Direct access to 2-aminopyrazolo[1,5-a]pyridines via N-amination/cyclization reactions of 2-pyridineacetonitriles

We describe the straightforward synthesis of 6-substituted-2-aminopyrazolo[1,5-a]pyridines from 2-pyridineacetonitriles by N-amination with O-(mesitylsulfonyl)hydroxylamine and subsequent base-promoted cyclization. This N-amination/intramolecular cyclization reaction allows access to a variety of 6-substituted-2-aminopyrazolo[1,5-a]pyridines in a one-pot procedure, in moderate to good yields.     

Palladium-catalyzed tandem allenyl and aryl C-N bond formation: efficient access to N-functionalized multisubstituted indoles

An efficient palladium-catalyzed synthesis of N-functionalized multisubstituted indoles from easily accessible ortho-haloarylallenes and primary amines has been developed. A wide range of electronically and structurally varied nitrogen fragments could be introduced through this tandem C-N bond-forming process by tuning the reaction conditions.     

A convenient access to 1,5-anhydroketoses

A convenient, versatile entry into the 1,5-anhyroketose series is described and their conversion into enolones, enolone oximes and γ-pyrones.     

Direct access to 1,4-benzothiazine 4,4-dioxides and 4-oxides via a domino reaction

The domino reactions of 2-fluoro benzensulfonyl acetonitrile and α-chloro oximes in the presence of Cs₂CO₃ in aprotic high boiling point solvents have been achieved to provide isoxazole?fused 4H-1,4-benzothiazine-4,4-dioxides via an unprecedented transition metal-free one-pot addition/cyclization process. The tunable synthesis of either isoxozolo-1,4-benzothiazin-4-oxides or their precursor 5-aminoisoxazoles can be controlled depending on the solvent selection. The observed products were characterized by means of (IR, ¹H, ¹³C NMR and HRMS) and physical methods.     

Cu(II)-catalyzed intermolecular amidation of C-acylimine: a convenient access to gem-diamino acid derivatives

C-Acylimines 1 undergo intermolecular amidation with amides 2 to produce monoacyl gem-diamino acid derivatives 3 upon treatment with Cu(OTf)(2) (20 mol%)/ PPh(3) (20 mol%) under mild conditions. This method provides an efficient access to gem-diamino acid equivalents with good to excellent yields.     

Covalent attaching protein to graphene oxide via diimide-activated amidation

In this paper, graphene oxide nanosheets (GOS) are functionalized by bovine serum albumin (BSA) via diimide-activated amidation under ambient conditions. The obtained GOS–BSA conjugate is highly water-soluble. Results of atomic force microscopy (AFM), Raman spectra and Fourier transform infrared spectroscopy analysis confirm that GOS–BSA conjugate contains both GOS and BSA protein. AFM image shows that GOS are fully exfoliated. Results of cyclic volatammograms show that the protein in the GOS–BSA conjugate retains its bioactivity. The present method may also provide a way to synthesize graphene-based composites with other biomolecules.     

A new route to indazolone via amidation reaction of o-carboxyazobenzene

One new route for the synthesis of amino-substituted indazol-3,5-dione via the amidation reaction of o-carboxyazobenzenes is reported. Optimization which includes effects of the solvents, molar ratio of starting materials, and dehydrating agents on this reaction has been studied. A possible reaction mechanism has been proposed on the basis of the product's structure, and the steric hindrance could be the main reason for low yield.     

Direct access to anthranilic acid derivatives via CO2 incorporation reaction using arynes

CO2 was found to be directly convertible into anthranilic acid derivatives of great synthetic value through a three-component coupling using arynes and amines. Zwitterions arising from nucleophilic attack of amines to arynes serve as key intermediates in the coupling.     

Direct amidation of azoles with formamides via metal-free C-H activation in the presence of tert-butyl perbenzoate

A novel and simple method for the direct amidation of azoles with formamides has been developed. The reaction could occur smoothly in the presence of tert-butyl perbenzoate (TBPB) as an oxidant under metal- and base-free conditions. Direct dehydrogenative cross-coupling of formamides and azoles generated the corresponding products in good yields.     

General synthesis of meso-amidoporphyrins via palladium-catalyzed amidation

A series of meso-amidoporphyrins were facilely synthesized by direct reactions of meso-brominated porphyrins with amides via palladium-catalyzed amidation reaction. Using a combination of palladium precursor Pd(OAc)(2) or Pd(2)(dba)(3) and phosphine ligand Xantphos, both 5-bromo-10,20-diphenylporphyrin and 5,15-dibromo-10,20-diphenylporphyrin, as well as their zinc complexes, can be effectively coupled with a wide variety of amides to give the corresponding mono- and bis-substituted meso-amidoporphyrins in high yields under mild conditions. [reaction: see text]     

Synthesis of indolines via a domino Cu-catalyzed amidation/cyclization reaction

A highly efficient one-pot procedure for the synthesis of indolines and their homologues based on a domino Cu-catalyzed amidation/nucleophilic substitution reaction has been developed. Substituted 2-iodophenethyl mesylates and related compounds afforded the corresponding products in excellent yields. No erosion of optical purity was observed when transforming enantiomerically pure mesylates under the reaction conditions.     

