Search

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.

An enzyme which is capable of catalyzing C–H amination reactions is considered to be a dream tool for chemists due to its pharmaceutical potential and greener approach. Recently, the Arnold group achieved this feat using an engineered CYP411 enzyme, which further undergoes a random directed evolution which increases its efficiency and selectivity. The present study provides mechanistic insight and the root cause of the success of these mutations to enhance the reactivity and selectivity of the mutant enzyme. This is achieved by means of comprehensive MD simulations and hybrid QM/MM calculations. The study shows that the efficient C–H amination by the engineered CYP411 is a combined outcome of electronic and steric effects. The mutation of the axial cysteine ligand to serine relays electron density to the Fe ion in the heme, and thereby enhances the bonding capability of the heme-iron to the nitrogen atom of the tosyl azide. In comparison, the native cysteine-ligated P450 cannot bind the tosyl azide. Additionally, the A78V and A82L mutations in P411 provide ‘bulk’ to the active site which increases the enantioselectivity via a steric effect. At the same time, the QM/MM calculations elucidate the C–H amination by the iron nitrenoid, revealing a mechanism analogous to Compound I in the native C–H hydroxylation by P450., Computer simulation method reveals the mechanism of C–H amination reaction due to a single site mutation.

Diazo-transfer reaction of tosyl azide and alkyl 2-cyanoacetates in the presence of pyridine at 0 °C gives the corresponding alkyl 2-cyano-2-diazoacetates. This material readily undergoes nucleophilic attack by pyridinium 1-cyano-2-alkoxy-2-oxoethan-1-ide to form dialkyl (Z)-3-amino-2-cyano-4-diazopent-2-enedioates. The X-ray structure of a typical product is reported, as well as DFT computational studies that illuminate the structural features of these stable diazo compounds.

(5-Methyl-1,3-thiazolidin-2-ylidene) ketones, depending on the substituent in the ylidene part of the molecule, interact with tosyl azide to form (5,6-dihydro[1,3]thiazolo[3,2-c][1,2,3]triazol-3-yl) ketones and N-[(5,6-dihydro[1,3]thiazolo[3,2-c][1,2,3]triazol-3-yl)alkylidene]-tosylamides.

The formation mechanism and electronic structures of iron porphyrin nitrene intermediates, as well as the nitrene-mediated intermolecular C-H amination, have been studied by performing DFT and ab initio complete active space self-consistent field (CASSCF) calculations. Compared with that of cobalt porphyrin nitrene and iron porphyrin carbene, the formation of iron porphyrin nitrene shows similar but different characteristics. The common feature is that all their formation is required to undergo the "far" or "close" complexes, but these complexes correspond to different energies relative to their respective reactants (isolated metalloporphyrins and azides), which is considered as one main reason to determine the reaction barriers. The overall free energy barrier for the formation of iron porphyrin nitrene was calculated to be 10.6 kcal/mol on a triplet-state surface, which is lower than those of cobalt porphyrin nitrene and iron porphyrin carbene. The departure of N2 from the close complexes formed by iron porphyrin and tosyl azide is nearly barrierless. For iron porphyrin nitrene, both CASSCF and unrestricted DFT calculations revealed that the triplet and open-shell singlet complexes correspond to very similar energies. The triplet nitrene complex can be described as [(por)(-OCH3)FeII═NTs]- ↔ [(por)(-OCH3)FeIII═N•-Ts]- ↔ [(por)(-OCH3)FeIV═N2-Ts]-, while the oss nitrene complex can be described as [(por)(-OCH3)FeIII-N•-Ts]-. Since the N atom bears a similar spin density as in cobalt porphyrin nitrene, the iron porphyrin nitrene exhibits similar activity in hydrogen abstraction. In addition, the intermolecular C-H amination catalyzed by iron porphyrin nitrene follows the hydrogen atom abstraction/radical recombination mechanism with a free energy barrier of 7.1 kcal/mol on the triplet-state surface. In general, the medium reactivity and easily prepared characteristic of iron porphyrin nitrene makes it a potential catalyst for C-H amination.

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.

