Lewis Acid Induced Anomerization of <i>Se</i>-Glycosides. Application to Synthesis of α-<i>Se</i>-GalCer

The TiCl₄ induced anomerization of selenium glycosides of galacturonic acid derivatives is reported. The reaction was successful for galacturonic acid when various alkyl, alkenyl, alkynyl, saccharide, steroid, and lipid groups were attached to the anomeric Se atom. An increased amount of TiCl₄ and/or higher temperature were needed to ensure completion of the reaction in some cases. Yields were higher for reactions carried out at higher dilution. The reaction was applied to the synthesis of Se-based mimics of the potent immunostimulant α-GalCer (KRN7000)

Cesium Reduction of a Lithium Diamidochloroberyllate

Room temperature reaction of elemental cesium with the dimeric lithium chloroberyllate [{SiNDipp}BeClLi]2 [{SiNDipp} = {CH2SiMe2N(Dipp)}2, where Dipp = 2,6-di-isopropylphenyl, in C6D6 results in activation of the arene solvent. Although, in contrast to earlier observations of lithium and sodium metal reduction, the generation of a mooted cesium phenylberyllate could not be confirmed, this process corroborates a previous hypothesis that such beryllium-centered solvent activation also necessitates the formation of hydridoberyllium species. These observations are further borne out by the study of an analogous reaction performed in toluene, in which case the proposed generation of formally low oxidation state beryllium radical anion intermediates induces activation of a toluene sp3 C–H bond and the isolation of the polymeric cesium benzylberyllate, [Cs({SiNDipp}BeCH2C6H5)]∞

Lewis Acid Induced Anomerization of <i>Se</i>-Glycosides. Application to Synthesis of α-<i>Se</i>-GalCer

The TiCl₄ induced anomerization of selenium glycosides of galacturonic acid derivatives is reported. The reaction was successful for galacturonic acid when various alkyl, alkenyl, alkynyl, saccharide, steroid, and lipid groups were attached to the anomeric Se atom. An increased amount of TiCl₄ and/or higher temperature were needed to ensure completion of the reaction in some cases. Yields were higher for reactions carried out at higher dilution. The reaction was applied to the synthesis of Se-based mimics of the potent immunostimulant α-GalCer (KRN7000)

Lewis Acid Induced Anomerization of <i>Se</i>-Glycosides. Application to Synthesis of α-<i>Se</i>-GalCer

The TiCl₄ induced anomerization of selenium glycosides of galacturonic acid derivatives is reported. The reaction was successful for galacturonic acid when various alkyl, alkenyl, alkynyl, saccharide, steroid, and lipid groups were attached to the anomeric Se atom. An increased amount of TiCl₄ and/or higher temperature were needed to ensure completion of the reaction in some cases. Yields were higher for reactions carried out at higher dilution. The reaction was applied to the synthesis of Se-based mimics of the potent immunostimulant α-GalCer (KRN7000)

Use of Sublimation Catalysis and Polycrystalline Powder Templates for Polymorph Control of Gas Phase Crystallization

In pursuit of a solvent-free green alternative to solution-based processes, we have applied the combined use of catalytic additives and polycrystalline powder templates for polymorph control of gas phase crystallization to a range of pharmaceuticals and related compounds. Complementary volatile additives have been found that can catalyze the sublimation of a range of typical active pharmaceutical ingredients (APIs). Sublimation temperatures are typically reduced by up to 20 °C, and the process is accelerated. The use of polycrystalline powder templates for polymorph control has also been successfully applied in several cases. Temperature control at the sites of both sublimation and desublimation is often required. The absence of even traces of solvent in the polymorphs produced appears to give the samples higher stability than samples obtained by crystallization from solution. Complete polymorph control was achieved with the following APIs, carbamazepine (five polymorphs), metaxalone (two polymorphs), mefenamic acid (two polymorphs), paracetamol (two polymorphs), and <i>ortho</i>-, <i>meta</i>-, and <i>para</i>-amino benzoic acids (one, four, and two polymorphs respectively)

A Model System for the Synthesis of Complanadine Alkaloids by “Diverted Kondrat’eva” Oxazole–Olefin Cycloaddition

A synthetic approach to complanadine alkaloids is described which employs a Kondrat’eva reaction to construct the pyridine rings. The viability of this approach is demonstrated by its application to a model substrate accessed from unfunctionalized decalin. The key transformation affords the desired tetracyclic architecture with unprecedented incorporation of substituents on the pyridine ring, implicating the oxazole α-hydroxy group as an active participant in the cycloadduct fragmentation process