Convenient access to 4-O-glycosylated 1,5-anhydro-d-fructoses via disaccharide-derived 2-hydroxyglycal esters

Efficient six-step protocols are described for the conversion of common disaccharides, such as maltose, cellobiose, or lactose, into the corresponding 4-O-glycosyl-1,5-anhydro-d-fructoses. Overall yields of 40-45% are favorably compared to the alternative eleven-step procedure from their monosaccharide components (∼15%).     

Rapid stereoselective access to key pumiliotoxin precursors from a common intermediate

Epoxidation and dihydroxylation of 8-methyl-2,3,6,8a-tetrahydro-1H-indolizin-5-one proceeded from the concave face with good selectivity and gave advanced precursors for pumiliotoxin and allopumiliotoxin synthesis, respectively. The origin of the selectivity is believed to be stereoelectronic in nature and allows rapid entry to three different pumiliotoxin classes from a common intermediate.     

Conformational features and chemical behavior of 5H, 7H-dibenzo[B,g][1,5] dithiocin oxides: 1,5-Oxygen shift via a dithiodication intermediate

Some 5H,7H-dibenzo[b,g][1,5]dithiocin oxides ( 4–8 ) and their related compounds 9–13 were prepared and the assignment of the most favorable conformation was carried out on the basis of the characteristic ¹H NMR spectral data. Only a single conformer (BC: boatchair form) exists for 4 , 5 , and 8–13 , while two conformers (BC and TB: twist-boat form) are apparent for 6 and 7 . Oxidation and methylation of 4 gave exclusively a single geometrical isomer ( 8 and 13 , respectively). These results are interpreted as a sterically preferential attack of electrophiles on the BC conformer of the starting material. A 1,5-oxygen shift of 4 occurred smoothly to give 6 in the presence of trifluoroacetic acid in CDCl₃ solution. The mechanistic investigation is described briefly. Differences in chemical behavior between dibenzodithiocin 12-oxide 4 and dibenzothiazocine 12-oxide 2 are also discussed on the basis of the conformational features.     

A convenient access to the 1,5-anhydro forms of d-tagatose,l-rhamnulose and d-xylulose via 2-hydroxyglycal esters

Zemplén methanolysis or a three-step protocol comprising hydroxylaminolysis, de-O-acetylation and deoximination smoothly and efficiently convert the benzoylated 2-hydroxy-d-glycals of d-galactose, l-rhamnose and d-xylose into their configurationally related 1,5-anhydro-ketoses, thereby providing convenient access to the 1,5-anhydro forms of d-tagatose, l-rhamnulose and d-xylulose. Invariably obtained as amorphous solids, they are best characterized through their highly crystalline oximes.     

Three-step synthesis of ethyl canthinone-3-carboxylates from ethyl 4-bromo-6-methoxy-1,5-naphthyridine-3-carboxylate via a Pd-catalyzed Suzuki-Miyaura coupling and a Cu-catalyzed amidation reaction

Ethyl canthin-6-one-1-carboxylate (1b) and nine analogues 1c-k were prepared from readily prepared ethyl 4-bromo-6-methoxy-1,5-naphthyridine-3-carboxylate (2b) via a three-step non-classical approach that focused on construction of the central pyrrole (ring B) using Pd-catalyzed Suzuki-Miyaura coupling followed by Cu-catalyzed C-N coupling. Furthermore, treatment of the ethyl canthinone-1-carboxylate 1b with NaOH in DCM/MeOH (9:1) gave the canthin-6-one-1-carboxylic acid (6) in high yield. All compounds are fully characterized.     

Facile access to a benzoazepinoquinazolinone via a free radical cyclization

An efficient synthetic protocol based on a free-radical cascade reaction via 6-exo-trig and 7-endo-trig cyclization processes is described for a new substituted benzoazepinoquinazolinone system which could in principle be used to form the cyclopropanequinone system found in duocarmycins.     

Synthesis of amides via palladium-catalyzed amidation of aryl halides

A new and efficient method for the synthesis of amides via palladium-catalyzed C-C coupling of aryl halides with isocyanides is reported, by which a series of amides were formed from readily available starting materials under mild conditions. This transformation could extend its use to the synthesis of natural products and significant pharmaceuticals.     

Reductive amidation of nitroarenes: a practical approach for the amidation of natural products

A simple and practical approach for the one-pot conversion of nitroarenes into amide derivatives has been developed. Zinc and acetic acid are utilized as a reducing agent, and acyl chloride and triethylamine are used as the acylating agent in DMF with good yield (∼60%) of the amide. This method was applicable to manzamine A (1), where the yield of 6-cyclohexamidemanzamine A (7) was significantly improved (56%) by this approach relative to (17%) by beginning with the amine.