Nitrene Insertion Research Articles

Sequential Nitrene Transfers to an Organometallic Half-Sandwich Iridium Complex

Nitrene transfer to an iridium(Cp*) complex with a pyridyl-amide bidentate ligand drives an unexpected outer-sphere C–H activation and amide functionalization reaction mediated by this metal center. This is a significant departure from C–N bond-forming processes in mononuclear rhodium and iridium catalysts, which require C–H activation at the metal center prior to nitrene transfer and insertion (an inner-sphere C–H insertion pathway). The mechanism likely involves a high oxidation state iridium-imido reactive species capable of hydrogen atom abstraction and a radical-based rearrangement during the formation of the ultimate iridium product.

Synthetic Studies on Indolocarbazoles: A Facile Synthesis of Staurosporinone Analogues

AbstractSynthesis of indolocarbazoles was achieved through thermal electrocyclization followed by triethyl phosphite‐mediated nitrene insertion reactions. Total synthesis of staurosporinone analogues was achieved from commercially available 2‐methylindole. The CDK5/p25 kinase inhibition potential of some representative staurosporinone analogues was explored by using the TRFRET kinase assay.

Intramolecular C–H Amination Reaction Provides Direct Access to 1,2‐Disubstituted Diamondoids

AbstractWe present a new approach to disubstituted diamondoids from corresponding carboxylic acids. A dirhodium‐acetate‐catalyzed (1 mol‐%) nitrene insertion reaction of sulfamides was, for the first time, applied to intramolecular C–H functionalization reactions of rigid tricyclic frameworks. This straightforward approach enables the effective and regioselective synthesis of a variety of diamondoid‐based cyclic sulfamidates, which are synthetically valuable building blocks. Reductive deprotection of the sulfamidate moiety leads to corresponding 1,3‐amino alcohol derivatives. Oxidation of the sulfamidate moiety by KMnO4 provides access to 1,3‐keto alcohols or imines. Finally, we report the synthesis of Vildagliptin® analogues as new antidiabetic drug candidates (DPP‐4 inhibitors).

Mechanistic Investigations of the AuCl3-Catalyzed Nitrene Insertion into an Aromatic C-H Bond of Mesitylene.

The AuCl3-catalyzed nitrene insertion into an aromatic C-H bond of mesitylene demonstrates a unique activity and chemoselectivity in direct C-H aminations. Mechanisms for catalytic nitrene insertion are examined here using theory. The AuCl3 catalyst favors formation of a complex with the PhI═NNs (Ns = p-nitrobenzenesulfonyl) substrate, followed by the appearance of the key (N-chloro-4-nitrophenylsulfonamido)gold(III) chloride intermediate (INT5). However, the putative gold(III)-nitrene analogue (AuCl3-NNs complex) is thermodynamically unfavorable compared with INT5. Therefore, INT5 is suggested to play a critical role in the AuCl3-promoted aromatic C-H bond amination, a prediction in contrast to the previously reported crucial metal-nitrene intermediates. The activation of a C(sp(2))-H bond of mesitylene via σ-bond metathesis is proposed based on INT5, and the subsequent detailed pathways for the aromatic C-H bond amination are computationally explored. A chemoselective nitrene insertion into a mesitylene aromatic C-H bond, instead of a benzylic C-H bond, is rationalized for the AuCl3-catalyzed amination.

Vinylic MIDA Boronates: New Building Blocks for the Synthesis of Aza-Heterocycles.

A two-step synthesis of structurally diverse pyrrole-containing bicyclic systems is reported. ortho-Nitro-haloarenes coupled with vinylic N-methyliminodiacetic acid (MIDA) boronates generate ortho-vinyl-nitroarenes, which undergo a "metal-free" nitrene insertion, resulting in a new pyrrole ring. This novel synthetic approach has a wide substrate tolerance and it is applicable in the preparation of more complex "drug-like" molecules. Interestingly, an ortho-nitro-allylarene derivative furnished a cyclic β-aminophosphonate motif.

