An Efficient Ugi‐Azide Four‐Component Approach for the Preparation of Novel 1‐(1H‐tetrazol‐5‐yl)‐10‐chloro‐1,2,3,4‐tetrahydropyrazino[1,2‐a] Indoles

The synthesis of novel 1‐(1H‐tetrazol‐5‐yl)‐10‐chloro‐1,2,3,4‐tetrahydropyrazino[1,2‐a] indole derivatives starting from the initially prepared 1‐(2‐bromoethyl)‐3‐chloro‐1H‐indole‐2‐carbaldehyde is described. A variety of likely biologically relevant pyrazino[1,2‐a] indole‐based 1,5‐disubstituted tetrazoles was obtained in moderate to high yields via an Ugi‐azide reaction. These reactions presumably proceed by the imine formation, intramolecular cyclization to iminium ion, and nucleophilic addition tandem reactions, respectively.     

Regioselective Synthesis of 2‐Acylquinazolines and 3H‐1,4‐Benzodiazepin‐3‐ones by a Ugi 4CC/Staudinger/aza‐Wittig Sequence

α‐Acylamino‐carboxamide azides 1 , obtained from Ugi reactions of o‐azidobenzaldehyde, amines, benzoylformic acid, and isocyanides, reacted with triphenylphosphine to give various 2‐acylquinazolines 3 and/or 3H‐1,4‐benzodiazepin‐3‐ones 4 in moderate to good yields via sequential Staudinger and intramolecular aza‐Wittig reaction.     

Liquid‐phase synthesis of mixture‐based bicyclic β‐lactam libraries

Five sets of 27‐membered combinatorial libraries of alicyclic β‐lactams were prepared via liquid‐phase Ugi 4‐center 3‐component reactions (U‐4C‐3CR) utilizing 3 different cis β‐amino acids, 3 different isonitriles and 5×3 sets of aldehydes. Through combinations of the building blocks of one of these libraries, all of the possible sublibraries were also generated. A few azetidinone derivatives were synthesized individually by parallel synthesis.     

2,3,4,6‐Tetra‐O‐acetyl‐α‐d‐glucopyranosyl azide

The Cu^I‐catalysed 1,3‐dipolar cycloaddition of an azide and a terminal alkyne is becoming an increasingly popular tool for synthetic chemists. This is the most representative of the so‐called `click reactions' and it is used to generate 1,4‐disubstituted triazoles in high yield. During studies on such cycloaddition reactions, a reduced reactivity of an α‐glucosyl azide with respect to the corresponding β‐anomer was observed. With the aim of understanding this phenomenon, the structure of the title compound, C₁₄H₁₉N₃O₉, has been determined at 140 K. The glucopyranosyl ring appears in a regular ⁴C₁ chair conformation with all the substituents in equatorial positions, except for the anomeric azide group, which adopts an axial orientation. The observed bond lengths are consistent with a strong anomeric effect, which is reflected in a change in dipolar character and hence reduced reactivity of the α‐glucosyl azide.     

Synthesis of Novel 2‐Oxoquinoline Derivatives via Ugi‐Four‐Component‐Heck Reaction

The present study provides an efficient strategy for the preparation of novel N‐substituted‐4‐methyl‐quinolin‐1(2H)‐one derivatives via two‐step Ugi/Heck reaction. The procedure is based on the Ugi coupling between 2‐bromoanilines, various aromatic aldehydes, vinylacetic acid, and isocyanides, and then intramolecular Heck reaction, which leads to the formation of the title compounds in good yields.     

Stereoselective Synthesis of α‐ and β‐Glycofuranosyl Amides by Traceless Ligation of Glycofuranosyl Azides

A highly stereoselective synthesis of α‐ or β‐glycofuranosyl amides based on the traceless Staudinger ligation of glycofuranosyl azides of the galacto, ribo, and arabino series with 2‐diphenylphosphanyl‐phenyl esters has been developed. Both α‐ and β‐isomers can be obtained with excellent selectivity from a common, easily available precursor. The process does not depend on the anomeric configuration of the starting azide but appears to be controlled by the C2 configuration and by the protection/deprotection state of the substrates. A mechanistic interpretation of the results, supported by ³¹P NMR experiments, is offered and merged with our previous mechanistic analysis of pyranosyl azide ligation reactions.     

