Carbon-nitrogen Bond Cleavage Research Articles

Synthesis of 3-iodoindoles by the Pd/Cu-catalyzed coupling of N,N-dialkyl-2-iodoanilines and terminal acetylenes, followed by electrophilic cyclization.

[reaction: see text] 3-Iodoindoles have been prepared in excellent yields by coupling terminal acetylenes with N,N-dialkyl-o-iodoanilines in the presence of a Pd/Cu catalyst, followed by an electrophilic cyclization of the resulting N,N-dialkyl-o-(1-alkynyl)anilines using I2 in CH2Cl2. Aryl-, vinylic-, alkyl-, and silyl-substituted terminal acetylenes undergo this process to produce excellent yields of 3-iodoindoles. The reactivity of the carbon-nitrogen bond cleavage during cyclization follows the following order: Me > n-Bu, Me > Ph, and cyclohexyl > Me. Subsequent palladium-catalyzed Sonogashira, Suzuki, and Heck reactions of the resulting 3-iodoindoles proceed smoothly in good yields.

Stereoselective Synthesis of Nuphar Quinolizidine Alkaloid, (‐)‐Deoxynupharidine.

A stereoselective synthetic route to Nuphar quinolizidine alkaloid, (−)-deoxynupharidine, was established by employing reductive carbon–nitrogen bond cleavage, followed by simultaneous recyclization of a proline derivative with samarium diiodide, and an intramolecular ring-closing metathesis, as the key steps.

Stereoselective synthesis of Nuphar quinolizidine alkaloid, (−)-deoxynupharidine

A stereoselective synthetic route to Nuphar quinolizidine alkaloid, (−)-deoxynupharidine, was established by employing reductive carbon–nitrogen bond cleavage, followed by simultaneous recyclization of a proline derivative with samarium diiodide, and an intramolecular ring-closing metathesis, as the key steps.

Carbon–nitrogen bond cleavage in pyridine ring systems mediated by organometallic thorium(iv) complexes

Thorium(IV) alkyl and aryl complexes of the type (C(5)Me(5))(2)ThR(2)(R = CH(2)Ph, Ph) have been found to mediate the facile ring-opening and dearomatization of the pyridine ring of pyridine N-oxide under ambient conditions to afford the first thorium eta(2)-(O,N)-oximate complexes.

Enantioselective Synthesis of (+)-Aphanorphine by Means of SamariumDiiodide Promoted Reductive Carbon-Nitrogen Bond-Cleavage Reaction

An enantioselective synthesis of (+)-aphanorphine has been achieved by application of a samarium diiodide promoted reductive carbon-nitrogen bond-cleavage reaction to a 1-methoxycarbonyl-1,2,3,4-tetrahydroisoquinoline providing a benzazepinone derivative as a key step.

Transition Metal Catalyzed Ring Opening Reactions of 2‐Phenyl‐3‐vinyl Substituted 2H‐Azirines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Transition metal catalyzed ring opening reactions of 2-phenyl-3-vinyl substituted 2 H-azirines

Treatment of 2-phenyl-3-vinyl-substituted 2 H-azirines with Grubbs' catalyst induces a clean rearrangement and affords products derived from carbon–nitrogen bond cleavage of the 2 H-azirine ring. However, when the reaction was carried out using Wilkinson's catalyst in an alcoholic solvent, the only product obtained in high yield corresponded to an α,β-unsaturated oxime.

Grubb’s and Wilkinson catalyzed reactions of 2-phenyl-3-vinyl substituted 2H-azirines

Treatment of 2-phenyl-3-vinyl-substituted 2H-azirines with Grubbs' catalyst induces a clean rearrangement and affords products derived from carbon-nitrogen bond cleavage of the 2H- azirine ring. However, when the reaction was carried out using Wilkinson's catalyst in an alcoholic solvent, the only product obtained in high yield corresponded to an α,β-unsaturated oxime

HIV-1 protease: characterization of a catalytically competent enzyme-substrate intermediate.

