A domino reaction for the synthesis of pyrrolo[2,1-a]isoquinolines from 2-aryl-pyrrolidines and alkynes promoted by a four-component catalytic system under aerobic conditions.

Pyrrolo[2,1-a]isoquinoline derivatives were synthesized from 2-aryl-pyrrolidines and alkynes via an oxidative dehydrogenation/cyclization coupling/dehydrogenative aromatization domino process. This reaction was promoted by a four-component catalytic system which included [RuCl2(p-cymene)]2, CuCl, copper acetate monohydrate and TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) under aerobic conditions.

Palladium-Catalyzed Carbonylative Dearomatization of Indoles to Achieve Carbonyl-Containing Spirocyclic Indolenines Bearing an All-Carbon Quaternary Center.

A Pd-catalyzed carbonylative dearomatization via an acyl Pd complex has been developed. Diversified carbonyl-containing spirocyclic indolenines with an all-carbon quaternary center were constructed in an efficient and straightforward way with good to excellent yields. The protocol features a simple catalytic system, operational simplicity, a broad substrate scope, easy scale-up, and versatile transformations. In addition, the asymmetric reaction was initially explored with moderate enantioselectivity.

Palladium-Catalyzed Dearomatization of Indoles with Alkynes: Construction of Spirocyclohexaneindolenines.

A palladium-catalyzed dearomatization of indoles with alkynes has been developed, providing an efficient route to access a variety of synthetically useful spirocyclohexaneindolenines in moderate to good yields. The current method features a simple catalytic system, operational simplicity, and good functional group compatibility, which will contribute substantially to the development of dearomatization to access spiro compounds. Besides, the ubiquitous existence of spiro molecules, including spirocyclohexaneindolenines, in drugs and biological active molecules suggests the potential application of this methodology in medicinal chemistry.

Copper-catalyzed selective C5-H bromination and difluoromethylation of 8-aminoquinoline amides using ethyl bromodifluoroacetate as the bifunctional reagent.

A simple and effective method for the copper-catalyzed selective C5-H bromination and difluoromethylation of 8-aminoquinoline amides with ethyl bromodifluoroacetate as the bifunctional reagent was developed. The combination of cupric catalyst and alkaline additive results in a C5-bromination reaction, whereas cuprous catalyst combined with silver additive results in the C5-difluoromethylation reaction. This method has a broad substrate scope and allows for easy and convenient access to desired C5-functionalized quinolones with good to excellent yields.

Copper-catalysed benzylic C-H coupling with alcohols via radical relay enabled by redox buffering.

Cross-coupling reactions enable rapid, convergent synthesis of diverse molecules and provide the foundation for modern chemical synthesis. The most widely used methods employ sp2-hybridized coupling partners, such as aryl halides or related pre-functionalized substrates. Here, we demonstrate copper-catalysed oxidative cross coupling of benzylic C-H bonds with alcohols to afford benzyl ethers, enabled by a redox-buffering strategy that maintains the activity of the copper catalyst throughout the reaction. The reactions employ the C-H substrate as the limiting reagent and exhibit broad scope with respect to both coupling partners. This approach to direct site-selective functionalization of C(sp3)-H bonds provides the basis for efficient three-dimensional diversification of organic molecules and should find widespread utility in organic synthesis, particularly for medicinal chemistry applications.

Direct Hiyama Cross-Coupling of (Hetero)arylsilanes with C(sp2)-H Bonds Enabled by Cobalt Catalysis.

We report a chelation-assisted C-H arylation of various indoles with sterically and electronically diverse (hetero)arylsilanes enabled by cost-effective Cp*-free cobalt catalysis. Key to the success of this strategy is the judicious choice of copper(II) fluoride as a bifunctional sliane activator and catalyst reoxidant. This methodology features a broad substrate scope and good functional group compatibility. The synthetic versatility of this protocol has been highlighted by the gram-scale synthesis and late-stage diversification of biologically active molecules.

Copper-catalyzed aerobic cyclizations of tetrahydroisoquinolines with bromoketones and alkenes for the synthesis of 5,6-dihydropyrrolo[2,1-a]isoquinolines.

A new copper-catalyzed oxidative cyclization protocol was developed for the synthesis of 5,6-dihydropyrrolo[2,1-a]isoquinolines via a three-component reaction of tetrahydroisoquinolines with bromoketones and electron-deficient alkenes with air as a terminal oxidant. A variety of functional groups survived under the reaction conditions and the target products were obtained in good yields. This reaction features such advantages as eco-friendly reaction conditions, a simplified operation process and a broad substrate scope.

Application of primary halogenated hydrocarbons for the synthesis of 3-aryl and 3-alkyl indolizines.

