DDQ-Catalyzed Direct C(sp³)–H Amination of Alkylheteroarenes: Synthesis of Biheteroarenes under Aerobic and Metal-Free Conditions

A strategy for oxidative Csp³–H/N–H cross-coupling is presented. This reaction successfully utilizes 2,3-dichloro-5,6-dicyano-<i>p</i>-benzoquinone (DDQ) and <i>tert</i>-butyl nitrite (TBN) as co-catalysts to construct the biomedical applicable biheteroarenes under aerobic conditions. Notably, this amination reaction is successful with a wide range of alkylheteroarenes and could be used as a functionalization tactic for pharmaceutical research and other areas. Furthermore, preliminary mechanistic studies indicate that the C–N bond formation proceeds through the nucleophilic attack of azole to the carbon cation

Electro-oxidative C(sp3)–H Amination of Azoles via Intermolecular Oxidative C(sp3)–H/N–H Cross-Coupling

A method for electrooxidative C­(sp3)–H amination via intermolecular oxidative C­(sp3)–H/N–H cross-coupling has been developed under metal- and oxidant-free conditions. The C­(sp3)–H bonds adjacent to oxygen, nitrogen, and sulfur atoms could all react smoothly with various amines to give the corresponding products with moderate to good yields (30–93%). In addition, the C­(sp3)–H bonds of benzylic and allylic are also tolerated in this reaction. A preliminary mechanistic study indicates that the C–H cleavage of tetrahydrofuran is probably not involved in the rate-determining step

External Oxidant-Free Dehydrogenative Lactonization of 2‑Arylbenzoic Acids via Visible-Light Photocatalysis

An external oxidant-free C–H functionalization/C–O bond formation reaction for constructing benzo-3,4-coumarins accompanied by quantitative H₂ evolution has been developed. High functional group tolerance and excellent reaction efficiency are shown in this transformation. Meanwhile, the substrates containing heterocyclic substituents such as thienyl-, pyridinyl-, and pyrrolylbenzoic acids displayed good performance. Importantly, this reaction can be performed with good efficiency on a gram scale. A cyclic voltammetry study and density functional theory calculations could provide insight into the mechanism of this reaction

From Ketones, Amines, and Carbon Monoxide to 4‑Quinolones: Palladium-Catalyzed Oxidative Carbonylation

A novel method of palladium-catalyzed oxidative carbonylation of ketones, amines, and carbon monoxide for the synthesis of 4-quinolones has been developed. This protocol provides a straightforward route to construct useful 4-quinolone derivatives from inexpensive chemicals

Anti-Markovnikov Oxidation of β‑Alkyl Styrenes with H₂O as the Terminal Oxidant

Oxygenation of alkenes is one of the most straightforward routes for the construction of carbonyl compounds. Wacker oxidation provides a broadly useful strategy to convert the mineral oil into higher value-added carbonyl chemicals. However, the conventional Wacker chemistry remains problematic, such as the poor activity for internal alkenes, the lack of anti-Markovnikov regioselectivity, and the high cost and chemical waste resulted from noble metal catalysts and stoichiometric oxidant. Here, we describe an unprecedented dehydrogenative oxygenation of β-alkyl styrenes and their derivatives with water under external-oxidant-free conditions by utilizing the synergistic effect of photocatalysis and proton-reduction catalysis that can address these challenges. This dual catalytic system possesses the single anti-Markovnikov selectivity due to the property of the visible-light-induced alkene radical cation intermediate

Spectroscopic and Theoretical Study of Spin-Dependent Electron Transfer in an Iron(III) Superoxo Complex

