Search

This contribution reviews all the synthetic work on tetrodotoxin that has appeared in the literature through June 2011.

Photolysis of aryl azides to give nitrenes, and their subsequent rearrangement in the presence of water to give 3H-azepinones, is performed in continuous flow in a photoreactor constructed of fluorinated ethylene polymer (FEP) tubing. Fine tuning of the reaction conditions using the flow reactor allowed minimization of secondary photochemical reactions.

The in-depth study of electrochemical (EC) synthesis can require a powerful mass spectrometry (MS) analytical platform which can discover and identify fleeting intermediates in EC reactions. Here we report a floating electrolytic electrospray ionization (FE-ESI) strategy that can perform EC processes in a floating electrolytic cell and monitor intermediates by high-resolution MS. Compared with previous EC-MS methods, a significant advantage of FE-ESI-MS is that it allows one to modulate the electrolytic and electrospray process individually, ensuring its high sensitivity in discovering intermediates and universality to investigate redox reactions in different scenarios. This powerful platform has been successfully used to investigate the EC reductive coupling of p-tolylboronic acid and p-nitrotoluene. A series of nitrene intermediates were discovered and identified by FE-ESI-MS, indicating that a hidden mechanism involving nitrene formation might play a key role in EC reductive coupling process., (© 2023 Wiley-VCH GmbH.)

The stepwise decomposition of carbonyl diisocyanate, OC(NCO)2, has been studied by using IR spectroscopy in solid argon matrices at 16 K. Upon irradiation with an ArF laser ( λ=193 nm), carbonyl diisocyanate split off CO and furnished a new carbonyl nitrene, OCNC(O)N, in its triplet ground state. Two conformers of the nitrene, syn and anti, that were derived from the two conformers of OC(NCO)2 (62 % syn- syn and 38 % syn- anti) were identified and characterized by combining IR spectroscopy and quantum chemical calculations. Subsequent irradiation with visible light ( λ>395 nm) caused the Curtius rearrangement of the nitrene into OCNNCO. In addition to the expected decomposition products, N2 and CO, further photolysis of OCNNCO with the ArF laser yielded NOCN, through a diazomethanone (NNCO) intermediate. To further validate our proposed reaction mechanism, ArF-laser photolysis of the closely related NNNNCO and cyclo-N2CO in solid argon matrices were also studied. The observations of NOCN and in situ CO-trapped product OCNNCO provided indirect evidence to support the initial generation of NNCO as a common intermediate during the laser photolysis of OCNNCO, NNNNCO, and cyclo-N2CO. [ABSTRACT FROM AUTHOR]

Short-distance molecular-modeling constraints are advantageous for elucidating the structures of individual proteins and protein conformational changes. Commonly used amine-reactive crosslinks are relatively long (14 Å), partly due to the length of the lysine side-chain, and are sparsely distributed throughout a protein. Short-distance non-specific crosslinkers can provide a larger number of tighter molecular-modeling constraints. Here we describe the use of a short-range homo-trifunctional isotopically-coded non-specific photo-reactive crosslinking reagent, 2,4,6-triazido-1,3,5-triazine (TATA)- 12 C 3 / 13 C 3 , for MS-based protein crosslinking studies. Upon activation by 254 nm UV light, TATA- 12 C 3 / 13 C 3 generates up to three nitrene radicals capable of non-selective crosslinking at ~ 5 Å. This reagent was validated using cyclohexane, several test peptides, and myoglobin, and was found to react with a large number of amino acids, forming multiple crosslinked products. The myoglobin crosslinks detected by MS agreed with the known structure of myoglobin; arranging the protein's secondary-structure motifs into their correct fold was possible based solely on the constraints imposed by the crosslinks. Finally, TATA was used to crosslink the α-synuclein monomer. The 10 short-distance constraints provided by TATA crosslinking led to an initial model of the molten-globule form of the native α-synuclein monomer; this provides a suggested structure for the precursor of the misfolded α-synuclein proteoforms involved in synucleopathies. Biological significance The isotopically labeled short-range non-specific crosslinker TATA- 12 C 3 / 13 C 3 was characterized for use in crosslinking-based protein structural studies. The crosslinking products of TATA can provide a distance constraint of merely 5Ǻ between crosslinked residues. TATA- 12 C 3 / 13 C 3 had broad reactivity, crosslinking a wide variety of amino acids, including lysine, glutamic and aspartic acid, asparagine, glutamine, glycine, alanine, valine, proline, methionine, serine, cysteine, tyrosine, and the N-terminus. The short-distance crosslinking constraints provided by TATA allowed us to predict the fold of myoglobin using a combination of these distance constraints with a prediction of myoglobin's secondary structure motifs. TATA was also used to crosslink α-synuclein in its native, molten globule form, which has not been characterized using other structural biology techniques. The distance constraints provided by the crosslinks allowed for the manual modeling of a rudimentary structure for the α-synuclein monomer. [ABSTRACT FROM AUTHOR]

