An efficient approach to the stereoselective synthesis of 2,6-disubstituted dihydropyrans via stannyl-Prins cyclization

A general method has been developed for the stereoselective construction of 2,6-disubstituted dihydropyrans based on the Lewis acid-catalyzed intramolecular reactions of oxocarbenium ions with vinylstannanes. This novel methodology was applied to the enantioselective total synthesis of (−)-centrolobine.     

BiBr3-initiated tandem addition/silyl-Prins reactions to 2,6-disubstituted dihydropyrans

A tandem addition/silyl-Prins reaction efficiently affords cis-2,6-disubstituted dihydropyrans (DHPs) using 5 mol % of BiBr3 in CH2Cl2. The reaction occurs between delta-triethylsilyloxyvinyltrimethylsilanes and a variety of aldehydes to give good to excellent isolated yields of DHPs. The diastereoselectivities in the crude products are significantly affected by aldehyde substitution with electron-rich aldehydes, providing 2-3:1 (cis:trans) and neutral (or electron-poor) aldehydes affording dr > or = 19:1 (cis:trans).     

Synthesis of julolidines via one-pot cascade three component Povarov reaction in the presence of silica sulfuric acid

In this report, synthesis of julolidines via one-pot cascade reaction of aniline derivatives with a mixture of styrene and formaldehyde in the presence of silica sulfuric acid as an efficient catalyst has been studied under aerobic condition. By presented method, various julolidines are obtained under mild and transition metal-free conditions. The reaction is proceeded with imine formation and followed by an Aza-Diels-Alder cycloaddition with styrene gave julolidine derivatives. The catalyst can be recycled and reused multiple times to catalyze the reaction.     

Synthesis of 3-alkylidene-piperidin-4-ones via one-pot cascade transylidation-olefination

3-Alkylidene-piperidin-4-ones with diverse C-5 substitution patterns are synthesized via a one-pot cascade transylidation-olefination sequence. Tributylphosphorus ylides show distinct higher reactivity as compared to triphenyl analogs. t-Butanol is the solvent of choice for transylidation, while the Wittig olefination of aliphatic aldehydes requires MeCN as the solvent.     

An efficient one-pot asymmetric synthesis of biaryl compounds via Diels-Alder/retro-Diels-Alder cascade reactions

[reaction: see text] A single-step chirality transfer method for the synthesis of axially chiral biaryl compounds by construction of the second aromatic ring via a Diels-Alder/retro-Diels-Alder cascade reaction is reported. This methodology should find broad application in the synthesis of natural products and asymmetric catalysts.     

Synthesis,structure, ADME and biological activity of three 2,6-disubstituted thiosemicarbazone derivatives

Three new 2,6-disubstituted thiosemicarbazone derivatives of pyridine, namely, 2-{amino[6-(pyrrolidin-1-yl)pyridin-2-yl]methylidene}-N,N-dimethylhydrazine-1-carbothioamide, C₁₃H₂₀N₆S, 2-{amino[6-(piperidin-1-yl)pyridin-2-yl]methylidene}-N,N-dimethylhydrazine-1-carbothioamide, C₁₄H₂₂N₆S, and 2-[amino(6-phenoxypyridin-2-yl)methylidene]-N,N-dimethylhydrazine-1-carbothioamide monohydrate, C₁₅H₁₇N₅OS·H₂O, have been synthesized and characterized by NMR spectroscopy and low-temperature single-crystal X-ray diffraction. In addition, their antibacterial and anti-yeast activities have been determined. The ability of the tested compounds to inhibit bacterial growth was comparable to vancomycin as a reference drug. Compared to isoniazid (MIC 0.125 and 8 µg ml⁻¹), the compounds showed the ability to inhibit the growth of Mycobacterium tuberculosis to a moderate degree for the standard strain and at the same level or higher (MIC 4–8 µg ml⁻¹) for the resistant strain. All three compounds adopt the zwitterionic form in the crystal structure regardless of the presence or absence of solvent molecules.     