Indolizine is an important heterocyclic compound with several interesting properties that make it suitable for numerous applications in many fields, such as biology, medicine and materials. However, the synthesis of 3-alkyl indolizines from bulky primary halogenated alkanes has not yet been reported. Herein, a transition-metal-free synthetic route to 3-aryl and 3-alkyl indolizines from electron-deficient alkenes, pyridines and primary halogenated hydrocarbons has been reported for the first time using a tandem reaction. The key step of this method is the oxidative dehydrogenative aromatization of a tetrahydroindolizine intermediate with 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) as the oxidant. The advantages of this protocol are its use of easily available and low-cost starting materials, the transition-metal-free conditions and its ready scalability.

Synthesis of Pyrrole via a Silver-Catalyzed 1,3-Dipolar Cycloaddition/Oxidative Dehydrogenative Aromatization Tandem Reaction.

Pyrroles are an important group of heterocyclic compounds with a wide range of interesting properties, which have resulted in numerous applications in a variety of fields. Despite the importance of these compounds, there have been few reports in the literature pertaining to the synthesis of pyrroles from simple alkenes using a one-pot sequential 1,3-dipolar cycloaddition/aromatization reaction sequence. Herein, we report the development of a benzoyl peroxide-mediated oxidative dehydrogenative aromatization reaction for the construction of pyrroles. We subsequently developed a one-pot tandem reaction that combined this new method with a well-defined silver-catalyzed 1,3-dipolar cycloaddition reaction, thereby providing a practical method for the synthesis of multisubstituted pyrroles from easy available alkenes. The mechanism of this oxidative dehydrogenative aromatization reaction was also examined in detail.

Structural, spectral and magnetic studies of two Co(II)-N-heterocyclic diphosphonates based on multinuclear units.

Two examples of Co(II)-N-heterocyclic coordination polymers based on 1-hydroxyethylidenediphosphonic acid (H5L=CH3C(OH)(PO3H2)2), namely 0.5(H3NCH2CH2NH3)·[Co6(Cl2)(H3L)2(H2L)(HL)(2,2'-bipy)6] 1 and 2(NH4)·[Co3(HL)2(H2O)2(phen)2]·2(H2O) 2, have been solvothermally obtained by introducing the second ligands 2,2'-bipyridine/1,10-phenanthroline (2,2'-bipy/phen) and characterized by powder X-ray diffraction (PXRD), elemental analysis, IR, TG-DSC. The single-crystal X-ray diffractions show that compound 1 possesses a 0-D structure with hexa-nuclear cluster [Co6(O-P-O)8] built through single/double O-P-O bridges and compound 2 displays a 1-D ladder-like chain structure with magnetic topology building blocks [Co4(O-P-O)4]n. Then H-bonding and π-π stacking interactions further expand the two low-dimensional structures into three-dimensional supramolecular frameworks. Fluorescent measurements reveal that both the maximum emission peaks of 1-2 are centered at 423nm, mainly deriving from intraligand π*-π transition state of N-heterocyclic ligand 2,2'-bipy/phen, respectively. Magnetism data indicate that 1 exhibits antiferromagnetic behavior within hexa-nuclear Co(II) clusters, while 2 shows weak ferromagnetic interactions in 1-D topology Co(II)-chain, showing promising potential as magnetic materials.

Synthesis of pyrrolo[2,1,5-cd]indolizines through dehydrogenative Heck annelation of indolizines with diaryl acetylenes using dioxygen as an oxidant.

A dehydrogenative Heck annelation reaction of indolizine with diaryl acetylene via dual C-H bond cleavage was developed. Oxygen gas was employed as a clean oxidant in this catalysis under base-free conditions. Diarylpyrrolo[2,1,5-cd]indolizines were synthesized with high atom economy. In addition, kinetic isotope experiments provided evidence for C-H bond metalation of the 5-position of the indolizine as the rate-limiting step.

Aza-Wacker-type reaction between electron-deficient olefins and N-alkylsulfonamides.

A palladium-catalyzed oxidative amination protocol of electron-deficient olefins by aza-Wacker-type reaction with N-alkylsulfonamides was developed. The presence of the stoichiometric amount of methanesulfonic acid was crucial for the success of this transformation. The reactions were conducted in green solvent under mild conditions and scalable with excellent E-type stereoselectivity. In addition, a Pd(II)/Pd(0) catalytic cycle with the existence of a very strong oxidant (Selectfluor) was proposed.

Copper(II)-catalyzed indolizines formation followed by dehydrogenative functionalization cascade to synthesize 1-bromoindolizines.

A one-pot, three-component cascade reaction between pyridine, α-acylmethylbromide, and maleic anhydride leading to direct access of 1-bromoindolizines in high yields has been developed. This protocol is accomplished via a reaction sequence of 1,3-dipolar cycloaddition of the pyridinium ylide with maleic anhydride, oxidative decarboxylation of the primary cycloadduct, and dehydrogenative bromination of the resulting 1-unsubstituted indolizine. Copper chloride was used as a catalyst and oxygen as the terminal oxidant. This reaction represents the first example of transition-metal-catalyzed direct dehydrogenative bromination of indolizine at the C-1 position. Moreover, the obtained 1-bromoindolizines can be transformed to other 1-substituted indolizines such as 1-arylindolizines via a simple reaction process.