For the first time, a highly regioselective intermolecular sulfonylamidation unactivated secondary Csp3−H bond has been achieved using IrIII catalysts. The introduced N, N'-bichelating ligand plays a crucial role in enabling iridium-nitrene insertion into a secondary Csp3−H bond via an outer-sphere pathway. Mechanistic studies and density functional theory (DFT) calculations demonstrated that a two-electron concerted nitrene insertion was involved in this Csp3−H amidation process. This method tolerates a broad range of linear and branched-chain N-alkylamides, and provides efficient access to diverse γ-sulfonamido-substituted aliphatic amines. [ABSTRACT FROM AUTHOR]

15N-Labeling demonstrates that the two nitrogen atoms in the 2-pyridylnitrene radical cation 2·+ become equivalent prior to fragmentation in the mass spectrometer. Furthermore, the mass spectra of 6- and 7-tetrazolo[1,4- a]pyridine are identical, as are those of 5- and 8-tetrazolo[1,5- a]pyridine, thereby again demonstrating interconversion of the nitrogen atoms in 2-pyridylnitrenes. These rearrangements parallel the reactions established under thermal (flash vacuum pyrolysis) and photochemical condition. Calculations of the energies of ground and transition states at the CASPT2(7,8) level support the notion that 2-pyridylnitrenes undergo very easy and exothermic ring expansion to 1,3-diazacycloheptatetraene 3, both in the neutrals and the radical cations. In addition, the ring opening to 4-cyanobutadienylnitrene 4 can take place in both the neutrals and the radical cations with modest activation barriers. [ABSTRACT FROM AUTHOR]

The recently developed nitrene transfer reaction onto gold-activated alkynes provides a route to safe and accessible synthons of α-diazo imides. This reaction is rather unique in that it requires AuI in catalytic amounts; however, this promiscuous metal is only used to activate the alkyne moiety. After such activation is obtained, the nitrene-transfer process occurs through an outer-sphere mechanism, in which the metal acts only as a spectator. Density functional theory was applied to elucidate this peculiar reaction and to provide a mechanistic explanation for the experimentally observed isomers at the double bond and imine sites. [ABSTRACT FROM AUTHOR]

Previous direct C−H nitrogenation suffered from simple amidation/amination with limited atom-economy and is mostly limited to C(sp2)−H substrates. In this work, anthranil was designed as a novel bifunctional aminating reagent for both C(sp2)−H and C(sp3)−H bonds under rhodium(III) catalysis, thus affording a nucleophilic aniline tethered to an electrophilic carbonyl. A tridendate rhodium(III) complex has been isolated as the resting state of the catalyst, and DFT studies established the intermediacy of a nitrene species. [ABSTRACT FROM AUTHOR]

N,N-Dihalosulfonamides are important reagents for various organic transformations. Simplicity, efficiency, and a unique chemical behaviour make this class of compounds synthetically useful. N,N-Dibromo- p-toluenesulfonamide (TsNBr2) is an efficient source of electrophilic bromine, which, at the same time, also provides the nucleophilic sulfonamide counterpart to form a C-N bond. This reagent has also been found to be a suitable precursor of nitrene. These diverse properties led to the development of various important organic transformations under catalyst-free and relatively mild reaction conditions. However, the strong oxidizing nature of this reagent sometimes appears as a limitation for a desired functional group transformation. 1 Introduction 2 Cohalogenation of Olefins 3 Activation of Alkynes with TsNBr2 4 Oxidation Reactions 5 Nitrene Transfer Reactions 6 Hofmann Rearrangement Using TsNBr2 7 Bromination of Aromatic Compounds 8 Cleavage of Oximes 9 Miscellaneous Reactions 10 Conclusion [ABSTRACT FROM AUTHOR]

