CC Bond Cleavage

A novel, manganese‐catalyzed oxidative azidation of cyclobutanols is described. A wide range of primary, secondary, and tertiary alkyl azides were generated in synthetically useful yields and exclusive regioselectivity. Aside from linear alkyl azides, otherwise elusive medium‐sized cyclic azides were also readily prepared. Preliminary mechanistic studies reveal that the reaction likely proceeds by a radical‐mediated C? C bond cleavage/C? N₃ bond formation pathway.     

Nickel‐Catalyzed Chemo‐, Regio‐ and Diastereoselective Bond Formation through Proximal CC Cleavage of Benzocyclobutenones

The first catalytic intermolecular proximal C1? C2 cleavage of benzocyclobutenones (BCB) without prior carbonyl activation or employing noble metals has been developed. This protocol operates at room temperature and is characterized by an exquisite chemo‐, regio‐ and diastereoselectivity profile, constituting a unique platform for preparing an array of elusive carbocyclic skeletons.     

Rhodium(I)‐Catalyzed Decarbonylative Spirocyclization through CC Bond Cleavage of Benzocyclobutenones: An Efficient Approach to Functionalized Spirocycles

The rhodium‐catalyzed formation of all‐carbon spirocenters involves a decarbonylative coupling of trisubstituted cyclic olefins and benzocyclobutenones through C? C activation. The metal–ligand combination [{Rh(CO)₂Cl}₂]/P(C₆F₅)₃ catalyzed this transformation most efficiently. A range of diverse spirocycles were synthesized in good to excellent yields and many sensitive functional groups were tolerated. A mechanistic study supports a hydrogen‐transfer process that occurs through a β‐H elimination/decarbonylation pathway.     

Density Functional Theory Calculations on Oxidative CC Bond Cleavage and NO Bond Formation of [RuII(bpy)2(diamine)]2+ via Reactive Ruthenium Imide Intermediates

DFT calculations are performed on [Ru^II(bpy)₂(tmen)]²⁺ ( M1 , tmen=2,3‐dimethyl‐2,3‐butanediamine) and [Ru^II(bpy)₂(heda)]²⁺ ( M2 , heda=2,5‐dimethyl‐2,5‐hexanediamine), and on the oxidation reactions of M1 to give the C?C bond cleavage product [Ru^II(bpy)₂(NH=CMe₂)₂]²⁺ ( M3 ) and the N?O bond formation product [Ru^II(bpy)₂(ONCMe₂CMe₂NO)]²⁺ ( M4 ). The calculated geometrical parameters and oxidation potentials are in good agreement with the experimental data. As revealed by the DFT calculations, [Ru^II(bpy)₂(tmen)]²⁺ ( M1 ) can undergo oxidative deprotonation to generate Ru‐bis(imide) [Ru(bpy)₂(tmen‐4 H)]⁺ ( A ) or Ru‐imide/amide [Ru(bpy)₂(tmen‐3 H)]²⁺ ( A′ ) intermediates. Both A and A′ are prone to C?C bond cleavage, with low reaction barriers (ΔG^≠) of 6.8 and 2.9 kcal mol^?1 for their doublet spin states ² A and ² A′ , respectively. The calculated reaction barrier for the nucleophilic attack of water molecules on ² A′ is relatively high (14.2 kcal mol^?1). These calculation results are in agreement with the formation of the Ru^II‐bis(imine) complex M3 from the electrochemical oxidation of M1 in aqueous solution. The oxidation of M1 with Ce^IV in aqueous solution to afford the Ru^II‐dinitrosoalkane complex M4 is proposed to proceed by attack of the cerium oxidant on the ruthenium imide intermediate. The findings of ESI‐MS experiments are consistent with the generation of a ruthenium imide intermediate in the course of the oxidation.     

Metal‐Free Oxidative CC Bond Formation through CH Bond Functionalization

The formation of C?C bonds embodies the core of organic chemistry because of its fundamental application in generation of molecular diversity and complexity. C?C bond‐forming reactions are well‐known challenges. To achieve this goal through direct functionalization of C?H bonds in both of the coupling partners represents the state‐of‐the‐art in organic synthesis. Oxidative C?C bond formation obviates the need for prefunctionalization of both substrates. This Minireview is dedicated to the field of C?C bond‐forming reactions through direct C?H bond functionalization under completely metal‐free oxidative conditions. Selected important developments in this area have been summarized with representative examples and discussions on their reaction mechanisms.     

