Trimethylsilyl Azide Research Articles

Visible‐Light‐Enabled Multicomponent Cascade Transformation from Indoles to 2‐Azidoindolin‐3‐yl 2‐Aminobenzoates

AbstractThe synthesis of 2‐azido‐1‐benzoylindolin‐3‐yl 2‐benzamidobenzoate commencing from (1H‐indol‐1‐yl)(phenyl)methanone and trimethylsilyl azide (TMSN3) under oxygen atmosphere is described in this paper. This transformation proceeds via a sequential dearomatization and ring‐opening cascade reaction of indoles in a cascade manner.magnified image

Building a Robust and Conductive Solid Electrolyte Interphase on Li-Metal Anode for High-Performance Li-Metal Batteries

For the first time, trimethylsilyl azide (C3H9N3Si, hereinafter denoted as TSA) is used as an efficient additive in a fluoroethylene carbonate (FEC)-based carbonate electrolyte solution. Along with an LiF-rich compound, the addition of 0.1 M TSA to the FEC-based electrolyte induces a conductive Li3N-rich solid–electrolyte interphase layer on the Li-metal surface and allows the formation of a dense Li-deposit morphology, suppressing the dendritic growth of Li and improving the Li+ ionic conductivity. In a practical Li-metal battery using a 2 mol% Al-doped full-concentration gradient Li[Ni0.75Co0.10Mn0.15]O2 (Al2-FCG75) cathode, the TSA additive greatly improves the cycling stability and rate capability, even under practical operating conditions.1. S.-J. Park, J.-Y. Hwang and Y.-K. Sun,J. Mater. Chem. A, 2019, 7, 13441-13448.2. S.-J. Park, J.-Y. Hwang, C. S. Yoon, H.-G. Jung and Y.-K. Sun, ACS Appl. Mater. Interfaces, 2018, 10, 17985.

Iron-Catalyzed Alkylazidation of 1,1-Disubstituted Alkenes with Diacylperoxides and TMSN3.

An iron-catalyzed radical alkylazidation of electron-deficient alkenes is reported. Alkyl diacyl peroxides work as the alkyl source, and trimethylsilyl azide acts as the azido reservoir. This method features mild reaction conditions, wide substrate scope, and good functional group tolerance, providing a range of α-azido esters, an α-azido ketone, and an α-azido cyanide in high yields. These azides can be easily transferred into many kinds of amino acid derivatives.

Silver-Catalyzed Activation of Terminal Alkynes for Synthesizing Nitrogen-Containing Molecules.

Alkynes are one of the most abundant chemicals in organic chemistry, and therefore the development of catalytic reactions to transform alkynes into other useful functionalities is of great value. In recent decades, extraordinary advances have been made in this area with transition-metal catalysis, and silver-based reagents are ideal for the activation of alkynes. This high reactivity is probably due to the superior π-Lewis acidic, carbophilic behavior of silver(I), allowing it to selectively activate carbon-carbon triple bonds (C≡C) through the formation of a silver-π complex. Within this field, we have been interested in the activation and subsequent reactions of readily accessible terminal alkynes for the synthesis of nitrogen-containing compounds, which has generally received less attention than methods involving internal alkynes. This is possibly due to the lack of suitable reactive reaction partners that are compatible under transition metals. Therefore, a thorough understanding of the factors that influence homogeneous silver catalysis and the identification of the appropriate reaction partners can provide a powerful platform for designing more efficient silver-catalyzed reactions of terminal alkynes. In this context, we envisioned that using readily available, environmentally benign, and inexpensive trimethylsilyl azide (TMSN3) or an isocyanide as the nitrogen-donor would be the key to develop novel reactions of terminal alkynes.This Account describes our efforts since 2013 toward the development of novel silver-catalyzed tandem reactions of terminal alkynes with either TMSN3 or isocyanides for the assembly of various nitrogen-containing compounds. The first section of this Account discusses the initial developments in the silver-catalyzed hydroazidation of terminal alkynes with TMSN3 and the subsequent advances made in our laboratory. We first describe the discovery and experimental and computational mechanistic investigations of silver-catalyzed hydroazidation reactions, which is the most efficient strategy reported to date for accessing vinyl azides. Mechanistic study of this hydroazidation reaction provides an alternative activation mode for terminal alkyne conversion in transition metal catalysis. We then present the chemistry of in situ generated vinyl azides, including one-pot tandem radical addition/cyclization or migration reactions of terminal alkynes to access a variety of nitrogen-containing molecules. Finally, we discuss the one-pot, multistep tandem hydroazidation and 1,2-azide migratory gem-difluorination of terminal alkynes for the synthesis of β-difluorinated alkyl azides. The second section describes the silver-catalyzed coupling reactions between terminal alkynes and isocyanides, which offer a straightforward method for accessing synthetically useful building blocks, such as pyrroles, allenamides, benzofuran, vinyl sulfones, indazolines, propiolonitriles, and pyrazoles. The high efficiency, mild conditions, low cost, broad substrate scope, high chemo- and regioselectivity, step economy, and ecofriendliness of the developed approaches make them attractive and practical. The progress in this area provides guiding principles for designing new reactions of terminal alkynes that can be extended to various nitrogen-containing molecules of interest to medicinal and materials chemists.