Ligand‐free,copper‐catalyzed,one‐pot,three‐component synthesis of novel 1,2,3‐triazole‐linked indoles in magnetized water

Magnetized water (MW) is used as a green and new solvent‐promoting medium for the one‐pot, three‐component synthesis of novel 1,2,3‐triazole‐linked indoles catalyzed by copper iodide. A broad range of 2‐aryl‐1‐(prop‐2‐ynyl)‐1H‐indole‐3‐carbaldehydes were reacted with alkyl halides and sodium azide via copper‐catalyzed azide–alkyne cycloaddition reactions in MW in the absence of any ligand. This method offers the advantages of short reaction times, green procedure, low cost, simple work‐up, quantitative reaction yields, and no need for any organic solvent.     

Stereoselective Synthesis of (Z)‐4‐(2‐Bromovinyl)benzene‐sulfonyl Azide and Its Synthetic Utility for the Transformation to (Z)‐N‐[4‐(2‐Bromovinyl)benzenesulfonyl]imidates

A novel method for the stereoselective synthesis of (Z)‐4‐(2‐bromovinyl)benzenesulfonyl azide by simultaneous azidation and debrominative decarboxylation of anti‐2,3‐dibromo‐3‐(4‐chlorosulfonylphenyl)propanoic acid using NaN₃ only was developed. Facile transformation of (Z)‐4‐(2‐bromovinyl)benzenesulfonyl azide to (Z)‐N‐[4‐ (2‐bromovinyl)benzenesulfonyl]imidates was also achieved by Cu‐catalyzed three‐component coulping of (Z)‐4‐(2‐bromovinyl)benzenesulfonyl azide, terminal alkynes and alcohols/phenols.     

catena‐Poly[[{4‐bromo‐2‐[2‐(dimethyl­amino)ethyl­imino­methyl]­phenol­ato}­copper(II)]‐μ‐azido]

The title complex, [Cu(C₁₁H₁₄BrN₂O)(N₃)]_n, is an inter­esting azide‐bridged polynuclear copper(II) compound. The Cu^II atom is five‐coordinated in a square‐pyramidal configuration, with one O and two N atoms of one Schiff base and one terminal N atom of a bridging azide ligand defining the basal plane, and another terminal N atom of another bridging azide ligand occupying the axial position. The {4‐bromo‐2‐[2‐(dimethyl­amino)ethyl­imino­meth­yl]phenolato}copper(II) moieties are linked by the bridging azide ligands, forming polymeric chains running along the b axis. Adjacent chains are further linked by weak Br⋯Br inter­actions into a sheet.     

Regioselective Synthesis of the 5,6‐Dihydro‐4H‐furo[2,3‐c]pyrrol‐4‐one Skeleton: A New Class of Compounds

We hereby report the first preparation of the 5,6‐dihydro‐4H‐furo[2,3‐c]pyrrol‐4‐one ( 3 ) and its derivatives starting from methyl 3‐(methoxycarbonyl)furan‐2‐acetate ( 8 ). The ester functionality connected to the methylene group was regiospecifically converted to the desired monohydrazide 9 . Conversion of 9 into the acyl azide 10 followed by Curtius rearrangement gave the corresponding isocyanate derivative 11 (Scheme 2). Reaction of 11 with different nucleophiles produced urethane and urea derivatives (Scheme 3). Intramolecular cyclization reactions provided the target compounds (Scheme 5). Removal of the amine‐protecting group formed the title compound 3 .     

The Design and Synthesis of Novel 2,3‐Dihydrobenzo[f]isoquinolin‐4(1H)‐ones via Sequential Ugi–Heck Reactions by Using an Efficient Heterogeneous Palladium Nanocatalyst

A facile and efficient synthesis of N‐alkyl‐2‐(1, 2 dihydro‐1‐methylene‐4‐oxobenzo[f] isoquinoline‐3(4H)‐yl)‐2‐phenylacetamides is performed by the consecutive, two‐step procedure that consists of Ugi and Heck reactions. The Heck reaction was performed both by homogenous and a designed heterogeneous catalyst. The heterogeneous catalyst is a coordinated palladium to 1, 10‐phenanthroline attached to chitosan@Fe3O4 magnetite nanoparticles, which was shown to be more efficient than the homogenous Pd(OAc)₂/PPh₃ catalyst with good to excellent yields.     