A triazole (1-(p-tolylthio)-1H-1,2,3-triazole-4-carboxylic acid, TTC) film was prepared via an in-situ click-assembling reaction between tosyl azide (TA) and propiolic acid (PA) on Cu, Cu2O and CuO substrates. Its surface wettability, antibacterial activity and anticorrosion ability were evaluated by surface characterizations, antibacterial testing and electrochemical measurements. The modified-Cu2O film exhibits the best overall performance. The anticorrosion protection efficiency of the modified-Cu2O film for copper is 91.1%. The modified-Cu2O film shows a superior hydrophobicity with a contact angle of 137° and it also has the best antibacterial activity. The FT-IR and surface analysis (SEM and XPS) reveal that the excellent anticorrosion ability of the modified-Cu2O film is mainly due to the massive TTC film assembled on its surface. The large amount of TTC also contributes to the best hydrophobicity and antibacterial activity. The theoretical calculations show that the TTC film is formed via the horizontal adsorption of a triazole ring and O atoms in the TTC molecule.

A new synthesis of tetraazaperopyrenes (TAPPs) starting from a halogenated perylene derivative 3,4,9,10‐ tetrabromo‐1,6,7,12‐tetrachloroperylene (1) gave access to bay‐substituted TAPPs for the first time. Selective lithiation of the bromine‐positions and subsequent addition of tosyl azide led to the formation of the tetraazidotetrachloroperylene (2), which was subsequently reduced by addition of sodium borohydride to the corresponding tetraaminotetrachloroperylene (3). Oxidation to its semiquinoidal form 4 and subsequent cyclization with acid chlorides gave rise to a series of bay‐chlorinated TAPPs. Whereas the aromatic core of the previously studied ortho‐substituted TAPPs was found to be planar, the steric pressure of the two chlorine substituents on each side leads to the twist of the peropyrene core of approximately 30 degrees, a structural feature also observed in other bay‐substituted perylene derivatives. An experimental and computational analysis reveals that introducing chloride substituents at these positions leads to slightly increased electron affinities (EA) enabling the selective generation and characterization of the reduced mono‐anionic radicals and closed shell di‐anionic species. These anions were isolated and characterized by UV/Vis spectroscopy and EPR or NMR, respectively. Processing of the bay‐chlorinated TAPPs in n‐channel organic TFTs revealed electron mobilities of 0.001 to 0.003 cm2 V−1 s−1. These reduced electron mobilities compared to the ortho‐halogenated TAPPs are thought to be rooted in the less densely packed solid‐state structures., First twisted—then TAPPed: Previously inaccessible bay‐substituted tetratazaperopyrenes (TAPPs) were obtained from “twisted” perylene‐containing bay‐substituents. The resulting TAPPs were found to be readily reduced to their radical monoanions and closed shell dianions.

The reaction of [(Dpp-Bian)Mg(THF)3] (I) (Dpp-Bian is 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene) with tosyl azide (TosN3) affords the binuclear amide complex [(Dpp-Bian)Mg(THF)(NTos)(THF)Mg(Dpp-Bian)] (II) in which the magnesium atoms are linked with the nitrogen atom by the bridging p-tolylsulfamide group. In the presence of pyridine, the reaction leads to the compound [(Dpp-Bian)Mg(Py)(NTos)(Py)Mg(Dpp-Bian)] (III) in which NTos has different coordination modes with the metal atoms. The diimine ligand is in the radical anion state in both compounds. New paramagnetic compounds II and III are characterized by IR spectroscopy, EPR spectroscopy, elemental analysis, and X-ray diffraction analysis (СFА files CCDC no. 1878433 (II · 1.5C5H12) and 1878432 (III · 2C7H8 · 0.5OC4H8)).

Treatment of N-chlorodimethylamine with sodium azide in dichloromethane does not lead to N-azidodimethylamine, as thought for more than 50 years. Instead, surprisingly, (azidomethyl)dimethylamine is generated with good reproducibility. A plausible reaction mechanism to explain the formation of this product is presented. The reaction of lithium dibenzylhydrazide with tosyl azide does not result in the creation of an N-azidoamine, which can be detected by IR spectroscopy at ambient temperature, as it was claimed previously. Additional experiments with diazo group transfer to lithium hydrazides show that intermediate N-azidoamines are very short-lived or their formation is bypassed by direct generation of 1,1-diazenes via synchronous cleavage of two N-N bonds.

An acetic acid-promoted approach that enables the synthesis of 1,4,5-trisubstituted 1,2,3-triazole derivatives has been achieved. This transformation employs readily available primary amines, 1,3-dicarbonyls and tosyl azide as the starting materials via a cycloaddition reaction under metal-free conditions. The reaction provides a simple access to fully substituted 1,2,3-triazoles from commercial substrates in moderate to excellent yields.

