A dynamic picture of the halolactonization reaction through a combination of ab initio metadynamics and experimental investigations

Abstract

Ab initio dynamics of the halolactonization reaction provide insights into the diastereoselectivity of the reaction. Noncovalent interactions between the substrate, halogen source and solvent are revealed to direct the formation of the syn-product.

Brønsted Acid‐Catalyzed Enantioselective Iodocycloetherification Enabled by Triphenylphosphine Selenide Cocatalysis

“…For bromo‐ and iodocycloetherfications, which proceeded exclusively by anti ‐addition, a reaction via a cyclic haliranium ion intermediate is likely. Compared to the respective halolactonization, the amount of syn ‐isomer formed is negligible suggesting that syn ‐directing interactions such as a hydrogen bond between the NXS reagent and the hydroxyl group are missing [22] . For the enantioselective iodocycloetherification, it is remarkable that only the combination of the Se=PPh 3 cocatalyst and 3 b leads to high enantioselectivities.…”

“…[21] Furthermore, even uncatalyzed halolactonization reactions of trisubstituted alkenes are not always stereospecific and recent theoretical results suggest that depending on halogen, alkene and reaction conditions, halolactonizations can proceed via different pathways. [22] For the above described iodocycloetherifications of 1,2-disubstituted alkenes, only the antiaddition products could be isolated, but diastereoselectivity for 1,1-substituted alkenes was unclear due to the terminal alkene. To enable the observation of diastereoselectivity in this type of starting materials, a methyl-substituted derivative 11 was prepared with exclusive (E)-geometry of the alkene (see supporting information for details).…”

Unusual Single Electron Transfer Reactions between Alkenes and Iodine Electrophiles†

“…[1a] Additionally, Jackson and co-workers proposed a new coherent Ad E 3-type path of nucleophile-assisted alkene activation (NAAA), in which the alkene is activated by the nucleophilic partner's simultaneous electron donation for the electrophilic attack. [2] Up to now, the electrophilic addition of alkenes and halogen electrophiles mainly involves a typical halonium ion intermediate.…”

Inadequacy of Continuum Solvation for Polar Reactions: Predicting the Mechanism of Carbonyl–Olefin Metathesis

“…While the natural remedy is to model the solvent explicitly (46)(47)(48)(49)(50), this introduces many new degrees of freedom that require extensive sampling. Here, we immersed our model system in a sphere of 100 molecules of 1,2-dichloroethane ( 51) and chose to sample from the resulting ensemble by using ab initio molecular dynamics (AIMD) (52)(53)(54)(55).…”