As the prototype Curtius rearrangement reaction, carbamoyl azide decomposes into aminoisocyanate and molecular nitrogen. However, the key intermediate carbamoylnitrene was previously undetected, even though the decomposition of carbamoyl azides has been studied frequently since its discovery in the 1890s. Upon ArF laser (λ=193 nm) photolysis, the stepwise decomposition of the two simplest carbamoyl azides H2NC(O)N3 and Me2NC(O)N3, isolated in solid noble gas matrices, occurs with the formation of the corresponding carbamoylnitrenes H2NC(O)N and Me2NC(O)N. Both triplet species are characterized for the first time by combining matrix-isolation IR spectroscopy and quantum-chemical calculations. Subsequent visible-light irradiations cause efficient rearrangement of these nitrenes into the respective aminoisocyanates. [ABSTRACT FROM AUTHOR]

The species 4-nitrenopyridine 1-oxide is known to exhibit triplet nitrene dominated chemistry to yield azo-dimer products exclusively, even at room temperature. As such, this species, and its analogue 4-nitrenoquinoline 1-oxide, are useful models to probe the mechanism of formation of azo-dimers, which is postulated to proceed by self-reaction of the nitrene or reaction of nitrene with the parent azide. A laser flash photolysis study is described where the kinetics of formation of azo-dimer were found to be most adequately modeled by competition between both mechanisms, and rate coefficients for the competing reactions were determined. [ABSTRACT FROM AUTHOR]

The RhII-catalyzed oxyamination and diamination of alkenes generate 1,2-amino alcohols and 1,2-diamines, respectively, in good to excellent yields and with complete regiocontrol. In the case of diamination, the intramolecular reaction provides an efficient method for the preparation of pyrrolidines, and the intermolecular reaction produces vicinal amines with orthogonal protecting groups. These alkene difunctionalizations proceed by aziridination followed by nucleophilic ring opening induced by an Rh-bound nitrene generated in situ, details of which were uncovered by both experimental and theoretical studies. In particular, DFT calculations show that the nitrogen atom of the putative [Rh]2=NR metallanitrene intermediate is electrophilic and support an aziridine activation pathway by N ⋅⋅⋅N=[Rh]2 bond formation, in addition to the N ⋅⋅⋅[Rh]2=NR coordination mode. [ABSTRACT FROM AUTHOR]

Substituted and functionalized tryptophans are interesting building blocks in peptidic natural products. Stereoselective allylic alkylations of small peptides using stannylated allylic substrates allow the synthesis of stannylated peptides, which can be subjected to Stille couplings using (substituted) o-iodoanilines. Subsequent azidation and photochemical nitrene insertion allows the direct incorporation of modified tryptophans into peptides. [ABSTRACT FROM AUTHOR]

Functionalization of C-H bonds has received significant attention in organic chemistry during the last decade and it is still a 'hot' topic. In particular, C-H modification of natural products has benefitted from this development. Carbohydrates are densely functionalized natural products, and methods for their functionalization are therefore very attractable. This review presents methods from the last five decades and gives an overview of the developments in C-H functionalization of carbohydrates. It covers all methods in which a C-H bond is broken: from radical abstractions and carbene insertion to new metal-catalyzed approaches. The review systematically covers the carbohydrates position-by-position and hence gives a quick overview. [ABSTRACT FROM AUTHOR]

As the prototype Curtius rearrangement reaction, carbamoyl azide decomposes into aminoisocyanate and molecular nitrogen. However, the key intermediate carbamoylnitrene was previously undetected, even though the decomposition of carbamoyl azides has been studied frequently since its discovery in the 1890s. Upon ArF laser ( λ=193 nm) photolysis, the stepwise decomposition of the two simplest carbamoyl azides H2NC(O)N3 and Me2NC(O)N3, isolated in solid noble gas matrices, occurs with the formation of the corresponding carbamoylnitrenes H2NC(O)N and Me2NC(O)N. Both triplet species are characterized for the first time by combining matrix-isolation IR spectroscopy and quantum-chemical calculations. Subsequent visible-light irradiations cause efficient rearrangement of these nitrenes into the respective aminoisocyanates. [ABSTRACT FROM AUTHOR]

