Palladium‐Catalyzed Divergent Arylation with Triazolopyridines: One‐Pot Synthesis of 6‐Aryl‐2‐α‐styrylpyridines

We have developed a new strategy for palladium‐catalyzed arylation reactions with triazolopyridines, wherein two different chemical transformations (C‐3 vs. C‐7) are observed by differentiating the substrates using different bases. The reactive palladium carbenoids were directly generated from triazolopyridines and underwent denitrogenative arylations with aryl bromides. Intriguingly, when potassium carbonate was replaced with potassium tert‐butoxide, direct C H arylation occurred at the most acidic position (C‐7). Moreover, two different catalytic arylation events were successfully performed in a one‐pot sequence, providing a convenient access to 6‐aryl‐2‐α‐styrylpyridines.

     

One‐Pot Assembly of Fused Heterocycles via Oxidative Palladium‐Catalyzed Cyclization of Arylols and Iodoarenes

A one‐pot, two‐step cyclization reaction of iodoarenes with diversified arylols, including 4‐hydroxyquinoline, quinolinone, 4‐hydroxypyridine and phenol, has been developed. By using this palladium‐catalyzed formal tandem O‐arylation, dehydrogenative cross‐coupling reaction, a variety of biologically significant fused benzo[4,5]furo heterocycles and dibenzofurans were quickly assembled in high yields with excellent regioselectivity. Notably, the efficient one‐pot reaction led to the heterocycles via sequential oxidation, iodination, isomerization and cyclization steps without purification of any reaction intermediates.

     

One‐Pot Synthesis of Spirooxazino Derivatives via Enzyme‐ Initiated Multicomponent Reactions

A novel enzyme‐initiated multicomponent reaction from readily available aldehyde, nitrostyrene, cyclohexanone and acetamide substrates was discovered, enabling the facile construction of six new C C/ N bonds and two rings in single step, one‐pot operation, for the synthesis of spirooxazino derivatives in moderate to high yields. Several methods such as isotope labelling and enzyme mutation were used to probe the possible mechanism of this complex synthesis.

     

Synthesis of Benzoxazole and Benzimidazole Derivatives via Ligand‐Free Copper(I)‐Catalyzed Cross‐Coupling Reaction of o‐Halophenols or o‐Haloanilines with Carbodiimides

A novel and efficient synthesis of benzoxazole and benzimidazole derivatives via a ligand‐free, copper(I)‐catalyzed, one‐pot cascade process has been developed. A variety of carbodiimides coupled with o‐halophenols or o‐haloanilines to give the products in moderate to excellent yields under the mild conditions.     

Copper(I)‐Catalyzed One‐Pot Synthesis of 2‐Iminobenzo‐ 1,3‐oxathioles from ortho‐Iodophenols and Isothiocyanates

A novel and efficient formation of 2‐iminobenzo‐1,3‐oxathioles from readily available precursors via a copper(I)‐catalyzed one‐pot cascade process has been developed. Various 2‐iminobenzo‐1,3‐oxathioles, which might be useful in pharmaceutical and biochemical areas, were conveniently synthesized in good to excellent yields.     

A New One‐Pot Synthesis of Polysubstituted Indoles from Pyrroles and β‐Nitroacrylates

The reaction of β‐nitroacrylates with pyrroles, under solvent‐ and catalyst‐free conditions, allows the formation of Friedel–Crafts adducts which, after in situ treatment with Amberlyst 15 in isopropyl alcohol under reflux, provide polysubstituted indoles, via a benzannulation reaction, in a one‐pot process.     

One‐Pot/Four‐Step/Palladium‐Catalyzed Synthesis of Indole Derivatives: The Combination of Heterogeneous and Homogeneous Systems

One‐pot, four‐step syntheses of indoles using both solid‐supported heterogeneous and homogeneous palladium catalysts and reagents were carried out. Such a combination of these two‐phase catalysts and reagents causes a dramatic increase in yield, and it is a simple process. The presented methodology is effective for four‐step reactions to provide various functionalized indoles.     

Synthesis of Benzoindolines via a Copper‐Catalyzed Reaction of 1‐Bromoethynyl‐2‐(cyclopropylidenemethyl)arenes with N‐Allylsulfonamide

A copper‐catalyzed tandem reaction of 1‐bromoethynyl‐2‐(cyclopropylidenemethyl)arenes with N‐allylsulfonamide proceeds smoothly, affording functionalized benzoindolines in moderate to good yields. The transformation is a four‐step cascade involving Ullmann coupling, aza‐Claisen rearrangement, 6π‐electrocyclization, and intramolecular rearrangement.     

