Dinitrogen Extrusion Research Articles

Strain‐Driven [3+2] Cycloaddition of Triazine 1‐Oxides with Arynes/Cyclooctyne: Access to Benzisoxazoles/Cyclooctene‐Fused Isoxazoles

AbstractThe 4‐carboxylates of 1,2,3‐triazine 1‐oxides undergo [3+2] cycloaddition with in situ generated benzynes and naphthyne and also with cyclooctyne that, following extrusion of dinitrogen, form isoxazole‐3‐propenoate derivatives in high yields and diastereocontrol. This practical method occurs at room temperature and provides a wide range of isoxazole‐based heterocycles with diverse functionality. 1,2‐Naphthyne, an unsymmetrical alkyne, forms only one regioisomeric product, exemplifying inherent regioselectivity. Although high, stereoselectivity is not 100 % in most cases, indicating that the loss of dinitrogen is stepwise. Derivative reactions of benzisoxazoles suggest their versatility.

Reductions of Arenes using a Magnesium-Dinitrogen Complex.

In this contribution, we present "Birch-type", and other reductions of simple arenes by the potassium salt of an anionic magnesium dinitrogen complex, [{K(TCHPNON)Mg}2(μ-N2)] (TCHPNON=4,5-bis(2,4,6-tricyclohexylanilido)-2,7-diethyl-9,9-dimethyl-xanthene), which acts as a masked dimagnesium(I) diradical in these reactions. This reagent is non-hazardous, easy-to-handle, and in some cases provides access to 1,4-cyclohexadiene reduction products under relatively mild reaction conditions. This system works effectively to reduce benzene, naphthalene and anthracene through magnesium-bound "Birch-type" reduction intermediates. Cyclohexadiene products can be subsequently released from the magnesium centres by protonolysis with methanol. In contrast, the reduction of substituted arenes is less selective and involves competing reaction pathways. For toluene and 1,3,5-triphenylbenzene, the structural authentication of "Birch-type" reduction intermediates is conclusive, although the formation of corresponding 1,4-cyclohexadiene derivatives was low yielding. Reduction of anisole did not yield an isolable "Birch-type" intermediate, but instead gave a C-O activation product. Treating triphenylphosphine with [{K(TCHPNON)Mg}2(μ-N2)] resulted in the extrusion of both biphenyl and dinitrogen to afford a magnesium(II) phosphanide [{K(TCHPNON)Mg(μ-PPh2)}2]. Reduction of fluorobenzene proceeded via C-F activation of the arene, and isolation of the magnesium(II) fluoride [{K(TCHPNON)Mg(μ-F)}2]. Finally, the two-electron reduction of 1,3,5,7-cyclooctatetraene (COT) with [{K(TCHPNON)Mg}2(μ-N2)] yielded a complex, [{K(TCHPNON)Mg}2(μ-COT)], incorporating the aromatic dianion (COT2-).

Polycyclic Pyrazolidines by Tandem Diazomalonate Dipolar Cycloadditions and CpRu-Catalyzed Carbene Additions.

Thanks to the ability of diazo derivatives to react either as 1,3-dipoles and as carbenes after dinitrogen extrusion, combinations of oxa or aza benzonorbornadienes and diazomalonates afford polycyclic pyrazolidines via a three-step sequence of (i) a highly diastereoselective [3+2]-cycloaddition, (ii) a CpRu-catalyzed carbene addition, and (iii) a second dipolar cycloaddition. Of importance, step (II) represents a unique access to novel bench-stable N,N-cyclic azomethine imines, which behave as effective 1,3-dipoles in combination with electron-poor dipolarophiles. Each step proceeds efficiently and the 3-step process can be performed in one-pot to yield a polycyclic pyrazolidine in excellent overall yield (90 %).

Nitrate reduction enables safer aryldiazonium chemistry.

Aryldiazonium salts remain a staple in organic synthesis and are still prepared largely in accord with the protocol developed in the 19th century. Because of the favorable reactivity that often cannot be achieved with other aryl(pseudo)halides, diazonium chemistry continues to grow. Facile extrusion of dinitrogen contributes to the desired reactivity but is also reason for safety concerns. Explosions have occurred since the discovery of these reagents and still result in accidents. In this study, we report a diazonium chemistry paradigm shift based on nitrate reduction using thiosulfate or dihalocuprates as electron donors that avoids diazonium accumulation. Because nitrate reduction is rate-limiting, aryldiazoniums are produced as fleeting intermediates, which results in a safer and often more efficient deaminative halogenation in a single step from anilines.