Synthesis of Antitumor Carbazole‐Amonafide Structural Hybrids

AbstractA facile synthesis of new antitumor [4,5‐bc]carbazole‐amonafide derivatives is described. These compounds represent a new class of structural hybrids that contain the medicinally important carbazole and amonafide cores. The synthesis involves a Suzuki–Miyaura coupling of bromoamonafide with arylboronic acid reagents followed by the introduction of an azide group and subsequent regiospecific thermal nitrene insertion to yield carbazole‐amonafide hybrids in good yields. Preliminary antiproliferative assays against cancer and benign cell lines identified compounds with selective antitumor activity that exhibited submicromolar IC50 values.

Reactions of iodine-nitrene reagents with boranes

Reactions of the boranes (C6F5)2BR (R = C6F5, Ph, H) with the nitrene-iodine reagents XC6H4SO2N=IPh, X = Me, Cl and MeSO2N=IPh effect the insertion of nitrene into the B–C and B–H bonds affording the species (C6F5)2BN(SO2C6H4X)R (X = Me, R = C6F5 1, Ph 3, H, 4, X = Cl, 5, X = NO2, 7) and (C6F5)2BN(SO2Me)H 6).

Reversible redox modulation of a lanthanide emissive molecular film.

Herein we demonstrate redox switchable emission from a sensitised, europium-ferrocene containing, molecular film assembled by a novel nitrene-based strategy. Electrochemical modulation of europium emission upon switching the ferrocene moiety's redox state is ascribed to the reversible generation of a quenching ferrocenium species.

Computational exploration of the mechanism of copper-catalyzed aromatic C-H bond amination of benzene via a nitrene insertion approach.

The mechanism of aromatic C-H amination of benzene via a nitrene insertion approach catalyzed by the Tp(Br3)Cu(NCMe) complex was computationally investigated. The results of computational studies show that addition of the nitrene moiety of the Tp(Br3)Cu-nitrene intermediate to benzene, and therefore, to form an aziridine intermediate, is more favorable than the nitrene moiety induced hydrogen atom abstraction from a sp(2) C-H bond of benzene. Subsequently, the cleavage of a C-N bond of the aziridine intermediate followed by an H-atom transfer step might occur, due to the driving force of the rearomatization, to afford the desired aromatic C-H amination product. For toluene, computational results suggest that the benzylic C-H amination via hydrogen atom abstraction followed by radical rebound path is more favorable than the aromatic C-H amination via a nitrene addition path, which is in accord with experimental results.

An Energetic N‐Oxide and N‐Amino Heterocycle and its Transformation to 1,2,3,4‐Tetrazine‐1‐oxide

AbstractThis study reports the preparation of 1‐amino‐1,2,3‐triazole‐3‐oxide (DPX2) and its transformation to 1,2,3,4‐tetrazine‐1‐oxide. DPX‐2 provides insight into a novel N‐oxide/N‐amino high‐nitrogen system, being the first energetic material in this class. The ability of this material to undergo a nitrene insertion forming 1,2,3,4‐tetrazine‐1‐oxide was also studied, and evidence for this material, the first non‐benzoannulated 1,2,3,4‐tetrazine‐1‐oxide, is presented. The existence of both of these materials opens new strategies in energetic materials design. DPX2 was characterized chemically (Infrared, Raman, NMR, X‐ray) and as a high explosive in terms of energetic performances (detonation velocity, pressure, etc.) and sensitivities (impact, friction, electrostatic). DPX‐2 was found to possess good thermal stability and moderate sensitivities, indicating the viability of N‐amino N‐oxides as a strategy for the preparation of new energetic materials.

Reactivity of a stable phosphinonitrene towards small molecules.

The room-temperature stable phosphinonitrene 1 undergoes a thermal rearrangement into heterocycle 2 through a process involving a nitrene insertion into a CH bond. In the presence of acetonitrile, a nitrene-acetonitrile adduct has been isolated; then it first rearranges into a ketenimine and subsequently into a rare example of diazaphosphete. Compound 1 also splits water, carbon dioxide, carbon disulfide, and elemental sulfur, although it reacts with white phosphorus, leading to a P5 N cluster formally resulting from the insertion of the PN moiety into a P-P edge of the P4 tetrahedron.