Triazole‐Assisted Ruthenium‐Catalyzed CH Arylation of Aromatic Amides

Site‐selective ruthenium(II)‐catalyzed direct arylation of amides was achieved through C?H cleavages with modular auxiliaries, derived from easily accessible 1,2,3‐triazoles. The triazolyldimethylmethyl (TAM) bidentate directing group was prepared in a highly modular fashion through copper(I)‐catalyzed 1,3‐dipolar cycloaddition and allowed for ruthenium‐catalyzed C?H arylations on arenes and heteroarenes, as well as alkenes, by using easy‐to‐handle aryl bromides as the arylating reagents. The triazole‐assisted C?H activation strategy was found to be widely applicable, to occur under mild reaction conditions, and the catalytic system was tolerant of important electrophilic functionalities. Notably, the flexible triazole‐based auxiliary proved to be a more potent directing group for the optimized ruthenium(II)‐catalyzed direct arylations, compared with pyridyl‐substituted amides or substrates derived from 8‐aminoquinoline.     

Ruthenium‐Catalyzed meta‐Selective CH Bromination

The first example of a transition‐metal‐catalyzed, meta‐selective C? H bromination procedure is reported. In the presence of catalytic [{Ru(p‐cymene)Cl₂}₂], tetrabutylammonium tribromide can be used to functionalize the meta C? H bond of 2‐phenylpyridine derivatives, thus affording difficult to access products which are highly predisposed to further derivatization. We demonstrate this utility with one‐pot bromination/arylation and bromination/alkenylation procedures to deliver meta‐arylated and meta‐alkenylated products, respectively, in a single step.     

Rhodium‐Catalyzed ortho‐Selective CF Bond Borylation of Polyfluoroarenes with BpinBpin

An ortho‐selective C? F bond borylation between N‐heterocycle‐substituted polyfluoroarenes and Bpin‐Bpin with simple and commercially available [Rh(cod)₂]BF₄ as a catalyst is now reported. The reaction proceeds under mild reaction conditions with high efficiency and broad substrate scope, even toward monofluoroarene, thus providing a facile access to a wide range of borylated fluoroarenes that are useful for photoelectronic materials. Preliminary mechanistic studies reveal that a Rh^III/V catalytic cycle via a key intermediate rhodium(III) hydride complex [(H)Rh^IIIL_n(Bpin)] may be involved in the reaction.     

Ruthenium‐Catalyzed C7 Amidation of Indoline CH Bonds with Sulfonyl Azides

A ruthenium‐catalyzed direct C7 amidation of indoline C?H bonds with sulfonyl azides was developed. This procedure allows the synthesis of a variety of 7‐amino‐substituted indolines, which are useful in pharmaceutical. The good functional tolerances, as well as the mild conditions, are prominent feature of this method.     

Intramolecular Cooperative CC Bond Cleavage Reaction of 1,3‐Dicarbonyl Compounds with 2‐Iodoanilines to Give o‐(N‐Acylamino)aryl Ketones and Multisubstituted Indoles

A copper‐catalyzed C?C bond cleavage reaction of 1,3‐dicarbonyl compounds with 2‐iodoanilines was developed. In this process, the ortho effect played an important role in the reactivity and a new reaction pathway that involved a (2‐aminophenyl)‐bis‐(1,3‐dicarbonyl) copper species was clearly observed by a time‐course HRMS analysis of the reaction mixture. Unlike the previous reports, both the nucleophilic and electrophilic parts of the 1,3‐dicarbonyl compound were coupled with 2‐iodoaniline by C?C bond cleavage to form o‐(N‐acylamino)aryl ketones, which could be efficiently converted into multisubstituted indoles.     

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.     

Ruthenium–Porphyrin‐Catalyzed Diastereoselective Intramolecular Alkyl Carbene Insertion into CH Bonds of Alkyl Diazomethanes Generated In Situ from N‐Tosylhydrazones

With a ruthenium–porphyrin catalyst, alkyl diazomethanes generated in situ from N‐tosylhydrazones efficiently underwent intramolecular C(sp³)? H insertion of an alkyl carbene to give substituted tetrahydrofurans and pyrrolidines in up to 99 % yield and with up to 99:1 cis selectivity. The reaction displays good tolerance of many functionalities, and the procedure is simple without the need for slow addition with a syringe pump. From a synthetic point of view, the C? H insertion of N‐tosylhydrazones can be viewed as reductive coupling between a C?O bond and a C? H bond to form a new C? C bond, since N‐tosylhydrazones can be readily prepared from carbonyl compounds. This reaction was successfully applied in a concise synthesis of (±)‐pseudoheliotridane.     

Rhodium‐Catalyzed CS and CN Functionalization of Arenes: Combination of CH Activation and Hypervalent Iodine Chemistry

Rhodium‐catalyzed sulfonylation, thioetherification, thiocyanation, and other heterofunctionalizations of arenes bearing a heterocyclic directing group have been realized. The reaction proceeds by initial Rh^III‐catalyzed C?H hyperiodination of arene at room temperature followed by uncatalyzed nucleophilic functionalization. A diaryliodonium salt is isolated as an intermediate, which represents umpolung of the arene substrate, in contrast to previous studies that suggested umpolung of the coupling partner.     

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.