Reaction of Boranephosphonate Diesters with Pyridines or Tertiary Amines in the Presence of Iodine: Synthetic and Mechanistic Studies

2020 ◽  
Vol 85 (6) ◽  
pp. 4312-4323 ◽  
Author(s):  
Justyna Gołębiewska ◽  
Jacek Stawinski
Keyword(s):  
Tertiary Amines ◽  
Mechanistic Studies

scholarly journals Cobalt Hydride Oxidase Catalysis Enabled Hydroamination of Unactivated Olefins

2021 ◽  
Author(s):  
Wei-Ting Ye ◽  
Rong Zhu
Keyword(s):  
Building Blocks ◽  
Single Step ◽  
Tertiary Amines ◽  
Mechanistic Studies ◽  
Organic Transformations ◽  
Design Elements ◽  
Alkyl Radicals ◽  
Solvent Free Conditions ◽  
Oxidative Processes ◽  
Nitrogen Nucleophiles

Dioxygen is an abundant, selective, and sustainable oxidant that is considered ideal for organic transformations. Oxidative processes using dioxygen as the electron acceptor without oxygen atom incorporation into the substrate are often referred to as oxidase reactions. However, the ground state triplet nature of dioxygen makes such a synthetically valuable pathway incompatible with simple free alkyl radicals, a ubiquitous class of reactive intermediates in the daily synthesis of pharmaceuticals, agrochemicals, and complex natural products. Here we report that a combination of strong cage effect and bimetallic radical-polar crossover successfully addresses this problem, and opens up an oxidase pathway in cobalt hydride catalysis. This leads to a general and chemoselective method that tackles several key challenges in catalytic hydroamination, a fundamental transformation for amine synthesis. Under balloon pressure of dioxygen at ambient temperature, we demonstrate single-step intra- and intermolecular formal addition of a variety of nitrogen nucleophiles, including free amines, sulfonamides, amides, and carbamates, to unactivated alkenes in the presence of a silane, under solvent-free conditions. Important medicinal chemistry building blocks such as a-branched tertiary amines can be easily accessed, which are often difficult targets otherwise due to their steric hindrance and reducing nature. Mechanistic studies including stoichiometric experiments with well-defined organocobalt complexes provide support for the key hypothesis, which points the way to the development of sustainable processes involving other nucleophiles based on the same design elements.

scholarly journals Photoenzymatic Synthesis of 𝜶-Tertiary Amines By Engineered Flavin-Dependent ‘Ene’-Reductases

2021 ◽  
Author(s):  
Xin Gao ◽  
Joshua Turek-Herman ◽  
Young Joo Choi ◽  
Ryan Cohen ◽  
Todd Hyster
Keyword(s):  
Asymmetric Catalysis ◽  
Tertiary Amines ◽  
Mechanistic Studies ◽  
Common Motif ◽  
Ct Complex

𝛼-tertiary amines are a common motif in pharmaceutically important molecules but are challenging to prepare using asymmetric catalysis. Here, we demonstrate engineered flavin-dependent ‘ene’-reductases (EREDs) can catalyze radical additions into oximes to prepare this motif. Two different EREDs were evolved into competent catalysts for this transformation with high levels of stereoselectivity. Mechanistic studies indicate that the oxime contributes to the enzyme templated CT-complex formed between the substrate and cofactor. These products can be further deri-vatized to prepare a variety of motifs, highlighting the ver-satility of ERED photoenzymatic catalysis for organic syn-thesis.

scholarly journals Visible-light-mediated α-phosphorylation of N-aryl tertiary amines through the formation of electron-donor–acceptor complexes: synthetic and mechanistic studies

2019 ◽  
Vol 6 (1) ◽  
pp. 41-44 ◽  
Author(s):  
Valentin Quint ◽  
Nourhène Chouchène ◽  
Moheddine Askri ◽  
Jacques Lalevée ◽  
Annie-Claude Gaumont ◽  
...  
Keyword(s):  
Visible Light ◽  
Electron Donor ◽  
Secondary Phosphine ◽  
Phosphine Oxides ◽  
Tertiary Amines ◽  
Mechanistic Studies ◽  
Donor Acceptor

A visible light-mediated photocatalyst-free approach for the oxidative α-CH functionalization of N-aryl tertiary amines with secondary phosphine oxides has been developed.

scholarly journals Cobalt Hydride Oxidase Catalysis Enabled Hydroamination of Unactivated Olefins

2021 ◽  
Author(s):  
Wei-Ting Ye ◽  
Rong Zhu
Keyword(s):  
Building Blocks ◽  
Single Step ◽  
Tertiary Amines ◽  
Mechanistic Studies ◽  
Organic Transformations ◽  
Design Elements ◽  
Alkyl Radicals ◽  
Solvent Free Conditions ◽  
Oxidative Processes ◽  
Nitrogen Nucleophiles

Dioxygen is an abundant, selective, and sustainable oxidant that is considered ideal for organic transformations. Oxidative processes using dioxygen as the electron acceptor without oxygen atom incorporation into the substrate are often referred to as oxidase reactions. However, the ground state triplet nature of dioxygen makes such a synthetically valuable pathway incompatible with simple free alkyl radicals, a ubiquitous class of reactive intermediates in the daily synthesis of pharmaceuticals, agrochemicals, and complex natural products. Here we report that a combination of strong cage effect and bimetallic radical-polar crossover successfully addresses this problem, and opens up an oxidase pathway in cobalt hydride catalysis. This leads to a general and chemoselective method that tackles several key challenges in catalytic hydroamination, a fundamental transformation for amine synthesis. Under balloon pressure of dioxygen at ambient temperature, we demonstrate single-step intra- and intermolecular formal addition of a variety of nitrogen nucleophiles, including free amines, sulfonamides, amides, and carbamates, to unactivated alkenes in the presence of a silane, under solvent-free conditions. Important medicinal chemistry building blocks such as a-branched tertiary amines can be easily accessed, which are often difficult targets otherwise due to their steric hindrance and reducing nature. Mechanistic studies including stoichiometric experiments with well-defined organocobalt complexes provide support for the key hypothesis, which points the way to the development of sustainable processes involving other nucleophiles based on the same design elements.

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.

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