Efficient Synthesis of 4H-3,1-Benzoxazine Derivatives via One-Pot Sequential Passerini-Azide/Palladium-Catalyzed Azide–Isocyanide Coupling/Cyclization Reaction

A new, one-pot method for the synthesis of 4H-3,1-benzoxazine derivatives has been developed. The Passerini-azide reactions of 2-azidobenzaldehydes, trimethylsilyl azide, and isocyanides produced azide intermediate without separation, which then reacted with isocyanides to give 4H-3,1-benzoxazine derivatives via a tandem one-pot palladium-catalyzed azide–isocyanide coupling/cyclization reaction in moderate to good yields.

Divalent Ytterbium Iodide Supported by β‐Diketiminato Based Tridentate Ligand: Synthesis, Structure and Small Molecule Activation†

Summary of main observation and conclusionDivalent ytterbium iodide [LYb(μ‐I)(THF)]2 (1; L = [MeC(NDIPP)CHC(Me)NCH2CH2NMe2]−, DIPP = 2,6‐(iPr)2C6H3) was synthesized and its reactivity was studied. Complex 1 was synthesized by salt metathesis of YbI2(THF)2 with the potassium salt of ligand (KL) in high yield. In the reactions with trimethylsilyl azide, azobenzene, sulfur and diphenyl disulfide, complex 1 acts as a 2e reductant. In the reaction with CO2, the central carbon atom of β‐diketiminato backbone in 1 nucleophilically attacks the CO2 molecule to give a divalent ytterbium carboxylate.

Me CAAC=N- : A Cyclic (Alkyl)(Amino)Carbene Imino Ligand.

A cyclic (alkyl)(amino)carbene (CAAC) has been shown to react with a covalent azide similar to the Staudinger reaction. The reaction of MeCAAC with trimethylsilyl azide afforded the N‐silylated 2‐iminopyrrolidine (MeCAAC=NSiMe3), which was fully characterized. This compound undergoes hydrolysis to afford the 2‐iminopyrrolidine and trimethylsiloxane which co‐crystallize as a hydrogen‐bonded adduct. The N‐silylated 2‐iminopyrrolidine was used to transfer the novel pyrrolidine‐2‐iminato ligand onto both main‐group and transition‐metal centers. The reaction of the tetrabromodiborane bis(dimethyl sulfide) adduct with two equivalents of MeCAAC=NSiMe3 afforded the disubstituted diborane. The reaction of MeCAAC=NSiMe3 with TiCl4 and CpTiCl3 afforded MeCAAC=NTiCl3 and MeCAAC=NTiCl2Cp, respectively.

Copper and manganese co-mediated cascade aza-Michael addition/cyclization and azidation of 1,3-enynes: regioselective synthesis of fully substituted azido pyrroles.

