First synthesis of 2′-oxabicyclo[3.1.0]hexyl nucleosides with a north conformation

The first synthesis of 2′-oxabicyclo[3.1.0]hexyl nucleosides, a novel class of bicyclonucleosides, with a north conformation was successfully accomplished starting from (S)-epichlorohydrin via a tandem alkylation-lactonization, a less steric hindrance-dependent silylation in equilibrium and a coupling reaction with nucleobases under Vorbruggen conditions. Addition of acetic acid prevented a benzoyl group from migrating during desilylation with TBAF. ¹H NMR and X-ray crystallographic analysis indicated that the anomeric effect worked on the β-2′-oxabicyclo[3.1.0]hexyl nucleosides.     

An efficient stereoselective synthesis of 1-iodo- or 1-phenyl selenenyl-2-aryl-3-azabicyclo[3.1.0]hexane via electrophilic cyclization of benzyl-2-arylmethylidenecyclopropylmethyl-amines

The reaction of benzyl-2-arylmethylidenecyclopropylmethyl-amine 1 with iodine in the presence of potassium carbonate or PhSeBr stereoselectively gives ring-closure product 1-iodo-2-aryl-3-azabicyclo[3.1.0]hexane or 1-phenylselenenyl-2-aryl-3-azabicyclo[3.1.0]hexane in good yields at room temperature. A plausible reaction mechanism has been proposed.     

N-Arylmethyl-7-azabicyclo[2.2.1]heptane derivatives: synthesis and reaction mechanisms

N-Arylmethyl-7-azabicyclo[2.2.1]heptane (I) derivatives have been synthesized by deprotection of N-protected, N-(arylmethyl)cyclohex-3-enamines, bromination of the resulting secondary cyclohex-3-enamines, followed by base-promoted cyclization (route a), or by bromination of N-protected, N-(arylmethyl)cyclohex-3-enamines followed by deprotection and base-mediated cyclization (route b). In these protocols we have observed that the bromination of the key intermediates (12, 13, and 19) is stereoselective leading to major trans-3-cis-4-dibromides (14, 17, and 20), whose mild base-mediated heterocyclization (on compound 14), or the two-step acid hydrolysis plus base-promoted cyclization (on compounds 17 and 20), gave products 6 and 7 in good yield. A mechanistic investigation using DFT has been carried out to explain the results observed in this work.     

Lewis acid catalyzed reactions of methylenecyclopropylcarbinols with acetals for the construction of 3-oxabicyclo[3.1.0]hexane derivatives

Reactions of methylenecyclopropylcarbinols 1 with acetals 2 in the presence of Lewis acid Sc(OPf)₃ produce the ring-closure products 3-oxabicyclo[3.1.0]hexane in moderate to high total yields along with the products in trans-configuration as the sole or major one. The plausible reaction mechanism has been discussed, which is based on the Prins-type reaction mechanism.     

Synthesis of 1H-pyrrolo[3,2-c]quinoline derivatives via palladium-catalyzed heteroannulation of 2-aryl-3-iodo-4-(phenylamino)quinolines and 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinolines

Palladium(0)/copper iodide catalyzed Sonogashira cross-coupling of 2-aryl-3-iodo-4-(phenylamino)quinolines with terminal alkynes afforded series of 1,2,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines in a single-step operation. Conversely, the 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives were found to undergo PdCl₂(PPh₃)₂/CuI catalyzed intramolecular Heck reaction to yield the corresponding 1,3,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines.     

Novel synthesis of α-nitroalkenes from nitroalkanes via halogenation of intermediate N,N-bis(silyloxy)enamines

An approach to conjugated nitroalkenes via oxidation of N,N-bis(silyloxy)enamines with bromine or iodine in the presence of tetra-n-butylammonium acetate is described. The acetate ion plays a key role by acting as a mild desilylating reagent. This new strategy allows the synthesis of α-nitroalkenes from the corresponding nitroalkanes.     

