Solvent Effects and Mechanistic Studies for Re2O7-Catalyzed Allylative Annulation Reactions

<div> <div> <div> This article reviews prior work studying reaction kinetics in solution, with the goal of using this information to improve detailed kinetic modeling in the solvent phase. Both experimental and computational methods for calculating reaction rates in liquids are reviewed. Previous studies, which used such methods to determine solvent effects, are then analyzed based on reaction family. Many of these studies correlate kinetic solvent effect with one or more solvent parameters or properties of reacting species, but it is not always possible, and investigations are usually done on too few reactions and solvents to truly generalize. From these studies, we present suggestions on how best to use data to generalize solvent effects for many different reaction types in a high throughput manner. </div> </div> </div>

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Bringing Biocatalysis into the Deuteration Toolbox

10.26434/chemrxiv.7982864 ◽

2019 ◽

Cited By ~ 1

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

Chemicals labelled with the heavy hydrogen isotope deuterium (2H) 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 2H 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 2H2O (D2O) 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 2H-labelling techniques due to requirements for suitable deuterated reducing equivalents. By facilitating transfer of deuterium atoms from 2H2O solvent to NAD+, with H2 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.

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

10.26434/chemrxiv.7355069 ◽

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 SmI2in 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-exo-trig ketyl olefin cyclization reactions.

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