Divergent reactivity of U(iii) and U(ii) complexes with organoazides via isolable diazenylimido intermediates

The first uranium organoazide complexes were isolated as U(v) and U(iv) diazenylimido complexes. They exhibited divergent reactivity to yield U(iv) azido or U(iv) imido products via C–N bond cleavage or dinitrogen extrusion.

Direct Spectroscopic Identification of BN-Arynes and Subtle Steric Effects on Nitrogen Fixation.

1,2-Azaborinines are the BN analogues of arynes through exchange of the formal CC triple bond by an isoelectronic BN bond. The BN-arynes are an underexplored class of reactive intermediates. Dibenzo[c,e][1,2]azaborinine (10,9-BN-phenanthryne) 1 was inferred as reactive intermediate by trapping reactions. Here it is shown that 1 can be generated in the gas phase by thermolysis from the pyridine adduct of 9-azido-9-borafluorene by cleavage of the dative bond with pyridine and dinitrogen extrusion. The ionization potential of 1 is 8.2 eV with ionization resulting from the π HOMO. Under cryogenic matrix isolation conditions, 9-azido-9-borafluorene photolysis results in isomerization to the dinitrogen adduct of 1 without involvement of a triplet borylnitrene intermediate. Photochemical nitrogen extrusion from 1 ⋅ N2 is not possible and nitrogen fixation is irreversible under cryogenic conditions. In contrast, 2,4,7,9-tetra-tert-butyldibenzo[c,e][1,2]azaborinine can be photogenerated from the corresponding azidoborole precursor under cryogenic matrix isolation conditions, and nitrogen fixation is precluded due to steric hindrance. The BN stretching vibration at about 1750 cm-1 is much weaker than in typical linear diaryl iminoboranes.

Base-Stabilized Phosphinidene Oxide, Imide and Sulfide.

Oxidation of a base-stabilized phosphinidene (κ2 -NNP)P (12, NNP=phosphinoamidinate) with N2 O afforded a labile phosphinidene oxide (κ2 -NNP)P=O (16) which was characterized by NMR spectroscopy. Further oxidation of 16 by N2 O or reaction of 12 with two equivalents of pyridine oxide afforded the isolable dioxide (κ2 -NNP)PO2 which was characterized by NMR and SC XRD. Trapping of 16 with tolyl isocyanate resulted in P=O/N=C metathesis, eventually affording a urea-ligated phosphine (κ1 -NNP)P(NTol)2 C=O (17) The mechanism of this reaction was elucidated by DFT calculations. Reactions of phosphinidene 12 with azides generated transient imines (NNP)P=NR, which in the case of R=Tol underwent cycloaddition with tolyl Isocyanate to afford the urea product 17, and in the case of R=SiMe3 reacts with N3 SiMe3 via the addition of N-Si across the P=N bond affording, after the extrusion of dinitrogen, a P,N-heterocyclic compound. Both products of the reactions with azides have been fully characterized, both in solution and the solid-state. Finally, reaction of phosphinidene 12 with one equivalent of sulfur resulted in the isolation of the base-stabilized phosphinidene sulfide (κ2 -NNP)P=S that has also been fully characterized.

Synthesis and Reactivity of an Anionic Diazoolefin.

Bent (hetero)allenes such as carbodicarbenes and carbodiphosphoranes can act as neutral C-donor ligands, and diverse applications in coordination chemistry have been reported. N-Heterocyclic diazoolefins are heterocumulenes, which can function in a similar fashion as L-type ligands. Herein, we describe the synthesis and the reactivity of an anionic diazoolefin. This compound displays distinct reactivity compared to neutral diazoolefins, as evidenced by the preparation of diazo compounds via protonation, alkylation, or silylation. The anionic diazoolefin can be employed as an ambidentate, X-type ligand in salt metathesis reactions with metal halide complexes. Extrusion of dinitrogen was observed in a reaction with PCl(NiPr2)2, resulting in a stable phosphinocarbene.

Synthesis and Reactivity of an Anionic Diazoolefin

AbstractBent (hetero)allenes such as carbodicarbenes and carbodiphosphoranes can act as neutral C‐donor ligands, and diverse applications in coordination chemistry have been reported. N‐Heterocyclic diazoolefins are heterocumulenes, which can function in a similar fashion as L‐type ligands. Herein, we describe the synthesis and the reactivity of an anionic diazoolefin. This compound displays distinct reactivity compared to neutral diazoolefins, as evidenced by the preparation of diazo compounds via protonation, alkylation, or silylation. The anionic diazoolefin can be employed as an ambidentate, X‐type ligand in salt metathesis reactions with metal halide complexes. Extrusion of dinitrogen was observed in a reaction with PCl(NiPr2)2, resulting in a stable phosphinocarbene.

A theoretical study on the photochemical generation of phenylborylene from phenyldiazidoborane.

