Silver Ion Mediated Desulfurization-Condensation of Glucosyl Isothiocyanate With Hydroxy Acids

ABSTRACT

Desulfurization-condensation of 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocyanate with α-hydroxy acids and salicylic acid in the presence of silver trifluoroacetate and triethylamine gave glucosylamino heterocycles in good yields, while the reaction with β-hydroxy acids afforded N-glucosyl olefinic amides with the evolution of carbon dioxide.     

Homoenolate dianions of secondary amides via tin/lithium exchange

Treatment of N-phenyl- a well as N-methyl-3-(tri-bar|n-butylstannyl)-propionamide with 2 equiv of bar|n-butyllithium in the presence of 1,4-diazabicyclo[2.2.2]octane at ?78°C in tetrahydrofuran produced the corresponding dilithio derivatives (homoenolate dianions) $\text{4}$ and $\text{8}$ respectively. Reaction with various electrophiles (1 equiv) gave the terminally substituted amides in good yields.     

Facile synthesis of dihaloheterocycles via electrophilic iodocyclization

An efficient and facile electrophilic iodocyclization for the synthesis of various O-, N-, and S-containing dihaloheterocycles has been developed. A wide range of the substituted propargyl alcohols having -OH, -NTs, and -SAc functional groups reacted with molecular iodine or bromoiodine at ambient temperature to produce the corresponding dihalogenated O-, N-, and S-containing five- and six-membered heterocycles in good to high yields; Under optimized solvent conditions, the reactions of various substituted but-2-yn-1-ones bearing -OH, -NTs, and -SAc functional groups at C4-position, with iodine or bromoiodine at ambient temperature afforded the corresponding 3,4-diiodo- and 3-bromo-4-iodo-substituted furans, pyrroles, and thiophenes in good to high yields. Further transformation of the resulting iodine- or bromine-containing products to polyaromatics potentially of useful as organo-material intermediates has been investigated.     

Radical-based transformation of vicinal diols to olefins via thioxocarbamate derivatives: a simple approach to 2′,3′-didehydro-2′,3′-dideoxynucleosides

The bis-O-thioxocarbamate derivatives obtained from the reaction of vicinal diols with phenyl isothiocyanate are shown to be reduced with tris(trimethylsilyl)silane in the presence of azobisisobutyronitrile to afford the corresponding olefins in good yields. In this way, 2′,3′-didehydro-2′,3′-dideoxy analogs of adenosine, guanosine, inosine, cytidine and uridine were prepared by the radical-based deoxygenation of the corresponding ribonucleosides via the bis-O-thioxocarbamate derivatives.     

Aza-Ferrier rearrangement of glycals with amides promoted by molecular iodine

Amidoglycosidation of tri-O-acetyl-d-glucal with different N-nucleophiles such as t-butyl carbamate, N-benzyl carbamate, N-ethyl carbamate, tosyl amide, and mesyl amide has been achieved using an equimolar amount of molecular iodine under mild and neutral conditions to afford the corresponding N-glycosyl amides in good yields with a preferential α-anomeric selectivity. The use of iodine makes this method simple, convenient, and cost-effective. This is the first report on aza-Ferrier rearrangement using molecular iodine.     

Synthesis of glyco-1-ynitols via 1,1-dibromo-1-alkenes from partially and unprotected aldoses

We report the synthesis of 1,1-dibromo-1-alkenes from partially and unprotected aldoses and the synthesis of glyco-1-ynitols from these dibromocompounds. The 1,1-dibromo-1-alkenes were obtained by the reaction of dibromomethyl-triphenylphosphonium bromide in the presence of zinc in refluxing 1,4-dioxane. As an example, when the reaction is performed on 2-deoxy-5-O-trityl-d-ribofuranose (1) the corresponding 1,1-dibromo-1-olefin, (2R,3S)-6,6-dibromo-1-O-trityl-hex-5-ene-1,2,3-triol (12), is obtained in 89% yield. These smooth reaction conditions led also to the achievement of the other olefins from other sugars with good yields (44-90%). The reaction of these olefins with n-butyllithium in THF at low temperature afforded the corresponding alkynes. So the reaction of (2R,3S)-6,6-dibromo-1-O-trityl-hex-5-ene-1,2,3-triol (12) with this alkyllithium reagent led to (2R,3S)-1-O-trityl-hex-5-yne-1,2,3-triol (23) in 87% yield. Other glyco-1-ynitols were obtained with satisfying yields (64-87%).     