Use of Sublimation Catalysis and Polycrystalline Powder Templates for Polymorph Control of Gas Phase Crystallization

In pursuit of a solvent-free green alternative to solution-based processes, we have applied the combined use of catalytic additives and polycrystalline powder templates for polymorph control of gas phase crystallization to a range of pharmaceuticals and related compounds. Complementary volatile additives have been found that can catalyze the sublimation of a range of typical active pharmaceutical ingredients (APIs). Sublimation temperatures are typically reduced by up to 20 °C, and the process is accelerated. The use of polycrystalline powder templates for polymorph control has also been successfully applied in several cases. Temperature control at the sites of both sublimation and desublimation is often required. The absence of even traces of solvent in the polymorphs produced appears to give the samples higher stability than samples obtained by crystallization from solution. Complete polymorph control was achieved with the following APIs, carbamazepine (five polymorphs), metaxalone (two polymorphs), mefenamic acid (two polymorphs), paracetamol (two polymorphs), and <i>ortho</i>-, <i>meta</i>-, and <i>para</i>-amino benzoic acids (one, four, and two polymorphs respectively)

A Simple Protocol for NMR Analysis of the Enantiomeric Purity of Chiral Hydroxylamines

A practically simple three-component chiral derivatization protocol for determining the enantiopurity of chiral hydroxylamines by ¹H NMR spectroscopic analysis is described, involving their treatment with 2-formylphenylboronic acid and enantiopure BINOL to afford a mixture of diastereomeric nitrono-boronate esters whose ratio is an accurate reflection of the enantiopurity of the parent hydroxylamine

A Model System for the Synthesis of Complanadine Alkaloids by “Diverted Kondrat’eva” Oxazole–Olefin Cycloaddition

A synthetic approach to complanadine alkaloids is described which employs a Kondrat’eva reaction to construct the pyridine rings. The viability of this approach is demonstrated by its application to a model substrate accessed from unfunctionalized decalin. The key transformation affords the desired tetracyclic architecture with unprecedented incorporation of substituents on the pyridine ring, implicating the oxazole α-hydroxy group as an active participant in the cycloadduct fragmentation process

Stereoelectronic Effects in C–H Bond Oxidation Reactions of Ni(I) N‑Heterocyclic Carbene Complexes

Activation of O₂ by the three-coordinate Ni­(I) ring-expanded N-heterocyclic carbene complexes Ni­(RE-NHC)­(PPh₃)Br (RE-NHC = 6-Mes, <b>1</b>; 7-Mes, <b>2</b>) produced the structurally characterized dimeric Ni­(II) complexes Ni­(6-Mes)­(Br)­(μ-OH)­(μ-O-6-Mes′)­NiBr (<b>3</b>) and Ni­(7-Mes)­(Br)­(μ-OH)­(μ-O-7-Mes′)­NiBr (<b>4</b>) containing oxidized <i>ortho</i>-mesityl groups from one of the carbene ligands. NMR and mass spectrometry provided evidence for further oxidation in solution to afford bis-μ-aryloxy compounds; the 6-Mes derivative was isolated, and its structure was verified. Low-temperature UV–visible spectroscopy showed that the reaction between <b>1</b> and O₂ was too fast even at ca. −80 °C to yield any observable intermediates and also supported the formation of more than one oxidation product. Addition of O₂ to Ni­(I) precursors containing a less electron-donating diamidocarbene (6-MesDAC, <b>7</b>) or less bulky 6- or 7-membered ring diaminocarbene ligands (6- or 7-<i>o</i>-Tol; <b>8</b> and <b>9</b>) proceeded quite differently, affording phosphine and carbene oxidation products (Ni­(OPPh₃)₂Br₂ and (6-MesDAC)O) and the mononuclear Ni­(II) dibromide complexes (Ni­(6-<i>o</i>-Tol)­(PPh₃)­Br₂ (<b>10</b>) and (Ni­(7-<i>o</i>-Tol)­(PPh₃)­Br₂ (<b>11</b>)) respectively. Electrochemical measurements on the five Ni­(I) precursors show significantly higher redox potentials for <b>1</b> and <b>2</b>, the complexes that undergo oxygen atom transfer from O₂