Continuous Flow Synthesis of -Sulfonyl-1,2,3-triazoles for Tandem Relay Cu/Rh Dual Catalysis.

The continuous flow synthesis of -sulfonyl-1,2,3-triazoles, which are convenient reactive azavinyl carbene precursors, for tandem relay Cu/Rh dual catalysis has been developed. Most reactions readily proceeded at 75 °C in a short residence time of 13.09 min in the presence of 2.

Divergent Asymmetric Synthesis of Chiral Spiroheterocycles through Pd-Catalyzed Enantio- and Diastereoselective [3 + 2] Spiroannulation.

The palladium-catalyzed divergent asymmetric synthesis of chiral spiro-furanindoline derivatives is described. The zwitterionic alkoxy π-allyl Pd(II) intermediate, generated catalytically from vinyl ethylene carbonate (VEC), could undergo ligand-controlled enantio- and diastereoselective dipolar [3 + 2] spiroannulation with indole-based azadienes to afford the optically active spiro-furanindolines embedding an all-carbon quaternary stereocenter in high yields (up to 99%) with good to excellent stereoselectivities (up to 99% ee and up to >94:6 dr).

Electrochemically driven stereoselective approach to -1,2-diol derivatives from vinylarenes and DMF.

We have developed an electrochemically driven strategy for the stereoselective synthesis of protected -1,2-diols from vinylarenes with ,-dimethylformamide (DMF). The newly developed system obviates the need for transition metal catalysts or external oxidizing agents, thus providing an operationally simple and efficient route to an array of protected -1,2-diols in a single step. This reaction proceeds an electrooxidation of olefin, followed by a nucleophilic attack of DMF.

Catalyst-controlled divergent transformations of -sulfonyl-1,2,3-triazoles into isoquinolin-3-ones and 2-aminoindanones.

Novel catalyst-controlled divergent intramolecular reactions of N-sulfonyl-1,2,3-triazoles with tethered-allylic alcohol have been developed. In the presence of the Pd(0) catalyst alone, 1-vinylated 1,4-dihydroisoquinolin-3-ones were formed, whereas 3-vinylated 2-aminoindanones were accessed under tandem, one-pot, Rh(ii)/Pd(0) dual catalytic conditions. Based on deuterium-labelling experiments and isolation of the intermediate, a plausible reaction mechanism has been proposed.

Synergistic Pd(0)/Rh(II) Dual Catalytic [6 + 3] Dipolar Cycloaddition for the Synthesis of Monocyclic Nine-Membered -Heterocycles and Their Alder-ene Rearrangement to Fused Bicyclic Compounds.

The catalytic construction of a monocyclic medium-sized -heterocyclic ring represents a formidable challenge in organic synthesis. Herein we report the synergistic palladium(0)/rhodium(II) dual catalytic cycloaddition of vinylpropylene carbonates with -sulfonyl-1,2,3-triazoles to afford monocyclic nine-membered -heterocycles. The catalytically generated 1,6-dipole-equivalent zwitterionic π-allyl palladium(II) complex and the 1,3-dipole-equivalent α-imino rhodium(II) carbenoid intermediate react with each other in a formal [6 + 3] dipolar cycloaddition to furnish nine-membered oxazonines, which can be transformed into -fused [4.

Synergistic Dual Transition Metal Catalysis.

Synergistic catalysis, a type of plural catalysis which utilizes at least two different catalysts to enable a reaction between two separately activated substrates, has unlocked a plethora of previously unattainable transformations and novel chemical reactivity. Despite the appreciable utility of synergistic catalysis, specific examples involving two transition metals have been limited, as ensuring a judicious choice of reaction parameters to prevent deactivation of catalysts, undesirable monocatalytic event(s) leading to side products, or premature termination and other potentially troublesome outcomes present a formidable challenge. Excluding those driven by photocatalytic mechanisms, this review will highlight the reported examples of reactions that make use of two simultaneous catalytic cycles driven by two transition metal catalysts.