Towards the preparation of 2″-deoxy-2″-fluoro-adenophostin A. Study of the glycosylation reaction

The synthesis of 2″-deoxy-2″-fluoro-adenophostin A framework starting from tri-O-acetylglucal and adenosine is described. The key steps are the formation of the 2-deoxy-2-fluoroglycosyl donor by electrophilic fluorination of tri-O-acetylglucal and the stereoselective glycosylation of a suitable adenosine derivative. The glycosylation reaction was optimized affording the desired 2″-deoxy-2″-fluoroglycoside with excellent α-stereoselectivity and in good yields, taking into account that glycosylations using nucleosides as glycosyl acceptors do not usually give excellent results. In that sense, an improvement of the glycosylation step with respect to that of the reported adenophostin synthesis, using adenosine derivatives as glycosyl donors, has been made.     

Selective Palladium‐Catalyzed Aminocarbonylation of Olefins to Branched Amides

A general and efficient protocol for iso‐selective aminocarbonylation of olefins with aliphatic amines has been developed for the first time. Key to the success for this process is the use of a specific 2‐phosphino‐substituted pyrrole ligand in the presence of PdX₂ (X=halide) as a pre‐catalyst. Bulk industrial and functionalized olefins react with various aliphatic amines, including amino‐acid derivatives, to give the corresponding branched amides generally in good yields (up to 99 %) and regioselectivities (b/l up to 99:1).     

A novel three-component reaction of N-fluoropyridinium salts: a facile approach to imidazo[1,2-a]pyridines

The reaction of N-fluoropyridinium triflate with isonitriles in acetonitrile and propionitrile in the presence of NaBH(OAc)₃ led to the formation of the corresponding imidazo[1,2-a]pyridines in 44-73% yields. The proposed reaction mechanism involves the intermediate formation of a highly reactive carbene species and apparent reduction of the pyridinium intermediate with NaBH(OAc)₃ to yield the targeted heterocycles.     

Synthesis and characterization of d-glucosamine-derived low molecular weight gelators

Carbohydrate-based low molecular weight gelators are an interesting class of molecules with many potential applications. Previously, we have found that certain esters and carbamates of 4,6-O-benzylidene-α-d-methyl-glucopyranoside are low molecular weight gelators for a variety of solvents, including water. In order to obtain effective and robust sugar-based organogelators and understand the structure and gelation relationship, we extended our studies using 4,6-O-benzylidene-α-d-methyl-2-deoxy-2-amino-glucopyranoside as the headgroup. A series of amides and ureas were prepared from the protected d-glucosamine and the corresponding isocyanates or acid chlorides, in good yields. The self-assembling properties of these compounds were studied in several solvents, including water and aqueous solutions. Comparing to the ester and carbamate derivatives previously prepared from d-glucose, the amides and urea derivatives afforded more robust gels at lower concentrations typically. Most of these compounds were found to be efficient low molecular weight hydrogelators (LMHGs) for aqueous solutions at concentrations lower than 0.5 wt %. The preparation and characterization of these compounds are reported here.     

A facile preparation of o-acelated β-d-ribofuranosyl cyanide,an important intermediate of c-nucleoside synthesis

Tri-O-benzoyl and tri-O-acetyl derivatives of the title compound are obtained from the corresponding 1-O-acetates in good yields by treatment with cyanotrimethylsilane.     

Efficient Synthesis of Novel Thiazol‐2‐ylidene‐amides Using Carbonylthiourea Building Blocks

In this work, an efficient and versatile synthesis of novel thiazol‐2‐ylidene‐amides from various carbonylthiourea derivatives is described. A sequential alkylation–cyclization reaction between thioureas and propargyl bromide in the presence of DABCO in refluxing ethanol afforded 4‐methylthiazol‐2(3H)‐ylidene‐amide derivatives in good yields.     

Synthesis of modified Weinreb amides: N-tert-butoxy-N-methylamides as effective acylating agents

An efficient preparation of N-methyl-O-tert-butylhydroxylamine hydrochloride has been settled, which allowed the synthesis of modified Weinreb amides. Nucleophilic addition of organolithium and Grignard reagents on these N-tert-butoxy-N-methylamides afforded efficiently the corresponding ketones and reduction with DIBAL furnished the corresponding aldehydes in good yields up to 97%.     

