Synthesis of Benzofuropyridines and Dibenzofurans by a Metalation/Negishi Cross-Coupling/S_NAr Reaction Sequence

An efficient methodology for the synthesis of benzofuropyridines and dibenzofurans from fluoropyridines or fluoroarenes and 2-bromophenyl acetates is reported. This streamlined one-pot procedure consists of a four-step directed ortho-lithiation, zincation, Negishi cross-coupling, and intramolecular nucleophilic aromatic substitution, allowing for the facile assembly of a diverse set of fused benzofuro heterocycles

Generation and Ring Opening of Aziridines in Telescoped Continuous Flow Processes

A simple method for the preparation of a variety of <i>N</i>-sulfonyl aziridines (10 examples) from 1,2-amino alcohols under continuous flow conditions is described. Using flow based methods, the aziridines can be further ring opened with oxygen, carbon, and halide nucleophiles or ring expanded to imidazolines by Lewis acid promoted reaction with nitriles. Telescoping the aziridine generation and ring opening steps together in a microfluidic reactor allows the chemistry to be undertaken with limited exposure to the potentially hazardous aziridine intermediates

Generation and Ring Opening of Aziridines in Telescoped Continuous Flow Processes

A simple method for the preparation of a variety of <i>N</i>-sulfonyl aziridines (10 examples) from 1,2-amino alcohols under continuous flow conditions is described. Using flow based methods, the aziridines can be further ring opened with oxygen, carbon, and halide nucleophiles or ring expanded to imidazolines by Lewis acid promoted reaction with nitriles. Telescoping the aziridine generation and ring opening steps together in a microfluidic reactor allows the chemistry to be undertaken with limited exposure to the potentially hazardous aziridine intermediates

Relieving Steric Strain at Octahedral Platinum(IV): Isomerization and Reductive Coupling of Alkyl and Aryl Chlorides

Oxidation of monocyclometalated platinum­(II) complexes results in octahedral platinum­(IV) complexes. Depending on the substitution, two different reactions occur: either a simple isomerization, resulting in the exchange of ligand positions, or a reductive coupling of aryl chloride. With a doubly cyclometalated complex, stability of the oxidized form is dependent on isomeric form: whereas the <i>trans</i> isomer is robust, being manipulable in air at room temperature, the <i>cis</i> isomer decomposes at −20 °C and above. Reductive coupling at this <i>cis</i> isomer is 100% selective for alkyl chloride over aryl chloride and is suggested to be a concerted process

Relieving Steric Strain at Octahedral Platinum(IV): Isomerization and Reductive Coupling of Alkyl and Aryl Chlorides

Oxidation of monocyclometalated platinum­(II) complexes results in octahedral platinum­(IV) complexes. Depending on the substitution, two different reactions occur: either a simple isomerization, resulting in the exchange of ligand positions, or a reductive coupling of aryl chloride. With a doubly cyclometalated complex, stability of the oxidized form is dependent on isomeric form: whereas the <i>trans</i> isomer is robust, being manipulable in air at room temperature, the <i>cis</i> isomer decomposes at −20 °C and above. Reductive coupling at this <i>cis</i> isomer is 100% selective for alkyl chloride over aryl chloride and is suggested to be a concerted process

Oxidative Addition of MeI to a Rollover Complex of Platinum(II): Isolation of the Kinetic Product

A pair of new Pt­(II)/Pt­(IV) 2,2′-bipyridine cyclometalated rollover complexes have been synthesized and characterized. [Pt­(bpy-H)­(CH₃)­(PMe₃)] (<b>1</b>), where bpy-H = κ²<i>N</i>,<i>C</i>-2,2′-bipyridine, was obtained from the electron-rich precursor <i>cis</i>-[Pt­(CH₃)₂(DMSO)₂] with a one-pot, two step synthesis; its reactivity has been tested with CH₃I, giving the corresponding Pt­(IV) complex <i>cis</i>-[Pt­(bpy-H)­(CH₃)₂(I)­(PMe₃)] (<b>2</b>), which was fully characterized. Crystals suitable for X-ray analysis were obtained and allowed the determination of the structure of isomer <b>2A</b> which is the product of the <i>trans</i> addition of CH₃I, usually thought of as the <i>kinetic</i> product

