Synthesis of Urea Derivatives from CO2 and Silylamines

A series of thirty‐three N,N′‐diaryl, dialkyl, and alkyl‐aryl ureas have been prepared in pyridine or toluene by reaction of silylamines with CO₂. This protocol is shown to provide facile access to ¹³C‐labeled ureas, as well as chiral and macrocyclic ureas. These reactions proceed through initial generation of the corresponding silylcarbamates, which subsequently react with silylamine under thermal conditions to afford the thermodynamically favored urea and disilyl ether.     

Pnictogen-Bonding Catalysis: An Interactive Tool to Uncover Unorthodox Mechanisms in Polyether Cascade Cyclizations

Pnictogen-bonding catalysis and supramolecular σ-hole catalysis in general is currently being introduced as the non-covalent counterpart of covalent Lewis acid catalysis. With access to anti-Baldwin cyclizations identified as unique characteristic, pnictogen-bonding catalysis appeared promising to elucidate one of the hidden enigmas of brevetoxin-type epoxide opening polyether cascade cyclizations, that is the cyclization of certain trans epoxides into cis-fused rings. In principle, a shift from S_N2- to S_N1-type mechanisms could suffice to rationalize this inversion of configuration. However, the same inversion could be explained by a completely different mechanism: Ring opening with C−C bond cleavage into a branched hydroxy-5-enal and the corresponding cyclic hemiacetal, followed by cascade cyclization under conformational control, including stereoselective C−C bond formation. In this report, a pnictogen-bonding supramolecular Sb^V catalyst is used to demonstrate that this unorthodox polyether cascade cyclization mechanism occurs.     

Facile Synthesis of Chiral Cyclic Ureas through Hydrogenation of 2‐Hydroxypyrimidine/Pyrimidin‐2(1H)‐one Tautomers

A facile access to optically active cyclic ureas was developed through palladium‐catalyzed asymmetric hydrogenation of pyrimidines containing tautomeric hydroxy group with up to 99 % ee. Mechanistic studies indicated that reaction pathway proceed through hydrogenation of C=N of the oxo tautomer pyrimidin‐2(1H)‐one, acid‐catalyzed isomerization of enamine–imine, and hydrogenation of imine pathway. In addition, the chiral cyclic ureas are readily converted into useful chiral 1,3‐diamine and thiourea derivatives without loss of optical purity.     

Functionalization of Piperidine Derivatives for the Site-Selective and Stereoselective Synthesis of Positional Analogues of Methylphenidate

Rhodium-catalyzed C−H insertions and cyclopropanations of donor/acceptor carbenes have been used for the synthesis of positional analogues of methylphenidate. The site selectivity is controlled by the catalyst and the amine protecting group. C−H functionalization of N-Boc-piperidine using Rh₂(R-TCPTAD)₄, or N-brosyl-piperidine using Rh₂(R-TPPTTL)₄ generated 2-substitited analogues. In contrast, when N-α-oxoarylacetyl-piperidines were used in combination with Rh₂(S-2-Cl-5-BrTPCP)₄, the C−H functionalization produced 4-susbstiuted analogues. Finally, the 3-substituted analogues were prepared indirectly by cyclopropanation of N-Boc-tetrahydropyridine followed by reductive regio- and stereoselective ring-opening of the cyclopropanes.     

Direct N−H Activation to Generate Nitrogen Radical for Arylamine Synthesis via Quantum Dots Photocatalysis

Represented herein is the first example of N-radical generation direct from N−H bond activation under mild and redox-neutral conditions. The in situ generated N-radical intercepts a reduced heteroarylnitrile/aryl halide for C−N bond formation under visible-light irradiation of quantum dots (QDs). A series of aryl and alkylamines with heteroarylnitriles/aryl halides exhibit high efficiency, site-selectivity and good functional-group tolerance. Moreover, consecutive C−C and C−N bond formation using benzylamines as substrates is also achieved, producing N-aryl-1,2-diamines with H₂ evolution. The redox-neutral conditions, broad substrate scope, and efficiency of N-radical formation are advantageous for organic synthesis.     

