Stepwise Hydrogen Atom and Proton Transfers in Dioxygen Reduction by Aryl-Alcohol Oxidase

<div>We report here a catalytic, Markovnikov selective, and scalable synthetic method for the synthesis of saturated sulfur heterocycles, which are found in the structures of pharmaceuticals and natural products, in one step from an alkenyl thioester. Unlike a potentially labile alkenyl thiol, an alkenyl thioester is stable and easy to prepare. The powerful Co catalysis via a cobalt hydride hydrogen atom transfer and radical-polar crossover mechanism enabled simultaneous cyclization and deprotection. The substrate scope was expanded by the extensive optimization of the reaction conditions and tuning of the thioester unit.</div>

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Synthesis of Spongidine A, D and Petrosaspongiolide L Methyl Ester Using Pyridine C-H Functionalization

10.26434/chemrxiv.10303883 ◽

2019 ◽

Author(s):

Florian Bartels ◽

Manuela Weber ◽

Mathias Christmann

Keyword(s):

Natural Products ◽

Methyl Ester ◽

Hydrogen Atom ◽

Phospholipase A2 ◽

Late Stage ◽

Hydrogen Atom Transfer ◽

Ring System ◽

Tetracyclic Core ◽

Intramolecular Hydrogen ◽

Phospholipase A2 Inhibitors

<div>An efficient strategy for the synthesis of the potent phospholipase A2 inhibitors spongidine A and D is presented. The tetracyclic core of the natural products was assembled via an intramolecular hydrogen atom transfer‐initiated Minisci reaction. A divergent late‐stage functionalization of the tetracyclic ring system was also used to achieve a concise synthesis of petrosaspongiolide L methyl ester.</div>

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Intramolecular Proton Transfer in the Isomerization of Hydroxyacetone: A Detailed Characterization Based on Reaction Force Analysis and the Bond Fragility Spectrum

10.26434/chemrxiv.12049062 ◽

2020 ◽

Author(s):

Wallace Derricotte ◽

Huiet Joseph

Keyword(s):

Chemical Potential ◽

Reaction Force ◽

Intramolecular Proton Transfer ◽

Intermediate Energy ◽

Force Analysis ◽

Activation Energy Barrier ◽

Detailed Characterization ◽

Proton Transfers ◽

Reaction Force Constant

The mechanism of isomerization of hydroxyacetone to 2-hydroxypropanal is studied within the framework of reaction force analysis at the M06-2X/6-311++G(d,p) level of theory. Three unique pathways are considered: (i) a step-wise mechanism that proceeds through formation of the Z-isomer of their shared enediol intermediate, (ii) a step-wise mechanism that forms the E-isomer of the enediol, and (iii) a concerted pathway that bypasses the enediol intermediate. Energy calculations show that the concerted pathway has the lowest activation energy barrier at 45.7 kcal mol<sup>-1</sup>. The reaction force, chemical potential, and reaction electronic flux are calculated for each reaction to characterize electronic changes throughout the mechanism. The reaction force constant is calculated in order to investigate the synchronous/asynchronous nature of the concerted intramolecular proton transfers involved. Additional characterization of synchronicity is provided by calculating the bond fragility spectrum for each mechanism.

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