Azide Insertion Research Articles

Retinoids Molecular Probes by Late-stage Azide Insertion - Functional Tools to Decrypt Retinoid Metabolism.

Studying the complex and intricate retinoids metabolic pathways by chemical biology approaches requires design and synthesis of biologically functional molecular probes. Only few of such molecular retinoid probes could be found in literature, most of them bearing a molecular structure quite different from natural retinoids. To provide close-to-native retinoid probes, we have developed a versatile late-stage method for the insertion of azide function at the C4 position of several retinoids. This one-step process opens straightforward access to different retinoid and carotenoid probes from commercially available precursors. We have further demonstrated that the different molecular probes retain ability of the original compound to activate genes' transcription, despite azide insertion, highlighting biological activities that were further validated in zebrafish in vivo model. The present work paves the way to future studies on vitamin A's metabolism.

Activation of Diazo Compounds by Fluorinated Triarylborane Catalysts

AbstractThe diverse applicability of diazo compounds as versatile reagents has enlarged the chemical toolbox in organic synthesis. Over the past few decades, transition-metal-catalyzed diazo compound activation has ignited the classical synthetic methodology via utilizing highly reactive metal carbenoid species. Many reviews have also appeared in the literature that show the advantages and disadvantages of metal-catalyzed activation of diazo compounds. Recently, tris(pentafluorophenyl)borane-mediated diazo activation reactions has remodeled this research area due to the potential for mild, environmentally friendly, metal-free, nontoxic reaction conditions, and the diverse reactivity patterns of boranes towards diazo compounds. In this review, we discuss the reactivity of the boron–diazo precursor adducts with compounds using catalytic and stoichiometric halogenated triarylboranes and, the mechanism of N2 release from the diazo reagent. This generates the reactive carbene species as a key intermediate which can further be exploited for O–H, N–H, S–H, and C–H insertions, azide insertion, carbonate transfer, C–C and C=C bond forming reactions, [2+2] or [2+4] cascade cyclization reactions, annulation reactions, etc.1 Introduction2 Diazo Activation Using Stoichiometric Boranes3 Diazo Activation Using Catalytic B(C6F5)3 4 B(C6F5)3-Catalyzed Diazo Activation Reactions5 Conclusions

Copper(I) Chloride Mediated Amination of Halobenzenes via Azides: Scope, Mechanistic Aspects, and C–C Cleavage Reactions

Selective azidation-amination of long-chain alkanoyl halobenzenes with sodium azide, promoted by copper(I) chloride, is reported. The protocol is, apart from CuCl and NaN3, additive free and allows the isolation of versatile amine-azides. Alkyl cleavage occurs as a side reaction through an unusual Schmidt-type azide insertion adjacent to the carbonyl group, forming alkyl nitriles possibly via radical pathways. Mechanistic studies involving 15N labeling experiments and test substrates indicate that the reaction occurs via 1-azido-4-alkanoyl benzenes. The amination is applicable for substrates with electron-withdrawing groups and proceeds under mild conditions. The mechanism of the amine formation involves nitrenes. Intermediates were trapped by carrying out the reaction in the presence of the 2,2,6,6-(tetramethylpiperidin-1-yl)oxyl stable radical and characterized by high-resolution mass spectrometry. The intermediates are consistent with earlier mechanistic proposals.

Computational Studies on Reactions of Some Organic Azides with C−H Bonds

AbstractThe computational methods, B3LYP and MP2 with the basis set 6‐311++G(d,p) have been used to decipher the energetics and mechanisms of different nitrene reactions, namely organic azide decomposition, singlet and triplet nitrene addition to different kinds of C−H bonds, azide insertion into C−H bonds and substitution reaction of azides to alkanes. The addition of singlet nitrene to the C−H bond is exothermic, with one‐step addition accompanied by a considerable barrier, where the sequence of facility H>Ac>Me indicates the electrophilic nature of the nitrene reactant. In the case of triplet nitrene, the initial step involves smaller barriers and is endothermic due to the formation of radicals as intermediate products, and the final step involves the coupling of radicals and is hence exothermic. The direct azide addition has higher barrier then the stepwise addition reaction. The Hammond postulate can be used to differentiate the transition state geometries for different reaction steps as “early” or “late”.

Photoactivatable Fluorogens by Intramolecular C-H Insertion of Perfluoroaryl Azide.

