Transformations of N-arylpropiolamides to indoline-2,3-diones and acids via C≡C triple bond oxidative cleavage and C(sp^2)–H functionalization

A new palladium-catalyzed oxidative conversion of N-arylpropiolamides and H2O to various indoline-2,3-diones and acids through the C≡C triple bond cleavage and C(sp2)–H functionalization is described,which is promoted by a cooperative action of catalytic CuBr2,2,2,6,6-tetramethyl-1-piperidinyloxy(TEMPO)and O2.The method provides a practical tool for transformations of alkynes by means of a C–H functionalization strategy,which enables the formation of one C–C bond and multiple C–O bonds in a single reaction with high substrates compatibility and excellent functional group tolerance.     

Efficient synthesis of 2-arylquinazolines via copper-catalyzed dual oxidative benzylic C–H aminations of methylarenes

A novel copper-catalyzed dual oxidative benzylic C–H aminations of methylarenes with 2-aminobenzoketones in the presence of ammonium acetate was developed. This reaction represents a new avenue for 2-arylquinazolines with good yields. A key intermediate was detected and the kinetics isotope effect(KIE) indicated that C–H bond cleavage was the rate-determining step.     

Electrochemically mediated decarboxylative acylation of N-nitrosoanilines with α-oxocarboxylic acids

An efficient palladium-catalyzed electrooxidation C–H acylation reaction of N-nitrosoanilines with α-oxocarboxylic acids was developed. The anodic oxidation of the Pd(Ⅱ) intermediate was found to be the key to complete the reaction. In this case, the N-nitroso group was observed to be an effective directing group for C–H activation reaction. Moreover, the synthetic transformation of derivatives of natural products(L-menthol, dehydroepiandrosterone, and pregnenolone) was successfully realized. Fi...     

Regioselective introduction of vinyl trifluoromethylthioether to remote unactivated C(sp~3)–H bonds via radical translocation cascade

Described herein is an efficient protocol for the regioselective introduction of a vinyl trifluoromethylthioether to remote unactivated C(sp~3)–H bonds. The cascade process involves the vinyl radical-mediated 1,5-hydrogen atom transfer(HAT) and remote vinyl migration. During the transformation, inert C–H and C–C bonds are consecutively cleaved under mild conditions.The reaction features good functional group tolerance, broad substrate scope, and high regio-/stereo-selectivity.     

Amides as surrogates of aldehydes for C–C bond formation:amide-based direct Knoevenagel-type condensation reaction and related reactions

Aldehydes are perhaps the most versatile compounds that enable many C–C bond forming reactions, which are not amenable for other subclasses of carbonyl compounds. We report the first use of amides as surrogates of aldehydes for C–C bond formation,namely, the direct Knoevenagel-type condensation based on amides. The one-pot method consists of controlled reduction of an amide with LDBIPA [Li Al H(i Bu)2(Oi Pr)], Lewis acid-mediated release of a reactive iminium ion intermediate, nucleophilic addition, and in situ elimination of amine. The reaction shows good functional group tolerance. We also demonstrated that the Schwartz reagent could be used as an alternative of LDBIPA. The employment of nitromethane and a silyl enol ether as the nucleophiles opens an avenue for the unprecedented amide-based nitro-aldol condensation reaction and aldol condensation reaction, respectively.     

Enzyme-catalyzed asymmetric domino aza-Michael/aldol reaction for the synthesis of 1,2-dihydroquinolines using pepsin from porcine gastric mucosa

An unprecedented enzyme-catalyzed asymmetric domino aza-Michael/aldol reaction of 2-aminobenzaldehyde and a,b-unsaturated aldehydes is achieved. Pepsin from porcine gastric mucosa provided mild and efficient access to diverse substituted 1,2-dihydroquinolines in yields of 38%–97% with 6%–24%enantiomeric excess(ee). This work not only provides a novel method for the synthesis of dihydroquinoline derivatives, but also promotes the development of enzyme catalytic promiscuity.     

Palladium-catalyzed oxidative cyclopropanation of enamides and norbornenes initiated by C–H activation

A novel palladium-catalyzed oxidative cyclopropanation of enamides and norbornenes has been developed. The reaction proceeded through palladium-catalyzed vinyl C–H bond activation of enamides followed by two migratory insertions, β-(N)H elimination and hydrolyzation cascade steps. The reaction tolerates a range of functional groups and provides an effective method for the synthesis of cyclopropane-fused norbornanes in good yields under mild conditions.     

