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Carbon–nitrogen bonds abound in chemistry and biology, and, as such, it is essential for contemporary organic chemists to develop better methods for their synthesis. The current state of the art in this field is the SN2 addition, the reductive amination and the Buchwald-Hartwig amination, among others. These approaches are widely used yet suffer, however, from overalkylation, potential tautomerizations and the use of rare transition metal catalysts, respectively. Inspired by the materials synthesis carried out across the UCSB Campus Green from the Chemistry Department, we developed a novel single electron method for the synthesis of these bonds. Specifically, we used electron deficient alkyl halides and low valent copper catalysts to form a transient carbon-centered radical, which can add into a nitrosoarene nitrogen in a nucleophilic-like fashion, furnishing our desired C¬–N bond. This approach allows for high-yielding bond formation with mild conditions onto sterically congested molecules, among other benefits. In my first example of this work, we developed an ipso-substitution allowing access to electron rich nitrosoarenes, which had previously been relatively inaccessible. We employed this method in a three-component-two-step-one-pot coupling to access sterically hindered anilines. We next used this method in the synthesis of N¬–O macrocycles and amino alcohols. In the final application of this synthetic method, brominated pyrroloindolines were aminated in excellent yields using this radical based method. We employed this method at gram scales in the key step of a total synthesis of the natural product (+)-asperazine A.

C-Nitroso species are characterized by a unique nitrogen–oxygen combination located next to a carbon backbone, which confers them a unique ambiphilic and high reactivity towards nucleophilic, electrophilic but also radical species. Although this ambivalence can be seen as a strong asset for developing versatile synthetic aminohydroxylation and/or hydroxylamination processes mainly through nitroso Diels–Alder, nitroso ene, and nitrosoaldol reactions, it also contributes to complex optimization and rationalization arising from the many competitive pathways, that is, the occurrence of regioisomers and stereoisomers, as well as dimerization and tautomerization side-reactions. Complex reactivity profiles are usually seen by synthetic organic chemists as major hurdles to overcome, despite the armada of analytical and purification methods available to them, and hence to achieve selective and exploitable developments of such reactions. The rise of computational chemistry and resources has certainly changed their perspectives, since it provides a very different angle to gather insights on intrinsic properties, reactivity, and mechanisms. In silico chemistry also provides a robust alternative to time and resource-consuming synthetic work and can therefore contribute to alleviate wasteful preparations by guiding the chemist toward the best combination of reagents to achieve high selectivity and yield. The synergistic combination of synthetic organic chemistry and computational chemistry, within the specific context of the complex chemistry of C-nitroso species, is discussed in this work. This review aims at giving an overview of the molecular and chemical properties obtained through computational chemistry as an enabling support for the rationalization and optimization of reactions relying on ambiphilic C-nitroso species over the 3 last decades. It provides clear, concise, and illustrated guidelines for the synthetic chemist in search of inspiration through computations.

A series of mixed oxides-supported niobium-based catalysts has been synthesized and applied towards oxidation reactions of benzylamine derivatives. Under the optimized reaction conditions, the selectivity to oxime enhanced, leading to the main product with up to 72 %. Moreover, even α-substituted benzylamines were well tolerated and led to oximes in good isolated yields. It is important to mention; four equivalents of the harmless and inexpensive hydrogen peroxide were employed as oxidizing agent. Mechanism hypothesis suggested that the reaction proceed to selective benzylamine oxidation into nitroso intermediate, following by formation of the corresponding oxime tautomer mediated by an unstable water produced by NbOx supported catalyst. This consists the first mixed oxides-supported niobium-based catalyst for selective oxidation of benzylamines to oximes.

A nitrogen-doped carbon supported Co/Ni bimetallic catalyst 2wt%Co/Ni@NC-700-10 was prepared and found to be efficient in the reductive N-formylation of 2,4-diamino-5-nitroso-6-hydroxypyrimidine (DANHP) to 2,4-diamino-5-formyl-6-hydroxypyrimidine (DAFHP) for the synthesis of guanine. Under optimal conditions, the conversion of DANHP reached up to 95.6% with a DAFHP selectivity of 97.6%. The characterization results revealed that the cobalt/nickel nanoparticles of the catalyst uniformly dispersed and encapsulated in the nitrogen-dopped carbon, and the catalyst has the characters of large surface area, as well as uniform dispersion and small diameters of metal nanoparticles in the form of Co/Ni alloy, which endowed its good catalytic performance in the reaction.