The intramolecular benzylic C−H amination catalyzed by bimetallic paddlewheel complexes was investigated by using density functional theory calculations. The metal-metal bonding characters were investigated and the structures featuring either a small HOMO-LUMO gap or a compact SOMO energy scope were estimated to facilitate an easier one-electron oxidation of the bimetallic center. The hydrogen-abstraction step was found to occur through three manners, that is, hydride transfer, hydrogen migration, and proton transfer. The imido N species are more preferred in the Ru-Ru and Pd-Mn cases whereas coexisting N species, namely, singlet/triplet nitrene and imido, were observed in the Rh-Rh and Pd-Co cases. On the other hand, the triplet nitrene N species were found to be predominant in the Pd-Ni and Pd-Zn systems. A concerted asynchronous mechanism was found to be modestly favorable in the Rh-Rh-catalyzed reactions whereas the Pd-Co-catalyzed reactions demonstrated a slight preference for a stepwise pathway. Favored stepwise pathways were seen in each Ru-Ru- and Pd-Mn-catalyzed reactions and in the triplet nitrene involved Pd-Ni and Pd-Zn reactions. The calculations suggest the feasibility of the Pd-Mn, Pd-Co, and Pd-Ni paddlewheel complexes as being economical alternatives for the expensive dirhodium/diruthenium complexes in C−H amination catalysis. [ABSTRACT FROM AUTHOR]

A gold-catalyzed regioselective [3+2] cycloaddition of ynamides with 1,4,2-dioxazoles was developed and offers a novel approach to obtain highly functionalized oxazoles under mild reaction conditions. 1,4,2-Dioxazole was found to act as an efficient N-acyl nitrene equivalent to trigger a facile generation of α-imino gold–carbene intermediate through the elimination of a ketone. [ABSTRACT FROM AUTHOR]

The formally CoIV carbene Co(OR)2( = CPh)2) is formed upon the reaction of diphenyldiazomethane with the cobalt bis(alkoxide) precursor Co- (OR))2(THF))2. Structural, spectroscopic, and theoretical studies demonstrate that Co(OR))2(=CPh)2) has significant high-valent CoIV= CPh)2 character with non-negligible spin density on the carbene moiety. [ABSTRACT FROM AUTHOR]

Alkene aziridination by azides through uncatalyzed thermal gas phase routes has been studied using the DFT B3LYP/6-31G(d,p) method, where the possible role of discrete nitrene intermediates is emphasized. The thermal decomposition of azides is studied using the MP2/aug-cc-pVDZ strategy as well. The MP2 (but not the B3LYP) results discount the existence of singlet alkylnitrenes where the alkyl group has an α-hydrogen. Addition of the lowest lying singlet and triplet nitrenes R-N (R = H, Me, Ac) to four different alkene substrates leading to aziridine formation was studied by the B3LYP method. Singlet nitrenes with alkenes can yield aziridines via a concerted mechanism, where H-N insertion takes place without a barrier, whereas Me-N shows larger barriers than Ac-N. Methyl substitution in the alkene favors this reaction. Triplet nitrene addition to alkenes is studied as a two-step process, where the initially formed diradical intermediates cyclize to form aziridines by ISC (intersystem crossing) and collapse. Scope for C-C bond rotation in the diradical leads to loss of stereochemical integrity for triplet nitrene addition to cis- and trans-2-butenes. Geometries of the transition states in the various reaction steps studied here are described as 'early' or 'late' in good accordance with the Hammond postulate. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Pyrolysis of azido- meta -meconine yields only a single product 1D, which has been characterized spectroscopically ( 1 H NMR, 13 C NMR, HSQC, DEPT & MS). These results reveal that the fused five-member lactone ring can influence the product selectivity. The DFT calculations suggest the formation of favourable oxazolidine intermediate compared to azirine ( 1Z ) and ketenimine ( 1H ) intermediates. The isodesmic analysis showed that the fused lactone aryl nitrene ( 1N ) would have more strain to form azirine ( 1Z ) intermediate than the corresponding aryl nitrene ( 1M ). [ABSTRACT FROM AUTHOR]

Sigmatropic rearrangements, while rare in biology, offer opportunities for the efficient and selective synthesis of complex chemical motifs. A 'P411' serine-ligated variant of cytochrome P450BM3 has been engineered to initiate a sulfimidation/[2,3]-sigmatropic rearrangement sequence in whole E. coli cells, a non-natural function for any enzyme, providing access to enantioenriched, protected allylic amines. Five mutations in the enzyme substantially enhance its activity toward this new function, demonstrating the evolvability of the catalyst toward challenging nitrene transfer reactions. The evolved catalyst additionally performs the highly enantioselective imidation of non-allylic sulfides. [ABSTRACT FROM AUTHOR]