Organic borylenes are a kind of highly reactive species, which play important roles in a lot of reactions as vigorous intermediates. In this work, we investigated the photochemical generation mechanisms of phenylborylene (PhB) together with the side product N-phenylnitrenoiminoborane (PhNBN) from phenyldiazidoborane (PhBN6) by extrusion of dinitrogen in the two lowest electronic singlet states (S0 and S1) based on the complete active space self-consistent field (CASSCF) and its second-order perturbation (CASPT2) methods combined with time-dependent density functional theory (TD-DFT) calculations. Our results show that the reaction PhBN6 → PhB + 3N2 involves stepwise N2 extrusion three times and the azido region rearrangement. Moreover, we found that the studied photo-induced processes are kinetically feasible because the highest energy barrier is only 0.36 eV and excitation with light of wavelength 254 nm can provide enough excess energy to overcome these energy barriers. Importantly, we revealed that several conical intersections between S1 and S0 states participate and facilitate the studied photochemical processes. Our results not only clarify the experimental observations, (H. F. Bettinger, J. Am. Chem. Soc. 2006, 128, 2534), but also provide valuable insights into borylene chemistry.

Dinitrogen extrusion from diazene in organic synthesis

Radical-mediated reactions have many advantages in the construction of complex molecular scaffolds by forging chemical bonds of high challenge. Diazenes, including 1,1-diazenes and 1,2-diazenes, can generate biradical species via nitrogen extrusion under thermal or photochemical conditions. The superior reactivity of the generated biradical enables various types of synthetic transformations with excellent chemoselectivity and has been applied to the complex natural products synthesis. In this mini-review, the modes of reaction are summarized and discussed, namely ring contraction via nitrogen deletion, homo or hetero-dimerization, trimethylenemethane (TMM)-diyl cycloaddition. Applications of these classes of reactions in complex natural product synthesis are illustrated. Last but not least, the current state, future directions, and opportunities for dinitrogen extrusion reaction from diazenes are highlighted and discussed.

Intermolecular [5 + 1]-Cycloaddition between Vinyl Diazo Compounds and tert-Butyl Nitrite to 1,2,3-Triazine 1-Oxides and Their Further Transformation to Isoxazoles.

1,2,3-Triazine 1-oxides are formed by nitrosyl addition from tert-butyl nitrite to the vinylogous position of vinyl diazo compounds. This transformation, which is a formal intermolecular [5 + 1] cycloaddition, occurs under mild conditions, with high functional group tolerance and regioselectivity, and can be employed for late-stage functionalization. Upon heating at refluxing chlorobenzene temperature, these triazine-N-oxides undergo dinitrogen extrusion to form isoxazoles in very high yields.

Zinc-Enabled Annulation of Trifluorodiazoethane with 2H-Azirines to Construct Trifluoromethyl Pyrazolines, Pyrazoles, and Pyridazines.

A diethylzinc-promoted unconventional annulation reaction of 2,2,2-trifluorodiazoethane with 2H-azirines is described. This transformation involves two [3 + 2] cycloaddition steps and one dinitrogen extrusion process in one pot, thus giving a broad array of 3-trifluoromethyl pyrazolines in good yields with excellent diastereoselectivities. Further transformations provide facile access to 3-trifluoromethyl pyrazoles and 3,5-ditrifluoromethyl pyridazines with good efficiency.

Computational study on the mechanism of the reaction of benzenesulfonyl azides with oxabicyclic alkenes.

The reaction of benzenesulfonyl azides with oxabicyclic alkenes to form aziridines could either proceed via initial [3 + 2] cycloaddition to form triazoline intermediates which then leads to aziridines, or via initial dinitrogen cleavage of the benzenesulfonyl azide to afford a nitrene intermediate followed by addition of this nitrene species across the olefinic C-C bond of the oxabicyclic alkene. Calculations at the DFT M06-2X/6-311G(d,p) level indicate that the initial [3 + 2] cycloaddition reaction of benzenesulfonyl azide and oxabicyclic alkene has barriers of 15.0kcal/mol (endo) and 10.3kcal/mol (exo) and rate constants of 5.23 × 103s-1 (endo) and 3.86 × 106s-1 (exo) whereas the pathway involving initial formation of nitrene species has a high activation barrier of 39.2kcal/mol and rate constant of 8.92 × 10-12s-1, indicating that the reaction will go through the former route to form an exo triazoline intermediate. The exo triazoline can either undergo a concerted C-C, N-N bond cleavage to form a ring-opened intermediate, a reaction that has a barrier of 23.4kcal/mol, followed by dinitrogen extrusion and C-C, C-N bond regeneration with barriers of 29.1 and 23.5kcal/mol respectively to form endo aziridines, or it can undergo direct nitrogen extrusion to form the exo product, a reaction with a barrier of 38.3kcal/mol. Since the rate-determining step of the former route is 9.2kcal/mol more favored than the latter, the former route rate is favored. The rate constants of the rate-determining steps are 1.30 × 10-5s-1 (endo) and 3.16 × 10-11s-1 (exo), indicating that endo aziridine would be formed as the major product and this is in conformity with the experimental observations of Chen et al. (J. Org. Chem. 18:11863-11872, 2019). The position of substituents on the benzene group of the benzenesulfonyl azide affects the endo/exo diastereoselectivity.Graphical abstract.