1,2-Oxazines were synthesised via a copper-catalysed aerobic acyl nitroso Diels–Alder reaction from 1,4-disubstituted 1,3-dienes and N-Boc-hydroxylamine. From this, 1,2-oxazinanes were obtained in a novel follow-up reaction path. The stability of several 1,2-oxazines and 1,2-oxazinanes towards organometallic compounds was tested to rate their operability as cyclic chiral Weinreb amide auxiliaries. 3,6-Di-tert-butyl-1,2-oxazinane gave the best results and was introduced as a chiral Weinreb amide-type auxiliary to yield chiral α-substituted ketones in a diastereomeric ratio of up to 98:2. The removal of the auxiliary can be performed with BuLi to form unsymmetrical α-chiral ketones. Thereafter, the chiral auxiliary can be re-isolated and purified by sublimation under vacuum.

We present here a metal-free, visible-light- and triphenylphosphine-mediated intermolecular, reductive amination between nitroarenes and boronic acids at ambient temperature without any photocatalyst. Mechanistically, a slow reduction of nitroarenes to a nitroso and, finally, a nitrene intermediate occurs that leads to the amination product with concomitant 1,2-aryl/-alkyl migration from a boronate complex. A wide range of nitroarenes underwent C-N coupling with aryl-/alkylboronic acids providing high yields.

The structure of the title salt, ammonium carbamoyl­cyano­nitro­somethanide, NH4 +·C3H2N3O2 −, features the co-existence of different hydrogen-bonding patterns, which are specific to each of the three functional groups (nitroso, carbamoyl and cyano) of the methanide anion. The relatively simple scheme of these inter­actions allows the delineation of the supra­molecular synthons, which may be applicable to crystal engineering of hydrogen-bonded solids containing polyfunctional methanide anions., The structure of the title salt, ammonium carbamoyl­cyano­nitro­somethanide, NH4 +·C3H2N3O2 −, features the co-existence of different hydrogen-bonding patterns, which are specific to each of the three functional groups (nitroso, carbamoyl and cyano) of the methanide anion. The nitroso O-atoms accept as many as three N—H⋯O bonds from the ammonium cations [N⋯O = 2.688 (3)–3.000 (3) Å] to form chains of fused rhombs [(NH4)(O)2]. The most prominent bonds of the carbamoyl groups are mutual and they yield 21 helices [N⋯O = 2.903 (2) Å], whereas the cyano N-atoms accept hydrogen bonds from sterically less accessible carbamoyl H-atoms [N⋯N = 3.004 (3) Å]. Two weaker NH4 +⋯O=C bonds [N⋯O = 3.021 (2), 3.017 (2) Å] complete the hydrogen-bonded environment of the carbamoyl groups. A Hirshfeld surface analysis indicates that the most important inter­actions are overwhelmingly O⋯H/H⋯O and N⋯H/H⋯N, in total accounting for 64.1% of the contacts for the individual anions. The relatively simple scheme of these inter­actions allows the delineation of the supra­molecular synthons, which may be applicable to crystal engineering of hydrogen-bonded solids containing polyfunctional methanide anions.

The acyl nitroso Diels–Alder reaction of 1,3‐dienes with electrochemically oxidised hydroxamic acids is described. By using alternating current electrolysis, their typical electro‐induced decomposition could be suppressed in favour of the 1,2‐oxazine cycloaddition products. The reaction was optimised using Design of Experiments (DoE) and a sensitivity test was conducted. A mixture of triethylamine/hexafluoroisopropanol served as supporting electrolyte in dichloromethane, thus giving products of high purity after evaporation of the volatiles without further purification. The optimised reaction conditions were applied to various 1,3‐dienes and hydroxamic acids, giving up to 96 % isolated yield., Hydroxamic acids were electrochemically oxidised to initiate acyl nitroso Diels–Alder reactions with 1,3‐dienes. By using alternating current, their often encountered electrochemically induced decomposition could be suppressed to generate the desired cycloaddition products in up to 96 % yield. The optimisation of this reaction was performed using the Design of Experiments approach.