Studies toward the construction of substituted piperidine-2-ones and pyridine-2-ones from Baylis-Hillman adducts: discovery of a facile synthesis of 5-methyl-4-oxo-6-aryl-3-aza-bicyclo[3.1.0]hexane-1-carboxylates

Studies toward the construction of functionalized piperidone derivatives from derivatives of Baylis-Hillman adducts are described. Interestingly the 6-oxo-4-aryl-piperidine-3-carboxylates generated during the study serve as precursor for the facile synthesis of 4-oxo-6-aryl-3-aza-bicyclo[3.1.0]hexane-1-carboxylates.     

Cascade reaction for 3-pyrrolines and pyrroles from nitroallylic acetates and N-mesyl 2-aminoethanones

Cascade reactions of nitroallylic acetates with methanesulfonyl 2-aminoethanones affords either the 3-pyrrolines or the pyrroles in one pot depending on reaction solvents and temperature. A possible mechanism for the entire sequence is proposed.     

N-Heterocyclic carbene (NHC) catalyzed annulation of enals and vinyl ketones: a novel synthesis of [2H]-pyranones

Homoenolate annulation of vinyl ketones led to the synthesis of dihydropyranones in contrast to cyclopentenes obtained by the homoenolate annulation of chalcones, another class of α,β-unsaturated ketones.     

Convergent Synthesis of 2H-Chromenes - a Formal [3+3] Cycloaddition by a One-pot, Three-Step Cascade

In cases in which the palladium-catalyzed coupling of a bromoquinone with a vinyl stannane affords a vinyl quinone that enolizes, the resulting ortho-quinone methide undergoes an oxa-6π electrocyclization. Enolization is promoted by the presence of a polar additive. The net conversion is a formal [3+3] cycloaddition that gives 2H-chromenes. Because the first two steps of the cascade are catalyzed, the overall conversion is an example of multicatalysis. Yields for the optimized, one-pot protocol are dramatically improved over the conventional stepwise process.     

Efficient synthesis of indoles using [3,3]-sigmatropic rearrangement of N-trifluoroacetyl enehydrazines

[3,3]-Sigmatropic rearrangement of N-trifluoroacetyl enehydrazines provides a novel method for the construction of indoles. N-Trifluoroacetyl enehydrazine having a cyclopentene ring smoothly underwent [3,3]-sigmatropic rearrangement followed by cyclization to give indolines in excellent yield. On the other hand, both cyclohexenyl N-trifluoroacetyl enehydrazine and acyclic N-trifluoroacetyl enehydrazine gave indoles in good yield. Additionally, the substituent effect on the benzene ring was also studied. The rearrangement of N-trifluoroacetyl enehydrazines proceeded smoothly even under either aqueous or solvent-free conditions.     

Improved synthesis of N-alkyl substituted dithieno[3,2-b:2′,3′-d]pyrroles

A new, convergent and improved synthetic method to prepare N-alkyl substituted dithienopyrroles is described. The procedure consists of a Pd-catalyzed amination of 3,3′-dibromo-2,2′-bithiophene. The reaction conditions were optimized, which makes this method applicable to prepare these molecules easily in high yields and on a large scale.     

A facile synthesis of isoindolo[2,1-a]quinolin-11-one via [4+2] reactions of N-acyliminium intermediates with olefines

A facile synthesis of isoindolo[2,1-a]quinolin-11-one has been developed to attain new molecules of this family via [4+2] reactions of N-acyliminium cation, produced from 2,3-dihydro-3-hydroxy-2-arylisoindol-1-one, in the presence of BF₃·OEt₂ with olefins in moderate to good yields at ambient temperature.     