Highly stereocontrolled synthesis of fluorinated 2,6-trans dihydropyrans via Prins cyclization

A highly efficient method for the synthesis of fluorinated 2,6-trans dihydropyrans via BF₃·Et₂O-promoted Prins cyclization of allenic alcohols and aldehydes is developed. Various 2,6-trans fluorodihydropyrans are obtained in moderate to good yields with excellent diastereoselectivities.     

Catalyst-free,ethylene glycol promoted one-pot three component synthesis of 3-amino alkylated indoles via Mannich-type reaction

A highly efficient and sustainable approach for the multi-component synthesis of biologically important 3-amino alkylated indoles has been investigated via Mannich-type reaction under catalyst-free, ethylene glycol as a recyclable promoting medium. The wide applicability of the present method was examined with various substrates viz substituted aldehydes, indoles and secondary amines. This method will be useful for a large scale synthesis of 3-amino alkylated indoles without the use of column chromatography. The present method provides higher environmental compatibility and sustainability factors such as smaller E-factor (0.433) and higher atom-economy (AE = 93.3%).     

Nano-sulfated zirconia as an efficient, recyclable and environmentally benign catalyst for one-pot three component synthesis of amidoalkyl naphthols

One pot synthesis of amidoalkyl naphthols by reaction of aromatic aldehydes,2-naphthol and amide/urea using nano-sulfated zirconia as a catalyst is reported.The reaction was carried out under solvent-free conditions.The method gave good yields of amidoalkyl naphthols in short reaction time.The catalyst is recycled for five consecutive times without loss of activity.     

Synthesis of chiral iodo-N,O-acetonide aminal scaffolds via an efficient cascade reaction of amino acid-derived epoxides

Novel amino acid-derived iodo-N,O-acetonide aminals were developed as chiral, non-epimerizable scaffolds to facilitate complex molecule synthesis. These scaffolds are readily prepared from commercially available amino acid derivatives in ?6 steps, contain an orthogonally-protected β-hydroxy amine moiety, and feature a directly reactive alkyl-iodide group for facile substitution chemistry. Further, a novel ring opening/cyclization cascade reaction was developed to prepare these compounds efficiently (59-72%) from readily available epoxide derivatives.     

Asymmetric synthesis of trifluoromethyl substituted dihydropyrans via organocatalytic cascade Michael-hemiketalization reaction

Asymmetric conjugate addition of ethyl 4,4,4-trifluoroacetoacetate and other trifluoromethyl substituted nucleophiles to β,γ-unsaturated α-keto esters has been developed. The reaction efficiently provided dihydropyrans via cascade Michael-hemiketalization pathways. Quinine-derived thiourea was identified to be the best catalyst. A number of trifluoromethyl substituted dihydropyrans with three consecutive chiral centers were obtained in excellent yields, diastereoselectivities, and enantioselectivities. The product was readily transformed to the corresponding tetrahydropyridine without the loss of the optical purity.     

Synthesis of poly-substituted pyrazolo[1,5-a]quinolines through one-pot two component cascade reaction

A diversity-oriented method for the synthesis of novel poly-substituted pyrazolo[1,5-a]quinolines has been developed on the basis of an S_NAr/Knoevenagel cyclization cascade reaction or an S_NAr/Dieckmann–Thorpe cyclization cascade reaction. The methods provide a variety of poly-substituted pyrazolo[1,5-a]quinolines bearing an amino, alkyl or aryl substituent at the 5-position. In addition, a diversity-oriented method for the synthesis of 2-substituted pyrazolo[1,5-a]quinolines from a readily available 2-[[(trifluoromethyl)sulfonyl]oxy]pyrazolo[1,5-a]quinoline has also been disclosed.     

Synthesis, NMR spectroscopic characterisation and reactions of 2,6-difluorophenylxenon fluoride, 2,6-F2C6H3XeF

[2,6-F₂C₆H₃Xe][BF₄] is quantitatively transferred into 2,6-F₂C₆H₃XeF in reactions with [NMe₄]F. The latter has been isolated as a colourless solid which is stable in dichloromethane solution at room temperature for approximately 1 h. 2,6-F₂C₆H₃XeF readily reacts with Me₃SiX (X = Cl, Br, CN, NCO, OCOCF₃, OSO₂CF₃, C₆F₅, 2,6-F₂C₆H₃) to give compounds of general compositions 2,6-F₂C₆H₃XeX which were identified by multinuclear NMR experiments. Evidence was found for C₆H₅Xe(2,6-F₂C₆H₃) as a product of the reaction with C₆H₅SiF₃.     

