The use of anhydrous CeCl3 as a catalyst for the synthesis of 3-sulfenyl indoles

Anhydrous CeCl₃ was successfully used as a catalyst for the synthesis of several 3-sulfenyl indoles in good to excellent yields through the reaction of indole with N-(alkylthio) and N-(arylthio)phthalimides in DMF.     

Phthalimide-N-sulfenyl chloride in the Ti-catalyzed asymmetric sulfenylation of β-keto esters

The enantioselective sulfenylation of β-keto esters was carried out using phthalimide-N-sulfenyl chloride in the presence of a Ti(TADDOLato) catalyst affording up to 60% ee. X-ray crystal structures of product compounds 3a and 9a were determined.     

A novel direct N-alkenylation of nitrogen-containing heterocycles with magnesium alkylidene carbenoids

Treatment of magnesium alkylidene carbenoids, which were generated from 1-chlorovinyl p-tolyl sulfoxides with isopropylmagnesium chloride at −78 °C in toluene, with N-lithio nitrogen-containing heterocycles (e.g., indole, indazole, phenothiazine, and phenoxazine) gave N-alkenylated products in moderate to good yields. The intermediate of this reaction was found to be the alkenyl anion, which could be trapped with iodoalkanes using CuI as a catalyst to give the heterocycles having fully substituted alkenes on the nitrogen. The alkenyl anion intermediate could be trapped also with benzoyl chloride and phenyl isocyanate. This reaction offers a quite novel and direct N-alkenylation of nitrogen-containing heterocycles.     

Direct N- and C-alkenylation of nitrogen-containing heterocycles with magnesium alkylidene carbenoids

Treatment of magnesium alkylidene carbenoids, which were generated from 1-chlorovinyl p-tolyl sulfoxides with isopropylmagnesium chloride at −78 °C in toluene, with N-lithio nitrogen-containing heterocycles gave N-alkenylated products in moderate to good yields. Also, the reaction of C-lithio indoles, which were generated from N-protected indoles, with magnesium alkylidene carbenoids gave C-2 or C-3 alkenylated products, corresponding to the protective group. The intermediate of these reactions were found to be the alkenyl anion, which could be trapped with electrophiles to give the heterocycles having fully substituted alkenes.     

Zur synthese einiger neuer heterocyclisch substituierter stannane

The in 2-position trimethylstannylated heterocycles are formed in good yields by reaction of the lithiated heterocycles benzothiazole, N-methylbenzimidazole, N-methylimidazole, N-methyltriazole, pyridine, chinoline and thiazole with trimethylchlorostannane. The thermolabile lithium compounds are synthesized by metallation or by metal-halogen exchange reactions according to known procedures.     

A new method for the preparation of unsymmetrical 1,4-substituted piperazine derivatives

Symmetrical and unsymmetrical N,N′-piperazine derivatives of (−)-norephedrine and o-aminophenol were synthesized stereoselectively in yields >70% by reduction of the corresponding N,N′-ethylenebisoxazolidine heterocycles. The stereochemistry at the ring fusion carbons was established by NMR spectroscopy and X-ray crystallography.     

Heck cross-coupling of vinyl heteroaromatic compounds with aryl and heteroaryl halides using Pd(II) complex under phosphine-free conditions

The palladium-catalyzed cross-coupling reaction of vinyl heteroaromatic compounds with aryl bromides and heteroaryl bromides is described using air and moisture stable N,N′,N″,O-tetrafunctional Pd catalyst under phosphine-free conditions. As a result a variety of trans-1,2-disubstituted vinyl heterocycles were obtained in high to good yields.     

Reactions of 2-alkylimidazoles and 2-methylbenzimidazoles with 1,3-diacid chlorides. Synthesis of highly functionalized hetero-cycles under mild conditions

Highly functionalized heterocycles were synthesized in one-pot reactions of 2-alkylimidazoles or 2-methylbenzimidazoles with 1,3-diacid chlorides. Some of the cyclizations proceed through cyclic-N,N′-ketene acetal intermediates.     

Cyclisation reactions of bis-protected guanidines

The cyclisation of N-allyl- and N-homoallylguanidines using DMDO or I₂/K₂CO₂ leading to novel heterocycles is reported.     

Multisubstituted N-fused heterocycles via transition metal-catalyzed cycloisomerization protocols

Two complementary protocols for assembly of multisubstituted N-fused heterocycles have been developed. It was demonstrated that 1,3-disubstituted N-fused heterocycles, including indolizines, pyrroloquinoxalines, and pyrrolothiazoles can easily be synthesized via an exceptionally mild and efficient method involving a novel silver-catalyzed cycloizomerization of propargyl-containing heterocycles. Alternatively, 1,2-disubstituted heterocycles can be accessed through the novel cascade transformation involving an alkyne-vinylidene isomerization with concomitant 1,2-shift of hydrogen, silyl, stannyl, or germyl groups. This mild and simple method allows for selective and highly efficient synthesis of indolizines, pyrroloisoquinolines, pyrroloquinoxalines, pyrrolopyrazines, and pyrrolothiazoles.     