The steady-state and pre-steady-state kinetic parameters for the interaction of E with the fluorogenic substrate 2-aminobenzoyl-Thr-Ile-Nle-Phe(p-NO(2))-Gln-Arg-NH(2) were determined in 1.25 M NaCl, 0.1 M MES-TRIS at pH 6.0 at 25 degrees C. At low concentrations of enzyme, the values of the K(m) and k(cat) calculated from steady-state data were 2.1 microM and 7.4 s(-1), respectively. At high concentrations of enzyme, the time-courses of fluorescence enhancement associated with catalysis were very dependent on the excitation wavelength used to monitor the reaction. Because the absorbance spectrum of the substrate overlapped the fluorescence emission spectrum of the enzyme, these abnormalities were attributed to fluorescence energy transfer between the enzyme and the substrate in an enzyme-substrate intermediate. The kinetic data collected with lambda(ex) = 280 nm and lambda(em) > 435 nm were analyzed according to the following mechanism in which EX was the species with enhanced fluorescence relative to substrate or products: [formula see text]. The values of the kinetic parameters with (1)H(2)O as the solvent were K = 13 microM, k(2) = 150 s(-1), k(-2) = 25 s(-1), and k(3) = 11 s(-1). The values of the kinetic parameters with (2)H(2)O as the solvent were K = 13 microM, k(2) = 210 s(-1), k(-2) = 12 s(-1), and k(3) = 4.4 s(-1). These values yielded solvent isotope effects of 2 on k(cat) and 0.9 on k(cat)/K(m). From analysis of the complete time-course of the fluorescence change (lambda(ex) = 280 nm and lambda(em) > 435 nm) during the course of substrate hydrolysis, the intermediate EX was determined to be 6.3-fold more fluorescent than the product, which, in turn, was 4.5-fold more fluorescent than ES or S. Rapid quench experiments with 2 N HCl as the quenching reagent confirmed that EX was a complex between enzyme and substrate. Consequently, the small burst in fluorescence observed when monitoring with lambda(ex) = 340 nm (0.3 product equiv per enzyme equivalent) was attributed to the fluorescence change upon transfer of substrate from an aqueous environment to a nonaqueous environment in the enzyme. These results were consistent with carbon-nitrogen bond cleavage being the major contributor to k(cat).

Direct Aromatic C–N Bond Cleavage Evidenced in the Hydrodenitrogenation of 2,6-Dimethylaniline over Cobalt-Promoted Mo/Al2O3 Sulfide Catalysts: A Reactivity and FT-IR Study

The hydrodenitrogenation of 2,6-dimethylaniline (DMA) was studied over a series of sulfided Co(0–4.7%)–Mo(8.7%)/Al2O3 catalysts at 573 K under 4 MPa total pressure and 0–56 kPa H2S partial pressure. Two NiMo samples were tested for comparison. The reaction network presents three parallel routes: dearomatization of DMA followed by either hydrogenation–elimination to dimethylcyclohexenes and dimethylcyclohexanes, or NH3 elimination to m-xylene, and disproportionation of DMA to 2-methylaniline and 2,4,6-trimethylaniline. We demonstrate that part of the xylene is formed by direct aromatic carbon–nitrogen bond cleavage through a nucleophilic substitution involving hydride species. On CoMo catalysts, in the presence of H2S, the amount of extra xylene is independent of Co content, while the dearomatization is promoted. Without H2S, this special substitution reaction is most important on the Mo catalyst, and strikingly Co acts as a poison. FT-IR spectroscopy of adsorbed carbon monoxide evidences a new type of sites on the sulfided catalysts after a mild hydrogen treatment. We propose that a site configuration located exclusively on unpromoted Mo atoms highly depleted in sulfur is responsible for the direct denitrogenation route. The NiMo couple behaves differently: xylene formation is independent of Ni content, which means that the specific Mo sites for direct C–N bond rupture are poisoned by nickel, even in the presence of H2S. The location of Co and Ni on the MoS2 slabs then appears different.

Concise enantiospecific synthesis of a coccinellied alkaloid, (-)-adalinine.

[reaction: see text] An enantiospecific synthesis of a coccinellied alkaloid, (-)-adalinine, was established starting from (S)-(-)-pyroglutamic acid, where a stereoselective Michael addition and a samarium iodide-promoted regioselective carbon-nitrogen bond cleavage reaction were involved as the key reactions.

Protonation state of methyltetrahydrofolate in a binary complex with cobalamin-dependent methionine synthase.