Dirhodium-catalyzed C-H amination is hypothesized to proceed via Rh2-nitrene intermediates in either the Rh2(II,Il) or Rh2(II,III) redox state. Herein, we report joint theoretical and experimental studies of the ground electronic state (GES), redox potentials, and C-H amination of [Rh2II,III(O2CCH3)4(L)n]+ (l_L) (L = none, Cl-, and H2O), [Rh2(esp)2]+ (2), and Rh2(espn)2Cl (3) (esp = α,α,α',α'-tetramethyl-1,3-benzenedipropanoate and espn = α,α,α',α'-tetramethyl-1,3-benzenedipropanamidate). CASSCF calculations on 1_L yield a wave function with two closely weighted configurations, (δ*)2(π1*)2(π2*)1 and (δ*)2(π1*)1(π2*)2, consistent with reported EPR g values [Chem. Phys. Lett. 1986, 130, 20--23]. In contrast, EPR spectra of 2 show g values consistent with the DFT-computed (π*)4δ*)1 GES. EPR spectra and Cl K-edge XAS for 3 are consistent with a (π*)4(<δ*)1 GES, as supported by DFT. Nitrene intermediates 2N_L and 3N_L are also examined by DFT (the nitrene is an NSO3R species). DFT calculations suggest a doublet GES for 2N_L and a quartet GES for 3N_L. CASSCF calculations describe the GES of 2N as Rh2(II,II) with a coordinated nitrene radical cation, (π*)4(δ*)2(δnitrene,1)1(πnitrene,2)0. Conversely, the GES of 3N is Rh2(II,III) with a coordinated triplet nitrene, (π*)4(δ*)1(πnitrene,1)1(πnitrene,2)1. Quartet transition states (4TSs) are found to react via a stepwise radical mechanism, whereas 2TSs are found to react via a concerted mechanism that is lower in energy compared to 4TSs for both 2N_L and 3N_L. The experimental (determined by intramolecular competition) and 2TS-calculated kinetic isotopic effect (KIE) shows a KIE ~ 3 for both 2N and 3N, which is consistent with a concerted mechanism. [ABSTRACT FROM AUTHOR]

Azidoformates are interesting potential nitrene precursors, but their direct photochemical activation can result in competitive formation of aziridination and allylic amination products. Herein, we show that visible-light-activated transition-metal complexes can be triplet sensitizers that selectively produce aziridines through the spin-selective photogeneration of triplet nitrenes from azidoformates. This approach enables the aziridination of a wide range of alkenes and the formal oxyamination of enol ethers using the alkene as the limiting reagent. Preparative-scale aziridinations can be easily achieved under continuous-flow conditions. [ABSTRACT FROM AUTHOR]

A facile and efficient one-pot synthesis of isoxazol-3(2 H)-ones has been developed starting from α-acyl cinnamides and tosyliminophenyliodinane catalyzed by copper(II) acetate [Cu(OAc)2] under very mild conditions involving a tandem aza-Michael addition and intramolecular cyclization sequence. [ABSTRACT FROM AUTHOR]

In the field of cobalt(II) porphyrin-catalyzed metallo-radical reactions, organic azides have emerged as successful nitrene transfer reagents. In the pursuit of employing ortho-YH substituted (Y = O, NH) aryl azides in Co(II) porphyrin-catalyzed nitrene transfer reactions, unexpected hydrogen atom transfer (HAT) from the OH or NH2 group in the ortho-position to the nitrene moiety of the key radical-intermediate was observed. This leads to formation of reactive ortho-iminoquinonoid (Y = O) and phenylene diimine (Y = NH) species. These intermediates convert to subsequent products in non-catalyzed reactions, as is typical for these free organic compounds. As such, the observed reactions prevent the anticipated cobalt-mediated catalytic radical-type coupling of the nitrene radical intermediates to alkynes or alkenes. Nonetheless, the observed reactions provide valuable insights into the reactivity of transition metal nitrene-radical intermediates, and give access to ortho-iminoquinonoid and phenylene diimine intermediates from ortho-YH substituted aryl azides in a catalytic manner. The latter can be employed as intermediates in one-pot catalytic transformations. From the ortho-hydroxy aryl azide substrates both phenoxizinones and benzoxazines could be synthesized in high yields. From the ortho-amino aryl azide substrates azabenzene compounds were obtained as the main products. Computational studies support these observations, and reveal that HAT from the neighboring OH and NH2 moiety to the nitrene radical moiety has a low energy barrier. [ABSTRACT FROM AUTHOR]