InBr3-catalyzed stereoselective synthesis of trans-2,6-disubstituted 3,6-dihydro-2H-pyrans

A new method for the stereoselective synthesis of trans-2,6-disubstituted 3,6-dihydro-2H-pyrans with a variety of substitution patterns is described, involving Lewis acid induced tandem allylation or cyanation of δ-hydroxy-α,β-unsaturated aldehydes to produce dihydropyrans in good yields and with trans-selectivity. This method is very useful for the synthesis of trans-2,6-disubstituted dihydropyran ring-containing natural products such as laulimalide, scytophycin C and many others.     

InCl3-catalyzed efficient one-pot synthesis of 2-pyrrolo-3′-yloxindoles

An InCl₃-catalyzed one-pot synthesis of 2-pyrrolo-3′-yloxindoles was achieved via three-component reaction of 3-phenacylideneoxindole, β-keto ester, and ammonium acetate at reflux by a sequential Michael addition followed by Paal-Knorr condensation.     

ZnCl2 promoted efficient,one-pot synthesis of 3-arylmethyl and diarylmethyl indoles

Anhydrous ZnCl₂ mediated convenient, one-pot synthesis of 3-arylmethyl and diarylmethyl indoles was accomplished in good yields. Under reaction condition, in situ formation of kinetically stable bis(indolyl)methane product was identified. Its subsequent conversion to the thermodynamically stable 3-diarylmethyl indole at elevated temperature and pressure was confirmed by carrying out pressure tube reaction with bis(indolyl)methane.     

Synthesis of 2,3-disubstituted pyrrolidines and piperidines via one-pot oxidative decarboxylation-beta-iodination of amino acids.

A new synthesis of 2,3-disubstituted pyrrolidines and piperidines is described. This mild procedure is based on the one-pot oxidative decarboxylation-beta-iodination of alpha-amino acid carbamates or amides. The iodine is introduced at the previously unfunctionalized 3-position. Different substituents can be introduced at C-2, e.g., hydroxy, alkoxy, allyl, alkyl, etc. A trans relationship between the C-2 and C-3 substituents is exclusively obtained. The influence of the solvent and the ring size of the starting amino acid are studied, as well as the nature of the protecting group on the nitrogen. The stereoselectivity of the reaction was also studied using chiral methyl (2S,4S)-4-acetyloxyproline-1-carboxylate (8). The products obtained can be manipulated to give bicyclic systems present in many natural products. By using the tandem decarboxylation-iodination-alkylation reaction, 2-substituted-3-iodopyrrolidines are formed, which are precursors of 2-substituted-2,5-dihydropyrrols.     

Synthesis of 3-substituted 4-piperidinones via a one-pot tandem oxidation-cyclization-oxidation process: stereodivergent reduction to 3,4-disubstituted piperidines

A novel approach to 3-substituted 4-piperidinones is described. The one-pot tandem oxidation-cyclization-oxidation of unsaturated alcohols 1a-e by PCC or PCC and trifluoromethanesulfonic acid affords piperidinones 2a-e in good yield. Reduction of 2a-e by L-Selectride gives the corresponding cis 3,4-disubstituted piperidines with diastereomeric ratios of >99:1. By contrast, reduction of 2a-e by Al-isopropoxydiisobutylalane gives the trans products with diastereomeric ratios of up to 99:1.     

An efficient synthesis of β-acylureas via a three-component, one-pot synthesis using TCS/ZnCl2

A simple and efficient one-pot, three-component synthesis of new trisubstituted ureas containing diastereotopic protons is achieved via the reaction of aromatic aldehydes, aromatic ketones, and dimethyl cyanamide using a TCS/ZnCl₂ reagent mixture at room temperature.