Sodium tetrakis[3,5-bis(trifluoromethyl)-phenyl]borate (NaBArF) catalyzes the [2 + 2] cycloaddition of 1,4-disubstituted cyclopenta-1,3-dien-2-yl esters with nitrsobenzene in toluene, affording two isolable regioisomers of 6-oxa-7-azabicyclo[3.2.0] heptanes, which thermally rearrange into the same 4-aminocyclopent-1-en-3-ones. In the case of 4-substituted cyclopenta-1,3-dien-2-yl esters, their initial [2 + 2] cycloaddition intermediates undergo a rapid ring expansion to afford six-membered piperidone derivatives efficiently.

4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY) and derivatives are an outstanding class of fluorescent dyes. Herein, we report on the introduction of a nitrosyl moiety into the BODIPY structure and its dramatic effect on the observed electrochemical reaction mechanism. 6-Nitrosyl-8-phenyl-BODIPY and its 5-nitrosyl positional isomer, compounds 2 and 3, respectively, were obtained from the meso precursor, 8-phenyl-BODIPY (1), by nitrosation. Electrochemical studies for 1–3 are reported. Cyclic voltammetry and differential pulse voltammetry in degassed DMF or in MeCN (reduction+oxidation), both with n-Bu4NPF6 (0.1 mol L−1), were obtained. Compound 1 displays the usual behaviour for 8-phenyl substituted BODIPYs. The addition of the acceptor nitroso group in compounds 2 (in position β) and 3 (in position α), leads to a different profile. For all the compounds, the nitroso group greatly facilitates the reductions. For compound 3 (EpIc=−0.238 V), the first to be reduced is the nitroso group, due to the stability of the electrogenerated radical anion, along with non-bonding interactions with the electronegative boron difluoride. This is different from compound 2 (EpIc=−0.351 V) with a β-nitroso group, where the nitroso-based facilitated reduction occurs in the substituted BODIPY core. Spectroelectrochemistry coupled with analysis through conceptual density functional theory (CDFT) corroborate the voltammetric results and explain the unexpected reactivity differences.

α-Tocopheramine has shown great promises as a stabilizer for synthetic and natural polymers, but is also investigated in various biomedical scenarios. Many studies have been hampered by the fact that the oxidation products of α-tocopheramine have not yet been properly identified and their analytical data are still lacking. In the present study, we synthesized and fully analytically characterized all N-oxidation products that can form upon oxidation of α-tocopheramine in aqueous media, including the hydroxylamine, nitroso, and nitro derivative, in this way providing standards for the identification of the so far elusive byproducts. Synthesis and stability of the derivatives are discussed. Graphic abstract

Spathodea campanulata Beauv. is an important plant widely used in traditional medicine for the treatment of hepatic disease. In the present study, we evaluate the phytochemical composition and hepatoprotective potential effect of the stem and root bark extracts of Spathodea companulata on dimethylnitrosamine (DEN) induced hepatic impairment in albino rats. Phytochemical compositions were analyzed using standard protocols. Forty-five male rats were grouped into 9 (A-I) of 5 rats each. Groups A-F were treated with stem bark extract, root bark extract, quercetin, DEN + stem bark extract, DEN + root bark extract, DEN + quercetin respectively while groups G-1 serve as control groups and were treated with corn oil only (Vehicle control), DEN only (Toxicant control), and distilled water (normal control) respectively. DEN was given at 25 mg/kg b.w., i.p on a weekly basis while all treatments were administered at 100 mg/kg BW orally for 60 days. Serum transaminase activities, body weight, and liver body weight ratio were evaluated. Results revealed the presence of alkaloids, cardiac glycoside, saponins, anthraquinone, steroids, and flavonoids in stem bark extract of Spathodea companulata, while the root bark contains cardiac glycoside, saponins, anthraquinonoid, steroids, and flavonoid. The DEN non-treated rat exhibited significant (p