One‐Pot synthesis of functional poly(methacrylate) by ATRP and 1,8‐Diazacyclo‐[5,4,0]undec‐7‐ene catalyzed transesterification

A facile one‐pot 1,8‐diazacyclo‐[5,4,0]undec‐7‐ene (DBU) catalyzed transesterification/atom transfer radical polymerization (ATRP) strategy has been successfully developed through the combination of copper/DBU‐catalyzed ATRP and DBU‐catalyzed transesterification reactions. Well‐defined poly(methacrylate)s with various side ester groups have been synthesized by ATRP and transesterification of acyl donor 2,2,2‐trifluoethyl methacrylate with various alcohols, such as benzyl alcohol, n‐butanol, iso‐propyl alcohol, methanol, triethylene glycol monomethyl ether, propargyl alcohol, and 6‐azido‐1‐hexanol by the one‐pot process. Kinetic studies indicate that the ATRP process proceeded in a controllable manner without the interference of the transesterification reactions. Expansion of the binary system to a higher level ternary system has been successfully achieved by the combination of copper(I)‐catalyzed azide–alkyne cycloaddition, transesterification, and ATRP reactions. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2998–3003     

An Efficient Two‐Step Synthesis of New 5‐Substituted‐1H‐tetrazoles of Biological Interest

A simple procedure for the synthesis and characterization of new 3‐alkoxy‐3‐(1H‐tetrazol‐5‐yl)propionic acids and 2‐(1H‐tetrazol‐5‐yl)tetrahydrofuran‐ and ‐(1H‐tetrazol‐5‐yl)‐2H‐pyran‐3‐carboxylic acids from the [2 + 3] cycloaddition reactions between the nitrile group of β‐cyanocarboxylic acids with sodium azide in the presence of zinc chloride is described. The tetrazolic acids were isolated in moderate to good yields and are structurally analogous to succinic acid.     

Nucleophile‐Dependent Regio‐ and Stereoselective Ring Opening of 1‐Azoniabicyclo[3.1.0]hexane Tosylate

1‐[(1R)‐(1‐Phenylethyl)]‐1‐azoniabicyclo[3.1.0]hexane tosylate was generated as a stable bicyclic aziridinium salt from the corresponding 2‐(3‐hydroxypropyl)aziridine upon reaction with p‐toluenesulfonyl anhydride. This bicyclic aziridinium ion was then treated with various nucleophiles including halides, azide, acetate, and cyanide in CH₃CN to afford either piperidines or pyrrolidines through regio‐ and stereoselective ring opening, mediated by the characteristics of the applied nucleophile. On the basis of DFT calculations, ring‐opening reactions under thermodynamic control yield piperidines, whereas reactions under kinetic control can yield both piperidines and pyrrolidines depending on the activation energies for both pathways.     

Facile syntheses of 4‐vinyl‐1,2,3‐triazole monomers by click azide/acetylene coupling

Synthetic strategies for the preparation of a new family of vinyl monomers, 4‐vinyl‐1,2,3‐triazoles, have been developed. These monomers are noteworthy as they combine the stability and aromaticity of styrenics with the polarity of vinylpyridines and the structural versatility of acrylate/methacrylate derivatives. To enable the wide adoption of these unique monomers, new methodologies for their synthesis have been elaborated which rely on Cu‐catalyzed azide/acetylene cycloaddition reactions—“click chemistry”—as the key step, with the vinyl substituent being formed by either elimination or Wittig‐type reactions. In addition, one‐pot “click” reactions have been developed from alkyl halides, which allow for monomer synthesis without isolation of the intermediate organic azides. The high yield and facile nature of these procedures has allowed a library of new monomers including the parent compound, 1‐H‐4‐vinyl‐1,2,3‐triazole, to be prepared on large scales. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2897–2912, 2008     

Properties and Reactions of Substituted 1,2‐Thiazetidine 1,1‐Dioxides: Functionalization and Reactions at C(4) of the β‐Sultam

The introduction of functional groups at the 4‐position of the β‐sultam ring was realized by the synthesis of mono‐ and disubstituted derivatives by reactions of N‐silylated β‐sultams with electrophiles in the presence of BuLi or LDA. As electrophiles, ketones, chlorosilanes, a β‐sultam, CO₂, chloroformiate, halogen, azodicarboxylate, phenyltriazoledione, tosyl azide, 1,3,5‐triazine, propyl nitrate, and phenyl isocyanate were used. Furthermore, a number of derivatives of these substitution products were synthesized. All products were characterized by standard spectroscopic methods, and conformations were studied, supported by calculation.     