N5-Methyltetrahydrofolate (CH(3)-H(4)folate) donates a methyl group to the cob(I)alamin cofactor in the reaction catalyzed by cobalamin-dependent methionine synthase (MetH, EC 2.1.1.3). Nucleophilic displacement of a methyl group attached to a tertiary amine is a reaction without an obvious precedent in bioorganic chemistry. Activation of CH(3)-H(4)folate by protonation prior to transfer of the methyl group has been the favored mechanism. Protonation at N5 would lead to formation of an aminium cation, and quaternary amines such as 5,5-dimethyltetrahydropterin have been shown to transfer methyl groups to cob(I)alamin. Because CH(3)-H(4)folate is an enamine, protonation could occur either at N5 to form an aminium cation or on a conjugated carbon with formation of an iminium cation. We used (13)C distortionless enhancement by polarization transfer (DEPT) NMR spectroscopy to infer that CH(3)-H(4)folate in aqueous solution protonates at N5, not on carbon. CH(3)-H(4)folate must eventually protonate at N5 to form the product H(4)folate; however, this protonation could occur either upon formation of the binary enzyme-CH(3)-H(4)folate complex or later in the reaction mechanism. Protonation at N5 is accompanied by substantial changes in the visible absorbance spectrum of CH(3)-H(4)folate. We have measured the spectral changes associated with binding of CH(3)-H(4)folate to a catalytically competent fragment of MetH over the pH range from 5.5 to 8.5. These studies indicate that CH(3)-H(4)folate is bound in the unprotonated form throughout this pH range and that protonated CH(3)-H(4)folate does not bind to the enzyme. Our observations are rationalized by sequence homologies between the folate-binding region of MetH and dihydropteroate synthase, which suggest that the pterin ring is bound in the hydrophobic core of an alpha(8)beta(8) barrel in both enzymes. The results from these studies are difficult to reconcile with an S(N)2 mechanism for methyl transfer and suggest that the presence of the cobalamin cofactor is important for CH(3)-H(4)folate activation. We propose that protonation of N5 occurs after carbon-nitrogen bond cleavage, and we invoke a mechanism involving oxidative addition of Co(1+) to the N5-methyl bond to rationalize our results.

Coenzyme B12 (cobalamin)-dependent enzymes.

The B12 or cobalamin coenzymes are complex macrocycles whose reactivity is associated with a unique cobalt-carbon bond. The two biologically active forms are MeCbl and AdoCbl and their closely related cobamide forms. MeCbl participates as the intermediate carrier of activated methyl groups. During the catalytic cycle the coenzyme shuttles between MeCbl and the highly nucleophilic cob(I)alamin form. Examples of MeCbl-dependent enzymes include methionine synthase and Me-H4-MPT: coenzyme M methyl transferase. AdoCbl functions as a source of carbon-based free radicals that are unmasked by homolysis of the coenzyme's cobalt-carbon bond. The free radicals are subsequently used to remove non-acid hydrogen atoms from substrates to facilitate a variety of reactions involving cleavage of carbon-carbon, carbon-oxygen and carbon-nitrogen bonds. Most reactions involve 1,2 migrations of hydroxy-, amino- and carbon-containing groups, but there is also one class of ribonucleotide reductases that uses AdoCbl. The structures of two cobalamin-dependent enzymes, methionine synthase and methylmalonyl-CoA mutase, have been solved. In both cases the cobalt is co-ordinated by a histidine ligand from the protein. The significance of this binding motif is presently unclear since in other cobalamin-dependent enzymes spectroscopic evidence suggests that the coenzyme's nucleotide 'tail' remains co-ordinated to cobalt when bound to the protein.

ChemInform Abstract: Catalytic Carbon—Nitrogen Bond Cleavage by Rh(I).

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Applications of a Novel Carbon—Nitrogen Bond Cleavage Reaction. Part 4. A New Biomimetic Synthesis of Benzo[c]phenanthridine Alkaloids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Low-Valent Titanium Mediated Reductive Deoxygenation of Carbonyls to MethylenesViaCarbon-Nitrogen Bond Cleavage in N-(Arylmethyl) Anilines

Abstract The reduction of aryl aldehydes and ketones in neutral medium, to the corresponding hydrocarbons via carbon-nitrogen bond cleavage of the intermediate N-(arylmethyl)anilines with low-valent titanium reagents is described. It provides a mild, convenient and selective pathway for deoxygenation of carbonyls without the production of any side product.