Enzymatic N N bond formation is rare. Herein, the mechanism for the N-nitrosation from Nδ-hydroxy-Nω-hydroxy-Nω-methyl-L-arginine (L-HMA) catalyzed by SznF, a non-heme iron enzyme, has been illustrated, using density functional calculations. The reaction proceeds through the deprotonation of L-HMA hydroxyls, the C O bond formation between the guanidine and the Fe O O• radical resulting in an Fe(II)-peroxo bridge, the C N bond dissociation yielding an Fe-bound NO− anion, the heterolytic O O bond cleavage forming an Fe(II)–O2−, the concerted proton transfer leading to an Fe(II)-hydroxide and an N− anion, the N N bond formation generating the N-nitrosourea product. The discovery of Fe(II)–O2− may be resulted from the unique co-coordination of two NO anions to Fe-oxyl. The natures of diverse NO groups during the reaction are assigned. Another mechanism including an O-N bond formation has been ruled out. This work gives deep insights into the enzymatic N N bond formation and advances the understanding of non-heme iron catalysis.

А para-chlorophenyl substituent was firstly obtained into the structure of pyridyl-substituted 4-nitrosopyrazole by cyclocondensation of hydrazine hydrate with the corresponding isonitroso-β-dicarbonyl compounds. The structure of previously unknown 3(5)-(4-chlorophenyl)-5(3)-pyridine-(3(4))-yl-4-nitroso-1H-pyrazoles and previously obtained 3(5)-alkyl(aryl)-5(3)-pyridine-(3(4))-yl-4-nitroso-1H-pyrazoles is proved and studied in detail by modern methods of analysis: mass spectrometry, 1H- and 13C NMR-spectroscopy

The kinetics of the reaction of phenylnitroso oxide, para-CH3-, para-CH3O-, and para-Br-phenylnitroso oxides with benzoquinones in acetonitrile at room temperature was studied by flash photolysis. Both nitroso oxide isomers were involved in the reaction, the rate constants for the cis forms being higher than for the trans isomers for all compounds under study. The reactivity of arylnitroso oxides (ArNOO) with benzoquinones was found to be dual. The electron-donating substituents in the ArNOO molecule increase the reactivity of both conformers with 1,4-benzoquinone, 2-chloro-1,4-benzoquinone, and chloranil. Arylnitroso oxides exhibited electrophilic properties in the reaction with duroquinone, which was determined from the positive slope of the Hammett dependence for the trans isomers of ArNOO (ρ = 0.68 ± 0.08, r = 0.994). The constants ρ for the reaction of the cis isomers with 1,4-benzoquinone (–1.5 ± 0.2, r = 0.990), 2-chloro-1,4-benzoquinone (–2.0 ± 0.2, r = 0.995), and chloranil (–4.8 ± 0.6, r = 0.98) and for the reaction of trans isomers with chloranil (–2.8 ± 0.3, r = 0.990) increased in magnitude with the electron deficiency of the double bond. Along with the negative slope of the Hammett dependence, they suggest a nucleophilic attack of nitroso oxide on benzoquinone. For the reaction of trans-nitroso oxides with 2-chloro-1,4-benzoquinone and 1,4-benzoquinone, the Hammett dependence is nonlinear.

It is of particular interest to develop new antibacterial agents with low risk of drug resistance development and low toxicity toward mammalian cells to combat pathogen infections. Although gaseous signaling molecules (GSMs) such as nitric oxide (NO) and formaldehyde (FA) have broad-spectrum antibacterial performance and the low propensity of drug resistance development, many previous studies heavily focused on nanocarriers capable of delivering only one GSM. Herein, we developed a micellar nanoparticle platform that can simultaneously deliver NO and FA under visible light irradiation. An amphiphilic diblock copolymer of poly(ethylene oxide)-b-poly(4-((2-nitro-5-(((2-nitrobenzyl)oxy)methoxy)benzyl)(nitroso)amino)benzyl methacrylate) (PEO-b-PNNBM) was successfully synthesized through atom transfer radical polymerization (ATRP). The resulting diblock copolymer self-assembled into micellar nanoparticles without premature NO and FA leakage, whereas they underwent phototriggered disassembly with the corelease of NO and FA. We showed that the NO- and FA-releasing micellar nanoparticles exhibited a combinatorial antibacterial performance, efficiently killing both Gram-negative (e.g., Escherichia coli) and Gram-positive (e.g., Staphylococcus aureus) bacteria with low toxicity to mammalian cells and low hemolytic property. This work provides new insights into the development of GSM-based antibacterial agents.