An efficient Cu and Mn co-mediated aerobic oxidative cyclization and azidation reaction of 1,3-enynes with amines and trimethylsilyl azide (TMSN3) for the synthesis of fully substituted azido pyrroles has been developed. The three-component reaction has the characteristics of high regioselectivity, wide substrate scope, and mild reaction conditions. A preliminary mechanism for this transformation is proposed.

Synthesis of Complex Boron-Nitrogen Heterocycles Comprising Borylated Triazenes and Tetrazenes Under Mild Conditions.

The reactions of organic azides with diaryl(dihalo)diboranes(4) were explored, resulting in the observation of a number of surprising reactivity patterns. The reaction of phenyl azide with 1,2-diaryl-1,2-dihalodiboranes(4) resulted in the formation of five-membered rings comprising diboryl-triazenes with retention of the boron-boron bond, while the reaction of the peculiar 1,1-di(9-anthryl)-2,2-difluorodiborane(4) with phenyl azide yielded a six-membered ring bearing a diboryl-triazene, whereby the B-B bond was ruptured by the insertion of an arylnitrene-like reactive intermediate. Both types of heterocycles feature unprecedented connectivity patterns and are very rare examples of boryl triazenes beyond the more common 1,2,3-triazolatoboranes. They are also the product of a unique type of aryl migration from a boron center to the phenyl azide γ-nitrogen center. Lastly, the substitution of 1,2-diaryl-1,2-dihalodiboranes(4) with azide groups, using trimethylsilyl azide as the transfer reagent, yielded boryl-tetrazaboroles and diboryldiazadiboretidines (as side-products), invoking the intermediacy of the first N-boryl-substituted iminoboranes, which are BN isosteres of monoborylated alkynes. The synthetic results are complemented with mechanistic proposals derived from quantum-chemical calculations.

Adduct of NacNacAl with Benzophenone and Its Coupling Chemistry.

Reaction of NacNacAl (NacNac=[DippNC(Me)CHC(Me)NDipp]- ) with one equivalent of benzophenone affords a ketylate species NacNacAl(η2 (C,O)-OCPh2 ) that undergoes easy cyclization reactions with unsaturated substrates. The scope of substrates included benzophenone, aldimine (PhNC(Ph)H), quinoline, phenyl nitrile, trimethylsilyl azide, and a saturated cyclic thiourea. The latter substrate reacted by an unusual C-N cleavage that left the C=S functionality intact. The new products were characterized by NMR spectroscopy and X-ray diffraction analysis.

Synthesis of Enantiomerically Pure N-Boc-Protected 1,2,3-Triaminopropylphosphonates and 1,2-Diamino-3-Hydroxypropylphosphonates.

All possible isomers of 1,2,3-tri(N-tert-butoxycarbonylamino)propylphosphonate 6 were synthesized from the respective diethyl [N-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates 5 via opening the aziridine ring with trimethylsilyl azide (TMSN3) followed by hydrogenolysis in the presence of di-tert-butyl dicarbonate (Boc2O). [N-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates (1R,2R,1′S)-5a and (1S,2S,1′R)-5c were smoothly transformed into diethyl 3-acetoxy-1-benzylamino-2-[N-(1-phenylethyl)amino]propylphosphonates (1R,2R,1′S)-9a and (1S,2S,1′R)-9c, respectively by the opening of the aziridine ring with acetic acid. Transformations of [N-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates (1S,2R,1′S)-5b and (1R,2S,1′R)-5d into diethyl 3-acetoxy-1-benzylamino-2-[(1-phenylethyl)amino]propylphosphonates (1S,2R,1′S)-9b and (1R,2S,1′R)-9d were accompanied by the formation of ethyl {1-(N-benzylacetamido)-3-hydroxy-2-[(1-phenylethyl)amino]propyl}phosphonate (1S,2R,1′S)-10b and (1R,2S,1′R)-10d and 3-(N-benzylacetamido)-4-[N-(1-phenylethyl)]amino-1,2-oxaphospholane (3S,4R,1′S)-11b and (3R,4S,1′R)-11d as side products. Diethyl (1R,2R)-, (1S,2S)-, (1S,2R)- and (1R,2S)-3-acetoxy-1,2-di(N-tert-butoxycarbonylamino)propylphosphonates 7a–7d were obtained from the respective 3-acetoxy-1-benzylamino-2-[N-(1-phenylethyl)amino]propylphosphonates 9a–9d by hydrogenolysis in the presence of Boc2O.

