Stereoselective Approach to Multisubstituted Enolates from Unactivated Alkynes: Oxyalkylidenation of Alkynyl Ketone Enolates with Aldehydes

The preparation of multisubstituted enolates with precise regio- and stereocontrol is a nontrivial task when conventional deprotonation methods are used on the corresponding carbonyl compounds. We describe herein an approach to preparing stereodefined enolates by leveraging the stereoselective oxyfunctionalization of unactivated alkynes, particularly in the context of the alkynylogous aldol reaction. trans-Iodo(III)acetoxylation of alkynes and subsequent Sonogashira coupling allow for the facile preparation of multisubstituted enynyl acetates, which can be deacetylated by MeLi into the corresponding enolates. The alkynyl enolates react with aldehydes to afford γ,δ-unsaturated β-diketones through a cascade of alkynylogous aldol addition, intramolecular Michael addition, and ring opening of the oxetene intermediate

Synthesis and Reactivity of Methylpalladium Complexes Bearing a Partially Saturated IzQO Ligand

A saturated N-heterocyclic carbene–phenolate bidentate ligand, 3,3a,4,5-tetrahydroimidazo­[1,5-<i>a</i>]­quinolin-9-olate-1-ylidene (SIzQO), was synthesized and characterized. The SIzQO ligand was then treated with PdClMe­(pyridine)₂ and [Pd­(μ-Cl)­Me­(2,6-lutidine)]₂, which afforded <i>C</i>,<i>C</i>-<i>cis</i>-(SIzQO)­PdMe­(pyridine) and the thermodynamically unstable <i>trans</i> isomer <i>C</i>,<i>C</i>-<i>trans</i>-(SIzQO)­PdMe­(2,6-lutidine), respectively. The latter isomerizes at 40 °C into the corresponding <i>cis</i> isomer via a dissociative mechanism. These palladium/SIzQO complexes catalyze the polymerization of ethylene at 100–120 °C, although the catalytic activity is lower than that of a previously reported palladium/imidazo­[1,5-<i>a</i>]­quinolin-9-olate-1-ylidene (IzQO) system

Palladium/IzQO-Catalyzed Coordination–Insertion Copolymerization of Ethylene and 1,1-Disubstituted Ethylenes Bearing a Polar Functional Group

Coordination–insertion copolymerization of ethylene with 1,1-disubstituted ethylenes bearing a polar functional group, such as methyl methacrylate (MMA), is a long-standing challenge in catalytic polymerization. The major obstacle for this process is the huge difference in reactivity of ethylene versus 1,1-disubstituted ethylenes toward both coordination and insertion. Herein we report the copolymerization of ethylene and 1,1-disubstituted ethylenes by using an imidazo­[1,5-<i>a</i>]­quinolin-9-olate-1-ylidene-supported palladium catalyst. Various types of 1,1-disubstituted ethylenes were successfully incorporated into the polyethylene chain. In-depth characterization of the obtained copolymers and mechanistic inferences drawn from stoichiometric reactions of alkylpalladium complexes with methyl methacrylate and ethylene indicate that the copolymerization proceeds by the same coordination–insertion mechanism that has been postulated for ethylene

Palladium/IzQO-Catalyzed Coordination–Insertion Copolymerization of Ethylene and 1,1-Disubstituted Ethylenes Bearing a Polar Functional Group

Coordination–insertion copolymerization of ethylene with 1,1-disubstituted ethylenes bearing a polar functional group, such as methyl methacrylate (MMA), is a long-standing challenge in catalytic polymerization. The major obstacle for this process is the huge difference in reactivity of ethylene versus 1,1-disubstituted ethylenes toward both coordination and insertion. Herein we report the copolymerization of ethylene and 1,1-disubstituted ethylenes by using an imidazo­[1,5-<i>a</i>]­quinolin-9-olate-1-ylidene-supported palladium catalyst. Various types of 1,1-disubstituted ethylenes were successfully incorporated into the polyethylene chain. In-depth characterization of the obtained copolymers and mechanistic inferences drawn from stoichiometric reactions of alkylpalladium complexes with methyl methacrylate and ethylene indicate that the copolymerization proceeds by the same coordination–insertion mechanism that has been postulated for ethylene

Formal Aryne/Carbon Monoxide Copolymerization To Form Aromatic Polyketones/Polyketals

A palladium-catalyzed alternating copolymerization of [2.2.1]­oxabicyclic alkenes <b>1</b> with carbon monoxide afforded isomer mixtures of polyketones <b>2</b>_<b>ktn</b> and polyketals <b>2</b>_<b>ktl</b>. Subsequent acid-induced dehydration of polymer <b>2</b> furnished novel aromatic polymers consisting of polyketones <b>3</b>_<b>ktn</b> and polyketals <b>3</b>_<b>ktl</b> units. This formal aryne/carbon monoxide copolymerization thus generated the first example of poly­(aryne-<i>alt</i>-carbon monoxide)­s, in which <i>o</i>-arylene and carbonyl units are incorporated in an alternating fashion

