Tosyl Azide Research Articles

Copper(I)-Catalyzed Formal [4 + 2] Cyclocondensation of ortho-Hydroxybenzyl Alcohol, Aromatic Terminal Alkynes, and Sulfonyl Azides: An Alternative Approach to 2-Sulfonyliminocoumarins.

In this paper, an alternative and efficient copper(I)-catalyzed synthesis of 2-sulfonyliminocoumarins is developed through a three-component reaction of ortho-hydroxybenzyl alcohol, alkynes, and p-toluenesulfonyl azide. The proposed route for access to the 2-iminocoumarin ring involves a [4 + 2] hetero-Diels-Alder reaction between ortho-quinone methide and ketenimine intermediates generated in situ.

1,3-Dipolar Cycloaddition of Diazophosphonates with Methyl(Ethyl) Acrylate for the Synthesis of 5-Arylpyrazole-3-carboxylates

AbstractA wide range of α-aryl-α-diazophosphonates were easily prepared via modified diazo transfer reaction. Benzylphoshonates reacted with tosyl azide (TsN3) in the presence of potassium tert-butoxide (KOtBu) to afford diazophosphonates in yields up to 93% (generally 70–80%). Aryldiazophosponates were successfully explored for the synthesis of 5-aryl-substituted pyrazol-3-carboxylates in one pot by the 1,3-dipolar cycloaddition with alkyl acrylates followed by NaH treatment. The second stage led to elimination of the diethoxylphosphoryl moiety with the aromatization of cycle.

1,2,3-Thiadiazole as a Modifiable and Scalable Directing Group for ortho-C-H Functionalization.

In the last few decades, directed C-H bond functionalization has had enormous applicability in academia and industry. The development of a novel, readily accessible, and scalable directing group with modifiable ability is highly desirable in C-H functionalization. Herein, we report the 1,2,3-thiadiazole as a modifiable directing group for C-H amidation and alkynylation with dioxazolones, p-toluenesulfonyl azide, and bromoalkynes in high yield. The densely functionalized 1,2,3-thiadiazole products are modified into thioamide, multisubstituted furan, γ-thiapyrone, thiazole, and various alkynyl sulfides through simple and one-step reactions. The competition experiments reveal that the directing ability of 1,2,3-thiadiazole is slightly weaker than pyridine and bidentate amide but stronger than the widely used carboxylate.

Organic photosensitized aziridination of alkenes.

We report a new TADF-catalyzed aziridination of alkenes under visible light. In this protocol, a free triplet nitrene is in situ generated from the commercially available tosyl azide by energy transfer of the excited photocatalyst 4DPAIPN. Our finding enables the smooth installation of the strained aziridine ring into a remarkably wide scope of alkenes and pharmaceutical-derived olefins and natural products, as well as the synthesis of sitagliptin. This metal-free method provides a new opportunity for the late-stage modification of complex molecules or synthesis of nitrogen-containing pharmaceuticals.

A New Method for the Introduction of an Acylsulfonamide Moiety Applied to a 3-Substituted Functionalized Indole Framework ­Related to the Welwitindolinone Alkaloids

AbstractThe one-pot reaction between an α-formylcyclohexanone derivative and tosyl azide in the presence of rhodium trifluoroacetate dimer afforded an acylsulfonamide derivative. This transformation is proposed to arise from a domino mechanism involving the in situ generation, through the Regitz method, of an α-diazoketone, followed by its transformation into a rhodium carbenoid and its combination with N-tosylformamide, generated as a side product of the first step of the mechanism. Overall, this transformation leads to the generation of a C–N bond between the formyl carbon and the azide nitrogen adjacent to the sulfonyl group.

Metal/Support Interactions Regulate Substrate Binding in Fe/Co/Se Cluster Catalysts.

Here, we investigate the stereoelectronic requirements of a family of Fe/Co6Se8 molecular clusters to achieve a Goldilocks regime of substrate affinity for the catalytic coupling of tosyl azide and tert-butyl isocyanide. The reactivity of a catalytically competent iron-nitrenoid intermediate, observed in situ, is explored toward nitrene transfer and hydrogen-atom abstraction. The dual role of isocyanide, which, on the one hand, prevents catalyst degradation but, in large amounts, slows down reactivity, is exposed. The impact of distal changes (the number of neighboring active sites and the identity of supporting ligands) on the substrate affinity, electronic properties, and catalytic activity is investigated. Overall, the study reveals that the dynamic, push-pull interactions between the substrate (tBuNC), active site (Fe), and support (Co6Se8) create a regime where increased substrate activation occurs with facile dissociation.