Silver-catalysed direct amination of unactivated C–H bonds of functionalized molecules

Carbon-nitrogen bond formation from inert C-H bonds is an ideal organic transformation and a highly desirable method for the synthesis of N-containing molecules due to its high efficiency and atom economy. In this report, we develop a general reaction to achieve an unprecedented selective intramolecular amination of unactivated C-H bond in the absence of complex directing groups. Functionalized heterocyclic products are built up from readily available linear amines through simple and reliable silver catalysis, representing a new silver-based C-H functionalization. This method displays preference for primary sp(3) C-H bonds and exhibits distinct chemo- and regioselectivity compared to existing methods of direct amination (Hofmann-Löffler-Freytag reaction and nitrene insertion). The study highlights the manipulation of unfunctionalized groups in organic molecules to furnish complex structural units in the natural and bioactive molecules.

Tailoring SU-8 surfaces: covalent attachment of polymers by means of nitrene insertion.

The photoresist material SU-8 has found a variety of applications in microfabricated systems, such as microelectromechanical (MEMS) and lab-on-a-chip devices. Although the bulk properties of SU-8 are appropriate for many such applications, tailoring its surface-chemical properties has, until now, proven to be challenging but is essential in order to carry out any subsequent self-assembly steps. We have demonstrated that the SU-8 surface can be functionalized by the covalent grafting of a wide variety of polymers by means of nitrene insertion. This is readily achieved with poly(allylamine)-graft-perfluorophenyl azide (PAAm-g-PFPA) or poly(ethyleneimine)-graft-PFPA (PEI-g-PFPA), which can form covalent bonds to both the SU-8 surface and a functionalizing polymer. As examples, poly(diallyl-dimethylammonium chloride) (PDDA) and poly(styrenesulfonate) (PSS) have been covalently linked to a SU-8 substrate, yielding positively and negatively charged surfaces, respectively. The grafted polymers were characterized by means of X-ray photoelectron spectroscopy, and their charge characteristics were confirmed via charged-particle adsorption.

Molecular Iodine Assisted Electrocyclisation: Synthesis of Arcyriaflavin A and Formal Synthesis of Staurosporinone

A new method for the synthesis of the indolocarbazole alkaloid arcyriaflavin A is described. The synthetic strategy employs a graphite-catalysed alkenation, one-pot oxidation–Wittig reaction, iodine-catalysed electrocyclisation and nitrene insertion as the key steps. The strategy also constitutes a formal synthesis of another indolocarbazole alkaloid staurosporinone.

Microwave (MW) Assisted Electro-Active Tempo Functionalized Single Walled Carbon Nanotube (SWNT) Electrodes for Li-Ion Batteries