Catalytic enantioselective synthesis of β-amino alcohols by nitrene insertion

Chiral β-amino alcohols are important building blocks for the synthesis of drugs, natural products, chiral auxiliaries, chiral ligands and chiral organocatalysts. The catalytic asymmetric β-amination of alcohols offers a direct strategy to access this class of molecules. Herein, we report a general intramolecular C(sp~3)–H nitrene insertion method for the synthesis of chiral oxazolidin-2-ones as precursors of chiral β-amino alcohols. Specifically, the ring-closing C(sp~3)–H amination of N-benzoyloxycarbamates with 2 mol% of a chiral ruthenium catalyst provides cyclic carbamates in up to 99% yield and with up to 99% ee.The method is applicable to benzylic, allylic, and propargylic C–H bonds and can even be applied to completely non-activated C(sp~3)–H bonds, although with somewhat reduced yields and stereoselectivities. The obtained cyclic carbamates can subsequently be hydrolyzed to obtain chiral β-amino alcohols. The method is very practical as the catalyst can be easily synthesized on a gram scale and can be recycled after the reaction for further use. The synthetic value of the new method is demonstrated with the asymmetric synthesis of a chiral oxazolidin-2-one as intermediate for the synthesis of the natural product aurantioclavine and chiral β-amino alcohols that are intermediates for the synthesis of chiral amino acids, indane-derived chiral Box-ligands, and the natural products dihydrohamacanthin A and dragmacidin A.     

Fe3O4@MCM-48-OSO3H磁性核壳纳米粒子催化3,3′-双吲哚高效合成（英文）

Magnetite nanoparticles coated with sulfuric acid-functionalized mesoporous MCM-48 were syn-thesized and used as a catalyst in three-component domino reactions of indoles, arylglyoxal mono-hydrates andN-arylenaminones to furnish the desired 3,3′-bisindoles by formation of two C–C and one C–N bonds in a smooth cascade with good yields under mild reaction conditions. The catalyst was recovered easily and maintained activity in successive runs.     

Synthesis of unnatural amino acids through palladium-catalyzed C(sp~3)-H functionalization

Unnatural a-amino acids have been extensively used in the modern drug discovery and protein engineering studies. They have also found applications in the development of chiral molecular catalysts and the total synthesis of diverse natural products. Accordingly the development of cost-effective approaches for the preparation of unnatural a-amino acids has received increasing attentions. Among all the available methods for this purpose, direct C–H functionalization of simple amino acids represents one of the most attractive approaches because it exhibits good atom-economy and step-efficiency. In particular, selective functionalization of either the primary or secondary C(sp~3)–H bonds in the amino acids has been explored to make versatile C–C, C–N, C–O, C–B and C–F bonds to modify the side chain of amino acids and even peptides. The present review surveys the recent advances of synthesis of chiral unnatural a-amino acids and peptides through palladium-catalyzed functionalization of un-activated C(sp~3)–H bonds.     

Copper‐Catalyzed Domino Synthesis of 2‐Imino‐1H‐imidazol‐5(2H)‐ones and Quinoxalines Involving CC Bond Cleavage with a 1,3‐Dicarbonyl Unit as a Leaving Group

Although 2‐imino‐1H‐imidazol‐5(2H)‐ones have important biological activities in metabolism, their synthesis has rarely been investigated. Quinoxalines as “privileged scaffolds” in medicinal chemistry have been extensively investigated, but the development of novel and efficient synthetic methods remains very attractive. Herein, we have developed two copper‐catalyzed domino reactions for the synthesis of 2‐imino‐1H‐imidazol‐5(2H)‐ones and quinoxalines involving C?C bond‐cleavage with a 1,3‐dicarbonyl unit as a leaving group. The domino sequence for the synthesis of 2‐imino‐1H‐imidazol‐5(2H)‐ones includes aza‐Michael addition, intramolecular cyclization, C?C bond‐cleavage, 1,2‐rearrangement, and aerobic dehydrogenation reaction, whereas the domino sequence for the synthesis of quinoxalines includes aza‐Michael addition, intramolecular cyclization, elimination reaction, and C?C bond‐cleavage reaction. The two domino reactions have significant advantages including high efficiency, mild reaction conditions, and high tolerance of various functional groups.     

Enantioselective gold-catalyzed functionalization of unreactive sp3 C-H bonds through a redox-neutral domino reaction

Selectivity is golden: The first asymmetric redox-neutral domino reaction catalyzed by gold that results in the direct functionalization of unreactive sp(3) C-H bonds has been reported. This method consists of a heterocyclization/1,5-hydride transfer/cyclization reaction and provides synthetically valuable azepines with high enantioselectivities and in high yields (Tf = triflate; see scheme).     

Two palladium-catalyzed domino reactions from one set of substrates/reagents: efficient synthesis of substituted indenes and cis-stilbenoid hydrocarbons from the same internal alkynes and hindered Grignard reagents

Two types of domino reactions from the same internal alkynes and hindered Grignard reagents based on carbopalladation, Pd-catalyzed cross-coupling reaction, and a C-H activation strategy are described. The realization of these domino reactions relied on the control of the use of the ligand and the reaction temperature. Our study provides efficient access to useful polysubstituted indenes and cis-substituted stilbenes and may offer a new means of development of tandem/domino reactions in a more efficient way. [reaction: see text].     