Synthesis of the end-capped 5-(N,N-dimethylamino)naphthyl-1-ethynyl derivatives and their 1,4-di[5-(N,N-dimethylamino)naphthyl]-1,3-butadiynes: anti rotamer structure

A new family of the end-capped 5-(N,N-dimethylamino)naphthylethynyl chains were synthesized, as terminal acetylenes or poly(yne) structures, by heterocoupling between 5-iodo-N,N-dimethylnaphthalen-1-amine and 2-methyl-3-butyn-2-ol or 4-(5-iodo-1-naphthyl)-2-methyl-3-butyn-2-ol, catalyzed by the palladium-copper system. Catalytic homocoupling of the terminal acetylenes, affords to 1,4-dinaphthyl-1,3-butadiyne nanostructures. X-ray diffraction analysis of 1,4-di(α-naphthyl)-1,3-butadiyne shows that the naphthalene rings are in the anti configuration along the acetylene axis. All the conjugated compounds show an important fluorescent emission radiation.     

Rational use of substituted N-allyl and N,N-diallylanilines in the stereoselective synthesis of novel 2-alkenyltetrahydro-1-benzazepines

Two new series of 1,4-epoxy-2-exo-vinyl(isopropenyl)tetrahydro-1-benzazepines and cis-2-vinyl(isopropenyl)-4-hydroxytetrahydro-1-benzazepines were prepared by an efficient three/four-step route from available substituted N,N-diallylanilines and mono N-allylanilines. The amino-Claisen rearrangement and the sequential oxidation/intramolecular 1,3-dipolar cycloaddition reactions were used as the key steps in this synthesis. All the synthesized compounds were fully characterized by IR, GC-MS and NMR techniques.     

An easy access to diversely fused dioxa-2-aza-tricyclo[n.3.1.0]tetra/pentadecanes under solvent-free condition

Efficient syntheses of phenyl/N-heterocycle fused 6,13-dioxa-2-aza-tricyclo[8.3.1.0^2,8]tetradecanes have been accomplished from 8-hydroxy quinoline derivatives under solvent-free condition, using basic alumina as the solid support. The methodology was successfully extended for the synthesis of corresponding pentadecane derivatives under similar reaction conditions. In terms of its general applicability, product yield, reaction time and effortless separation techniques, the methodology is more valuable compared to the solution phase protocols.     

A facile procedure for synthesis of 3-[2-(N,N-dialkylamino)ethyl]-3-fluorooxindoles by direct fluorination of N,N-dialkyltryptamines

A practical procedure for the synthesis of 3-fluorooxindole derivatives having basic amine moieties was developed, which involves Selectfluor™-mediated oxidative fluorination of N,N-dialkyltryptamines in the presence of Lewis acid. This procedure was applied to an antimigraine drug, rizatriptan, to afford the corresponding 3-fluorooxindole, which is a potential fluorine-containing drug candidate.     

手性3-氧杂双环[3.1.0]-己-2-酮类化合物的不对称合成

采用手性铜催化剂(S)-7644, 利用重氮醋酸不饱和酯的分子内不对称卡宾加成环化, 合成了七个光学活性3-氧杂双环[3.1.0]-己-2-酮类化合物。产品经元素分析、红外、核磁确证了结构, 并测定了比旋光度和光学收率。     

A one-pot four-component synthesis of N-arylidene-2-aryl-imidazo[1,2-a]azin-3-amines

N-Arylidene-2-aryl-imidazo[1,2-a]azin-3-amines were synthesized via a one-pot, four-component condensation reaction using a 2-aminoazine, toluene-4-sulfonylmethyl isocyanide (TsCH₂NC), and two equivalents of readily available aromatic aldehydes. The reaction was performed in diethyl ether as the solvent, with p-toluenesulfonic acid (p-TSA) as the catalyst at reflux temperature.     

Easy access to N-alkylation of N-unsubstituted [60]fulleropyrrolidines: reductive amination using sodium triacetoxyborohydride

[60]Fulleropyrrolidines were used as secondary amines to react with aldehydes through reductive aminations to afford N-alkylated derivatives. In spite of the very weak base activity of the nitrogen atom of N-unsubstituted [60]fulleropyrrolidines, this method was found to be efficient at the aid of sodium triacetoxyborohydride. Several N-alkylated derivatives were synthesized and fully characterized.