Chemoselectivity of Tertiary Azides in Strain-Promoted Alkyne-Azide Cycloadditions

The strain-promoted alkyne-azide cycloaddition (SPAAC) is the most commonly employed bioorthogonal reaction with applications in a broad range of fields. Over the years, several different cyclooctyne derivatives have been developed and investigated in regard to their reactivity in SPAAC reactions with azides. However, only a few studies examined the influence of structurally diverse azides on reaction kinetics. Herein, we report our investigations of the reactivity of primary, secondary, and tertiary azides with the cyclooctynes BCN and ADIBO applying experimental and computational methods. All azides show similar reaction rates with the sterically non-demanding cyclooctyne BCN. However, due to the increased steric demand of the dibenzocyclooctyne ADIBO, the reactivity of tertiary azides drops by several orders of magnitude in comparison to primary and secondary azides. We show that this chemoselective behavior of tertiary azides can be exploited to achieve semiorthogonal dual-labeling without the need for any catalyst using SPAAC exclusively.     

Synthesis of polysubstituted N-H pyrroles from vinyl azides and 1,3-dicarbonyl compounds

Two synthetic methods for tetra- and trisubstituted N-H pyrroles are presented: (i) the thermal pyrrole formation by the reaction of vinyl azides with 1,3-dicarbonyl compounds via the 1,2-addition of 1,3-dicarbonyl compounds to 2H-azirine intermediates generated in situ from vinyl azides; (ii) the Cu(II)-catalyzed synthesis of pyrroles from alpha-ethoxycarbonyl vinyl azides and ethyl acetoacetate through the 1,4-addition reaction of the acetoacetate to the vinyl azides. By applying these two methods, regioisomeric pyrroles can be prepared selectively starting from the same vinyl azides.     

Developments on the Chemistry of Tellurium and Selenium Azides

Abstract

We have been carrying out systematic studies on the preparation and properties of tellurium halide and pseudohalide compounds with a focus on tellurium azides. We were successful in the synthesis of various tellurium azides of both covalent and ionic nature. Several tellurium(IV) azides, tellurium(II) azides, and the first tellurium(VI) azides can be prepared in reasonable amounts. The first structural information of selenium azides is obtained for covalent and ionic derivatives, and spectroscopic data for the existence of selenium(iv) polyazides.     

叠氮根电负性的量子化学研究

用ab initio, MINDO/3, MNDO和DV-Xa等量子化学方法计算研究了一些分子型和离子型(碱金属)叠氮化物及相应氯化物的平衡构型和电子结构。结构表明: 在分子型叠氮化物中叠氮根的电负性较氯小、与氮相当; 而在离子型金属叠氮化物中,叠氮根的电负性和氯相当或较氯稍大。将计算所得正则离域分子轨道进行定域化处理, 发现产生这种电负性差异的主要原因是上述两类叠氮化物中N2的成键状况不同, 本文对此进行了较为细致的分析。     

Hydrogenation of azides over copper nanoparticle surface using ammonium formate in water

Aryl azides undergo clean reduction by copper nanoparticles and ammonium formate in water. The surface hydrogen on copper nanoparticles is considered to be the active reducing species. A variety of functionalized aryl azides and aryl sulfonyl azides are reduced by this procedure to the corresponding amines with excellent chemoselectivity in high yields.     

Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(i)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides

The cycloaddition of azides to alkynes is one of the most important synthetic routes to 1H-[1,2,3]-triazoles. Here a novel regiospecific copper(I)-catalyzed 1,3-dipolar cycloaddition of terminal alkynes to azides on solid-phase is reported. Primary, secondary, and tertiary alkyl azides, aryl azides, and an azido sugar were used successfully in the copper(I)-catalyzed cycloaddition producing diversely 1,4-substituted [1,2,3]-triazoles in peptide backbones or side chains. The reaction conditions were fully compatible with solid-phase peptide synthesis on polar supports. The copper(I) catalysis is mild and efficient (>95% conversion and purity in most cases) and furthermore, the X-ray structure of 2-azido-2-methylpropanoic acid has been solved, to yield structural information on the 1,3-dipoles entering the reaction. Novel Fmoc-protected amino azides derived from Fmoc-amino alcohols were prepared by the Mitsunobu reaction.     