Pd-catalyzed benzylic C-h amidation with benzyl alcohols in water: a strategy to construct quinazolinones

A novel method for the synthesis of 4-phenylquinazolinones via a palladium-catalyzed domino reaction of o-aminobenzamides with benzyl alcohols is developed. This protocol involves N-benzylation, benzylic C-H amidation, and dehydrogenation in water, which may play an important role in the smooth generation of the (η(3)-benzyl)palladium species by activation of the hydroxyl group of the benzyl alcohol.     

Multicenter ligand transformations of thioureas on ruthenium clusters

The reaction of trirutheniumdodecacarbonyl with various thioureas was found to give, depending upon the substituents and the reaction conditions, a large variety of tri-, tetra-, penta-, and hexanuclear ruthenium clusters. The ligand systems observed in the products are derived from the thioureas employed; the fragmentation of the thiourea molecules involve N-H, C-S, C-H, and C-N activation processes.     

Synthesis of 3-(diarylmethylenyl)oxindole by a palladium-catalyzed domino carbopalladation/C-H activation/C-C bond-forming process

[reaction: see text] A highly efficient palladium-catalyzed synthesis of unsymmetrically substituted 3-(diarylmethylenyl)indolinones from readily accessible starting materials is developed. The domino reaction involves a sequence of intermolecular carbopalladation, C-H activation, and C-C bond formation. A plausible mechanistic pathway for the reaction is discussed on the basis of the kinetic isotope effect [K(H)/K(D) (intermolecular) = 1, K(H)/K(D) (intramolecular) = 2.7] as well as the electronic effect.     

Palladium catalyzed domino C-H activation strategy: An access to 9- fluorenones

Palladium catalyzed domino C-H functionalization reaction of arylaldehyde with dihaloarene has been developed to access 9-flourenone molecules. Bidentate ligand assisted strategy, single step reaction, high yield and excellent functional group tolerance make this method concise and effective for the synthesis of 9-flourenone. In addition, proposed method has been successfully employed to synthesise Tilorone in gram scale.     

Pd(OAc)2-catalyzed domino reactions of 1,2-dihaloarenes and 2-haloaryl arenesulfonates with Grignard reagents: efficient synthesis of substituted fluorenes

Pd(OAc)₂-catalyzed domino reactions of 1,2-dihalobenzenes and 2-haloaryl arenesulfonates with hindered Grignard reagents to form substituted fluorenes, which are believed to occur through palladium associated aryne intermediates, are described. Such palladium associated aryne reaction pathway was found to be favored by omitting the use of phosphine and N-heterocyclic carbene ligands for palladium catalysts and with better leaving groups. Our study suggested that Pd(leaving group)X associated arynes should be formed first and the sp³ C-H activation preferentially occurred at benzylic C-(1°)H bonds. The work described here provides a high yield, one-step access to substituted fluorenes from readily available 1,2-dihalobenzenes and 2-haloaryl arenesulfonates and hindered Grignard reagents, and this substituted fluorene-making method may find applications in the preparation of substituted fluorene-containing molecules including polymers.     

Synthesis of iodo-indoloazepinones in an iodine-mediated three-component domino reaction via a regioselective 7-endo-dig iodo-cyclization pathway

An efficient and rapid synthetic strategy for the naturally occurring indoloazepinone scaffold via a three-component reaction of indole-2-carboxamides, 1,3-disubstituted propargyl alcohols, and I(2) is described. The strategy involves a C-H functionalization-alkyne activation-intramolecular hydroamidation-deprotonation domino sequence. The salient feature of this sequence is regioselective electrophilic 7-endo-dig iodo-cyclization during the intramolecular hydroamidation to afford a seven-membered azepinone ring annulated to the indole.     

Understanding sulfone behavior in palladium-catalyzed domino reactions with aryl iodides

Unlike traditionally used acyclic 1,2-disubstituted alkenes, the reaction of alpha,beta-unsaturated phenyl sulfones with aryl iodides under Heck reaction conditions takes place mainly by means of a four-component domino process, involving one unit of the alkene and three units of the aryl iodide, affording substituted 9-phenylsulfonyl-9,10-dihydrophenanthrenes. We report here the results of a computational study on the mechanism of this domino arylation reaction. Based on these results we can explain why vinyl sulfones, unlike other electron-deficient alkenes such as enones, preferentially follow this domino pathway instead of the usual Heck pathway. The key step is a C-H activation process in which a five-membered palladacycle is formed. The greater ability of vinyl sulfones, relative to enones, to reach the transition state that leads to the formation of the initial palladacycle makes the difference.