Synthesis of 4-allylquinazolines from N-(2-cyanoaryl)amides via the In-mediated allylation of nitrile and dehydrative cyclization cascade

The reaction of allylindium reagents and N-(2-cyanoaryl)amides afforded 2-substituted-4-allylquinazolines in good yields via the indium-mediated Barbier-type allylation of nitrile and the following dehydrative cyclization cascade.     

CuI/Dabco as a highly active catalytic system for the Heck-type reaction

An efficient catalytic system using CuI/Dabco (triethylenediamine) for the Heck-type cross-coupling reaction was developed. In the presence of 10 mol % of CuI and 20 mol % of Dabco, the coupling of various aromatic iodides and 1-((Z)-2-bromovinyl)benzene with olefins was carried out efficiently and selectively to afford the corresponding internal olefins in moderate to good yields.     

A highly stereoselective construction of 1,2-trans-β-glycosidic linkages capitalizing on 2-azido-2-deoxy-d-glycosyl diphenyl phosphates as glycosyl donors

The scope of TMSOTf-promoted glycosidation of 2-azido-2-deoxyglycopyranosyl diphenyl phosphates is investigated. The 3,4,6-tri-O-benzyl-protected glucosyl and galactosyl donors and the 4,6-O-benzylidene-protected galactosyl donor each react with a range of acceptor alcohols in the presence of a stoichiometric amount of TMSOTf in propionitrile at −78 °C to afford 1,2-trans-β-linked disaccharides in high yields with α:β ratios ranging from 9:91 to 1:>99, regardless of the anomeric composition of the donor used. The use of propionitrile as a solvent at −78 °C has proven to be among the best choice for the highest levels of β-selectivity reported to date for this type of glycosidation. A plausible reaction mechanism, which features a large equilibrium preference for α-glycosyl-nitrilium ions over β-nitrilium ions, is proposed based on byproducts formed through their intermediacy and accounts for the observed excellent β-selectivities.     

Metal-free one-pot oxidative conversion of benzylic alcohols and benzylic halides into aromatic amides with molecular iodine in aq ammonia, and hydrogen peroxide

Various primary alcohols, particularly benzylic alcohols, could be converted into the corresponding aromatic amides in good yields in a one-pot manner by treatment with molecular iodine in aq. NH₃, followed by reaction with ∼30% aq H₂O₂. Similarly, various benzylic halides could be also converted into the corresponding aromatic amides in good yields in a one-pot manner by treatment with molecular iodine in aq NH₃, followed by reaction with ∼30% aq H₂O₂. The present reactions involve the metal-free one-pot oxidative conversion of benzylic alcohols and benzylic halides into the corresponding aromatic amides, respectively.     

Synthesis of the repeating trisaccharide unit of the cell wall lipopolysaccharide of Escherichia coli type 8

NIS/TfOH mediated glycosidation of methyl 3,4,6-tri-O-benzyl-α-d-mannopyranoside with phenyl 2-O-acetyl-3,4,6-tri-O-benzyl-1-thio-α-d-mannopyranoside furnished the corresponding disaccharide derivative in excellent yield and α-selectivity. Zémplen deacetylation of the same followed by reaction with BSP/Tf₂O-preactivated phenyl 4,6-O-benzylidene-2,3-di-O-benzyl-1-thio-α-d-mannopyranoside generated methyl 4,6-O-benzylidene-2,3-di-O-benzyl-β-d-mannopyranosyl-(1→2)-3,4,6-tri-O-benzyl-α-d-mannopyranosyl-(1→2)-3,4,6-tri-O-benzyl-α-d-mannopyranoside in very good yield and excellent β-selectivity. Pd/C catalyzed hydrogenation of the latter finally afforded the repeating trisaccharide of Escherichia coli 8 O-antigen as its methyl glycoside.     

p-Tolylsulfinyl amides: reagents for facile electrophilic functionalization of olefins

A variety of olefins were found to react with sulfinyl amides in the presence of POCl(3) to give beta-chlorosulfides and beta-hydroxysulfides in good yields. In the absence of nucleophiles, p-tolylsulfinyl amides were found to react with olefins with the formation of allylsulfoxides.     

First synthesis of methyl 3-amino-4-(het)aryl-1H-pyrrole-2-carboxylates as useful scaffolds in medicinal chemistry

The preparation of new methyl 4-(het)aryl-3-amino-1H-pyrrole-2-carboxylates was achieved starting from commercial arylacetonitriles. This four steps synthesis afforded with good yields interesting building-blocks useful in the access to many nitrogen heterocycles with potential therapeutic interest.