Intramolecular C−H Amination of N-Alkylsulfamides by tert-Butyl Hypoiodite or N-Iodosuccinimide

1,3-Diamines are an important class of compounds that are broadly found in natural products and are also widely used as building blocks in organic synthesis. Although the intramolecular C−H amination of N-alkylsulfamide derivatives is a reliable method for the construction of 1,3-diamine structures, the majority of these methods involve the use of a transition-metal catalyst. We herein report on a new transition-metal-free method using tert-butyl hypoiodite (t-BuOI) or N-iodosuccinimide (NIS), enabling secondary non-benzylic and tertiary C−H amination reactions to proceed. The cyclic sulfamide products can be easily transformed into 1,3-diamines. Mechanistic investigations revealed that amination reactions using t-BuOI or NIS each proceed via different pathways.     

One-Step Preparation of Fe/N/C Single-Atom Catalysts Containing Fe−N4 Sites from an Iron Complex Precursor with 5,6,7,8-Tetraphenyl-1,12-Diazatriphenylene Ligands

Fe/N/C single-atom catalysts containing Fe−N_x sites prepared by pyrolysis are promising cathode materials for fuel cells and metal-air batteries due to their high oxygen reduction reaction (ORR) activities. We have developed iron complexes containing N2- or N3-chelating coordination structures with preorganized aromatic rings in a 1,12-diazatriphenylene framework tethering bromo substituents as precursors to precisely construct Fe−N₄ sites in an Fe/N/C catalyst. One-step pyrolysis of the iron complex with carbon black forms atomically dispersed Fe−N₄ sites without iron aggregates. X-ray absorption spectroscopy (XAS) and electrochemical measurements revealed that the iron complex with N3-coordination is more effectively converted to Fe−N₄ sites catalyzing ORR with a TOF value of 0.21 e site⁻¹ s⁻¹ at 0.8 V vs. RHE. This indicates that the formation of Fe−N₄ sites is controlled by precise tuning of the chemical structure of the iron complex precursor.     

Re-Catalyzed Annulations of Weakly Coordinating N-Carbamoyl Indoles/Indolines with Alkynes via C−H/C−N Bond Cleavage

Described herein are rhenium-catalyzed [3+2] annulations of N-carbamoyl indoles with alkynes via C−H/C−N bond cleavage, which provide rapid access to fused-ring pyrroloindolone derivatives. For the first time, the weakly coordinating O-directing group was successfully employed in rhenium-catalyzed C−H activation reactions, enabled by the unique catalytic trio of Re₂(CO)₁₀, Me₂Zn and ZnCl₂. Mechanistic studies revealed that aminozinc species plays an important role in the reaction. Based on the mechanistic understanding, a more powerful catalytic trio of Re₂(CO)₁₀, [MeZnNPh₂]₂ and Zn(OTf)₂ was devised and applied successfully in the [4+2] annulations of indolines and alkynes affording pyrroloquinolinone derivatives.     

N-Terminal Selective C−H Azidation of Proline-Containing Peptides: a Platform for Late-Stage Diversification

A methodology for the C−H azidation of N-terminal proline-containing peptides was developed employing only commercially available reagents. Peptides bearing a broad range of functionalities and containing up to 6 amino acids were selectively azidated at the carbamate-protected N-terminal residue in presence of the numerous other functional groups present on the molecules. Post-functionalizations of the obtained aminal compounds were achieved: cycloaddition reactions or C−C bond formations via a sequence of imine formation/nucleophilic addition were performed, offering an easy access to diversified peptides.     