Palladium-Catalyzed Divergent Cyclopropanation by Regioselective Solvent-Driven C(sp )-H Bond Activation.

Reported is a tandem palladium-catalyzed Heck/regioselective C(sp )-H activation reaction for the divergent synthesis of spiro- and fused-cyclopropanated indolines from N-methallylated 2-bromoarylamides. The regioselectivity of the C-H bond activation in the σ-alkylPd intermediate is controlled by the solvent used. DFT calculations suggest that the polarity of solvent molecules could influence the transition-state energy, leading to a bifurcation of the C-H bond activation in the σ-alkylPd intermediate.

Transition metal-catalyzed site- and regio-divergent C-H bond functionalization.

Recent advances in transition metal-catalyzed C-H bond functionalization have profoundly impacted synthetic strategy. Since organic substrates typically contain several chemically distinct C-H bonds, controlling the regioselectivity of C-H bond functionalization is imperative to harness its full potential. Moreover, the ability to alter reaction pathways to selectively functionalize different C-H bonds in a substrate represents a greater opportunity and challenge.

Rh(II)/Mg(OBu)-Catalyzed Tandem One-Pot Synthesis of 1,4-Oxazepines and 1,4-Oxazines from N-Sulfonyl-1,2,3-triazoles and Glycidols.

A novel, one-pot route for the synthesis of nonaromatic ring-fused 1,4-oxazepines and 1,4-oxazines has been developed. The reaction features a sequential rhodium(II)-catalyzed reaction of N-sulfonyl-1,2,3-triazoles with glycidols, followed by a regioselective Lewis acid Mg(OBu)-catalyzed intramolecular ring-opening reaction. It has been found that the regioselectivity in the epoxide ring-opening was largely determined by the substituents on the glycidols.

Synthesis of α-methylene-δ-oxo-γ-amino esters via Rh(ii)-catalyzed coupling of 1-sulfonyl-1,2,3-triazoles with Morita-Baylis-Hillman adducts.

A rhodium(ii)-catalyzed coupling of 1-sulfonyl-1,2,3-triazoles, prepared from 1-alkynes and sulfonyl azides, with Morita-Baylis-Hillman (MBH) adducts afforded highly functionalized α-methylene-δ-oxo-γ-amino esters in excellent yields with broad functional group tolerance. This transformation can also be successfully accomplished as a multicomponent all-in-one-pot reaction of 1-alkynes, sulfonyl azides and MBH adducts in the presence of Cu(i) and Rh(ii) catalysts.

Pd-Catalyzed Aminocarbonylation of the Blaise Reaction Intermediate: One-Pot Synthesis of (Z)-3-Methyleneisoindolin-1-ones from Nitriles.

A highly efficient method for the one-pot synthesis of stereocontrolled (Z)-3-methyleneisoindolin-1-ones was developed starting from 2-bromoarylnitriles via tandem sequential reaction with a Reformatsky reagent (Blaise reaction), followed by Pd-catalyzed intramolecular aminocarbonylation with carbon monoxide at 1 atm pressure. It has been found that the conformational flexibility of the bisphophine ligand is of great importance to the success of this tandem aminocarbonylation reaction.

Tandem Blaise/Palladium-Catalyzed Ullmann Coupling for the One-Pot Synthesis of Enamino Ester-Functionalized Biaryls from Nitriles.

A novel Pd-catalyzed Ullmann-type homocoupling reaction of the Blaise reaction intermediate generated by the reaction of 2-bromo arylnitriles and a Reformatsky reagent has been developed for one-pot synthesis of enamino ester-functionalized biaryls 2 in good yields. The 2,2'-substituted enamine moieties of the coupling products could be cyclized under acidic conditions through the conjugate addition/deamination cascade to afford the seven-membered N-heterocyclics 3 with biaryl backbone in excellent yields.

Cu(I)/Rh(II)-Catalyzed Tandem Convergent Multicomponent Reaction for the Regio- and Stereocontrolled Synthesis of γ-Oxo-β-amino Esters.