The 4-coordinated RuII chalcogenolate complexes [Ru(STipp)2(PPh3)2] (Tipp = 2,4,6-triisopropylphenyl, 1) and [Ru(SeMes)2(PPh3)2] (Mes = 2,4,6-trimethylphenyl, 2) have been synthesized, and their reactions with PhICl2 and organic azides have been studied. Complex 2 synthesized from [RuII(PPh3)3Cl2] and NaSeMes displays a seesaw structure with P–Ru–P and Se–Ru–Se bond angles of 103.43(13) and 145.26(6)°, respectively. Natural bond order analyses revealed that in each of 1 and 2, there are two n → σ* (donor–acceptor) π interactions between the chalcogen lone pairs and the Ru–P antibonding molecular orbitals. The calculated second-order perturbation interaction energies of the two interactions for 1 (20.5 and 18.3 kcal mol−1) are stronger than those of 2 (13.6 and 11.0 kcal mol−1), suggesting the thiolate ligand (TippS−) is a stronger π-donor than the selenolate ligand (MesSe−) with respect to RuII. Chlorination of 1 with PhICl2 afforded the dichloride complex [Ru(STipp)2Cl2(PPh3)] (3), which was hydrolyzed to the hydroxo complex [Ru(STipp)2(OH)Cl(PPh3)] (4) after column chromatography on silica in air. Treatment of 4 with HCl and methyl triflate gave 3 and [Ru(STipp)2(OH)(OTf)(PPh3)] (OTf = triflate, 5), respectively. Reactions of 1 and 2 with p-tolyl azide (p-tolN3) afforded the tetrazene complexes [Ru{N4(p-tol)2}(ER)2(PPh3)] (ER = STipp (6), SeMes (7)), whereas that with tosyl azide (TsN3) gave the imido complexes [Ru(κ2-NTs)(STipp)2(PPh3)] (ER = STipp (8), SeMes (10)). The short Ru–Nimido distances in 8 [1.883(3) A] and 10 [1.892(2) A] are indicative of multiple bond character. Treatment of 8 with TsN3 afforded the tetrazene complex [Ru(N4Ts2)(STipp)2(PPh3)] (9), but no cycloaddition was found between 10 and TsN3. Nucleophilic attack of the imido ligand in 10 with methyl triflate yielded the amido complex [Ru(κ2-NMeTs)(SeMes)2(PPh3)](OTf) (11). The crystal structures of 2, 4, 6, and 8–11 have been determined.

An enzyme which is capable of catalyzing C-H amination reactions, is considered to be a dream tool for chemists due to its pharmaceutical potential and greener approach. Recently, the Arnold group achieved this feat using an engineered CYP411 enzyme, which further undergoes a random directed evolution which increases its efficiency and selectivity. The present study provides the mechanistic insight and the root cause of the success of these mutations to enhance the reactivity and selectivity of the mutant enzyme. This is achieved by means of comprehensive MD simulations and hybrid QM/MM calculations. The study shows that the efficient C-H amination by the so-engineered CYP411 is a combined outcome of electronic and steric effects. The mutation of axial cysteine ligand to serine relays electron density to the Fe ion in the heme, and thereby enhances the bonding capability of the heme-iron to the nitrogen atom of the tosyl azide. By comparison, the native cysteine-ligated P450, cannot bind the tosyl azide. On top, the A78V and A82L mutations in P411 provide ‘bulk’ to the active site which thereby increases the enantioselectivity via steric effect. At the same time, the QM/MM calculations elucidate the C-H amination by the iron nitrenoid, revealing a mechanism analogous to Compound I in the native- C-H hydroxylation by P450.