用聚乙二醇简便合成3-取代-1, 2, 3, 4-四氢吡啶并[3, 2-d]嘧啶-2, 4-二酮

用聚乙二醇作为可溶性聚合物载体和相转移催化剂高效简单的合成了1, 2, 3, 4-四氢吡啶并[3, 2-d]嘧啶类化合物。该合成路线为聚乙二醇与2, 3-吡啶二酸酐反应生成聚乙二醇支载的单酯1,接着1被转化成相应的聚乙二醇支载的酰基叠氮2,2经Curtius重排,与胺加成并同时关环给出目标产物,其总产率为84%-88%。     

Synthesis and reactions of pyrido[3,2,1‐jk]carbazole‐4,6‐diones

Pyrido[3,2,1‐jk]carbazoles 1 , synthesized from carbazoles and alkyl‐ or arylmalonates, gave regioselective electrophilic substitution reactions at position 5 such as chlorination to 5‐chloro derivatives 2 , nitration to 5‐nitro compounds 3 , or hydroxylation to 5‐hydroxy derivatives 4 . 5‐Hydroxy compounds 4 gave on treatment with strong bases ring contraction to 5 , 6 or the ring opening product 7 . Exchange of the chloro group in 2 with azide or amines gave the corresponding azides 8 and the 5‐amino derivatives 9 and 10 . Alkylation of 1 with benzyl chloride or allyl bromide resulted in the formation of 5‐C‐alkylated products 11 together with 4‐alkyloxy derivatives 12 . J. Heterocyclic Chem., 48, 1039 (2011).     

On the Mechanism of Copper(I)‐Catalyzed Azide–Alkyne Cycloaddition

The copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) reaction regiospecifically produces 1,4‐disubstituted‐1,2,3‐triazole molecules. This heterocycle formation chemistry has high tolerance to reaction conditions and substrate structures. Therefore, it has been practiced not only within, but also far beyond the area of heterocyclic chemistry. Herein, the mechanistic understanding of CuAAC is summarized, with a particular emphasis on the significance of copper/azide interactions. Our analysis concludes that the formation of the azide/copper(I) acetylide complex in the early stage of the reaction dictates the reaction rate. The subsequent triazole ring‐formation step is fast and consequently possibly kinetically invisible. Therefore, structures of substrates and copper catalysts, as well as other reaction variables that are conducive to the formation of the copper/alkyne/azide ternary complex predisposed for cycloaddition would result in highly efficient CuAAC reactions. Specifically, terminal alkynes with relatively low pK_a values and an inclination to engage in π‐backbonding with copper(I), azides with ancillary copper‐binding ligands (aka chelating azides), and copper catalysts that resist aggregation, balance redox activity with Lewis acidity, and allow for dinuclear cooperative catalysis are favored in CuAAC reactions. Brief discussions on the mechanistic aspects of internal alkyne‐involved CuAAC reactions are also included, based on the relatively limited data that are available at this point.     

High‐Yielding Synthesis of the Anti‐Influenza Neuraminidase Inhibitor (−)‐Oseltamivir by Two “One‐Pot” Sequences

The efficient asymmetric total synthesis of (?)‐oseltamivir, an antiviral reagent, has been accomplished by using two “one‐pot” reaction sequences, with excellent overall yield (60 %) and only one required purification by column chromatography. The first one‐pot reaction sequence consists of a diphenylprolinol silyl ether mediated asymmetric Michael reaction, a domino Michael reaction/Horner–Wadsworth–Emmons reaction combined with retro‐aldol/Horner–Wadsworth–Emmons reaction and retro Michael reactions, a thiol Michael reaction, and a base‐catalyzed isomerization. Six reactions can be successfully conducted in the second one‐pot reaction sequence; these are deprotection of a tert‐butyl ester and its conversion into an acyl chloride then an acyl azide, Curtius rearrangement, amide formation, reduction of a nitro group into an amine, and a retro Michael reaction of a thiol moiety. A column‐free synthesis of (?)‐oseltamivir has also been established.