@article{487c2fce280047c0b52e0ddfc479a114,
title = "Halogen Atom Participation in Guiding the Stereochemical Outcomes of Acetal Substitution Reactions",
abstract = "Acetal substitution reactions of α-halogenated five- and six-membered rings can be highly stereoselective. Erosion of stereoselectivity occurs as nucleophilicity increases, which is consistent with additions to a halogen-stabilized oxocarbenium ion, not a three-membered-ring halonium ion. Computational investigations confirmed that the open-form oxocarbenium ions are the reactive intermediates involved. Kinetic studies suggest that hyperconjugative effects and through-space electrostatic interactions can both contribute to the stabilization of halogen-substituted oxocarbenium ions.",
keywords = "Diastereoselectivity, Glycosylation, Halonium Ion, Hyperconjugation, Oxocarbenium Ion",
author = "Demkiw, {Krystyna M.} and Remmerswaal, {Wouter A.} and Thomas Hansen and {van der Marel}, {Gijsbert A.} and Cod{\'e}e, {Jeroen D.C.} and Woerpel, {K. A.}",
note = "Funding Information: We here demonstrate the strong influence of a single α‐halogen atom on the stereochemical outcome of acetal substitution reactions of furan‐ and pyran‐derived acetals. The stereoselectivities observed using nucleophiles of varying reactivities are consistent with the intermediacy of open‐form oxocarbenium ions as reactive intermediates and not with S2‐type substitution reactions of three‐membered‐ring onium ions. This interpretation is supported by computational and kinetic studies. N Funding Information: This research was supported by the National Institutes of Health, National Institute of General Medical Sciences (1R01GM129286 to K.A.W.), the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO-VICI VI.C.182.020 to J.D.C.C) and the European research Council (ERC-CoG-726072-“GLYCONTROL”, to J.D.C.C.). K.M.D. acknowledges the NYU Department of Chemistry for support in the form of a Margaret Strauss Kramer Fellowship. The authors acknowledge NYU's Shared Instrumentation Facility and the support provided by NSF award CHE-01162222 and NIH award S10-OD016343. The computational infrastructure was facilitated by SURFSara (2021/ENW/01070753 awarded to J.D.C.C.). The authors thank Dr. Chin Lin (NYU) for his assistance with NMR spectroscopy and mass spectroscopy and Dr. Chunhua (Tony) Hu (NYU) for his assistance with X-ray crystallography. Publisher Copyright: {\textcopyright} 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.",
year = "2022",
month = oct,
day = "17",
doi = "10.1002/anie.202209401",
language = "English (US)",
volume = "61",
journal = "Angewandte Chemie - International Edition",
issn = "1433-7851",
publisher = "John Wiley and Sons Ltd",
number = "42",
}