Molecules, capable of fluorescence turn-on by light, are highly sought-after in spatio-temporal labeling, surface patterning, monitoring cellular and molecular events, and high-resolution fluorescence imaging. In this work, we report a fluorescence turn-on system based on photoinitiated intramolecular C-H insertion of azide into the neighboring aromatic ring. The azide-masked fluorogens were efficiently synthesized via a cascade nucleophilic aromatic substitution of perfluoroaryl azides with carbazoles. The scaffold also allows for derivatization with biological ligands, as exemplified with d-mannose in this study. This photoinitiated intramolecular transformation led to high yields, high photo-conversion efficiency, and well-separated wavelengths for photoactivation and fluorescence excitation. The mannose-derivatized structure enabled spatio-temporal activation and showed high contrast and signal amplification. Live cell imaging suggested that the mannose-tagged fluorogen was transported to the lysosomes.

Boron-Catalyzed Azide Insertion of α-Aryl α-Diazoesters.

A challenging metal-free azide insertion of α-aryl α-diazoesters in the presence of B(C6F5)3 (5 mol %) was developed for the first time. The reaction features an easy operation, wide substrate scope, and mild conditions and affords the corresponding products in moderate to high yields. More importantly, alkene and alkyne functional groups were well tolerated because no cyclopropanation or cyclopropenation was observed. Furthermore, the corresponding azide products could be converted to primary amines or 1,2,3-triazole derivatives after simple transformations.

First total synthesis of theopederin B

Total synthesis of theopederin B, isolated from marine sponge, was accomplished by coupling pederic acid, as the left half, with trioxodecaline amine as the right half. Key reactions for synthesizing the amine were SmI 2-promoted Reformatsky reaction, stereoselective allylation followed by Sharpless asymmetric epoxidation for construction of the functionalized side chain, and 1,3-dioxane ring construction followed by azide insertion.

Reactivity of (C5Me5)3LaLx Complexes: Synthesis of a Tris(pentamethylcyclopentadienyl) Complex with Two Additional Ligands, (C5Me5)3La(NCCMe3)2

The limits of steric crowding in tris(pentamethylcyclopentadienyl) complexes have been expanded by isolation of the first compound with this ligand set and two additional ligands, (C(5)Me(5))(3)ML(2). This result was obtained in a study of the effect of added ligands on the reactivity of sterically crowded (C(5)Me(5))(3)La, 1. Although neither THF nor Ph(3)PO formed crystallographically characterizable (C(5)Me(5))(3)LaL(x) complexes with 1, these (C(5)Me(5))(3)La/L(x) mixtures displayed enhanced reactivity compared to 1 with substrates such as C(8)H(8) and CO(2). Attempts to use adamantyl azide, AdN(3), to make (C(5)Me(5))(3)LaL(x) complexes led to the first example of azide insertion into a metal cyclopentadienyl linkage to generate (C(5)Me(5))(2)La[eta(2)-(N,N')-(C(5)Me(5))NN'N''Ad](N(3)Ad). Addition of Me(3)CCN to 1 produced the first crystallographically characterized (C(5)Me(5))(3)ML(2) complex, (C(5)Me(5))(3)La(NCCMe(3))(2).

Oxazaborolidines from boracycles through the intramolecular azide insertion

Oxazaborolidines from boracycles through the intramolecular azide insertion

ChemInform Abstract: Reactions of Oxazolinium and Dihydrooxazinium Salts Prepared by an Azide Insertion Sequence: pH Control of Product Distribution.

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Reactions of Oxazolinium and Dihydrooxazinium Salts Prepared by an Azide Insertion Sequence: pH Control of Product Distribution

This is the publisher's version, also available electronically from https://www.thieme-connect.de.

7] Synthesis and use of radioactive photoactivatable NAD+ derivatives as probes for G-protein structure

This chapter describes synthesis and use of radioiodinated phenylazide nicotinamide adenine dinucleotide (NAD+) derivatives ([125I]AIPP-NAD+]. The synthesis and use of 2-azido-[32P]NAD+ is described briefly. The chapter describes the photocross-linking and label transfer using pertussis toxin 2-azido-[32P] adenosine diphosphate (ADP)-ribosylated transducin. An important feature of 2-azido-[32P]NAD+ is that the photoactive moiety and the radioactive atom are positioned on the same side of the phosphodiester bond. Thus, ADP-ribosylation of a G protein, followed by a photolytic reaction of the azide moiety with a neighboring polypeptide, can be used to transfer the molecule to the site of azide insertion by cleavage of the thioglycosidic linkage using mercuric acetate or cleavage of the phosphodiester bond using snake venom phosphodiesterase. Two control experiments were performed to determine the pertussis toxin and azide dependence of photocross-linking. The results showed that radiolabel incorporation into α1 is dependent on pertussis toxin treatment and that photoincorporation of radiolabel into transducin subunits is dependent on prior treatment with pertussis toxin. Evidence to support the identity of the cross-linked polypeptides is provided by immunoblotting using antisera specific for either αt or β and γ subunits.