An atom-economic intermolecular radical addition reaction of acyloxy nitroso compounds to electron-deficient alkenes mediated by visible light is reported. The starting nitroso derivatives are readily prepared by oxidation of the corresponding oximes prepared from ketones and the overall transformation represents an oxidative coupling of a ketone with a Michael acceptor. The cascade proceeds smoothly under mild conditions, providing a series of valuable functionalized oximes in moderate to good yields. Mechanistic studies suggest that these cascades proceed via addition/coupling processes that are controlled by the persistent radical effect (PRE) with NO acting as the persistent species.

The synthesis of cyclic polystyrene (PSt) with an alkoxyamine functionality has been accomplished by intramolecular radical coupling in the presence of a nitroso radical trap. Linear α,ω-dibrominated polystyrene, produced by the atom transfer radical polymerization (ATRP) of styrene using a dibrominated initiator, was subjected to chain-end activation via the atom transfer radical coupling (ATRC) process under pseudodilute conditions in the presence of 2-methyl-2-nitrosopropane (MNP). This radical trap-assisted, intramolecular ATRC (RTA-ATRC) produced cyclic polymers in greater than 90% yields, possessing ⟨G⟩ values in the 0.8–0.9 range as determined by gel permeation chromatography (GPC). Thermal-induced opening of the cycles, made possible by the incorporated alkoxyamine, resulted in a return to the original apparent molecular weight, further supporting the formation of cyclic polymers in the RTA-ATRC reaction. Liquid chromatography–mass spectrometry (LC-MS) provided direct confirmation of the cyclic ar...

The gas adsorption properties and NH3-SCR reaction mechanism over the Fe2O3/Ni(111) surface were investigated by a DFT-D study. The results show that the Fe2O3 cluster has more excellent gas adsorption performance than the Ni carrier. Single gas adsorption products are coordinated ammonia, nitroso, and adsorption oxygen, respectively. The presence of O2 promotes bimolecular adsorption. Three NH3-SCR reaction routes are revealed and mainly follow the Eley–Rideal mechanism. The reaction of NH3 and NO involves five steps: (1) NH3* dehydrogenation, (2) NH2NO* generation, (3) NHNO* generation, (4) NHNO* dissociation, and (5) H2O generation. NHNO* dissociation into N2 releases lots of energy. The reaction of O2 and NO eventually forms NO2, and is an energetically favorable process. Reaction of NO2 with NH3 involves three steps: (1) NH2NO2 generation, (2) NHNO2 generation, and (3) NHNO2 dissociation. NHNO2* decomposition and H2O* desorption as the rate-determining steps control the whole reaction rate. In addition, the reason for the high NOx conversion of “fast-SCR” is that NO2 reacts more easily with NH2 to form a nitrogen intermediate compared to NO.

Described herein is the development of an iron-catalyzed HAT induced radical cyclization hydro-oximation of 1,6-enynes. This transformation involves four step cascade processes: (i) iron-catalyzed hydrogen-atom transfer, (ii) intramolecular radical cyclization of the alkyne, (iii) NO radical capture by the vinyl radical, and (iv) tautomerization of a nitroso alkene to access the ketoximes. Detailed DFT calculations have provided evidence for the transformation processes and the stereoselective formation of ketoximes. Notably, the same strategy has also been applied for the synthesis of pyrrolo[3,2-d]isoxazoles with a quaternary stereocenter via a two-step transformation.

The automated reaction mechanisms and kinetics (AutoMeKin) program evolved from a transition state search using chemical dynamics simulations (TSSCDS). It combines a series of empirical, semi-empirical and ab initio calculation methods to provide a two-step transition state search process from low-level calculation to high-level calculation. However, in this process, with the lack of solution keywords, low-level calculation has the problem of low accuracy or high computational cost. To address this problem, the gau_xtb interface that combines the high efficiency of xTB and the comprehensiveness of Gaussian09 was incorporated into the AutoMeKin2020 in this work and after adding some keywords, the AMK-gau_xtb software was obtained. Meanwhile, to adapt to the interface, the MD sampling results used Quadratic Synchronous Transit 3 (QST3) for the low-level transition state search. As an application, the reaction in which the nitroso group is replaced by hydroxide anion during the alkaline hydrolysis of 2,4,6-trinitrotoluene (TNT) in the water phase was studied with AMK-gau_xtb. The results of Intrinsic Reaction Coordinate (IRC) calculations revealed that the reactions on the front side and back side are different, with higher energy barriers obtained for the reactions on the front side. In addition, the hydrogen atom of the hydroxide anion has a slightly higher energy barrier for motion toward the inside of the benzene ring than for motion out of the benzene ring. Examination of the transition state structures of the low-level and high-level results showed that all reactions involve the stretching and restoration of the benzene ring. This process will lead to the incorrect identification of several transition states by the gau_xtb-based low-level calculation, while high-level calculation eliminates these incorrect results. The results of this research showed that AMK-gau_xtb has high efficiency and high fault tolerance, and has potential for use in large-scale system transition state searches.

