Synthetic and Mechanistic Studies of the Cycloisomerization and Cyclization/Hydrosilylation of Functionalized Dienes Catalyzed by Cationic Palladium(II) Complexes

2002 ◽  
Vol 35 (10) ◽  
pp. 905-913 ◽  
Author(s):  
Ross A. Widenhoefer
Keyword(s):  
Mechanistic Studies ◽  
Cationic Palladium

Temporal and mechanistic studies on the resistance of glioma cells to temozolomide

2016 ◽  
Vol 228 (06/07) ◽  
Author(s):  
WP Roos ◽  
M Eich ◽  
S Quiros ◽  
AV Knizhnik ◽  
T Nikolova ◽  
...  
Keyword(s):  
Glioma Cells ◽  
Mechanistic Studies

Bringing Biocatalysis into the Deuteration Toolbox

2019 ◽  
Author(s):  
Jack Rowbotham ◽  
Oliver Lenz ◽  
Holly Reeve ◽  
Kylie Vincent
Keyword(s):  
Late Stage ◽  
Hydrogen Isotope ◽  
Reductive Amination ◽  
Mechanistic Studies ◽  
Ambient Conditions ◽  
Synthetic Pathway ◽  
Drug Candidates ◽  
Isotopic Selectivity ◽  
Reducing Equivalents

<p></p><p>Chemicals labelled with the heavy hydrogen isotope deuterium (<sup>2</sup>H) have long been used in chemical and biochemical mechanistic studies, spectroscopy, and as analytical tracers. More recently, demonstration of selectively deuterated drug candidates that exhibit advantageous pharmacological traits has spurred innovations in metal-catalysed <sup>2</sup>H insertion at targeted sites, but asymmetric deuteration remains a key challenge. Here we demonstrate an easy-to-implement biocatalytic deuteration strategy, achieving high chemo-, enantio- and isotopic selectivity, requiring only <sup>2</sup>H<sub>2</sub>O (D<sub>2</sub>O) and unlabelled dihydrogen under ambient conditions. The vast library of enzymes established for NADH-dependent C=O, C=C, and C=N bond reductions have yet to appear in the toolbox of commonly employed <sup>2</sup>H-labelling techniques due to requirements for suitable deuterated reducing equivalents. By facilitating transfer of deuterium atoms from <sup>2</sup>H<sub>2</sub>O solvent to NAD<sup>+</sup>, with H<sub>2</sub> gas as a clean reductant, we open up biocatalysis for asymmetric reductive deuteration as part of a synthetic pathway or in late stage functionalisation. We demonstrate enantioselective deuteration via ketone and alkene reductions and reductive amination, as well as exquisite chemo-control for deuteration of compounds with multiple unsaturated sites.</p><p></p>

Mechanistic Study and Development of Catalytic Reactions of Sm(II)

2018 ◽  
Author(s):  
Sandepan Maity ◽  
Robert Flowers
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Proton Donor ◽  
Catalytic Reactions ◽  
Mechanistic Study ◽  
Mechanistic Studies ◽  
Cyclization Reactions ◽  
Mechanistic Approach ◽  
Donor Source

Despite the broad utility and application of SmI<sub>2</sub>in synthesis, the reagent is used in stoichiometric amounts and has a high molecular weight, resulting in a large amount of material being used for reactions requiring one or more equivalents of electrons. We report mechanistic studies on catalytic reactions of Sm(II) employing a terminal magnesium reductant and trimethyl silyl chloride in concert with a non-coordinating proton donor source. Reactions using this approach permitted reductions with as little as 1 mol% Sm. The mechanistic approach enabled catalysis employing HMPA as a ligand, facilitating the development of catalytic Sm(II) 5-<i>exo</i>-<i>trig </i>ketyl olefin cyclization reactions.

Synthetic and Mechanistic Studies of a Versatile Heteroaryl Thioether Directing Group for Pd(II) Catalysis

2019 ◽  
Author(s):  
Andrew Romine ◽  
Kin Yang ◽  
Malkanthi Karunananda ◽  
Jason Chen ◽  
Keary Engle
Keyword(s):  
Mechanistic Studies ◽  
Salvianolic Acid ◽  
Wide Range ◽  
Computational Data ◽  
Synthetic Utility ◽  
Directing Group ◽  
High Yields ◽  
Julia Olefination ◽  
Reaction Progress Kinetic Analysis

A weakly coordinating monodentate heteroaryl thioether directing group has been developed for use in Pd(II) catalysis to orchestrate key elementary steps in the catalytic cycle that require conformational flexibility in a manner that is difficult to accomplish with traditional strongly coordinating directing groups. This benzothiazole thioether, (BT)S, directing group can be used to promote oxidative Heck reactivity of internal alkenes providing a wide range of products in moderate to high yields. To demonstrate the broad applicability of this directing group, arene C–H olefination was also successfully developed. Reaction progress kinetic analysis provides insights into the role of the directing group in each reaction, which is supplemented with computational data for the oxidative Heck reaction. Furthermore, this (BT)S directing group can be transformed into a number of synthetically useful functional groups, including a sulfone for Julia olefination, allowing it to serve as a “masked olefin” directing group in synthetic planning. In order to demonstrate this synthetic utility, natural products (+)-salvianolic acid A and salvianolic acid F are formally synthesized using the (BT)S directed C–H olefination as the key step.

Iridium-Catalyzed Silylation of C-H bonds in Unactivated Arenes: A Sterically-Encumbered Phenanthroline Ligand Accelerates Catalysis Enabling New Reactivity

2019 ◽  
Author(s):  
Caleb Karmel ◽  
Zhewei Chen ◽  
John Hartwig
Keyword(s):  
High Activity ◽  
Functional Group ◽  
Activity Analysis ◽  
High Reactivity ◽  
High Yield ◽  
Phen Ligand ◽  
Mechanistic Studies ◽  
Phenanthroline Ligand ◽  
First Time ◽  
New System

We report a new system for the silylation of aryl C-H bonds. The combination of [Ir(cod)(OMe)]<sub>2</sub> and 2,9-Me<sub>2</sub>-phenanthroline (2,9-Me<sub>2</sub>phen) catalyzes the silylation of arenes at lower temperatures and with faster rates than those reported previously, when the hydrogen byproduct is removed, and with high functional group tolerance and regioselectivity. Inhibition of reactions by the H<sub>2</sub> byproduct is shown to limit the silylation of aryl C-H bonds in the presence of the most active catalysts, thereby masking their high activity. Analysis of initial rates uncovered the high reactivity of the catalyst containing the sterically hindered 2,9-Me<sub>2</sub>phen ligand but accompanying rapid inhibition by hydrogen. With this catalyst, under a flow of nitrogen to remove hydrogen, electron-rich arenes, including those containing sensitive functional groups, undergo silylation in high yield for the first time, and arenes that underwent silylation with prior catalysts react over much shorter times with lower catalyst loadings. The synthetic value of this methodology is demonstrated by the preparation of key intermediates in the synthesis of medicinally important compounds in concise sequences comprising silylation and functionalization. Mechanistic studies demonstrate that the cleavage of the aryl C-H bond is reversible and that the higher rates observed with the 2,9-Me<sub>2</sub>phen ligand is due to a more thermodynamically favorable oxidative addition of aryl C-H bonds.

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