The mechanism of the reaction of N-methylindoles with tosyl azide to afford 3-diazoindolin-2-imines and 2-iminoindolines has been studied computationally at the DFT M06/6-311G(d,p) level. The formation of 3-diazoindolin-2-imine is found to proceed via a concerted [3 + 2] addition followed by dehydroaromatization and subsequent ring opening rather than via a concerted [3 + 2] addition followed by ring opening and subsequent dehydroaromatization. The initial [3 + 2] cycloaddition is the rate-determining step with an activation barrier of 17.0 kcal/mol. The formation of 2-iminoindoline is also found to proceed via the initial [3 + 2] cycloaddition followed by a dinitrogen extrusion in a concerted fashion and subsequent 1,2-hydride shift. The rate-determining step for the formation of 2-iminoindoline is either the initial [3 + 2] cycloaddition or the dinitrogen extrusion depending on the nature of indole used. The two competing steps after the initial [3 + 2] cycloaddition are the dehydroaromatization and dinitrogen extrusion step. Dehydroaromatization of dihydrotriazoloindole with singlet oxygen molecule has a barrier of 1.9 kcal/mol and reaction energy of − 54.6 kcal/mol, while with triplet oxygen molecule has high activation barrier of 27.2 kcal/mol and reaction energy of 25.7 kcal/mol leading to the formation of radical intermediates (HOO· + A·). Dehydroaromatization in the absence of oxygen is thermodynamically and kinetically not feasible due to the high activation barrier of 97.5 kcal/mol associated with this process under this condition. Thus, the dehydroaromatization step is predicted to occur with singlet oxygen. Also, dehydroaromatization of dihydrotriazoloindole by singlet oxygen molecule is kinetically and thermodynamically favored over the dinitrogen extrusion by 15.4 kcal/mol and 43.4 kcal/mol, respectively. The low activation barrier of the dehydroaromatization step by singlet oxygen compared to the dinitrogen extrusion step means that 3-diazoindolin-2-imine would be formed solely under this condition, confirming the experimental observation of Sheng et al. (Org Lett 16(4):1244–1247, 2014). In inert atmosphere, 2-iminoindoline becomes viable because the activation barrier for the initial loss of H2 that is likely to lead to the formation of 3-diazoindolin-2-imine is 85.5 kcal/mol higher than the dinitrogen extrusion step for the formation of 2-iminoindoline.

Here we report a cytochrome P450 variant that catalyzes C(2)-amidation of 1-methylindoles with tosyl azide via nitrene transfer. Before evolutionary optimization the enzyme exhibited two undesired side reactivities resulting in reduction of the putative iron-nitrenoid intermediate or cycloaddition between the two substrates to form triazole products. We speculated that triazole formation was a promiscuous cycloaddition activity of the P450 heme domain, while sulfonamide formation likely arose from surplus electron transfer from the reductase domain. Directed evolution involving mutagenesis of both the heme and reductase domains delivered an enzyme providing the desired indole amidation products with up to 8400 turnovers, 90% yield, and a shift in chemoselectivity from 2:19:1 to 110:12:1 in favor of nitrene transfer over reduction or triazole formation. This work expands the substrate scope of hemoprotein nitrene transferases to heterocycles and highlights the adaptability of the P450 scaffold to solve challenging chemoselectivity problems in non-natural enzymatic catalysis.

The click chemistry reaction between 2, 2-dimethylethynyl carbinol (MBY) and tosyl azide (TA) was used to form triazole films on copper surface. The effect of cuprous ions on the assembled films was investigated by the electrochemical measurements. The assembled films have the best protection efficiency of 93.8%. The attack of chloride ions gives out cuprous ions to catalyze the formation of compact triazole films. It shows that the assembled films have an anodic passivation role, and suppress the anodic corrosion reactions evidently. The role of cuprous ions on the films formation during the assembling process is discussed.

The synthesis of 4-acyl-NH-1,2,3-triazoles has been accomplished with high efficiency through the cycloaddition reactions between N,N-dimethylenaminones and tosyl azide. This method is featured with extraordinary sustainability by employing water as the sole medium, free of any catalyst or additive, authentically mild conditions (40 °C stirring) as well as practical scalability.

Six-coordinate rhodium(III) complexes coordinated by a planar trianionic ligand (L3-) are synthesized. One of the axial positions is occupied by chloride (Cl-), bromide (Br-), or iodide (I-), and another axial position is coordinated by a solvent molecule such as acetonitrile (AN), water (H2O), tetrahydrofuran (THF), or pyridine (PY) to complete an octahedral rhodium(III) center; [RhIII(L3-)(X)(Y)]- (1X/Y; X = Cl-, Br-, or I-, Y = AN, H2O, THF, or PY). Coordination of the AN, H2O, and THF ligands to the metal center is rather weak, so that these solvent molecules are easily replaced by PY to give [RhIII(L3-)(Cl)(PY)]-. In the electrochemical measurements, all complexes have two reversible redox couples based on the ligand-centered oxidation L3- to L•2- and to L-, as reflected by the very similar redox potentials regardless of the different axial ligands. The rhodium(III) complexes catalyze C-H bond amination of xanthene with tosyl azide (TsN3). Because the yields of the aminated product are nearly the same among the complexes, replacement of the axial solvent ligands with TsN3 readily occurs to give a nitrene-radical-bound rhodium(III) complex, [RhIII(L•2-)(N•Ts)(X)]-, as an active oxidant, which is generated by one-electron transfer from the trianionic L3- to the nitrene nitrogen atom. Generation of such a diradical intermediate was substantiated by the direct reaction of 1Cl/AN with TsN3 in the absence of the substrate (xanthene). In this case, a rhodium(III) iminosemiquinone complex, 2, was generated by the intramolecular reaction between the nitrene-radical moiety and the radical moiety of the ligand L•2-.