Photooxidation ot organic azides

The literature data on the mechanism of photooxidation of organic azides were systematized and analyzed. Particular attention was paid to reactions of azides in media with restricted mobility. The role of structural and chemical factors determining the realization of transltion states for different mechanisms is emphasized. The scheme for photooxidation of organic azides is suggested that describes the known experimental data well.     

C60与叠氮化合物的单加成反应

本文从实验以及理论研究两方面介绍了C60与叠氧化合物的单加成反应。依照叠氮化合物的不同,C60与叠氮合物的单加成反应可分为烷基叠氮化物与C60的反应,酰基叠氧化物与C60的反应以及苯基叠氮化与C60的反应三类,而反应产物则为C60亚氨基[6,6]闭环衍生物和C60亚氨基[5,6]开环衍生物两类,不同类型的反应具有不同的反应机理,某些C60亚氨基[5,6]开环衍生物可以转化为C60亚氨基[6,6]闭环衍生物。本文还介绍了碳纳米管与叠氮化合物的加成反应。     

Synthesis and properties of diacetylene azides

A three-stage method was developed for the synthesis of diacetylene azides from diacetylene alcohols prepared by Cadiot-Chodkiewicz reaction. By their bromination the corresponding diacetylene bromides were obtained whose azidation resulted in the target diacetylene azides. The attempt was performed to prepare azides of triacetylene series, but the low stability of the synthesized triacetylene alcohols prevented their conversion into the corresponding bromides.     

Efficient amidation from carboxylic acids and azides via selenocarboxylates: application to the coupling of amino acids and peptides with azides

A facile one-pot procedure for the coupling of carboxylic acid and azide via selenocarboxylate and selenatriazoline has been developed and successfully applied to the coupling of amino acids and peptides with azides. Selenocarboxylates are readily prepared by the reaction of the activated carboxylic acids with LiAlHSeH under mild conditions. The selenocarboxylates formed in situ are used to react directly with azides to form the corresponding amides via a selenatriazoline intermediate. Excellent yields were obtained for electron-deficient azides, and moderate to good yields were obtained for electron-rich azides. The selenocarboxylate/azide amidation reaction is clean and chemoselective. It provides an attractive alternative method to the conventional acylation of amines when an amide bond needs to be formed without going through an amine intermediate.     

RuCl3-promoted amide formation from azides and thioacids

Described here is the Ru(III)-promoted amide formation from azides and thioacids, which were shown not to form amides at room temperature in the absence of ruthenium. We believe that a complex formed by Ru(III) increases the reactivity of the thiocarbonyl species and therefore reaction with azides occurs at room temperature, even when less reactive (electron rich and/or sterically hindered) azides are employed.     

Glycosylthiomethyl chloride: a new species for S-neoglycoconjugate synthesis. Synthesis of 1-N-glycosylthiomethyl-1,2,3-triazoles

Reaction of O-acyl-protected glycosylthiols with dichloromethane afforded readily glycosylthiomethyl chlorides, which gave with sodium azide the corresponding glycosylthiomethyl azides 17-22. Reaction of these azides with dicyclopentadiene as dipolarophile led to tandem 1,3-dipolar cycloaddition/retro-Diels-Alder reaction furnishing the parent 1-glycosylthiomethyl-1,2,3-triazoles 23-25. Reaction of azides with acetylene derivatives gave directly 1-glycosylthiomethyl-1,2,3-triazoles which are ring-substituted.     

Synthesis of ferrocene conjugates with di- and triterpenes by click chemistry method

Reactions of propargyl dehydroabietate with ferrocenylalkyl azides led to the formation of substituted 1,2,3-triazoles. The corresponding 1,2,3-triazoles formed in the reaction of ferrocenylalkyl azides with propargyl betulonic ester.     

叠氮化合物还原成胺的研究进展

叠氮还原是向有机分子中引入氨基的重要方法。本文综述了近年来叠氮化合物还原成胺的研究进展,并对不同还原方法的适用范围及优缺点进行了简单评述。     

The allylic azide rearrangement: achieving selectivity

Allylic azides undergo a rapid [3.3]-sigmatropic rearrangement which results in dynamic equilibrium of several isomers. Thus, reactions of allylic azides usually result in mixtures of products. However, even small differences in reactivity of the isomeric allylic azides can be amplified to result in a single product in good to excellent yields. For example, the Cu(I)-catalyzed cycloaddition with alkynes selectively captures primary and secondary allylic azide isomers, whereas MCPBA epoxidation favors isomers which contain more electron-rich double olefins.     