The dipolar oxathiazyne-like sulfinylnitrene RS(O)N, a highly reactive α-oxo nitrene, has been rarely investigated. Upon flash vacuum pyrolysis of sulfinyl azide CF3S(O)N3 at 350 °C, an elusive sulfinylnitrene CF3S(O)N was generated in the gas phase in its singlet ground state and was characterized by matrix-isolation IR spectroscopy. Further fragmentation of CF3S(O)N at 600 °C produced CF3 and a novel iminyl radical OSN, an SO2 analogue, which were unambiguously identified by IR spectroscopy. Consistent with the experimental observations, DFT calculations clearly support a stepwise decomposition mechanism of CF3S(O)N3. [ABSTRACT FROM AUTHOR]

Possible mechanisms for Rh-promoted indole formation from vinyl/azidoarenes were examined computationally, and a mechanism is proposed in which the Rh catalyst promotes generation of a nitrene but is not directly involved in cyclization. [ABSTRACT FROM AUTHOR]

We report a metathesis reaction in which a nitrene fragment from an isocyanide ligand is exchanged with a nitrene fragment of an imido ligand in a series of niobium bis(imido) complexes. One of these bis(imido) complexes also promotes nitrene transfer to catalytically generate asymmetric dialkylcarbodiimides from azides and isocyanides in a process involving the Nb(V)/Nb(III) redox couple. [ABSTRACT FROM AUTHOR]

Rh(ii)-catalyzed diversified ring expansions controlled by single-electron-transfer (SET) have been disclosed in this communication, producing a series of indole-fused azetidines and 1H-carbazoles or related derivatives in moderate to good yields via Rh2III,II nitrene radical intermediates. The direction of ring expansion branches according to different ring sizes of methylenecycloalkanes. [ABSTRACT FROM AUTHOR]

The generation of 1,2-azaborine ( 4), the BN-analogue of ortho-benzyne, was recently achieved by elimination of tert-butyldimethylchlorosilane under the conditions of flash vacuum pyrolysis. The present investigation identifies by computational means pathways for the thermal isomerization and fragmentation of 1,2-azaborine. The computations were performed using single reference (hybrid/density functional, second order Møller-Plesset perturbation, and coupled cluster theories) as well as multiconfiguration methods (complete active space SCF based second order perturbation theory, multireference configuration interaction, and multiconfiguration coupled electron pair approximation) with basis sets up to polarized triple-ζ quality. The 1,2-azaborine is, despite the distortion of its molecular structure, the most stable C4H4BN isomer investigated. The formation of BN-endiyne isomers is highly unfavorable as the identified pathways involve barriers close to 80 kcal mol−1. The concerted fragmentation to ethyne and 2-aza-3-bora-butadiyne even has a barrier close to 120 kcal mol−1. The fragmentation of BN-enediynes has energetic requirements similar to enediynes. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A reinterpretation of the spectroscopic data for the products of flash vacuum pyrolysis (FVP) of 8- and 9-membered polymethylenetetrazoles 1 , 3 , 5 , and 7 with annelated benzene rings indicates that these are not cyanamides 2 , 4 , 6 , and 8 , but 9- and 10-membered cyclic carbodiimides 9 , 10 , 11 , and 12 . FVP of the corresponding tetrazolo[1,5- a ]azocine and tetrazolo[1,5- a ]azonine derivatives 13 and 17 was investigated by isolation of the products in cryogenic matrices and by matrix photolysis and found to yield 9- and 10-membered cyclic carbodiimides 14 and 18 as transient intermediates en route to indolo[2,3- b ]quinoline 15 and dibenzo[ b,f ]naphthyridine 19 . [ABSTRACT FROM AUTHOR]

An efficient, straightforward method for the synthesis of thiazolo-2-pyridone embedded peptidomimetic polyheterocycles via a catalyst-free, microwave-assisted, intramolecular C-H amination reaction is reported. All the synthesized polyheterocycles were evaluated for their fluorescent properties and effect on a-synuclein amyloid formation. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of uranium(vi) mono(imido) complexes, by the oxidation of corresponding uranium(v) species, are presented. These experimental results, paired with DFT analyses, allow for the comparison of the electronic structure of uranium(vi) mono(oxo) and mono(imido) ligands within a conserved ligand framework and demonstrate that the magnitude of the ground state stabilization derived from the inverse trans-influence (ITI) is governed by the relative charge localization on the multiply bonded atom or group. [ABSTRACT FROM AUTHOR]