N-Sulfonyl phosphoramidate derivatives of oligodeoxyribonucleotides containing N-tosyl phosphoramidate groups are first reported. The synthesis is based on Staudinger reaction between tosyl azide and 3′,5′-dinucleoside β-cyanoethyl phosphite comprising the immobilized oligonucleotide, which is obtained by the phosphoramidite coupling during the solid-phase oligonucleotide synthesis. The N-tosyl phosphoramidate group was stable under conditions of the oligonucleotide synthesis, in particular, upon acidic detritylation followed by the removal of protective groups and cleavage from the polymer support by the treatment with concentrated aqueous ammonia at 55°C. The stability of DNA and RNA duplexes of the model oligonucleotides containing N-tosyl phosphoramidate groups was only slightly lower than that of native DNA:DNA and DNA:RNA duplexes, respectively.

A scalable access to functionalized 1,1’- and 1,2-ferrocenyl azides has been realized in flow. By halogen‒lithium exchange of ferrocenyl halides and subsequent reaction with tosyl azide, a variety of functionalized ferrocenyl azides was obtained in high yields. To allow a scalable preparation of these potentially explosive compounds, an efficient flow protocol was developed accelerating the reaction time to minutes and circumventing accumulation of potentially hazardous intermediates. Switching from homogeneous to triphasic flow amidst process was key for handling a heterogeneous reaction mixture formed after a heated reactor section. The corresponding and synthetically versatile ferrocenyl amines were then prepared by a reliable reduction process.

2-Azido-4,6-dimethoxy-1,3,5-triazine (ADT) was reported recently as a new "intrinsically safe" diazo-transfer reagent. This assessment was based on differential scanning calorimetry data indicating that ADT exhibits endothermic decomposition. We present DSC data on ADT that show exothermic decomposition with an initiation temperature ( Tinit) of 159 °C and an enthalpy of decomposition (Δ HD) of -1135 J g-1 (-207 kJ mol-1). We conclude that ADT is potentially explosive and must be treated with caution, being of comparable exothermic magnitude to tosyl azide (TsN3). A maximum recommended process temperature for ADT is 55 °C.

Unique derivatives of androstene and estrane series containing N-sulfonylimidate pendants were prepared from 17α-ethynyl steroids via Cu-catalyzed azide–alkyne cycloaddition to tosyl azide in the presence of alcohols. The synthesized compounds were screened for cytotoxicity against human breast cancer cell lines and ERα agonist activity. The hit compound 3,17β-dimethoxy-17α-[iso-propyl-2′-N-tosylacetimidate]estra-1,3,5(10)-triene (4n) had no ERα-mediated hormonal activity and was found to exhibit potent cytotoxic effect in an ERα-positive breast cancer cell line. N-Sulfonylimidate 4n displayed high antiproliferative potency against triple-negative MDA-MB-231 breast cancer cells, while it was non-toxic towards normal mammary epithelial cells. Compound 4n was found to alter activity of various signaling pathways (NF-κB, Slug, cyclin D1, ERK) supporting the growth and invasiveness of tumor cells.

A series of polyacrylonitrile fiber (PANF)-supported copper(II) catalysts were prepared through the immobilization of Cu(II) into prolinamide-modified PANF (PANPA-2F) and subsequently used for the synthesis of diverse N-arylimidazoles from arylboronic acids and imidazole. The prepared Cu(II)@PANPA-2Fs were well characterized by mechanical strength, FT-IR, XRD, XPS and SEM. Among them, CuCl2@PANPA-2F exhibited excellent catalytic performance, and its activity was significantly affected by the Cu loading. This catalytic system also displayed good activity in the synthesis of N-arylsulfonamides from arylboronic acids and tosyl azide. It was highly efficient in gram-scale reactions and could be reused five times. The advantages of low cost, easy preparation, good durability and facile recovery make the fiber catalyst attractive.