1,3-Dipolar cycloaddition reaction of indoles with tosyl azide, subsequent dehydroaromatization and ring-opening cascade: a computational study

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.

Selenium dioxide promoted dinitrogen extrusion/direct selenation of arylhydrazines and anilines

A novel, efficient, economical strategy for the coupling and direct selenation of arylhydrazines to selenides using SeO2 has been developed. Our method employs SeO2 as the selenium source with hydrazines as coupling reactants to generate selenides via dinitrogen extrusion. This reagent also helped to generate ArSe substitued aniline derivatives via C–H functionalization reaction in good yields. The application of this method in gram scale was also carried out.

Photochemical Synthesis of Azoarenes from Aryl Azides on Cu(100): A Mechanism Unraveled

Thermal, photochemical, and metal-facilitated routes to aryl nitrenes via the extrusion of dinitrogen from aryl azides adsorbed on a single-crystal copper surface have been investigated. Only by ir...

New chromium, molybdenum, and cobalt complexes of the chelating esp ligand

Bimetallic carboxylates of Rh(II) are widely recognized for their ability to catalyze carbene transfer reactions such as the cyclopropanation of olefins using organic diazo compounds as carbene precursors. A major goal in catalysis is to find cheaper, more Earth-abundant alternatives to precious metal catalysts. There is therefore currently great interest in the bimetallic paddlewheel chemistry of elements that have lower costs and greater terrestrial abundance than Rh. M2(esp)2(L)2 structures were synthesized and structurally characterized with M = Cr, Co, and Mo, where esp2− = α,α,α′,α′-tetramethyl-1,3-benzenedipropionate, a chelating di-carboxylate ligand that helps stabilize the bimetallic core. Cr2(esp)2(THF)2, Mo2(esp)2, and Co2(esp)2(EtOH)2 were tested as catalysts for decomposition of the diazo compound (4-bromophenyl)diazoacetate methyl ester in the presence of styrene; while the Cr2 and Mo2 complexes showed no difference from a background control, the Co2 complex was found to enhance the rate of dinitrogen extrusion and promote carbene addition to styrene to form the cyclopropane product.

Copper-catalyzed cyclopropanation reaction of but-2-ene.

The mechanism of the copper(I)-catalyzed cyclopropanation reaction for methyl diazoacetate with both (Z)- and (E)-but-2-ene stereoisomers has been studied using the 6-311++G(d,p) basis set by means of M06-2X and O3LYP functionals. According to both methods, the rate-limiting step is the formation of a copper-carbene intermediate, formed by association between methyl diazoacetate and bis(acetonitrile)-copper(I) ion with the concomitant extrusion of dinitrogen. Cis/trans diastereoselectivity for the cyclopropanation reaction of a 1,2-disubstituted alkene ((Z)-but-2-ene) has been theoretically studied for the first time through the proper location of transition states on the potential-energy surface with the O3LYP method, since no transition structures could be found with the M06-2X functional due to the extreme flatness of the potential-energy surface. The calculated stereoselectivities involving two acetonitrile ligands or one dichloromethane molecule show qualitative agreement with experimental data. This study allows attributing the origin of the selectivity to steric interactions between the ligands of the catalyst system and the olefin substituents. The comparison between the corresponding activation barriers for the direct insertion step shows a higher reactivity for the Z stereoisomer of but-2-ene, consistently with the larger reactant destabilization through steric interactions.

Displacement of Dinitrogen by Oxygen: A Methodology for the Catalytic Conversion of Diazocarbonyl Compounds to Ketocarbonyl Compounds by 2,6-Dichloropyridine-N-oxide.

Dirhodium(II) catalyzed dinitrogen extrusion from diazocarbonyl compounds by 2,6-dichloropyridine-N-oxide forms ketocarbonyl compounds in near-quantitative yields. Reactions occur at room temperature, and the pyridine product does not coordinate with dirhodium(II) to inhibit catalysis. Anhydrous tricarbonyl compounds, as well as dicarbonyl compounds, are conveniently prepared by this methodology, and they have been used in situ for catalytic ene and aldol transformations.