Synthesis and Reactivity of Methylpalladium Complexes Bearing a Partially Saturated IzQO Ligand

A saturated N-heterocyclic carbene–phenolate bidentate ligand, 3,3a,4,5-tetrahydroimidazo­[1,5-<i>a</i>]­quinolin-9-olate-1-ylidene (SIzQO), was synthesized and characterized. The SIzQO ligand was then treated with PdClMe­(pyridine)₂ and [Pd­(μ-Cl)­Me­(2,6-lutidine)]₂, which afforded <i>C</i>,<i>C</i>-<i>cis</i>-(SIzQO)­PdMe­(pyridine) and the thermodynamically unstable <i>trans</i> isomer <i>C</i>,<i>C</i>-<i>trans</i>-(SIzQO)­PdMe­(2,6-lutidine), respectively. The latter isomerizes at 40 °C into the corresponding <i>cis</i> isomer via a dissociative mechanism. These palladium/SIzQO complexes catalyze the polymerization of ethylene at 100–120 °C, although the catalytic activity is lower than that of a previously reported palladium/imidazo­[1,5-<i>a</i>]­quinolin-9-olate-1-ylidene (IzQO) system

Combining Genomics To Identify the Pathways of Post-Transcriptional Nongenotoxic Signaling and Energy Homeostasis in Livers of Rats Treated with the Pregnane X Receptor Agonist, Pregnenolone Carbonitrile

Transcriptomic, proteomic, phosphoproteomic, and metabolomic analyses were combined to determine the role of pregnane X receptor (PXR) in nongenotoxic signaling and energy homeostasis in liver after rats were repeatedly orally dosed with the PXR agonist pregnenolone carbonitrile (PCN) for 7 days. Analyses of mRNAs and proteins in the supernatant, membrane, and cytosolic fractions of enlarged liver homogenates showed diverse expression profiles. Gene set enrichment analysis showed that the synchronous increase in mRNAs and proteins involved in chemical carcinogenesis and the response to drug was possibly mediated by the PXR pathway and proteasome core complex assembly was possibly mediated by the Nrf2 pathway. In addition, levels of proteins in the endoplasmic reticulum lumen and involved in the acute-phase response showed specific increase with no change in mRNA level, and those composed of the mitochondrial inner membrane showed specific decrease. The analysis of phosphorylated peptides of poly­(A) RNA binding proteins showed a decrease in phosphorylation, possibly by casein kinase 2, which may be related to the regulation of protein expression. Proteins involved in insulin signaling pathways showed an increase in phosphorylation, possibly by protein kinase A, and those involved in apoptosis showed a decrease. Metabolomic analysis suggested the activation of the pentose phosphate and anaerobic glycolysis pathways and the increase of amino acid and fatty acid levels, as occurs in the Warburg effect. In conclusion, the results of combined analyses suggest that PXR’s effects are due to transcriptional and post-transcriptional regulation with alteration of nongenotoxic signaling pathways and energy homeostasis

Quantification of the Steric Influence of Alkylphosphine–Sulfonate Ligands on Polymerization, Leading to High-Molecular-Weight Copolymers of Ethylene and Polar Monomers

A series of palladium/​​alkylphosphine–​sulfonate catalysts were synthesized and examined in the homopolymerization of ethylene and the copolymerization of ethylene and polar monomers. Catalysts with alkyl­phosphine–​sulfonate ligands containing sterically demanding alkyl substituents afforded (co)­polymers whose molecular weight was increased by up to 2 orders of magnitude relative to polymers obtained from previously reported catalyst systems. The polymer molecular weight was found to be closely correlated to the Sterimol B5 parameter of the alkyl substituents in the alkyl­phosphine–​sulfonate ligands. Thus, the use of bulky alkyl­phosphine–​sulfonate ligands represents an effective and versatile method to prepare high-molecular-weight copolymers of ethylene and various polar monomers, which are difficult to obtain by previously reported methods

Additional file 1 of Factors associated with EMS on-scene time and its regional difference in road traffic injuries: a population-based observational study

Additional file 1

Stereoselective Synthesis of β‑Alkoxy-β-amido Vinylbenziodoxoles via Iodo(III)etherification of Ynamides

A trans-iodo(III)etherification reaction of ynamides with benziodoxole triflate and alcohols is reported. Despite the sensitivity of ynamides and enamides toward Brønsted acid, the reaction could be successfully performed under carefully controlled conditions to afford β-alkoxy-β-amido vinylbenziodoxoles in moderate to good yields. The products could be subjected to a sequence of cross-coupling via C–I(III) bond cleavage and electrophilic halogenation of the resulting α-alkoxyenamides, allowing for the preparation of densely functionalized esters