The ever-increasing demand for high-performing, light weight, economical, and safe power storage for high–tech portable devices and electric vehicles leads to augmented research efforts in the field of organic or organic/hybrid materials for energy storage devices.With the aim of performing a balance between battery (charge producing system) and capacitor (charge storing system), Carbon Nanotubes (CNTs) can work as a template that can be functionalized with stable electro-active redox group. Since both capacitors and batteries can provide limited usability, an electrode material that hosts both properties will be more rewarding for the development of battery technology. Owing to the electrical and physical properties, CNTs are challenging material for the energy storage devices. There are some noticeable works about producing Carbon Nanotube thin electrodes to fabricate paper battery [1-3]In the light of these investigations, rapid microwave (MW) assisted functionalization of Single Walled Carbon Nanotubes (SWNTs) with electro-active TEMPO group was successfully performed with one step nitrene insertion reaction without using any harshly oxidative methods which are uncontrollable and destructive for SWNT. Their role of Functionalized SWNT samples (f-SWNTs) were characterized as a host for Li storage and their performance as electro-active cathode material were investigated.f-SWNTs were easily dispersed in solvents and they can form stable dispersions during 1 month where as non-functionalized SWNTs coagulate immediately. This can be considered as an indication of a successful surface functionalization. Depending on the degree of functionalization of SWNTs (without losing its electrical properties) their dispersibility in H2O and NMP (N-Methyl-2-pyrrolidone) and free standing paper electrode forming possibilities increase (Fig.1). Output Open Circuit Voltage (O.C.V) of cells with SWNT and functionalized SWNT (f-SWNT) samples changes between 2.5-3.0V vs. Li metal. The Cyclic Voltammetry study of the TEMPO functionalized f- SWNT 1 sample vs. Li metal is seen in Fig. 2.The constructed 2016-size button cell of f-SWNT 1 displayed an initial specific capacity of 441 mAh/g which decreased to 127 mAh/g in the second cycle of charge- discharge (Fig. 3). This large first cycle irreversible capacity loss could be attributed to various causes such as the irreversible reduction of oxygenated functional groups that may be originally present on the CNT surface as well as the attached nitroxide radical functional group to its amine oxide form. This electrochemical reduction was known to be an irreversible process in non-aqueous carbonate electrolyte systems and may be responsible for the reduction in the charge capacity. In the fifth cycle it dropped to 54 mA/g and after tenth and fifteenth cycles this value was reduced to 35 and 28 mAh/g, repectively. The reversibility of nitroxide radical group of TEMPO under basic conditions may provide an opportunity for battery systems which is under investigation.The f-SWNT 1 was subjected to charge and discharge cycles between 3 and 4V vs. Li (Figure 4). The charge curve plateau between 3.6 and 3.7 V can be ascribed to irreversible electrochemical oxidation of nitroxide radicals to oxoammonium species. The charging capacity suddenly faded from 140 mAh/g to 20 mAh/g in 15 charge discharge cycles.

ChemInform Abstract: Enantiospecific Total Synthesis of N‐Methylwelwitindolinone D Isonitrile.

ChemInform Abstract: Enantiospecific Total Synthesis of N‐Methylwelwitindolinone D Isonitrile.

Photochemistry of covalently functionalized graphene oxide with phenothiazinyl units

Phenothiazinyl units have been covalently attached to graphene oxide (GO) by nitrene insertion onto CC bonds. Laser flash photolysis of this material indicates that tethering of phenothiazinyl units to GO enhances significantly the interaction with respect to mixtures of both components, leading to the observation of photoinduced electron transfer.

Chemoselective silver-catalyzed nitrene insertion reactions

Abstract A review of recent developments in silver(I)-catalyzed nitrene insertions into olefin and C–H bonds is presented, with a particular emphasis on reactions where the chemoselectivity can be tuned to promote either aziridination or C–H amination. The scope and synthetic utility of various silver catalysts are described, as well as preliminary investigations into the mechanisms of silver-catalyzed aminations.

Concomitant Nitrene and Carbene Insertion Accompanying Ring Expansion: Spectroscopic, X-ray, and Computational Studies

Reinvestigation of the thermolysis of azido-meta-hemipinate (I) yielded, in addition to known II, unusual products III and IV. These products are formed via a rare intramolecular nitrene insertion into an adjacent methoxy C-H bond followed by an intermolecular reaction during a ring-expansion and a ring-extrusion reaction followed by a carbene insertion. The structures of the new compounds were confirmed using a battery of techniques, including HRMS (ESI-QTOF) and 2D NMR as well as X-ray crystallography for compound IV. Density functional theory methods were used to support the proposed mechanism of formation of the products.

Iron-catalyzed efficient intermolecular amination of C(sp3)–H bonds with bromamine-T as nitrene source

[Fe(N4Py)(CH3CN)](ClO4)2 can efficiently catalyze intermolecular nitrene insertion of sp3 C–H bonds with bromamine-T as the nitrene source, forming the desired tosylprotected amines with NaBr as the by-product.