The first example of a highly regio- and stereoselective catalytic method for the three-component one-pot synthesis of highly functionalized α-vinylated γ-oxo-β-amino esters is disclosed. In this catalytic triad, the Cu(I)-catalyst selectively catalyzes the cycloaddition of the 1-alkyne and sulfonyl azide first resulting in the corresponding 1-sulfonyl-1,2,3-triazole. An α-imino Rh(II)-carbene is generated from an open-chain α-imino diazo of the triazole, and this species reacts with γ-hydroxy α,β-unsaturated esters to form allylic (Z)-amino vinyl ethers.

Advances in tandem reactions with organozinc reagents.

The design and implementation of tandem reactions provides organic chemists with numerous challenges, in particular that of undesired cross-reactivity between substrates. Among organometallics, the use of organozinc reagents in tandem reactions provides several advantages as a result of their broad functional group tolerance and compatibility with transition metals. This review highlights prominent examples of recent advances in tandem reactions with organozinc reagents that illustrate their potential in organic synthesis.

From triazoles to imidazolines through the sequential N-H insertion of α-imino rhodium-carbenes into β-enamino esters/enamine-imine tautomerization/conjugate addition cascade.

A rhodium(II)-catalyzed denitrogenative coupling of N-sulfonyl-1,2,3-triazoles with ambiphilic β-enamino esters affords 2,5-dihydro-1H-imidazoles (3-imidazolines) with broad functional group tolerance. Mechanistic studies using a deuterium-labeled triazole suggest that the reaction proceeds in a cascade through the N-H insertion of an α-imino rhodium-carbene, followed by enamine-imine tautomerization and conjugate addition. Moreover, the reaction proceeds with high diastereoselectivity for α-substituted β-enamino esters (R(3) = Me, Ph) to give a single diastereomer.

Tandem one-pot synthesis of polysubstituted NH-pyrroles involving the palladium-catalyzed intramolecular oxidative amination of the zinc bromide complex of β-enamino esters.

The Pd-catalyzed oxidative olefin amination of the zinc bromide complex intermediate, formed by the sequential reaction of nitriles with a Reformatsky reagent and 1-alkynes, affords pyrrole derivatives in good to excellent yields. This tandem protocol provides a simple, efficient, and atom- and pot-economical way to quickly build polysubstituted NH-pyrroles starting from readily available reagents in a regiocontrolled manner with a broad substrate scope and high functional group tolerance. In contrast, the Pd-catalyzed oxidative olefin amination of an isolated α-vinyl-β-enamino ester did not proceed effectively, but the reaction efficiency can be restored by addition of n-BuZnBr or Zn(OAc)2, indicating the crucial role of the zinc complex in this transformation.

Supported ruthenium-carbene catalyst on ionic magnetic nanoparticles for olefin metathesis.

The Grubbs-Hoveyda ruthenium-carbene complex has been covalently immobilized on ionic magnetic nanoparticles utilizing an imidazolium salt linker. The supported catalyst exhibited excellent catalytic activity for ring-closing metathesis (RCM) and cross-metathesis (CM) in the presence of less than 1 mol % of ruthenium. The catalysts can easily be recovered magnetically and reused up to seven times with minimal leaching of ruthenium species.

Formation of four different aromatic scaffolds from nitriles through tandem divergent catalysis.

A zinc bromide complex, formed by the sequential reaction of nitriles with a Reformatsky reagent and terminal alkynes, is used as an intermediate for divergent palladium-catalyzed reactions. The reaction pathway of the intermediate is precisely controlled by the choice of the reaction solvent or the palladium catalyst to quickly form four different aromatic scaffolds--arylamines, aminoindenes, pyrroles, and quinolines--starting from readily available nitriles.

DMF as a source of oxygen and aminomethine: stereoselective 1,2-insertion of rhodium(II) azavinyl carbenes into the C═O bond of formamides for the synthesis of cis-diamino enones.