Oxidative Addition of MeI to a Rollover Complex of Platinum(II): Isolation of the Kinetic Product

A pair of new Pt­(II)/Pt­(IV) 2,2′-bipyridine cyclometalated rollover complexes have been synthesized and characterized. [Pt­(bpy-H)­(CH₃)­(PMe₃)] (<b>1</b>), where bpy-H = κ²<i>N</i>,<i>C</i>-2,2′-bipyridine, was obtained from the electron-rich precursor <i>cis</i>-[Pt­(CH₃)₂(DMSO)₂] with a one-pot, two step synthesis; its reactivity has been tested with CH₃I, giving the corresponding Pt­(IV) complex <i>cis</i>-[Pt­(bpy-H)­(CH₃)₂(I)­(PMe₃)] (<b>2</b>), which was fully characterized. Crystals suitable for X-ray analysis were obtained and allowed the determination of the structure of isomer <b>2A</b> which is the product of the <i>trans</i> addition of CH₃I, usually thought of as the <i>kinetic</i> product

Direct Formation of Tethered Ru(II) Catalysts Using Arene Exchange

An ‘arene exchange’ approach has been successfully applied for the first time to the synthesis of Ru(II)-based ‘tethered’ reduction catalysts directly from their ligands in one step. This provides an alternative method for the formation of known complexes, and a route to a series of novel complexes. The novel complexes are highly active in both asymmetric transfer and pressure hydrogenation of ketones

Direct Formation of Tethered Ru(II) Catalysts Using Arene Exchange

An ‘arene exchange’ approach has been successfully applied for the first time to the synthesis of Ru(II)-based ‘tethered’ reduction catalysts directly from their ligands in one step. This provides an alternative method for the formation of known complexes, and a route to a series of novel complexes. The novel complexes are highly active in both asymmetric transfer and pressure hydrogenation of ketones

Potent Half-Sandwich Iridium(III) Anticancer Complexes Containing C^∧N‑Chelated and Pyridine Ligands

We report the synthesis and characterization of eight half-sandwich cyclopentadienyl Ir^III pyridine complexes of the type [(η⁵-Cp^xph)­Ir­(phpy)­Z]­PF₆, in which Cp^xph = C₅Me₄C₆H₅ (tetramethyl­(phenyl)­cyclopentadienyl), phpy = 2-phenylpyridine as C^∧N-chelating ligand, and Z = pyridine (py) or a pyridine derivative. Three X-ray crystal structures have been determined. The monodentate py ligands blocked hydrolysis; however, antiproliferative studies showed that all the Ir compounds are highly active toward A2780, A549, and MCF-7 human cancer cells. In general the introduction of an electron-donating group (e.g., Me, NMe₂) at specific positions on the pyridine ring resulted in increased antiproliferative activity, whereas electron-withdrawing groups (e.g., COMe, COOMe, CONEt₂) decreased anticancer activity. Complex <b>5</b> displayed the highest anticancer activity, exhibiting submicromolar potency toward a range of cancer cell lines in the National Cancer Institute NCI-60 screen, ca. 5 times more potent than the clinical platinum­(II) drug cisplatin. DNA binding appears not to be the major mechanism of action. Although complexes [(η⁵-Cp^xph)­Ir­(phpy)­(py)]⁺ (<b>1</b>) and [(η⁵-Cp^xph)­Ir­(phpy)­(4-NMe₂-py)]⁺ (<b>5</b>) did not cause cell apoptosis or cell cycle arrest after 24 h drug exposure in A2780 human ovarian cancer cells at IC₅₀ concentrations, they increased the level of reactive oxygen species (ROS) dramatically and led to a loss of mitochondrial membrane potential (ΔΨm), which appears to contribute to the anticancer activity. This class of organometallic Ir complexes has unusual features worthy of further exploration in the design of novel anticancer drugs