Revealing Isolated M−N3C1 Active Sites for Efficient Collaborative Oxygen Reduction Catalysis

Single atom catalysts (SACs) are of great importance for oxygen reduction, a critical process in renewable energy technologies. The catalytic performance of SACs largely depends on the structure of their active sites, but explorations of highly active structures for SAC active sites are still limited. Herein, we demonstrate a combined experimental and theoretical study of oxygen reduction catalysis on SACs, which incorporate M−N₃C₁ site structure, composed of atomically dispersed transition metals (e.g., Fe, Co, and Cu) in nitrogenated carbon nanosheets. The resulting SACs with M−N₃C₁ sites exhibited prominent oxygen reduction catalytic activities in both acidic and alkaline media, following the trend Fe−N₃C₁ > Co−N₃C₁ > Cu−N₃C₁. Theoretical calculations suggest the C atoms in these structures behave as collaborative adsorption sites to M atoms, thanks to interactions between the d/p orbitals of the M/C atoms in the M−N₃C₁ sites, enabling dual site oxygen reduction.     

Enantioconvergent Palladium-Catalyzed Alkylation of Tertiary Allylic C−H Bonds

Enantioconvergent catalysis enables the conversion of racemic molecules into a single enantiomer in perfect yield and is considered an ideal approach for asymmetric synthesis. Despite remarkable advances in this field, enantioconvergent transformations of inert tertiary C−H bonds remain largely unexplored due to the high bond dissociation energy and the surrounding steric repulsion that pose unparalleled constraints on bond cleavage and formation. Here, we report an enantioconvergent Pd-catalyzed alkylation of racemic tertiary allylic C−H bonds of α-alkenes, providing a unique approach to access a broad range of enantioenriched γ,δ-unsaturated carbonyl compounds featuring quaternary carbon stereocenters. Mechanistic studies reveal that a stereoablative event occurs through the rate-limiting cleavage of tertiary allylic C−H bonds to generate σ-allyl-Pd species, and the achieved E/Z-selectivity of σ-allyl-Pd species effectively regulates the diastereoselectivity via a nucleophile coordination-enabled S_N2′-allylation pathway.     

Simple Synthetic Routes to N-Heterocyclic Carbene Gold(I)–Aryl Complexes: Expanded Scope and Reactivity

The discovery of sustainable and scalable synthetic protocols leading to gold–aryl compounds bearing N-heterocyclic carbene (NHC) ligands sparked an investigation of their reactivity and potential utility as organometallic synthons. The use of a mild base and green solvents provide access to these compounds, starting from widely available boronic acids and various [Au(NHC)Cl] complexes, with reactions taking place under air, at room temperature and leading to high yields with unprecedented ease. One compound, (N,N′-bis[2,6-(di-isopropyl)phenyl]imidazol-2-ylidene)(4-methoxyphenyl)gold, ([Au(IPr)(4-MeOC₆H₄)]), was synthesized on a multigram scale and used to gauge the reactivity of this class of compounds towards C−H/N−H bonds and with various acids, revealing simple pathways to gold–based species that possess attractive properties as materials, reagents and/or catalysts.     

Direct,Enantioselective, and Nickel(II) Catalyzed Reactions of N-Azidoacetyl Thioimides with Trimethyl Orthoformate: A New Combined Methodology for the Rapid Synthesis of Lacosamide and Derivatives

A direct and highly enantioselective reaction of N-azidoacetyl-1,3-thiazolidine-2-thione with trimethyl orthoformate catalyzed by Tol-BINAPNiCl₂ in the presence of TESOTf and 2,6-lutidine is reported. The heterocyclic scaffold can be easily removed by addition of a wide array of amines to give the corresponding enantiomerically pure 2-azido-3,3-dimethoxypropanamides in high yields. Appropriate manipulation of the N-benzyl amide derivative provides an efficient access to the antiepileptic agent lacosamide through a new enantioselective C−C bond-forming process. DFT computational studies uncover clues for the understanding of the remarkable stereocontrol of the addition of a nickel(II) enolate to a putative oxocarbenium intermediate from trimethyl orthoformate.     