Dearomatization of Indoles via Azido Radical Addition and Dioxygen Trapping To Access 2-Azidoindolin-3-ols.

Efficient copper-catalyzed aerobic oxidative dearomatization of indoles with trimethylsilyl azide (TMSN3) for the synthesis of 2-azidoindolin-3-ols has been developed. Molecular oxygen served as the oxygen-atom source in this transformation. The multicomponent reaction is appreciated by its high site- and diastereoselectivity, broad substrate scope, and mild conditions at room temperature.

Diastereoselective synthesis of multisubstituted isoindolines via Sequential Ugi and aza-Michael addition reaction

A new efficient and diastereoselective synthesis of multisubstituted isoindolines with two stereogenic centers via sequential Ugi/aza-Michael addition reaction was developed. Ugi-3CR of aldehydes 1, amines 2 and isocyanates 3 in the presence of catalytic amount of H3PO4 produced intermediates 4, which were then transformed to isoindolines 5 with good 1,3-trans diastereoselectivity in the presence of K2CO3 by intramolecular aza-Michael addition. Sequential Ugi-azide and aza-Michael addition reaction of aldehydes 1, amines 2 and trimethylsilyl azide 6 also produced 4-tetrazolyl substituted isoindolines 8 with good 1,3-trans diastereoselectivity in the presence of potassium carbonate.

Iron-Catalysed Remote C(sp3 )-H Azidation of O-Acyl Oximes and N-Acyloxy Imidates Enabled by 1,5-Hydrogen Atom Transfer of Iminyl and Imidate Radicals: Synthesis of γ-Azido Ketones and β-Azido Alcohols.

In the presence of a catalytic amount of iron(III) acetylacetonate [Fe(acac)3 ], the reaction of structurally diverse ketoxime esters with trimethylsilyl azide (TMSN3 ) afforded γ-azido ketones in good to excellent yields. This unprecedented distal γ-C(sp3 )-H bond azidation reaction went through a sequence of reductive generation of an iminyl radical, 1,5-hydrogen atom transfer (1,5-HAT) and iron-mediated redox azido transfer to the translocated carbon radical. TMSN3 served not only as a nitrogen source to functionalise the unactivated C(sp3 )-H bond, but also as a reductant to generate the catalytically active FeII species in situ. Based on the same principle, a novel β-C(sp3 )-H functionalisation of alcohols via N-acyloxy imidates was subsequently realised, leading, after hydrolysis of the resulting ester, to β-azido alcohols, which are important building blocks in organic and medicinal chemistry.

New Facile Synthesis of 3,4-Dihydroquinazoline-2(1H)-thiones by a Sequential Ugi-Azide/Staudinger/Aza-Wittig/Cyclization Reaction

A new facile synthesis of 3,4-dihydroquinazoline-2(1H)-thiones by an Ugi-azide/Staudinger/aza-Wittig/cyclization sequence has been developed. The Ugi-azide reactions of 2-azidobenzaldehydes, amines, trimethylsilyl azide, and isocyanides produced tetrazoles, which, when treated with methyldiphenylphosphane and CS2, produced 3,4-dihydroquinazoline-2(1H)-thiones in good overall yields via a sequential Staudinger/aza-Wittig/cyclization reaction.

Ammonium Hypoiodite-catalyzed Oxidative Dearomatizative Azidation of Arenols

The first transition metal-free catalytic oxidative dearomatizative azidation of arenols has been developed using hypoiodite catalysis with aqueous hydrogen peroxide and trimethylsilyl azide as an ...