Iterative One‐Pot α‐Glycosylation Strategy: Application to Oligosaccharide Synthesis

Based on the combined use of dimethylformamide (DMF) modulation and neighboring group participation, three iterative one‐pot α‐glycosylation methods, i.e., one‐pot (α,α)‐, one‐pot (β,α)‐, and one‐pot (α,β)‐glycosylations, were developed. These methods are applicable to a range of thioglycosyl donors, confer stereocontrol in α‐/β‐glycosidic bond formation, and thus provide for rapid access to oligosaccharides with various permutations of anomeric configurations. The utility of these one‐pot glycosylation methods is demonstrated in the synthesis of eight non‐natural and natural oligosaccharide targets, including the core 1 serine conjugate, core 8 serine conjugate, the D ‐Gal‐α(1→3)‐D ‐Glc‐α(1→3)‐L ‐Rha trisaccharide unit of the cell wall component in Streptococcus pneumoniae, and the D ‐Glc‐α(1→2)‐D ‐Glc‐α(1→3)‐D ‐Glc trisaccharide terminus of the N‐linked glycan precursor. Confirmation of the anomeric configurations of these oligosaccharides is evidenced by ¹H, ¹³C, ¹³C‐non‐proton decoupling, and heteronuclear correlation 2D NMR experiments. Global deprotection of selected oligosaccharide targets is illustrated.     

Palladium(II)‐Catalyzed One‐Pot Enantioselective Synthesis of Arylglycine Derivatives from Ethyl Glyoxylate,p‐Toluenesulfonyl Isocyanate and Arylboronic Acids

A palladium(II)‐catalyzed, one‐pot enantioselective synthesis of arylglycine derivatives from ethyl glyoxylate, p‐toluenesulfonyl isocyanate and arylboronic acids giving moderate to good yields and enantioselectivity has been developed. This reaction provides a convenient and efficient method for the synthesis of arylglycines.     

Palladium‐Catalyzed Heck Coupling‐Hydrogenation: Highly Efficient One‐Pot Synthesis of Dibenzyls and Alkyl Phenyl Esters

An efficient method for the synthesis of industrially important dibenzyls and alkyl phenyl esters via sequential Heck coupling and hydrogenation of the alkenyl double bond in one pot with a single recyclable catalyst under mild conditions has been realised. The catalyst was recovered by simple filteration and reused for several cycles with consistent activity.     

Copper‐Catalyzed C‐Arylation and Denitrogenation of Tetrazoles: Domino Synthesis of 1,3‐Diaminoisoquinoline Derivatives

An unexpected copper‐catalyzed sequential C‐arylation and denitrogenation of tetrazoles leading to 1,3‐diaminoisoquinoline derivatives has been developed, and the corresponding 1,3‐diaminoisoquinoline derivatives were obtained in moderate to good yields. The method provides a novel strategy for the synthesis of isoquinoline derivatives containing various functional groups.     

N‐Iodosuccinimide‐Promoted Rapid Access to Indeno[1,2‐c]pyrroles via [3+2] Annulation of Enamine‐alkynes

We have developed a metal‐free, N‐iodosuccinimide (NIS)‐promoted, cascade strategy for the efficient synthesis of biologically important indeno[1,2‐c]pyrroles via a [3+2] annulation process of enamine‐alkynes. This methodology had shown a very broad scope for diversely functionalized enamines and alkynes. We have also developed a one‐pot, multicomponent strategy for the direct synthesis of indeno‐pyrroles from diynones via enamine‐alkynes. Control experiments supported the involvement of NIS as an electrophilic activator via an ionic mechanism rather than a radical pathway.

     

Palladium‐Catalyzed One‐Pot Synthesis of 5‐(1‐Arylvinyl)‐1H‐benzimidazoles: Overcoming the Limitation of Acetamide Partners

A new one‐pot palladium‐catalyzed process between N‐tosylhydrazones, N‐(dihalophenyl)‐imidates, and amines was designed. This reaction involves Barluenga cross‐coupling and N‐arylation followed by cyclization to produce functionalized benzimidazoles. During this transformation, one C C bond and two C N bonds were created by a single palladium‐catalyzed reaction. Depending on the starting materials, a library of 5‐(1‐arylvinyl)‐1H‐benzimidazoles was synthesized. Among several arylvinylbenzimidazole derivatives evaluated, one compound exhibits excellent antiproliferative activity in the nanomolar concentration range against human colon carcinoma cell lines (HCT‐116) and human lung adenocarcinoma epithelial cell lines (A549).