One-pot Synthesis of 2-Aminoindole through SET Oxidative Cyclization: Concise Synthesis of Tryptanthrin and Phaitanthrin E.

An efficient domino approach for the synthesis of biologically important 2-aminoindole derivatives has been developed using CuBr2 -mediated SET oxidative cyclization as a key step. This one-pot multicomponent strategy utilizes readily available ethyl propiolate, tosyl azide, and substituted aryl amines as starting materials. The generality and scope of this mild method are demonstrated with a wide variety of substrates to furnish functionalized 2-aminoindoles in good yields. The synthetic power of this strategy is further exemplified in the concise synthesis of biologically important alkaloids, Phaitanthrin E and Tryptanthrin.

Origin of the Distinctive Electronic Structure of Co- and Fe-Porphyrin-Nitrene and Its Effect on Their Nitrene Transfer Reactivity

Metal-bound nitrene species are the crucial intermediate in catalytic nitrene transfer reactions exhibited by engineered enzymes and molecular catalysts. The electronic structure of such species and its correlation with nitrene transfer reactivity have not been fully understood yet. This work presents an in-depth electronic structure analysis and nitrene transfer reactivity of two prototypical metal-nitrene species derived from CoII(TPP) and FeII(TPP) (TPP = meso-tetraphenylporphyrin) complexes and tosyl azide nitrene precursor. Parallel to the well-known "cobalt(III)-imidyl" electronic structure of the Co-porphyrin-nitrene species, the formation mechanism and electronic structure of the elusive Fe-porphyrin-nitrene have been established using density functional theory (DFT) and multiconfigurational complete active-space self-consistent field (CASSCF) calculations. Electronic structure evolution analysis for the metal-nitrene formation step and CASSCF-derived natural orbitals advocates that the electronic nature of the metal-nitrene (M-N) core of Fe(TPP) is strikingly different from that of the Co(TPP). Specifically, the "imidyl" nature of the Co-porphyrin-nitrene [(TPP)CoIII-•NTos] (Tos = tosyl) (I1Co) is contrasted by the "imido-like" character of the Fe-porphyrin-nitrene [(TPP)FeIV[Formula: see text]NTos] (I1Fe). This difference between Co- and Fe-nitrene has been attributed to the additional interactions between Fe-dπ and N-pπ orbitals in Fe-nitrene, which is further complemented by the shortened Fe-N bond length of 1.71 Å. This stronger M-N bond in Fe-nitrene compared to the Co-nitrene is also reflected in the higher exothermicity (ΔΔH = 16 kcal/mol) of the Fe-nitrene formation step. The "imido-like" character renders a relatively lower spin population on the nitrene nitrogen (+0.42) in the Fe-nitrene complex I1Fe, which undergoes the nitrene transfer to the C═C bond of styrene with a considerably higher enthalpy barrier (ΔH‡ = 10.0 kcal/mol) compared to the Co congener I1Co (ΔH‡ = 5.6 kcal/mol) possessing a higher nitrogen spin population (+0.88) and a relatively weaker M-N bond (Co-N = 1.80 Å).

Synthesis of a Pyridoazepine Scaffold via Rhodium-Catalyzed Ring Expansion and Nitroacetamide Condensation

Pyridoazepines are privileged structures in the search for novel drug candidates. We present the synthesis of a versatile pyridoazepine scaffold employing a precedented rhodium(II)-catalyzed ring expansion and subsequent double-condensation-cyclization with nitroacetamide. The reactions applied several potentially hazardous reagents and intermediates, including p-toluenesulfonyl azide and nitroacetamide, the latter of which was determined to be potentially explosive and shock-sensitive. Reactions employed were derisked for laboratory scale work through DSC and TSU analysis in concert with optimization of reaction conditions. The key rhodium-catalyzed ring expansion was shown by TSU analysis to occur in a controllable manner with manageable nitrogen evolution. A new procedure is presented that enables preparation of nitroacetamide without excessive manipulation (i.e., extractive isolation) or isolation of dry solid. This article describes early safety studies used to derisk the preparation of multi-gram quantities of the target pyridoazepine.