The nitroso group served as a traceless directing group for the C–H functionalization of N-alkylanilines, ultimately removed after functioning either as an internal oxidant or under subsequent redu...

N-Acetyl-7-nitroindoline has a characteristic reaction in that its acetyl group is photo-activated to acetylate amines to form amides. In this study, the N-acetyl-7-nitroindoline part was connected to the 2'-deoxyribose part at the 3- or 5-position or to a glycerol unit at the 3-position through an ethylene linker (1, 2, and 3, respectively). They were incorporated into the oligodeoxynucleotides, and their photo-reactivities toward the complementary RNA were evaluated. The acetyl group of 1 was photo-activated to form the deacelylated nitroso derivative without affecting the RNA strand. The photoreaction with 2 suggested acetylation of the RNA strand. In contrast, compound 3 formed the photo-cross-linked adduct with the RNA. These results have shown the potential application of N-acetyl-7-nitroindoline unit in aqueous solutions.

The presence of low levels of N-nitroso-N,N-dimethylamine (NDMA) in ranitidine hydrochloride drug products has been reported by regulatory agencies. GlaxoSmithKline undertook a root cause analysis ...

A Rh(III)-catalyzed C-H arylation reaction of N-nitrosoanilines has been developed in which arylboronic acids were used as arylation reagents. It provides an efficient strategy for the synthesis of N-nitroso-[1,1'-biphenyl]-2-amine, which is an important starting material for the synthesis of N-hetero biaryl compounds, such as 2-amine-1,1'-biphenyl, carbazole, phenanthridone. This protocol can be applied to various N-alkyl substituted N-nitrosoanilines and N-nitrosoanilines with substituents on the phenyl ring. Arylboronic acids with both electron-donating and electron-withdrawing groups are tolerated.

Summary Functionalization of arenes represents the most efficient approach for constructing a core backbone of important aryl compounds. Compared with the well-developed electrophilic aromatic substitution and transition-metal-catalyzed C–H activation, nucleophilic aromatic substitution remains challenging because of the lack of a convenient route for rapid conversion of the σH adduct to other stable and versatile intermediates in situ. Guided by computational design, we were able to realize asymmetric nucleophilic aromatic substitution by introducing a nitroso group on naphthalene via chiral phosphoric acid catalysis. This strategy enables efficient construction of atropisomeric indole-naphthalenes and indole-anilines with excellent stereocontrol. Density functional theory (DFT) calculations provide further insights into the origins of enantioselectivity and the reaction mechanisms. The successful application in the synthesis of NOBINs (2-amino-2′-hydroxy-1,1′-binaphthyl) extends the utility of this strategy.

Dialkyl 5-amino-2-hydroxy-4,6-dimethylisophthalates were synthesized for the first time by the reduction of the corresponding nitroso derivatives with sodium dithionite. The pKa and pKBH+ values of the synthesized compounds were determined and taken into account to find conditions for their sulfonylation with p-toluenesulfonyl chloride and p-acetamidobenzenesulfonyl chloride. As a result, previously unknown sulfonylated derivatives of substituted aminoisophthalates with potential antimicrobial properties were obtained. The composition and structure of the products were confirmed by IR, UV, and 1H NMR spectroscopy and mass spectrometry. The geometric structure of the sulfonylated compounds was established by DFT calculations at the BP86-D3/def2-SVP level of theory. The antibacterial effect of 5-(4-acetamidobenzenesulfonamido)-2-hydroxy-4,6-dimethylisophthalate was revealed.