The self-assembled monolayer (SAMs) of 2-(1-tosyl-1H-1,2,3-triazol-4-yl) propan-2-ol (TTP) was in-situ assembled on copper surface via click chemistry reaction between 2, 2-dimethylethynyl carbinol (MBY) and tosyl azide (TA). The electrochemical results indicate that the click-assembled TTP film can strongly suppress the corrosion reaction of copper in 3 wt.% NaCl and its protection efficiency is 93.6%. Polarization curves show that TTP SAMs is an anodic passivation type inhibitor. The adsorption of TTP molecules on Cu2O (0 0 1) surface is in the flat orientation of the nearby triazole ring and O atoms.

The origin of site selectivity of quinoline N-oxide substrate in Ir(III)-catalyzed amidation with tosyl azide was investigated computationally. The reaction proceeds exclusively at the C8 position, instead of the C2 position, which has been reported previously in many other reactions. C2-Amidation is kinetically impossible under the reaction condition according to our calculations, with high apparent activation energy up to 51.1 kcal/mol. The high energetic span is caused by the deep-lying 5-membered amido insertion intermediate, in which a strong stabilization effect was observed due to nN → π*C═N delocalization. For C8-amidation, however, the 6-membered counterpart is relatively unstable, making the activation energy only about half the value of C2-amidation. Meanwhile, denitrogenation is found to be turnover-limiting in the reaction. The oxidation state changes of the Ir center during the stepwise C–N bond formation were investigated, and a considerably higher effective oxidation state was found in the...

Heat and shock sensitive tosyl azide was generated and used on demand in a telescoped diazo transfer process. Small quantities of tosyl azide were accessed in a 'one pot' batch procedure using shelf stable, readily available reagents. For large scale diazo transfer reactions tosyl azide was generated and used in a telescoped flow process, to mitigate the risks associated with handling potentially explosive reagents on scale. The in situ formed tosyl azide was used to rapidly perform diazo transfer to a range of acceptors, including beta-ketoesters, beta-ketoamides, malonate esters and beta-ketosulfones. An effective in-line quench of sulfonyl azides was also developed, whereby a sacrificial acceptor molecule ensured complete consumption of any residual hazardous diazo transfer reagent. The telescoped diazo transfer process with in-line quenching was used to safely prepare over 21 g of an alpha-diazocarbonyl in > 98% purity without any column chromatography.

An attempt to prepare a new triazole series by Cu catalyzed multicomponent reactions of tosyl azide, propargyl bromide and secondary amines led to the synthesis of enamidines. All the synthesized enamidines were evaluated for antiproliferative activities. The four molecules 4a–c and 4h showed higher anticancer activity with GI50 values less than the standard drug doxorubicin against human breast cancer cell line MCF-7. The virtual analysis ascertains the mode of action of these compounds via inhibition of human cell division protein kinase7 (CDK7).

A simple one-pot procedure for conversion of 2-iodo/2-nitro benzoic acids and dihydropyranone fused benzoic acids into corresponding anilines, using tosyl azide, under transition metal-free conditions is explained. TsN3, is one of the more stable azides, much cheaper and easy to handle. This method is environmentally benign, adoptable for large scale preparation. Different factors such as steric and electronic effect of 2-iodo/2-nitro substituents, and the effect of conformational constraints of the fused dihydropyranone ring on co-planarity of the aromatic ring should contribute to the success of this reaction. Tosyl nitrene was found to be involved in the decarboxylation reaction. As this method is simple, scalable and requires only simple reagents we expect this method to find widespread application in organic synthesis.

A photoinduced synthesis of aliphatic azides was achieved in a single step starting from the parent cyclic alkanes, as well as from tetrahydrofuran and pyrrolidine derivatives. The reaction proceeds via direct azidation of C(sp3)–H bonds in the presence of 4-benzoylpyridine under photoirradiation conditions utilizing tosyl azide as the azide source. The chemoselective C–H mono-azidation at room temperature and the formation of azide compounds in spite of their potential photolability are the key features of the present transformation.