The impact of redox non-innocence (RNI) on chemical reactivity is a forefront theme in coordination chemistry. A diamide diimine ligand, [{-CH=N(1,2- C6H4)NH(2,6-iPr2C6H3)}2]n (n=0 to -4), (dadi)n, chelates Cr and Fe to give [(dadi)M] ([1Cr(thf)] and [1Fe]). Calculations show [1Cr(thf)] (and [1Cr]) to have a d4 Cr configuration antiferromagnetically coupled to (dadi)2-*, and [1Fe] to be S= 2. Treatment with RN3 provides products where RN is formally inserted into the C-C bond of the diimine or into a C-H bond of the diimine. Calculations on the process support a mechanism in which a transient imide (imidyl) aziridinates the diimine, which subsequently ring opens. [ABSTRACT FROM AUTHOR]

A gold-catalyzed intermolecular reaction of vinyl azides and ynamides is described. This process presents an efficient and mild approach to multisubstituted 2-aminopyrroles in good-to-excellent yields. Control experiments were carried out to distinguish the reactivity between vinyl azides and the corresponding 2H-azirines. A plausible reaction mechanism was also proposed according to previous reports and our preliminary mechanistic studies. [ABSTRACT FROM AUTHOR]

Synthesis 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. [ABSTRACT FROM AUTHOR]

Almost all known members of the cytochrome P450 (CYP) superfamily conserve a key cysteine residue that coordinates the heme iron. Although mutation of this residue abolishes monooxygenase activity, recent work has shown that mutation to either serine or histidine unlocks non-natural carbeneand nitrene-transfer activities. Here we present the first crystal structure of a histidine-ligated P450. The T213A/C317H variant of the thermostable CYP119 from Sulfolobus acidocaldarius maintains heme iron coordination through the introduced ligand, an interaction that is accompanied by large changes in the overall protein structure. We also find that the axial cysteine C317 may be substituted with any other amino acid without abrogating folding and heme cofactor incorporation. Several of the axial mutants display unusual spectral features, suggesting that they have active sites with unique steric and electronic properties. These novel, highly stable enzyme active sites will be fruitful starting points for investigations of nonnatural P450 catalysis and mechanisms. [ABSTRACT FROM AUTHOR]

The CuSO 4 /ascorbate-mediated ‘click’ reaction of 2-(2-azidophenyl)-4,5-diaryloxazoles and arylacetylenes proceeded through an alternate pathway whereby reduction of the azide predominated over formation of the 1,2,3-triazole-forming cycloaddition. The unimolecular product, 2-(2-aminophenyl)-4,5-diphenyloxazole, was isolated which appears to be a formal reduction of the arylazide to the corresponding arylamine. A series of oxazoles which possessed various substituents (F, Cl, Br, OCH 3 ) on the 4,5-diaryl rings and having the 2-azido group on the 2-oxazolylphenyl position were submitted to the same ‘click’ conditions and gave the corresponding arylamine products (73–99%). The reaction appears to be specific toward the ortho -azido substitution of the polycyclic system, as the corresponding azidomethyl-substituted phenyl oxazoles do not give the ‘reduction’ products but gave the expected click products with the acetylenic co-reactants. [ABSTRACT FROM AUTHOR]

[Display omitted] • Black and blue phosphorene are significantly more reactive than graphene and hexagonal BN. • Nitrenes, carbenes and sulfur are the most promising reactants to functionalize phosphorene and protect it from oxidation. • The observed reaction between black phosphorene and azodiisobutyronitrile radicals is no likely to have occurred because physisorption is preferred. Herein, we studied the reactivity of black and blue phosphorene. They presented similar reaction energies, except for sulfur, benzynes, and nitrenes, which were more strongly bound to blue-phosphorene. Phosphorene is significantly more reactive than graphene and hexagonal-BN. The reaction energies did not reveal a significant variation for coverages around 6–1.5 %, for black-phosphorene. However, if the functional groups are agglomerated, reaction energies were improved by 16–17 kcal/mol. For blue-phosphorene, carbenes or nitrenes can promote significant structural changes at lower coverages, which are manifested by the appearance of three and five-membered rings. We provide evidence that the reported covalent functionalization of phosphorene with azodiisobutyronitrile radicals does not occur as physisorption is preferred. Nitrenes and carbenes do not undergo a [2 + 1] cycloaddition, favoring the formation of open structures. Organic reagents and sulfur are the functional groups that can pave the way toward synthesizing phosphorene monolayers with superior stability. [ABSTRACT FROM AUTHOR]