Chemoselective Chan-Lam and reductive nitroarene coupling of boronic acid using an octahedral Ni-DMAP complex as catalyst

An octahedral Ni-DMAP complex has been developed as catalyst for C–N and C–S cross coupling and reductive nitroarene coupling using boronic acid as coupling partner. Reaction of amines, thiols, azides, and tosyl azides with boronic acids could be achieved in presence of 10 mol % of the catalyst in methanol at 80 °C without using extra base. The current protocol is highly selective for primary amines in presence of secondary amines, thiols and phenols. Reductive coupling of a range of nitroarenes and boronic acids was also successfully achieved using the same catalyst.

Metal-free transfer hydrogenation/cycloaddition cascade of activated quinolines and isoquinolines with tosyl azides.

The difficulty in isolating cyclic enamines emanating from their intrinsic instability has impeded their exploration in cycloaddition reactions. Here, we achieved a metal-free domino reaction providing quinoline and isoquinoline-derived cyclic amidines by the cycloaddition of azides with in situ generated enamines via dearomatization.

Metal-Support Interactions in Molecular Single-Site Cluster Catalysts.

This study provides atomistic insights into the interface between a single-site catalyst and a transition metal chalcogenide support and reveals that peak catalytic activity occurs when edge/support redox cooperativity is maximized. A molecular platform MCo6Se8(PEt3)4(L)2 (1-M, M = Cr, Mn, Fe, Co, Cu, and Zn) was designed in which the active site (M)/support (Co6Se8) interactions are interrogated by systematically probing the electronic and structural changes that occur as the identity of the metal varies. All 3d transition metal 1-M clusters display remarkable catalytic activity for coupling tosyl azide and tert-butyl isocyanide, with Mn and Co derivatives showing the fastest turnover in the series. Structural, electronic, and magnetic characterization of the clusters was performed using single crystal X-ray diffraction, 1H and 31P nuclear magnetic resonance spectroscopy, electronic absorption spectroscopy, cyclic voltammetry, and computational methods. Distinct metal/support redox regimes can be accessed in 1-M based on the energy of the edge metal's frontier orbitals with respect to those of the cluster support. As the degree of electronic interaction between the edge and the support increases, a cooperative regime is reached wherein the support can deliver electrons to the catalytic site, increasing the reactivity of key metal-nitrenoid intermediates.

One-Pot Synthesis of 1,2,3-Triazole-Fused Polycyclic Systems via Sequential Annulation of 1,n-Enynes with Tosyl Azide

AbstractAn efficient one-pot sequential annulation of 1,n-enynes with tosyl azide is reported, providing a series of novel N-alkyl 1,2,3-triazole-fused polycyclic scaffolds in moderate to excellent yields under mild reaction conditions.

Multi-active Site Dynamics on a Molecular Cr/Co/Se Cluster Catalyst.

This study uncovers the interconnected reactivity of the three catalytically active sites of an atomically precise nanocluster Cr3(py)3Co6Se8L6 (1(py)3, L = Ph2PNTol-, Ph = phenyl, Tol = 4-tolyl). Catalytic and stoichiometric studies into tosyl azide activation and carbodiimide formation enabled the isolation and crystallographic characterization of key catalytically competent metal-imido intermediates, including the tris(imido) cluster 1(NTs)3, the catalytic resting state 1(NTs)3(CNtBu)3, and the site-differentiated mono(imido) cluster 1(NTs)(CNtBu)2. In the stoichiometric regime, nitrene transfer proceeds via a stepwise mechanism, with the three active sites engaging sequentially to produce carbodiimide. Moreover, the chemical state of neighboring active sites was found to regulate the affinity for substrates of an individual Cr-imido edge site, as revealed by comparative structural analysis and CNtBu binding studies.

Synthesis of α-Aryldiazophosphonates via a Diazo Transfer Reaction.

The simple synthetic procedure for preparation of α-aryl-α-diazophosphonates via a diazo transfer reaction is proposed. Benzylphosphonates reacted with tosyl azide (TsN3) in the presence of potassium tert-butoxide (KOtBu) to afford diazophosphonates in a yield up to 79%. The proposed method is general. The reaction uses easily available starting materials, tolerates various functional groups, and may be applied for multi-gram scale synthesis.