Recent drug recalls (e.g., valsartan and ranitidine) linked to the discovery of nitrosamine impurities have led to increased regulatory scrutiny in the manufacturing process of marketed medicines, ...

The structures and reactivities of organic phosphinidene chalcogenides have been mainly inferred from trapping or complexation experiments. Phosphinidene chalcogenide derivatives appear to be an elusive family of molecules that have been suggested as reactive intermediates in multiple organophosphorus reactions. The quest to isolate "free" phosphinidene chalcogenides remains a challenge in the field. Here, we present the synthesis, IR, and UV/Vis spectroscopic identification of hitherto elusive phenylphosphinidene oxide and phenylphosphinidene sulfide from the corresponding phosphonic diazide precursors. We isolated these higher congeners of nitroso- and thionitrosobenzene in argon matrices at 10 K. The spectral assignments are supported by B3LYP/6-311++G(3df,3pd) and MP2/cc-pVTZ computations.

The field of metabolic engineering has achieved biochemical routes for conversion of renewable inputs to structurally diverse chemicals, but these products contain a limited number of chemical functional groups. In this review, we provide an overview of the progression of uncommon or 'nonstandard' functional groups from the elucidation of their biosynthetic machinery to the pathway optimization framework of metabolic engineering. We highlight exemplary efforts from primarily the last 5 years for biosynthesis of aldehyde, ester, terminal alkyne, terminal alkene, fluoro, epoxide, nitro, nitroso, nitrile, and hydrazine functional groups. These representative nonstandard functional groups vary in development stage and showcase the pipeline of chemical diversity that could soon appear within customized, biologically produced molecules.

The results of the DFT studies on the mechanism of the PIII/PV=O catalyzed reductive amination of nitrosoarenes using ArB(OH)2 yielding diaryl amines are reported. This allowed a comparison of the reaction paths and key intermediates of the Cu(I)- and P(III)-mediated reductive aminations of aryl boronic acids using alkylnitrites, nitroso- or nitroarenes, and revealed important similarities in the catalytic reactivity of transition-metal and main-group elements in C(sp2)–N bond-forming reactions. It is shown that both transformations occur via ambiphilic nitrenoid-type key intermediates, the reactivity of which towards the aryl boronic acid is attributed to the presence of both a Lewis acid center (Cu or P) and a Lewis base center (the N or O atoms of the ‘N=O’ component).

Amino and nitro substituted 1,2,5-oxadiazole-2-oxide isomers and their ring-opened nitroso forms have been subjected to density functional treatment at the level of B3LYP/6-311++G(d,p). The transition states for the ring opening processes are obtained and the corresponding activation energies have been calculated. Also, 1,3- and 1,5-proton tautomerism yielding imine, oxime and aci forms are investigated. For all the structures, the stabilities, the HOMO, LUMO energies and the interfrontier molecular orbital energy gaps are obtained and the effects of substituents (NH2 and NO2) are discussed.

C25H39N2O3PRh, triclinic, P21/n (no. 14), a = 13.505(5) Å, b = 14.266(5) Å, c = 13.405(4) Å, β = 91.280(3)°, V = 2574.8(15) Å3, Z = 4, R gt (F) = 0.0399, wR ref (F 2) = 0.1026, T = 100 K.

The π-facial selectivity of Diels-Alder cycloadditions of 5-monosubstituted cyclopentadienes is known experimentally and has been extensively studied computationally. Previous studies on 5-monosubstituted cyclopentadienes by the Burnell and Houk groups showed that facial selectivity arises principally from hyperconjugative aromaticity or antiaromaticity of polar groups that cause distortion of the cyclopentadiene; steric effects of nonpolar groups can also be important. We have now explored the stereoselective cycloaddition of 5,5-unsymmetrically substituted cyclopentadienes to an acyl nitroso dienophile reported by Kan and co-workers. Computational studies with M06-2X/6-311+G(d,p) indicate that the stereoselectivity in the cycloadditions of 5,5-unsymmetrically substituted cyclopentadienes is not just a simple combination of effects found for monosubstituted counterparts. Substituent conformations and diene-dienophile steric and electronic interaction effects all influence stereoselectivity. Predictions are made about several as-yet-unstudied cyclopentadiene cycloadditions.