The mechanism of aromatic C–H amination of benzene via a nitrene insertion approach catalyzed by the TpBr3Cu(NCMe) complex was computationally investigated. The results of computational studies show that addition of the nitrene moiety of the TpBr3Cu–nitrene intermediate to benzene, and therefore, to form an aziridine intermediate, is more favorable than the nitrene moiety induced hydrogen atom abstraction from a sp2 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. [ABSTRACT FROM AUTHOR]

Aromatic polyazides are widely used as starting materials in organic synthesis and photochemical studies, as well as photoresists in microelectronics and as cross-linking agents in polymer chemistry. Some aromatic polyazides possess high antitumor activity, while many others are of considerable interest as high-energy materials and precursors of high-spin nitrenes and C3N4 carbon nitride nanomaterials. The use of aromatic polyazides in click-reactions may be a new promising direction in the design of various supramolecular systems possessing interesting chemical, physical and biological properties. This review is devoted to the synthesis, properties and applications of six-membered aromatic compounds containing three and more azido groups in the ring. [ABSTRACT FROM AUTHOR]

Thiophosphoryl nitrenes, R2P(S)N, are thiazirine-like intermediates that have been chemically inferred from trapping products in early solution studies. In this work, photolysis of the simplest thiophosphoryl azide, F2P(S)N3, in solid noble-gas matrices enabled a first-time spectroscopic (IR and UV-vis) identification of the thiophosphoryl nitrene F2P(S)N in its singlet ground state. Upon visible-light irradiation (≥495 nm), it converts into the thionitroso isomer F2P-N= S, which can also be produced in the gas phase from flash vacuum pyrolysis of F2P(S)N3. Further irradiation of F2P-NS with 365 nm UV light leads to the reformation of F2P(S)N and isomerization to the thiazyl species F2P-S≡N. [ABSTRACT FROM AUTHOR]

A highly efficient and versatile chemical cycle has been developed for the production of isocyanates through the molecular fixation of N2, CO2 and R3ECl (E=C, Si, and Ge). Key steps include a 'one-pot' photolytic NN bond cleavage of a Group 6 dinuclear dinitrogen complex with in situ trapping by R3ECl to provide a metal terminal imido complex that can engage in simultaneous nitrene-group transfer and oxygen-atom transfer to generate an intermediate metal terminal oxo complex with release of the isocyanate product. Reaction of the oxo complex with additional equivalents of R3ECl regenerates a metal dichloride that is the precursor for dinuclear dinitrogen starting material. [ABSTRACT FROM AUTHOR]

Oxidation of the rhodium(I) ethylene complex, [(TPA)Rh( η 2 -CH 2 CH 2 )] + ( 1 , TPA = N , N , N -tris(2-pyridylmethyl)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. [ABSTRACT FROM AUTHOR]

We present the threshold photoelectron spectroscopy of the imidogen radical (NH) recorded in the photon energy region up to 1 eV above its first ionization threshold. The radical was produced by reaction of NH 3 and F in a microwave discharge flow-tube and photoionized using vacuum ultraviolet (VUV) synchrotron radiation. A double imaging coincidence spectrometer was used to record mass-selected spectra and avoid contributions from the byproducts present in the reactor and background gas. The energy region includes the ground X + 2 Π and first electronically excited a + 4 Σ − states of NH + . Strong adiabatic transitions and weak vibrational progressions up to v + = 2 are observed for both electronic states. The rotational profile seen in the origin band has been modeled using existing neutral and cationic spectroscopic constants leading to a precise determination of the adiabatic ionization energy at 13.480 ± 0.002 eV. [ABSTRACT FROM AUTHOR]

Gold-catalyzed cycloadditions of ynamides with azidoalkenes or 2 H-azirines give [3+2] or [4+3] formal cycloadducts of three classes. Cycloadditions of ynamides with 2 H-azirine species afford pyrrole products with two regioselectivities when the Cβ-substituted 2 H-azirine is replaced from an alkyl (or hydrogen) with an ester group. For ynamides substituted with an electron-rich phenyl group, their reactions with azidoalkenes proceed through novel [4+3] cycloadditions to deliver 1 H-benzo[ d]azepine products instead. [ABSTRACT FROM AUTHOR]