Structural studies of {Li} 2-lithiopyrrolidines using NMR spectroscopy

A selection of N-substituted 2-lithiopyrrolidines were prepared and their structures were investigated by ⁶Li and ¹³C NMR spectroscopy. Evidence is presented for aggregation and dynamic solvation effects, depending on the nature of the N-substituent and substituents on the pyrrolidine ring. Studies were performed with N-Boc (coordinating carbonyl group), N-methoxyethyl (coordinating methoxy group) and N-alkyl (no coordinating group) heterocycles to represent three different classes of organolithiums: dipole-stabilized, unstabilized and chelated, and unstabilized.     

Copper fluorapatite catalyzed N-arylation of heterocycles with bromo and iodoarenes

Copper exchanged fluorapatite (CuFAP) is an effective heterogeneous catalyst for N-arylation of heterocycles with bromo- or iodoarenes using K₂CO₃ as base. N-Arylated products were isolated in good to excellent yields, demonstrating the versatility of the reaction.     

Assembly of N-substituted pyrrolo[2,1-c][1,4]benzodiazepine-5,11-diones via copper catalyzed aryl amination

Copper-catalyzed amination of N-heterocycle derived aryl iodides followed by intramolecular condensative cyclization afforded N-substituted pyrrolo[2,1-c][1,4]-benzodiazepine-5,11-diones with good yields. By varying primary amines and substituents at aromatic ring of aryl iodides, a wide range of these heterocycles were assembled.     

Improved and expanded one-pot,two-component Boulton-Katritzky syntheses of N–N bond containing bicyclic heterocycles

Improved and expanded one-pot, two-component syntheses of bicyclic heterocycles containing a 3-N-acyl-3-amino-1,2-pyrazole motif from N′-hydroxy-carboxyamidines and acylbenzotriazoles have been developed. Importantly, this sequence obviates the need for hydrazine or N-aminating reagents to synthesize the key nitrogen–nitrogen (N–N) bond of these heterocycles, which is formed via Boulton-Katritzky rearrangement. A diverse array of pharmaceutically relevant N–N containing heterocycles has been prepared with this methodology using readily available reagents without the need for special equipment or conditions.     

An effective C-C double bond formation via Cu(I)-catalyzed dehydrogenation

A dehydrogenation method using Cu(I) and either N,N-di-tert-butylthiadiaziridine 1,1-dioxide or N,N-di-tert-butyldiaziridinone is reported. The dehydrogenation allows a facile introduction of C-C double bond(s) into various carbocycles and heterocycles such as oxazolines and thiazolines.     

Rearrangement of oxazolidinethiones to thiazolidinediones or thiazinanediones and their application for the synthesis of chiral allylic ureas and α-methyl-β-amino acids

A novel rearrangement has been found between oxazolidinethiones and acyl halides under N-acylation reaction conditions to afford N-substituted 2,4-thiazolidinediones and N-substituted 1,3-thiazinane-2,4-diones. These heterocycles were used for the synthesis of chiral allylic ureas and α-methyl-β-amino acids.     

Lanthanide(III)-catalyzed multi-component aza-Diels-Alder reaction of aliphatic N-arylaldimines with cyclopentadiene

The Ln(OTf)₃-catalyzed formal aza-Diels-Alder (or Povarov) reaction of cyclopentadiene with in situ generated N-arylimines containing enolizable protons is described. This three-component Povarov reaction generates highly functionalized C-2 aliphatic substituted tetrahydroquinolines, heterocycles that were previously inaccessible using the Povarov reaction, because of the instability of the intermediate aliphatic N-arylaldimine.     

Tandem cycloisomerization/Suzuki coupling of arylethynyl MIDA boronates

A tandem gold-catalyzed cycloisomerization/Suzuki cross-coupling sequence involving arylethynyl-N-methyliminodiacetic acid boronates is described. Combining the mildness of homogeneous gold catalysis with the versatility of N-methyliminodiacetic acid (MIDA) boronates, this tandem two-step method enables the rapid assembly of various aryl-substituted heterocycles without having to isolate or purify any heterocyclic MIDA boronate intermediates. Another major advantage of this method is that a wide range of heterocycles bearing different aryl groups may be made from a single MIDA boronate alkyne precursor.     

N,N-dimethyl-d-glucosamine as an efficient ligand for copper-catalyzed Ullmann-type coupling of N-H heterocycles with aryl halides

A new N,N-dimethyl-d-glucosamine ligand has been developed for the copper-catalyzed Ullmann-type coupling of N-H heterocycles (e.g., indoles, benzimidazoles, pyrazoles and triazoles) with aryl halides. This method was accomplished not only featuring excellent yields, mild reaction conditions and simple operation, but also showing eco-friendly and broad-spectrum substrates, and could be widely used in the construction of N-aryl heterocyclic systems.     

A general synthesis of quinolinones and benzothiazine 1,1-dioxides via ring closing metathesis

A general synthesis of quinolinones and benzothiazine 1,1-dioxides is presented. A series of N-phenylacrylamides and N-phenylethylenesulfonamides were studied for their ability to undergo ring closing methathesis to yield the corresponding quinolinones and benzothiazine 1,1-dioxides, respectively. The reactions are general in scope and represents a mild method for the preparation of these heterocycles.