Reactions of cyclopropanone acetals with alkyl azides: carbonyl addition versus ring-opening pathways

The Lewis acid-mediated reactions of substituted cyclopropanone acetals with alkyl azides were found to strongly depend on the structure of the ketone component. When cyclopropanone acetal was treated with alkyl azides, N-substituted 2-azetidinones and ethyl carbamate products were obtained, arising from azide addition to the carbonyl, followed by ring expansion or rearrangement, respectively. When 2,2-dimethylcyclopropanone acetals were reacted with azides in the presence of BF3.OEt2, the products obtained were alpha-amino-alpha'-diazomethyl ketones, which arose from C2-C3 bond cleavage of the corresponding cyclopropanone, giving oxyallyl cations that were captured by azides. Aryl-substituted cyclopropanone acetals, when subjected to these conditions, afforded [1,2,3]oxaborazoles exclusively, which were also the result of C2-C3 bond rupture, azide capture, and then loss of nitrogen. In the reactions of n-hexyl-substituted cyclopropanone acetals with alkyl azides, a mixture of 2-azetidinones and regioisomeric [1,2,3]oxaborazoles was obtained. The reasons for the different behavior of the various systems are discussed.     

Liquid azide salts

Ionic liquid azides from azidoethyl, alkyl, and alkenyl substituted derivatives of 1,2,4- and 1,2,3-amino-triazoles were prepared and examined for the first time to investigate their structural and physical properties. All reported salts possess melting points below 100 degrees C. The unique character of these newly discovered ionic liquid azides is based upon the fact that these molecules are not simple protonated salts like previously reported substituted hydrazinium azides. The presence of quaternary nitrogen confers both thermal stability and negligible volatility.     

The electronic absorption spectra of some acyl azides molecular orbital treatment

The electronic absorption spectra of benzoyl azide and its derivatives: p-methyl, p-methoxy, p-chloro and p-nitrobenzoyl azide were investigated in different solvents. The observed spectra differ basically from the electronic spectra of aryl azides or alkyl azides. Four intense pi-pi* transitions were observed in the accessible UV region of the spectrum of each of the studied compounds. The contribution of charge transfer configurations to the observed transitions is rather weak. Shift of band maximum with solvent polarity is minute. On the other hand, band intensity is highly dependent on the solvent used. The observed transitions are delocalized rather than localized ones as in the case with aryl and alkyl azides. The attachment of the CO group to the azide group in acyl azides has a significant effect on the electronic structure of the molecule. The arrangements as well as energies of the molecular orbitals are different in acyl azides from those in aryl azides. The first electronic transition in phenyl azide is at 276 nm, whereas that of bezoyle azide is at 251 nm. Ab initio molecular orbital calculations using both RHF/6-311G* and B3LYP/6-31+G* levels were carried out on the ground states of the studied compounds. The wave functions of the excited states were calculated using the CIS and the AM1-CI procedures.     

THE PHOTOCHEMISTRY OF ACETYL-SUBSTITUTED AROYL AZIDES: THE DESIGN OF PHOTOLABELING AGENTS FOR INERT SITES IN HYDROPHOBIC REGIONS

The photochemistry, photophysics and hydrolytic stability of three substituted aroyl azides were investigated. The azides were selected as model compounds for potential photolabeling agents based on the extreme electrophilic reactivity of aroylnitrenes. Each of the azides studied is a derivative of benzoyl azide containing an acyl group to act as an internal triplet sensitizer and an additional functional group useful for linking the azide to a site-selecting probe molecule. The findings show that benzoyl azides containing the three substituents in a 1,3,5-pattern might be useful for labeling of lipophilic molecules.     

Synthesis of aryl azides and vinyl azides via proline-promoted CuI-catalyzed coupling reactions

The coupling reaction of aryl halides or vinyl iodide with sodium azide under catalysis of CuI/L-proline works at relatively low temperature to provide aryl azides or vinyl azides in good to excellent yields.