Copper(II)-catalyzed carbon-carbon triple bond cleavage of internal alkynes for the synthesis of annulated indolizines.

Cleavage of C≡C bond in butynedioates via copper(II)-catalyzed reaction has been achieved, leading to the synthesis of benzo[f]pyrido[1,2-a]indole-6,11-diones in high yields by one-pot three-component reactions. In this unprecedented C≡C bond cleavage reaction of internal alkynes, both fragments from the alkyne are successively incorporated into the products.

Two novel Cu(II) diphosphonates: structural, spectral and magnetic studies.

By introducing the second organic N-heterocyclic ligands 2,2'-bipyridine (2,2'-bipy)/1,10-phenanthroline (phen), two mono-/bi-nuclear examples of Cu(II)-diphosphonate coordination polymers based on 1-hydroxyethylidenediphosphonic acid (H5L=CH3C(OH)(PO3H2)2), [Cu(H4L)2(2,2'-bipy)]·H2O 1 and [Cu(H3L)(phen)]2·(HOCH2CH2OH)0.52, have been solvothermally obtained and characterized by powder X-ray diffraction, elemental analysis, IR, TG-DSC. The single-crystal X-ray diffractions show that both the two compounds possess zero-dimensional structures, built from mononuclear unit [CuO4N2]n for 1 and binuclear unit [-Cu-O-P-O-]2n with a double O-P-O bridge for 2 in syn-anti fashion. Then H-bond or/and π-π interactions further expand the two zero-dimensional structures into the three-dimensional supramolecular frameworks. Fluorescent measurements reveal that the maximum emission peaks of 1-2 centered at 433.5nm for 1 and 434.5nm for 2, respectively, are mainly caused by intraligand π(*)-π emission state of N-heterocyclic ligands (λex=235nm). The further magnetic study shows the two coordination polymers exhibit antiferromagnetic behavior for 1 between the mononuclear units, while ferromagnetic behavior for 2 derived from double O-P-O bridges in syn-anti mode between the metal centers.

Coupling of methyl ketones and primary or secondary amines leading to α-ketoamides.

A metal-free oxidative coupling of methyl ketones and primary or secondary amines to α-ketoamides has been developed. Four intermediates, α-iodoketone, α-aminoketone, iminium intermediate, and α-hydroxy amine have been identified through a series of control experiments. The atom-economic methodology can be scaled-up, tolerates a variety of functional groups, and is operationally simple.

Tetrabutylammonium iodide catalyzed synthesis of allylic ester with tert-butyl hydroperoxide as an oxidant.

A metal-free C-H oxidation for the construction of allylic esters has been developed. The use of a commercially available and inexpensive catalyst and oxidant, and readily available starting materials, coupled with the operational simplicity of the reaction, renders the methodology a useful alternative to other approaches typically employed in the synthesis of allylic esters.

Structure and mechanism of the diterpene cyclase ent-copalyl diphosphate synthase.

The structure of ent-copalyl diphosphate synthase reveals three α-helical domains (α, ß and γ), as also observed in the related diterpene cyclase taxadiene synthase. However, active sites are located at the interface of the ßγ domains in ent-copalyl diphosphate synthase but exclusively in the α domain of taxadiene synthase. Modular domain architecture in plant diterpene cyclases enables the evolution of alternative active sites and chemical strategies for catalyzing isoprenoid cyclization reactions.

Synthesis of 1,2-annulated and 1,2-unsubstituted pyrrolo[2,1,5-de]quinolizin-5-ones (cycl[3.3.2]azin-5-ones) via [3+2] cycloadditions of 1-oxoquinolizinium ylides with cyclic alkenes.

1,2-Annulated pyrrolo[2,1,5-de]quinolizin-5-ones (cycl[3.3.2]azin-5-ones) 6a-6k, 8a-8b and 9 have been synthesized by one pot tandem reactions of 2-acetyl-N-phenacylpyridinium bromides (1a-1d) with electron-deficient cyclic alkenes (N-alkyl(aryl)maleimides, benzoquinones and naphthoquinone) in the presence of sodium carbonate as a base and tetrakispyridinecobalt(II) dichromate (TPCD) as an oxidant. These products are formed by 1.3-dipolar cycloaddition of the 1-oxoquinolizinium ylides generated in situ from 1a-1d with the alkene followed by dehydrogenation of the primary cycloadduct under the action of TPCD. Similar reactions of the ylides generated in situ from 1a-1f with maleic anhydride gave the 1,2-unsubstituted pyrrolo[2,1,5-de]quinolizin-5-ones 7a-7f via oxidative bisdecarboxylation and dehydrogenation of the primary cycloadducts under the action of TPCD.