15N NMR spectroscopy 24—chemical shifts and coupling constants of α-amino acid N-carboxyanhydrides and related heterocycles

The chemical shifts of amino acid N-carboxyanhydrides (NCAs) and cyclic or linear urethanes are less sensitive to solvent effects than those of amides and lactams. The values of the one-bond ¹⁵N? ¹H coupling constants depend on the solvent and are 5-8 Hz larger than those of ureas and amides. The ¹⁵N? ¹³C coupling constant of the N? CO group is also unusually high, while that of the N—CH group lies within the range known for N-acylated aliphatic amines. The one-bond ¹⁵N? ¹³C coupling constant was found to be insensitive to conformational changes.     

Synthesis and Structural Characterization of Divalent Transition Metal Alkynylamidinate Complexes

A series of new alkynylamidinate complexes of selected first and second row transition metals has been synthesized and fully characterized. Treatment of MCl₂ precursors (M=Mn, Fe, Co) with 2 equiv. of the lithium alkynylamidinates Li[c-C₃H₅−C≡C−C(NR′)₂] ⋅ THF (R′=ⁱPr (2), Cy (cyclohexyl) ( 2 )) afforded a series of binuclear complexes of the type M₂[c-C₃H₅−C≡C−C(NR)₂-κN:κN′]₂[c-C₃H₅−C≡C−C(NR)₂-κ²N,N′]₂ ( 3 : M=Mn, R=Cy; 4 a : M=Fe, R=ⁱPr; 4 b : M=Fe, R=Cy; 5 : M=Co, R=ⁱPr) with no significant metal-metal bonding. In marked contrast, a similar reaction of CrCl₂ with 2 equiv. of 1 afforded the homoleptic dinuclear chromium(II) complex Cr₂[c-C₃H₅−C≡C−C(NⁱPr)₂-κN:κN′]₄ ( 6 ) which supposedly comprises a Cr−Cr quadruple bond. Complex 6 could also be prepared in a more rational way and in better yield (61 %) by using dichromium(II) tetraacetate, Cr₂(OAc)₄, as starting material. Related reactions employing dimolybdenum(II) tetraacetate, Mo₂(OAc)₄, and 2 or 3 equiv. of 1 afforded the mixed-ligand paddle wheel-type complexes trans-Mo₂(OAc-κO:κO′)₂([c-C₃H₅−C≡C−C(NⁱPr)₂-κN:κN′]₂ ( 7 ) and Mo₂(OAc-κO:κO′)([c-C₃H₅−C≡C−C(NⁱPr)₂-κN:κN′]₃ ( 8 ). All title compounds were structurally characterized through single-crystal X-ray diffraction and spectroscopic techniques (NMR, IR, Raman).     

Versatile Para-Substituted Pyridine Lanthanide Coordination Complexes Allow Late Stage Tailoring of Complex Function

A series of cationic and neutral p−Br and p−NO₂ pyridine substituted Eu(III) and Gd(III) coordination complexes serve as versatile synthetic intermediates. Nucleophilic aromatic substitution occurs readily at the para position under mild conditions, allowing C−N and C−C bond forming reactions to take place, permitting the introduction of azide, amino and alkynyl substituents. For Eu(III) complexes, this approach allows late stage tuning of absorption and emission spectral properties, exemplified by the lowering of the energy of an LMCT transition accompanied by a reduction in the Eu−N_py bond length. Additionally, these complexes provide direct access to the corresponding Eu(II) analogues. With the Gd(III) series, the nature of the p-substituent does not significantly change the EPR properties (linewidth, relaxation times), as required for their development as EPR spin probes that can be readily conjugated to biomolecules under mild conditions.     

A simple one pot synthesis of condensed 1,2,4‐triazines by using the tandem aN‐SNipso and SNH‐SNipsa reactions

A new synthetic approach to condensed 1,2,4‐triazines based on using the tandem A_N‐S_N^ipso and S_N^H‐S_N^ipso reactions has been developed. 5‐Methoxy‐3‐penyl‐1,2,4‐triazine and its N₁‐methyl quaternary salt were found to react with C,N‐, C,O‐ and N,N'‐bifunctional nucleophiles (m‐phenylenediamine, resor‐cinol, semicarbazide and ureas) into triazacarbazoles, benzofuro[2,3‐e][1,2,4]‐triazines, and 6‐azapurine derivatives. In all cases nucleophiles attack first the unsubstituted C‐6 carbon of the triazine ring, while the final stage is replacement of the methoxy group affording cyclization products.     

