A synthesis of pyrido[2,1‐a]isoindoles is reported by the rhodium‐catalyzed direct oxidative C H acylation of 2‐aryl pyridines with terminal alkynes. The desired products were obtained in moderate to excellent yields. This is an efficient and clean method to construct C C/C N bonds in one step. In addition, the effective rhodium(III) catalyst was isolated and characterized by X‐ray crystallography.
A new and efficient method for the synthesis of 2‐vinylanilines from the reaction of arylhydrazine hydrochlorides with alkenes and diethyl ketone via a rhodium‐catalyzed C H activation is described. The oxidant‐free olefination reaction involves the in situ generation of an N NCR1R2 moiety as the oxidizing directing group thus providing an easy access to 2‐vinylanilines.
A novel palladium‐catalyzed C‐7 selective C H carbonylation of indolines with carbon monoxide for an expedient synthesis of pyrroloquinazolinediones, a structural motif with great potential in biologically active compounds, has been developed. Oxidation of the pyrroloquinazolinedione with 2,3‐dichloro‐5,6‐dicyano‐p‐benzoquinone (DDQ) could easily afford the corresponding indole‐based derivative in excellent yield.
An efficient and concise one‐pot strategy for the direct alkylation of quinoline N‐oxides via palladium‐catalyzed dual C H bonds activation has been developed. This methodology provides quinoline‐containing heterocyclic molecules in moderate to excellent yields.
A mild and efficient palladium‐catalyzed synthetic method for the C H functionalization of N‐(quinolin‐8‐yl)ferrocenecarboxamide has been developed. Various aryl iodides containing I, NO2, CN, COMe, CO2Et, and NH functionalities and also alkyl iodides underwent the Pd‐catalyzed intermolecular carbon‐carbon bond forming reaction with ferrocenecarboxamide successfully which led to a diverse array of bis(aryl/alkyl)ferrocenecarboxamides in 34–92% yields. Cross‐coupling of the ferrocenyl C H bond with aryl iodides can also be achieved utilizing an economical Ni catalyst. Additionally, selective monoalkylation of ferrocenecarboxamide was studied using sodium bicarbonate as base and dibenzylphosphoric acid as additive under Pd‐catalyzed reaction conditions. Subsequently, removal of the directing group, 8‐aminoquinoline, from bis(aryl)ferrocenecarboxamides led to bis(aryl)ferrocenes bearing versatile methyl ester and carboxaldehyde functional groups.
Rhodium‐catalyzed tandem annulation reactions via olefination and subsequent intramolecular C‐Michael‐type cyclization represent an efficient approach for the direct construction of C C bonds. The simple and atom‐economic strategy produces various alkylation derivatives of 7‐azaindole with a quaternary carbon center from 7‐azaindoles and olefins.
Chiral primary amine‐catalyzed asymmetric C H functionalization has been achieved. In this process, enantiotopic Csp3 H functionalization at the α‐position to the nitrogen atom of 4‐[ortho‐(dialkylamino)phenyl]but‐3‐en‐2‐one is activated by chiral 9‐amino(9‐deoxy)‐epi‐quinine to afford tetrahydroquinine derivatives with high enantioselectivities (up to 97% ee).
The use of cobalt as catalyst in direct C H activation protocols as a replacement for more expensive second row transition metals is currently attracting significant attention. Herein we disclose a facile cobalt‐catalyzed C H functionalization route towards sultam motifs through annulation of easily prepared aryl sulfonamides and alkynes using 8‐aminoquinoline as a directing group. The reaction shows broad substrate scope with products obtained in a highly regioselective manner in good to excellent isolated yields. Mechanistic insights suggest the formation of a Co(III)‐aryl key species via a rate‐determining arene C H activation during the annulation reaction.
An unprecedented palladium(II)‐catalyzed biomimetic aliphatic acyl (‐COR) group transfer was observed from acyl‐α‐peroxycoumarins to the ortho C H sites of directing arenes. Here, the C H activation is associated with a concomitant acyl group transfer via a Pd(II)‐catalyzed, redox‐neutral process. While methods for ortho aroylation (‐COAr) are well documented ortho acylation (‐COR) processes are scarce, hence the present redox‐neutral method is most ideal for o‐acylation of directing substrates.
A regioselective synthesis of indole‐3‐carboxylic acid esters from anilines and diazo compounds has been realized by making use of the pyrimidyl group‐assisted rhodium‐catalyzed C H activation and C N bond formation. The reaction proceeds under mild conditions, exhibits good functional group tolerance and scalability. Reutilization of the pyrimidyl directing group in the resulting products provided an efficient strategy for further C‐7 functionalization of indoles. Moreover, the pyrimidyl moiety could be readily removed as a leaving group to offer various free N H indoles.
A metal‐free C C bond formation method via the oxidative cross‐coupling reaction of isochroman and indole derivatives was established. Various α‐fuctionalized cyclic ethers were achieved in satisfactory yields using di‐tert‐butyl peroxide (DTBP) as the oxidant. This method is also a potentially efficient strategy for the construction of cyclic ether‐containing targets.
