A powerful approach to alkoxy radical-mediated remote C(sp~3)–H bonds functionalization

正The activation of inert C(sp~3)–H bonds with control of reactivity and selectivity is one of the central topics in chemical sciences.In this context,alkoxy radical-mediated 1,5-hydrogen atom transfer allows the regioselective transfor-     

Copper-catalyzed oxidative C‒H,N‒H coupling of azoles and thiophenes

C?H, N?H coupling of azole and thiophene derivatives takes place in the presence of a catalytic amount of Cu(OAc)₂ and an additive. The reaction of azoles smoothly occurs with several amines and amides catalyzed by 20 mol % of Cu(OAc)₂–2PPh₃ and 4 equiv of NaOAc under O₂ or in the presence of Ag₂CO₃ under N₂. The coupling reaction leads to a facile synthesis of a N-substituted analogue of 2,5-diarylthiazole, which shows photoluminescent properties with extended π-conjugation. Spectroscopic characteristics of the obtained thiazole derivatives are discussed by measurements of UV–vis absorption and photoluminescent spectra. Under the reaction conditions using Ag₂CO₃ as an additive and Cu(OAc)₂–2PPh₃ as a catalyst, thiophene derivatives also react with 2-pyrrolidone to undergo C?H, N?H amidation.     

Electrochemical dehydrogenative N–H/N–H coupling reactions

The N–N bond is present in many important organic compounds, such as hydrazines, pyrazoles, azos, etc. Many methods based on transition metal catalyzed N–N coupling or functionalization of hydrazine have been reported for the synthesis of N–N containing organic compounds. In recent years, electrochemical dehydrogenative N–H/N–H coupling has become a powerful tool for the construction of N–N bearing organic compounds. The electrochemical methods employ electrons as traceless redox reagents instead of chemicals and produce hydrogen as the only byproduct. In this review, we summarize the recent advances in the electrochemical dehydrogenative N–H/N–H coupling reactions with focus on the mechanistic insights and synthetic applications of these transformations.     

Copper-catalyzed intramolecular C–N coupling reaction of aryl halide with amide

An efficient and concise method for the ligand-free copper-catalyzed intramolecular C–N bond coupling was developed, which afforded various (NH)-phenanthridinones in good to excellent yields with tolerance of various substrates.     

New approach to the functionalization of δ-carboline derivatives

The possibility of transformation of 3-cyano-1-p-nitrophenyl--carbolin-2-one into 2-amino-3-cyano-1-p-nitrophenyl-1H-pyrido[3,2-b]indole derivatives and 2-imino-3-cyano-1-p-nitrophenyl-5H-pyrido[3,2-b]indole derivatives (-carbolines) is demonstrated. Methylation of 1-p-nitrophenyl-2-piperidino-1H--carboline followed by treatment with acetone in an alkaline medium yields 4-acetonyl-5-methyl-1,4-dihydro-5H-pyrido[3,2-b]indole derivative. The rearrangement of 2-arylimino-3-cyano-1-p-nitrophenyl-5H-pyrido[3,2-b]indoles into 2-(aryl)nitrophenylamino-3-cyano-5H-pyrido[3,2-b]indoles was accomplished on heating above the melting point or on treatment with potassium tert-butoxide. The structures of the resulting compounds were proved by ¹H and ¹³C NMR spectroscopy and X-ray diffraction analysis.     

Iron-catalyzed C(sp)–H functionalization of methyl azaarenes with α-oxoesters: a facile approach to lactic acid derivatives

A highly efficient method for the C(sp³)–H functionalization of methyl azaarenes to α-oxoesters in the presence of iron(II) acetate as an inexpensive, nontoxic catalyst with moderate-to-excellent yields has been developed. This transformation represents a facile approach to medicinally important lactic acid derivatives.     

An expedient approach to substituted triazolo[1,5-a][1,4]benzodiazepines via Cu-catalyzed tandem Ullmann C–N coupling/azide-alkyne cycloaddition

An approach to the synthesis of triazolo[1,5-a][1,4]benzodiazepines comprising copper catalyzed tandem Ullmann C–N coupling followed by azide-alkyne cycloaddition has been described. The reaction of o-azidobenzylbromide and N-propargylated aniline derivatives in the presence of CuI and base leads to the formation of triazolo[1,5-a][1,4]benzodiazepines. The reaction has been successfully generalized by synthesizing a number of triazolo[1,5-a][1,4]benzodiazepine derivatives in good to excellent yields.     

Electrochemical C–H/N–H cross-coupling of 2-phenylindolizines with phenothiazines to synthesize novel N-aryl phenothiazine derivatives

A facile and elegant method for synthesis of novel N–aryl phenothiazine derivatives from 2-phenylindolizines and phenothiazines through direct electrochemical oxidation has been developed. This approach was performed smoothly at room temperature without external oxidant and catalyst. Cyclic voltammetry and in situ FTIR techniques were applied to analyze the cross-coupling process of phenothiazines and 2-phenylindolizines, which helped to select the appropriate reaction potential. Under the optimized conditions, a broad range of substrates were well tolerated, affording the desired products in moderate to excellent isolated yields (up to 91%) with high regioselectivity. Meanwhile, a plausible mechanism involving a radical pathway has been proposed.     