     

Efficient Method for the Synthesis of Optically Active 2‐Amino‐2‐chromene Derivatives via One‐Pot Tandem Reactions

The asymmetric synthesis of functionalized 2‐amino‐2‐chromene derivatives with high enantioselectivities via one‐pot tandem reactions of functionalized α,β‐unsaturated ketones with malononitrile catalyzed by 9‐amino‐9‐deoxyepiquinine ( 1a ) in combination with (R)‐1,1′‐binaphth‐2,2′‐diyl hydrogen phosphate ( 1c ) is reported for the first time.     

Ligand‐Free Copper‐Manganese Spinel Oxide‐Catalyzed Tandem One‐Pot C–H Amidation and N‐Arylation of Benzylamines: A Facile Access to 2‐Arylquinazolin‐4(3H)‐ones

An efficient ligand‐free copper‐manganese (Cu‐Mn) spinel oxide‐catalyzed direct tandem C−H oxygenation and N‐arylation of benzylamines has been developed. The method has been utilized for the synthesis of medicinally important 2‐arylquinazolin‐4(3H)‐ones. Salient features of this method include recyclable catalyst, no ligand, excellent product yields, shorter reaction times and a broad substrate scope.

     

Copper‐Catalyzed Domino Synthesis of Isoquinolino[2,3‐a]quinazolinones

A copper‐catalyzed domino method for synthesis of isoquinolino[2,3‐a]quinazolinones has been developed using readily available, substituted methyl 2‐(2‐haloobenzamido)benzoates and nitriles as the starting materials. The domino process comprises an Ullmann‐type C‐arylation, intramolecular addition of NH with CN, and nucleophilic attack of amino to ester group. The inexpensive, convenient and efficient copper‐catalyzed method should provide a new and useful strategy for constructing nitrogen heterocycles.     

Nickel(II)‐Magnesium‐Catalyzed Cross‐Coupling of 1,1‐Dibromo‐1‐alkenes with Diphenylphosphine Oxide: One‐Pot Synthesis of (E)‐1‐Alkenylphosphine Oxides or Bisphosphine Oxides

A novel nickel(II)‐magnesium‐mediated cross‐coupling of diphenylphosphine oxide with a variety of 1,1‐dibromo‐1‐alkenes has been developed, which provides a powerful and general methodology for the stereoselective synthesis of various (E)‐1‐alkenylphosphine oxides or bisphosphine oxides, with operational simplicity of the procedure, good to high yields and broad substrate applicability. Mechanistic studies reveal that the reaction might involve a Hirao reduction, cross‐coupling and Michael addition.     

Copper(I)‐Catalyzed [3+2] Cycloaddition/Ring‐Opening Rearrangement/[4+2] Cycloaddition/Aromatization Cascade: An Unprecedented Chemo‐ and Stereoselective Three Component Coupling of Sulfonyl Azide,Alkyne and N‐Arylidenepyridin‐2‐ amine to Pyrido[1,2‐a]pyrimidin‐4‐imine

A novel synthetic protocol for the one‐pot chemo‐ and stereoselective construction of diversely functionalized pyrido[1,2‐a]pyrimidin‐4‐imines via copper(I)‐catalyzed [3+2] cycloaddition/ring‐opening rearrangement/[4+2] cycloaddition/aromatization cascade of sulfonyl azides, alkynes and N‐arylidenepyridin‐2‐amines under mild reaction conditions is reported. In addition, the catalytic activity of copper(I)‐modified zeolite, a recyclable, heterogeneous catalyst is also investigated, which gives improved yield compared to its homogeneous equivalents.     

Synthesis of 2,5‐Diaminoquinones by One‐Pot Copper‐Catalyzed Aerobic Oxidation of Hydroquinones and Addition Reaction of Amines

The aerobic oxidation of various hydroquinones was achieved by using copper nanoparticles entrapped in aluminum oxyhydroxide [Cu/AlO(OH)] at room temperature. Furthermore, 2,5‐diamino‐1,4‐benzoquinones were synthesized directly from hydroquinone and amines by a one‐pot procedure consisting of the copper‐catalyzed aerobic oxidation of hydroquinones and the double addition of amines to the resulting quinones.