The palladium‐catalyzed acylation of 2‐aryl‐1,2,3‐triazoles with aldehydes via C H bond activation is described. A wide variety of products was isolated in good to excellent yields. This finding provides a new and useful strategy for the synthesis of aromatic ketones.
A direct annulation reaction of N‐(2‐formylaryl)indoles has been developed, which can provide a new entry to biologically and medicinally important indole‐indolone scaffolds via a silver‐catalyzed direct oxidative coupling between aldehyde C H and sp2 C H bonds for the first time. Remarkably, this strategy displayed excellent functional group compatibilities, thereby suggesting its wide potential for applications in developing and synthesizing new drug‐like compounds containing indole‐indolone frameworks.
This report presents a new, one‐pot, facile, selective and green method for methoxycarbonylation of alcohols and synthesis of five‐ and six‐membered cyclic carbonates from corresponding alcohols with dimethyl carbonate (DMC) in the presence of molecular sieves without any additional solvent and catalyst. Syntheses of bifunctional structures comprising a six‐membered cyclic carbonate with allyl ether and methacrylate groups, respectively, for different polymerization modes, were also achieved and showed reproducibility on up‐scaling the processes.
Two efficient methods for the amination of 2‐halothiazoles are presented here. A first protocol requires a Pd/L system. Several 2‐aminothiazoles were synthesized under optimized conditions and isolated in good yields. The first palladium‐catalyzed C N coupling reactions between 2‐halothiazoles and primary alkylamines are presented. In a second part, ligand‐free copper‐catalyzed aminations of 2‐halothiazoles by alkylamines and aniline in a green solvent have been developed. The protocol is very effective for primary and secondary amines and perfectly tolerates the presence of another halide moiety on the 2‐halothiazole. The reaction occurs under the assistance of microwave irradiation, which drastically decreases the reaction time. The reaction leads to the formation of 2‐aminothiazoles, key molecules in pharmaceutical research.
A RhIII‐catalyzed tandem C H activation and C N bond formation reaction between oximes and diazo compounds for the synthesis of heterocycle‐fused pyridine N‐oxides has been developed. The reaction exhibits good functional group tolerance and regioselectivity. After simple transformation, the 1‐substituted, 1,3‐disubstituted, 1,4‐disubstituted and 1,3,4‐trisubstituted heterocycle‐fused pyridines were all obtained in high efficiency. Moreover, this strategy has also been expanded to the synthesis of a key intermediate for the construction of one potential anti‐HIV agent.
By using N,N‐dimethylformamide (DMF) as a methylenating reagent, the copper‐catalyzed C H activation of indole was demonstrated as an efficient and facile protocol for synthesizing 3,3′‐diindolylmethane (DIM) and its derivatives. The results indicate that copper chloride was the best catalyst among the investigated transition metal salts, which affords an excellent regioselectivity and good yield when tert‐butyl hydroperoxide (TBHP) was used as an oxidant.
Sequential copper‐catalyzed [3+2] cycloaddition, rhodium‐catalyzed O H insertion, intramolecular 1,8‐addition, and rearrangement starting from 1‐alkynes, N‐sulfonyl azides, and tropolones is demonstrated for the synthesis of the 2‐functionalized aminotropones in one pot. These results indicate that sequential functionalization of O H and C(sp2) O bonds smoothly occurs in the C(sp2) O H bonds of tropolone
A visible‐light photoredox‐catalyzed reaction of tetrahydroisoquinolines with β‐fluorinated gem‐diols results in the formation of C1‐monofluoromethylated tetrahydroisoquinolines via C(sp3) H bond activation. This protocol provides a new method to introduce a CF group with stable, easily‐prepared monofluorinated gem‐diol as CF source. A mechanistic investigation is presented based on control experiments.
Copper salts, which are abundant, relatively inexpensive and possess low toxicity, have long been used as versatile catalysts for various reactions in organic synthesis. Recently, the development of Cu‐catalyzed or ‐mediated C H functionalization reactions has gained significant attention. Since the pioneering work of Daugulis on the introduction of 8‐aminoquinoline and picolinic acid auxiliaries as removable directing groups in transition metal‐catalyzed C H bond activations, the combination of copper salts with these bidentate directing groups has emerged as an innovative strategy for the construction of carbon‐carbon or carbon‐heteroatom bonds through C H bond cleavage. In addition to the 8‐aminoquinoline and picolinamide systems, several other bidentate directing groups including the 2‐aminophenyloxazoline group by Yu and Dai and the PIP system by Shi, have been developed as well. This review intends to cover most of the recent advances on copper‐catalyzed or ‐mediated direct sp2 and sp3 C H bond functionalizations assisted by these bidentate directing groups. The major achievements in this area are discussed and catalogued by the type of bonds formed (C C, C O, C N, C S, C P etc.). Special attention is paid to the reaction mechanisms. Selected examples of substrates are listed as well. In addition, a personal outlook is given at the end.