Co-Catalyzed Metal-Ligand Cooperative Approach for N-alkylation of Amines and Synthesis of Quinolines via Dehydrogenative Alcohol Functionalization

Herein we report a cobalt-catalyzed sustainable approach for C−N cross-coupling reaction between amines and alcohols. Using a well-defined Co-catalyst 1 a bearing 2-(phenyldiazenyl)-1,10-phenanthroline ligand, various N-alkylated amines were synthesized in good yields. 1 a efficiently alkylates diamines producing N, N′-dialkylated amines in good yields and showed excellent chemoselectivity when oleyl alcohol and β-citronellol, containing internal carbon-carbon double bond were used as alkylating agents. 1 a is equally compatible with synthesizing N-heterocycles via dehydrogenative coupling of amines and alcohols. 1H-Indole was synthesized via an intramolecular dehydrogenative N-alkylation reaction, and various substituted quinolines were synthesized by coupling of 2-aminobenzyl alcohol and secondary alcohols. A few control reactions and spectroscopic experiments were conducted to illuminate the plausible reaction mechanism, indicating that the 1 a -catalyzed N-alkylation proceeds through the borrowing hydrogen pathway. The coordinated arylazo ligand participates actively throughout the reaction; the hydrogen eliminated during dehydrogenation of alcohols was set aside in the ligand backbone and subsequently gets transferred in the reductive amination step to imine intermediates yielding N-alkylated amines. On the other hand, 1 a -catalyzed quinoline synthesis proceeds through dehydrogenation followed by successive C−C and C−N coupling steps forming H₂O₂ as a by-product under air.     

Bonding Energetics of Palladium Amido/Aryloxide Complexes in DMSO: Implications for Palladium-Mediated Aniline Activation

Thermodynamic knowledge of the metal–ligand (M−L) σ-bond strength is crucial to understanding metal-mediated transformations. Here, we developed a method for determining the Pd−X (X=OR and NHAr) bond heterolysis energies (ΔG_het(Pd−X)) in DMSO taking [(tmeda)PdArX] (tmeda=N,N,N′,N′-tetramethylethylenediamine) as the model complexes. The ΔG_het(Pd−X) scales span a range of 2.6–9.0 kcal mol⁻¹ for ΔG_het(Pd−O) values and of 14.5–19.5 kcal mol⁻¹ for ΔG_het(Pd−N) values, respectively, implying a facile heterolytic detachment of the Pd ligands. Structure-reactivity analyses of a modeling Pd-mediated X−H bond activation reveal that the M−X bond metathesis is dominated by differences of the X−H and Pd−X bond strengths, the former being more influential. The ΔG_het(Pd−X) and pK_a(X−H) parameters enable regulation of reaction thermodynamics and chemoselectivity and diagnosing the probability of aniline activation with Pd−X complexes.     

The Unprecedented [S4N2O10]2− Anion in the Molecular Gold Complexes [Au2Br2(S4N2O10)2] and [Au2Cl2(S4N2O10)2](S2O5Cl2)

The reaction of hexachlorophosphazene, P₃N₃Cl₆, with SO₃ and the gold halides AuCl₃ and AuBr₃, respectively, leads to the new cyclic anionic tetramer, [S₄N₂O₁₀]²⁻, which is coordinated to Au³⁺ in the dimeric complexes [Au₂X₂(S₄N₂O₁₀)₂] (X=Cl, Br). The [S₄N₂O₁₀]²⁻ anion can be seen as the condensation product of two sulfate anions, [SO₄]²⁻_, and two amidosulfate anions, [NH₂SO₃]⁻.