N-doped TiO2 nanotubes catalyzed solvent-free domino strategy for the synthesis of α-keto triazoles

The present work describes the catalytic activity of nitrogen-doped TiO2 nanotubes (NTNTs) for solvent-free domino synthesis of a series of α-ketotriazoles from methyl ketones, N,N-dimethylformamide dimethyl acetal (DMF-DMA) and tosyl azide. The reaction proceeds through the in situ enaminone formation from methyl ketones and DMF-DMA followed by reaction with tosyl azide via a 1,3-dipolar cycloaddition. To our delight, NTNTs exhibited high catalytic activity towards the solvent-free synthesis of α-ketotriazoles from methyl ketones, DMF-DMA and tosyl azide as compared to both commercially available TiO2 and TNTs. The present domino strategy has several advantages which include its large substrate scope, low NTNT-2 loading, shorter reaction times and high yields. Further, the obtained α-ketotriazoles does not require column purification and NTNT-2 is used again for 7 cycles without significant loss of activity.

1,2-Acyl migration with α-imino rhodium carbenoids leading to substituted 1-naphthols.

A unique method for the synthesis of substituted 1-naphthols by a rhodium(II)-catalysed ring-expansion reaction of 2-triazolyl-1-indanone derivatives is reported. 1,2-Acyl migration occurs with an intermediate α-imino rhodium carbenoid generated from the triazolyl moiety.

Generation of Tosyl Azide in Continuous Flow Using an Azide Resin, and Telescoping with Diazo Transfer and Rhodium Acetate-Catalyzed O-H Insertion.

Generation of tosyl azide 12 in acetonitrile in flow under water-free conditions using an azide resin and its use in diazo transfer to a series of aryl acetates are described. Successful telescoping with a rhodium acetate-catalyzed O–H insertion has been achieved, thereby transforming the aryl acetate 8 to α-hydroxy ester 10, a key intermediate in the synthesis of clopidogrel 11, without requiring isolation or handling of either tosyl azide 12 or α-aryl-α-diazoacetate 9, or indeed having significant amounts of either present at any point. Significantly, the solution of α-diazo ester 9 was sufficiently clean to progress directly to the rhodium acetate-catalyzed step without any detrimental impact on the efficiency of the O–H insertion. In addition, the rhodium acetate-catalyzed O–H insertion process is cleaner in flow than under traditional batch conditions. Use of the azide resin offers clear safety advantages and, in addition, this approach complements earlier protocols for the generation of tosyl azide 12 in flow; this protocol is especially useful with less acidic substrates.

Cyclobutadiene Rhodium Complexes as Catalysts for the Synthesis of Amides from Electron‐rich Arenes, Tosyl Azide and CO

AbstractCyclobutadiene rhodium complexes [(C4R4)RhX]2 (R=Et, Ph; X=I, Cl) at 0.5 mol % loading catalyze the formation of aromatic amides from various indoles, tosyl azide, and carbon monoxide (1 atm). The reaction gives good yields of the target products (typically 60–85 %) and tolerates both donor and moderately acceptor substituents in the indoles (alkyl, OMe, Hal, COOMe, but not CN). The DFT calculations at the PBE/3ζ level revealed a new plausible mechanism for the reaction of TsN3 with CO via cycloaddition and formation of RhCON3 metallacycle, which is more favorable than the commonly assumed formation of nitrene intermediate.

One-pot multicomponent synthesis of N-sulfonyl amidines using magnetic separable nanoparticles-decorated N-heterocyclic carbene complex with copper

Magnetic separable nanoparticles-decorated N-heterocyclic carbene complex with copper (MNP[1-Methyl benzimidazole]NHC@Cu) has been prepared by covalent grafting of ionic liquid like 1-methyl benzimidazole unit on the surface of chlorofunctionalized Fe3O4 magnetic nanoparticles (MNPs) followed by metallation with copper(I) iodide. MNP[1-Methyl benzimidazole]NHC@Cu complex has been characterized by different techniques including Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), energy-dispersive X-ray (EDX) analysis, X-ray diffraction (XRD), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). MNP[1-Methyl benzimidazole]NHC@Cu complex was successfully implemented as heterogeneous catalyst in one-pot multicomponent synthesis of N-sulfonyl amidines from phenylacetylene, tosyl azide and amines at room temperature. Complex could be recycled six times without significant loss in the yield of product.