A novel rhodium(II)-catalyzed formal [3 + 2] cycloaddition of N-sulfonyl-1,2,3-triazoles with isoxazoles has been achieved that provides an efficient method for the synthesis of polysubstituted 3-aminopyrrole derivatives. An operationally simple one-pot synthesis of the titled compounds from terminal alkynes, tosyl azide, and isoxazoles was also developed. The presented reaction affords an illustrative example of employing 1,2,3-triazoles as the [2C]-component in relevant cycloaddition reactions.

Oxidation of the rhodium(I) ethylene complex, [(TPA)Rh(h 2 -CH2CH2)] þ (1 ,T PA¼ N,N,N-tris(2pyridylmethyl)amine) with a selection of nitrene precursors led to formation of N-substituted azarhodacyclobutanes. Appropriate choice of oxidant allowed for selective preparation of one isomer. For example, treatment of 1 with tosyl azide provided isomer 3 exclusively for the first time. Variation of the substituent on the ring-nitrogen was possible e.g., by employing nosyl iodinane precursor 8. Substituted carbamates were also screened, providing two rotamers of isomer type 3. In addition, preliminary reactivity studies revealing the increased chemical reactivity of the product complexes 14 and 15 are presented.

One of the greatest challenges in protein design is creating new enzymes, something evolution does all the time, starting from existing ones. Borrowing from nature’s evolutionary strategy, we have engineered a bacterial cytochrome P450 to catalyze highly enantioselective intermolecular aziridination, a synthetically useful reaction that has no natural biological counterpart. The new enzyme is fully genetically encoded, functions in vitro or in whole cells, and can be optimized rapidly to exhibit high enantioselectivity (up to 99% ee) and productivity (up to 1,000 catalytic turnovers) for intermolecular aziridination, demonstrated here with tosyl azide and substituted styrenes. This new aziridination activity highlights the remarkable ability of a natural enzyme to adapt and take on new functions. Once discovered in an evolvable enzyme, this non-natural activity was improved and its selectivity tuned through an evolutionary process of accumulating beneficial mutations., Engineered cytochrome P450 variants take on challenging non-natural reaction, aziridination of olefins, demonstrating the power of evolution to expand biocatalytic reaction space.

Reactivity studies of the thermally stable ruthenostannylene complex [Cp*(IXy)(H)2 Ru-Sn-Trip] (1; IXy=1,3-bis(2,6-dimethylphenyl)imidazol-2-ylidene; Cp*=η(5) -C5 Me5 ; Trip=2,4,6-iPr3 C6 H2 ) with a variety of organic substrates are described. Complex 1 reacts with benzoin and an α,β-unsaturated ketone to undergo [1+4] cycloaddition reactions and afford [Cp*(IXy)(H)2 RuSn(κ(2) -O,O-OCPhCPhO)Trip] (2) and [Cp*(IXy)(H)2 RuSn(κ(2) -O,C-OCPhCHCHPh)Trip] (3), respectively. The reaction of 1 with ethyl diazoacetate resulted in a tin-substituted ketene complex [Cp*(IXy)(H)2 RuSn(OC2 H5 )(CHCO)Trip] (4), which is most likely a decomposition product from the putative ruthenium-substituted stannene complex. The isolation of a ruthenium-substituted stannene [Cp*(IXy)(H)2 RuSn(=Flu)Trip] (5) and stanna-imine [Cp*(IXy)(H)2 RuSn(κ(2) -N,O-NSO2 C6 H4 Me)Trip] (6) complexes was achieved by treatment of 1 with 9-diazofluorene and tosyl azide, respectively.

An efficient, four-component reaction for the synthesis of hydrazono-sulfonamide adducts via in situ generated ketenimine was discovered. Highly porous copper benzenetricarboxylate [Cu(BTC)], a metal–organic framework (MOF), was used as a heterogeneous catalyst for the four-component coupling reaction involving aldehyde, alkyne, tosyl azide, and phenylhydrazine in a one pot process. For the first time, a copper(II) catalyst was utilized to generate a ketenimine intermediate. The Cu(BTC) catalyst was recycled and reused six times without any substantial loss in the yield. In addition, pyrene adduct (5r) shows remarkable aggregation induced emission enhancement (AIEE) properties, and was studied in detail using THF : water solvent mixtures. Adduct 5r is almost non-emissive in pure THF solution, however, it emits a greenish-yellow colour in the aggregated state. Formation of nano-aggregates was confirmed by TEM analysis. A theoretical DFT study supports the observed photophysical changes.