It was shown previously (<i>J. Am. Chem. Soc.</i> <b>2014</b>, <i>136</i>, 10846) that bubbling of O₂ into a solution of Fe^II(BDPP) (H₂BDPP = 2,6-bis­[[(<i>S</i>)-2-(diphenylhydroxymethyl)-1-pyrrolidinyl]­methyl]­pyridine) in tetrahydrofuran at −80 °C generates a high-spin (<i>S</i>_Fe = ⁵/₂) iron­(III) superoxo adduct, <b>1</b>. Mössbauer studies revealed that <b>1</b> is an exchange-coupled system, Ĥex=JŜFe·ŜR, where <i>S</i>_R = ¹/₂ is the spin of the superoxo radical, of which the spectra were not well enough resolved to determine whether the coupling was ferromagnetic (<i>S</i> = 3 ground state) or antiferromagnetic (<i>S</i> = 2). The glass-forming 2-methyltetrahydrofuran solvent yields highly resolved Mössbauer spectra from which the following data have been extracted: (i) the ground state of <b>1</b> has <i>S</i> = 3 (<i>J</i> < 0); (ii) |<i>J</i>| > 15 cm^–1; (iii) the zero-field-splitting parameters are <i>D</i> = −1.1 cm^–1 and <i>E</i>/<i>D</i> = 0.02; (iv) the major component of the electric-field-gradient tensor is tilted ≈7° relative to the easy axis of magnetization determined by the <i>M</i>_<i>S</i> = ±3 and ±2 doublets. The excited-state <i>M</i>_<i>S</i> = ±2 doublet yields a narrow parallel-mode electron paramagnetic resonance signal at <i>g</i> = 8.03, which was used to probe the magnetic hyperfine splitting of ¹⁷O-enriched O₂. A theoretical model that considers spin-dependent electron transfer for the cases where the doubly occupied π* orbital of the superoxo ligand is either “in” or “out” of the plane defined by the bent Fe–OO moiety correctly predicts that <b>1</b> has an <i>S</i> = 3 ground state, in contrast to the density functional theory calculations for <b>1</b>, which give a ground state with both the wrong spin and orbital configuration. This failure has been traced to a basis set superposition error in the interactions between the superoxo moiety and the adjacent five-membered rings of the BDPP ligand and signals a fundamental problem in the quantum chemistry of O₂ activation

Rhodium-Catalyzed Asymmetric Addition of Arylboronic Acids to β‑Nitroolefins: Formal Synthesis of (<i>S</i>)‑SKF 38393

An efficient enantioselective addition of an array of arylboronic acids to various β-nitrostyrenes catalyzed by a novel and reactive rhodium–diene catalyst (S/C up to 1000) was developed, providing β,β-diarylnitroethanes in good to high yields (62–99%) with excellent enantioselectivities (85–97% ee). The method was extended to 2-heteroarylnitroolefins and 2-alkylnitroolefins similarly providing the desired products with high enantioselectivities and yields. The usefulness of this method was demonstrated in the formal synthesis of the enantiomer of the dopamine receptor agonist and antagonist, SKF 38393

Visible-Light-Induced External Oxidant-Free Oxidative Phosphonylation of C(sp²)–H Bonds

Considering the synthetic value of phosphonates, developing powerful catalytic methods for the phosphonylation of C­(sp²)–H bonds is important. Herein, we achieve a visible-light-induced external oxidant-free oxidative phosphonylation of C­(sp²)–H bonds via the combination of photocatalysis and proton-reduction catalysis. Mechanistic studies indicate that the visible-light-induced electron-rich arene radical cation is the key reactive intermediate. The synthetic application of this approach is demonstrated in the late-stage functionalization of pharmaceutical molecules. This study may have significant implications for the functionalization of C­(sp²)–H bonds, especially for those that are sensitive to oxidative conditions

Characterization of a Paramagnetic Mononuclear Nonheme Iron-Superoxo Complex

O₂ bubbling into a THF solution of Fe^II(BDPP) (<b>1</b>) at −80 °C generates a reversible bright yellow adduct <b>2</b>. Characterization by resonance Raman and Mössbauer spectroscopy provides complementary insights into the nature of <b>2</b>. The former shows a resonance-enhanced vibration at 1125 cm^–1, which can be assigned to the ν­(O–O) of a bound super­oxide, while the latter reveals the presence of a high-spin iron­(III) center that is exchange-coupled to the superoxo ligand, like the Fe^III–O₂^– pair found for the O₂ adduct of 4-nitro­catechol-bound homo­proto­catechuate 2,3-dioxy­genase. Lastly, <b>2</b> oxidizes dihydro­anthracene to anthracene, supporting the notion that Fe^III–O₂^– species can carry out H atom abstraction from a C–H bond to initiate the 4-electron oxidation of substrates proposed for some nonheme iron enzymes