Carbon-Nitrogen Bond Cleavage in an .eta.2(N,C)-Pyridine Complex Induced by Intramolecular Metal-to-Ligand Alkyl Migration: Models for Hydrodenitrogenation Catalysis

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarbon-Nitrogen Bond Cleavage in an .eta.2(N,C)-Pyridine Complex Induced by Intramolecular Metal-to-Ligand Alkyl Migration: Models for Hydrodenitrogenation CatalysisSteven D. Gray, Keith J. Weller, Michael A. Bruck, Paula M. Briggs, and David E. WigleyCite this: J. Am. Chem. Soc. 1995, 117, 43, 10678–10693Publication Date (Print):November 1, 1995Publication History Published online1 May 2002Published inissue 1 November 1995https://doi.org/10.1021/ja00148a010RIGHTS & PERMISSIONSArticle Views719Altmetric-Citations100LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (2 MB) Get e-AlertsSupporting Info (4)»Supporting Information Supporting Information Get e-Alerts

Zirconium Chemistry Involving Benzamidinate Ligands. Reduction of [PhC(NSiMe3)2]2ZrCl2 to form an Imido-Iminoacyl Compound by Carbon-Nitrogen Bond Cleavage

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTZirconium Chemistry Involving Benzamidinate Ligands. Reduction of [PhC(NSiMe3)2]2ZrCl2 to form an Imido-Iminoacyl Compound by Carbon-Nitrogen Bond CleavageJohn R. Hagadorn and John ArnoldCite this: Organometallics 1994, 13, 12, 4670–4672Publication Date (Print):December 1, 1994Publication History Published online1 May 2002Published inissue 1 December 1994https://doi.org/10.1021/om00024a008RIGHTS & PERMISSIONSArticle Views247Altmetric-Citations65LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (407 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Reactions of RuClH(CO)(PPh3)3 with Allylic Amines: Insertions and an Unusual Carbon-Nitrogen Bond Cleavage of Allylic Amines

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReactions of RuClH(CO)(PPh3)3 with Allylic Amines: Insertions and an Unusual Carbon-Nitrogen Bond Cleavage of Allylic AminesKatsuma Hiraki, Takahiro Matsunaga, and Hiroyuki KawanoCite this: Organometallics 1994, 13, 5, 1878–1885Publication Date (Print):May 1, 1994Publication History Published online1 May 2002Published inissue 1 May 1994https://doi.org/10.1021/om00017a051RIGHTS & PERMISSIONSArticle Views525Altmetric-Citations48LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (904 KB) Get e-Alerts Get e-Alerts

Alternative model for mechanism-based inhibition of Escherichia coli ribonucleotide reductase by 2'-azido-2'-deoxyuridine 5'-diphosphate.

Ribonucleotide reductase (RDPR) from Escherichia coli is composed of two subunits, R1 and R2, and catalyzes the conversion of nucleotides to deoxynucleotides. The mechanism of inactivation of RDPR by 2'-azido-2'-deoxynucleoside 5'-diphosphate (N3UDP) has been examined using a variety of isotopically labeled derivatives: (1'-, 2'-, 3'-, or 4'-[2H])-N3UDPs and 2'-[15N3, 13C]-N3UDP. Electron paramagnetic resonance (EPR) and electron spin echo envelope modulation (ESEEM) spectroscopy studies using these compounds indicate that the 2' carbon-nitrogen bond to the azide moiety is cleaved prior to or upon formation of the nitrogen-centered radical derived from the azide moiety of N3UDP. EPR studies reveal no hyperfine interactions of the nitrogen-centered radical with the 1', 2', 3', or 4' hydrogens of N3UDP. ESEEM studies however, reveal that the 1' and 4' deuterons are 3.3 +/- 0.2 and 2.6 +/- 0.3 A, respectively, from the nitrogen-centered radical. Further support for carbon-nitrogen bond cleavage is derived from studies of the interaction of oxidized R1, C225SR1, and C462SR1 with R2 and N3UDP. In all three cases, in contrast to the results with the wild type R1, azide is detected. Nitrogen-centered radical is not observed with either oxidized R1 or C225SR1 but is observed with C462SR1. These results suggest that C225 is required for the conversion of azide into N2 and a nitrogen-centered radical. The dynamics of the inactivation of RDPR by N3UDP have also been examined. Use of [3'-2H]N3UDP reveals an isotope effect of approximately 2 on the loss of the tyrosyl radical and the rate of inactivation of RDPR. In both cases the kinetics are complex, suggesting multiple modes of inactivation. In addition, several modes of inactivation are required to explain the observation that loss of the tyrosyl radical is slower than the rate of inactivation. Studies using [5'-3H]N3UDP reveal that the rapid inactivation is the result of the formation of a tight noncovalent complex between modified nucleotide, nitrogen-centered radical and RDPR. Destruction of the nitrogen-centered radical is a slow process which appears to be accompanied by decomposition of the modified nucleotide into PPi, uracil, and 2-methylene-3(2H)-furanone. The latter covalently modifies R1 and ultimately leads to loss of approximately 50% of the activity of R1.