A new catalytic reaction in which all the atoms of a formamide are incorporated into the product through a formal stereoselective 1,2-insertion of rhodium(II) azavinyl carbenes, generated in situ from readily available N-sulfonylated 1,2,3-triazoles, into the C═O bond of DMF and other N,N-disubstituted formamides to afford cis-diamino enones is described.

New diarylamides and diarylureas possessing 8-amino(acetamido)quinoline scaffold: synthesis, antiproliferative activities against melanoma cell lines, kinase inhibition, and in silico studies.

Synthesis of a new series of diarylureas and diarylamides possessing 4-aryl-8-amino(acetamido)quinoline scaffold is described. Their in vitro antiproliferative activities against ten melanoma cell lines were tested. Compounds 1l, 2l, 3c, and 4c showed the highest potency against A375P cell line with IC50 values in sub-micromolar scale.

Tandem Blaise/retro-Blaise reaction for the nitrile-mediated regioselective intermolecular addition of unstabilized zinc ester enolates (Reformatsky reagents) to 1-alkynes and 1,3-enynes.

We report the novel use of a nitrile as a mediator to achieve the regioselective intermolecular addition of unstabilized zinc ester enolates (Reformatsky reagents) to 1-alkynes and 1,3-enynes. This reaction is made possible by a reversible addition of enolates to a nitrile (Blaise reaction), generating a zinc aza-enolate that, unlike zinc ester enolates, can add intermolecularly to 1-alkynes and 1,3-enynes. Subsequent removal of the nitrile through a retro-Blaise reaction generates the targeted addition product.

Imidazolium-salt-functionalized ionic-CNT-supported Ru-carbene/palladium nanoparticles for recyclable tandem metathesis/hydrogenation reactions in ionic liquids.

NP and tuck: Two different catalysts, a Ru-carbene complex and palladium nanoparticles, were immobilized onto the same imidazolium-salt-functionalized ionic CNTs. These supported dual-function catalysts showed excellent catalytic activity in tandem metathesis/hydrogenation reactions in an ionic liquid and could be recovered and reused four times. RCM = ring-closing metathesis.

An expedient and divergent tandem one-pot synthesis of pyrimidin-2,4-diones using the Blaise reaction intermediate.

A novel divergent tandem one-pot method for the synthesis of 3,5,6-trisubstituted 1H-pyrimidin-2,4-dione derivatives is developed. In the presence of 10 mol % of Cu(OAc)2, the α-substituted Blaise reaction intermediates (R(2) ≠ H) reacted with isocyanates chemoselectively to afford pyrimidin-2,4-diones, whereas the α-unsubstituted Blaise reaction intermediate (R(2) = H) showed a propensity to be a C-nucleophile toward electrophiles, permitting the installation of different functionalities at the 5-position through sequential tandem reactions.

Cu(OAc)2-catalyzed tandem Blaise/Pinner-type reaction for one-pot synthesis of pyrimidin-4-ones.

A novel tandem Blaise/Pinner-type reaction for the one-pot synthesis of pyrimidin-4-ones is described. The Blaise reaction intermediate, formed by addition of a Reformatsky reagent to a nitrile, reacted with a second nitrile chemoselectively in the presence of a catalytic amount of Cu(OAc)(2) to afford pyrimidin-4-ones.

Insight into the origin of the positive effects of imidazolium salt on electrocatalytic activity: ionic carbon nanotubes as metal-free electrocatalysts for oxygen reduction reaction.

We report remarkable metal-free electrocatalytic activities of the imidazolium salt-functionalized ionic multi-walled carbon nanotubes (IM-f-MWCNTs) in the oxygen reduction reaction (ORR). The electrocatalytic activity can be attributed to the induced polarization of the π-electrons of CNTs, thus accelerating interfacial electron transfer. The zwitterionic MWCNTs functionalized with poly(vinylimidazolium sulfonate) have a more positive surface charge and exhibit a better electrocatalytic activity than the poly(vinylbutylimidazolium chloride)-functionalized MWCNTs.