A tandem and tunable Pd catalyzed C–N coupling of heteroarenols with ureas via C–OH bond activation

At this circumstance for the first time, a facile and convenient method for heteroaryl ureas has been developed via a two-step process involving in situ C–OH activation followed by palladium catalyzed C–N coupling of heteroarenols with ureas, which show excellent functional group tolerance and give out rapid coupling in good to excellent yield.     

A convenient C–H functionalization platform for pyrroloiminoquinone alkaloid synthesis

Pyrroloiminoquinone alkaloids represent a structurally intriguing class of natural products that display an array of useful biological properties. Here, we present a versatile and scalable platform for the synthesis of this diverse family – and in particular the antitumor discorhabdins – built upon sequential selective C–H functionalization of tryptamine. The utility of this strategy is showcased through short formal syntheses of damirones A–C, makaluvamines D and I, and discorhadbin E. Additionally, we describe efforts to develop the first catalytic asymmetric entry to the discorhabdin subclass.     

Palladium-catalyzed relay C–H functionalization to construct novel hybrid-arylcyclophosphorus ligand precursors

A new relay C–H functionalization of di([1,1’-biphenyl]-2-yl)phosphine oxide to obtain esterified and hydroxylated products with different hypervalent iodines as oxidants under palladium catalysis is disclosed.This reaction provides a more effective and concise strategy for the synthesis of novel structural hybrid-arylcyclophosphorus ligand precursors with a wide range of substrates and good functional group tolerance.     

The 3-substitution of naphthalene-1,2-diones with boronic acids: a C–H functionalization approach to novel spirooxazine photochromics

The addition of alkyl and aryl boronic acids to naphthalene-1,2-diones in the presence of an excess of ammonium persulfate and catalytic silver nitrate to yield 3-functionalized naphthalene-1,2-diones is reported. The products of these reactions were then further processed to yield the corresponding novel spirooxazine photochromic dyes.     

Construction of fluorinated pyrazole derivatives via a one-pot tandem C–H insertion/electrophilic fluorination reaction

A series of 4-fluoro-pyrazole derivatives were synthesized in moderate to good yields via a one-pot tandem procedure involving an Rh₂(OAc)₄-catalyzed C–H insertion and an electrophilic fluorination with N-fluorobenzenesulfonimide (NFSI).     

Regio- and stereoselective C10β–H functionalization of sinomenine: an access to more potent immunomodulating derivatives

Regio- and stereoselective C_10β–H functionalization of sinomenine, an economically available natural immunomodulating alkaloid, has been studied, developed and successfully applied to the synthesis of new immunosuppressive sinomenine derivatives in a protecting-free fashion. Regioselective oxidation of sinomenine with (diacetoxyiodo)benzene (DIB) in water provided a single stable benzoquinone derivative 4, and subsequent 1,6-conjugated addition of 4 with alcohols, amines, and thiols afforded a new series of C_10β–H functionalized sinomenine derivatives stereoselectively. Some derivatives with a newly introduced 10β-bezenesulfanyl substituent exhibited much higher TNF-α inhibitory potency than their natural parent sinomenine. This work opens a convenient access to novel sinomenine derivatives with medicinal interests.     

Metal-free sequential dual oxidative amination of C(sp3)–H bonds: A direct approach to benzothiadiazine 1,1-dioxide derivatives

An efficient and metal-free Di-tert-butyl peroxide (DTBP)-promoted dual oxidative amination annulation of 2-amino arylsulfonamide with methylarene has been developed. This protocol provides straightforward access to benzothiadiazine 1,1-dioxide derivatives without using prefunctionalized substrates in good to excellent yields with good functional group tolerance.     

Synthetic approach to seco-tetracenomycin natural products saccharothrixone A–C

Design and development of first synthetic approach to the functionalized tetracyclic framework of structurally novel seco-tetracenomycin natural products saccharothrixones A–C has been reported. A thermal dehydro Diels-Alder reaction of an arenyne-alkyne unit has been utilized as the key synthetic step. This strategy has been extended for the generation of a small library of diversely functionalized tetracyclic systems of seco-tetracenomycins. An approach for the synthesis of poly-hydroxyl tetracyclic system has also been described. This report represents the first synthetic approach to the tetracenomycin natural products saccharothrixones A–C.     

Organocatalytic asymmetric tandem condensation-intramolecular rearrangement-protonation: an approach to optically active α-amino thioester derivatives

An unprecedented and conceptually novel chiral Br?nsted base/Br?nsted acid catalytic method for the enantioselective synthesis of α-amino thioesters through a tandem condensation-intramolecular rearrangement-protonation has been developed which provides a number of important synthetic building blocks in good yield and with moderate to good enantioselectivities.     

Recent advances in mechanochemical C–H functionalization reactions

The mechanochemical synthesis has provided a greener alternative to solution-based approaches by eliminating the use of organic solvents and reducing the energy consumption. The C–H functionalization is among the most concise and economical synthetic strategies. The combination of the benefits from these two methods provides new opportunities to further increase the efficiency and sustainability of organic synthesis. In this digest, we aim to provide a brief overview of the recent advances in mechanochemical C–H functionalization reactions.     

Ullmann-type C–N coupling reaction catalyzed by CuI/metformin

A facile and efficient method for Ullmann-type C–N coupling reaction of amine and aryl halide catalyzed by CuI/metformin in EtOH is described. The advantages of this method are the use of an inexpensive and readily available catalyst and ligand, easy workup, shorter reaction time, improved yields, and the use of green solvent. Furthermore, this procedure is applied successfully for the modification of natural products, such as Vindoline and Tabersonin.