Cooperation of Mn(III)/Brønsted Acid for the Synthesis of Quindoline Derivatives via Dehydroxylation/Azidation/Cyclization Cascade of Diaryl(1 H-indol-2-yl)methanols with Trimethylsilyl Azide.

A new synthesis of quindoline derivatives promoted by Mn(III)/Brønsted acid via a dehydroxylation/azidation/cyclization cascade of diaryl(1 H-indol-2-yl)methanols with trimethylsilyl azide was developed. The reaction features very effective transformation involving two C(sp2)-H and one C(sp3)-O bond cleavages, two C(sp2)-N bonds, and one N-heterocycle formation in a one-pot manner. A series of 11-arylquindolines were synthesized in good yields.

Trimethylsilyl Azide (TMSN3) Enhanced Li–O2 Battery Electrolytes

Li–O2 batteries (commonly called Li–air batteries) are plagued by reactions of reduced oxygen intermediates at the cathode, as well as instability of ether-based electrolytes on the Li metal anode. Here, we study the effect of adding a non-redox mediator, trimethylsilyl azide (TMSN3), to a diglyme-based electrolyte. The TMSN3 enables formation of a stable bis(TMS)peroxide from Li2O2 during discharge. The bis(TMS)peroxide can subsequently undergo decomposition during charging with a reduction in overpotential of up to 1000 mV relative to the decomposition potential of Li2O2. TMSN3 also results in formation of a robust solid electrolyte interphase (SEI), consisting of a composite of lithium nitride, reduced nitrates, and siloxanes that appear to limit both Li dendrite formation and bis(TMS)peroxide shuttling. The synergistic effect of TMSN3 on both the cathode and anode enables a high areal capacity of 3.8 mAh cm–2 at a high rate of 637 μA cm–2 for up to 30 cycles.

Anti-Markovnikov Hydroazidation of Alkenes by Visible-Light Photoredox Catalysis.

The anti-Markovnikov hydroazidation of alkenes has been accomplished under visible-light irradiation by using [Ir(dF(CF3 )ppy)2 (dtbbpy)]PF6 as the photocatalyst and trimethylsilyl azide as the azidating agent. The reactions were greatly facilitated by water, the beneficial effect of which can be attributed to its participation in the reaction as the hydrogen donor, as indicated by deuterium isotope experiments. The reactions proceed under solvent free conditions in the presence of water. 4-Dimethylaminopyridine also exhibited a beneficial effect on the reactions. The present method enabled hydroazidation of several types of unactivated alkenes with good yields and high regioselectivity.

Facile synthesis of 1,5-disubstituted tetrazoles by reacting a ruthenium acetylide complex with trimethylsilyl azide.

Treatment of [Ru]-C[triple bond, length as m-dash]CPh (1, [Ru] = (η5-C5H5)(dppe)Ru, dppe = Ph2PCH2CH2PPh2) with trimethylsilyl azide afforded the cationic nitrile complex {[Ru]NCCH2Ph}[N3] (2) and the further cycloaddition of 2 with trimethylsilyl azide at 60 °C afforded the N(2)-bound tetrazolato complex [Ru]N4CCH2Ph (3). The regiospecific alkylation of 3 gave a series of cationic N(2)-bound N(4)-alkylated-5-benzyl tetrazolato complexes {[Ru]N4(CH2R)CCH2Ph}[Br] (4a, R = C6F5; 4b, R = Ph; 4c, R = 4-CN-C6H4; 4d, R = 2,6-F2-C6H3; 4e, R = 6-CH2Br-C5NH3) and the subsequent cleavage of the Ru-N bond of 4a-4e gave N(1)-alkylated-5-benzyl tetrazoles N4(CH2R)CCH2Ph (5a-5e) in good to excellent yields and [Ru]-Br, which, on reacting with phenylacetylene, resulted in the formation of 1 thus forming a reaction cycle. The structures of 2, 3, 4a, 4c and 5a were confirmed by single-crystal X-ray diffraction analysis.