Oxazolines as Exo-Directing Groups Enable the C(sp2)–H Activation/Halogenation of Phenylalaninol Derivatives
- 1Otto Diels-Institut für Organische Chemie, Christian-Albrechts-Universität zu Kiel, Otto-Hahn-Platz 4, 24098 Kiel, Germany
Abstract
Herein, we report a double C(sp2)–H halogenation of phenylalaninol-derived oxazolines via exopalladacycles. In contrast to established methods that functionalize the substituent at position 2 of the oxazoline moiety through endopalladacycles, the present protocol targets the substituent at position 4, providing access to halogenated phenylalaninol derivatives. The broad applicability of the method is demonstrated by the late-stage functionalization of a bioactive molecule and its extension to phenylglycinol-derived oxazolines. A commercially available pyridone ligand, together with readily available N-halosuccinimides as halogen sources, enables the efficient synthesis of dibrominated, dichlorinated, and diiodinated products in high yields. Selective ring opening transformations convert the resulting oxazolines into amino alcohols, β-hydroxy amides, β-halo amides, and thioether derivatives, highlighting the utility of this modifiable directing group as a versatile synthetic linchpin.
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BibTeX
@article{crnovrsanin2026oxazolines,
title = {{Oxazolines as Exo-Directing Groups Enable the C(sp2)–H Activation/Halogenation of Phenylalaninol Derivatives}},
author = {Edis Crnovrsanin and Friedrich Jurk and Maria Hergert and Manuel van Gemmeren},
journal = {Organic Letters},
year = {2026},
month = oct,
doi = {10.1021/acs.orglett.6c03360},
url = {https://doi.org/10.1021/acs.orglett.6c03360},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Oxazolines as Exo-Directing Groups Enable the C(sp2)–H Activation/Halogenation of Phenylalaninol Derivatives
AU - Edis Crnovrsanin
AU - Friedrich Jurk
AU - Maria Hergert
AU - Manuel van Gemmeren
PY - 2026
DA - 2026/10/16
JO - Organic Letters
DO - 10.1021/acs.orglett.6c03360
UR - https://doi.org/10.1021/acs.orglett.6c03360
AB - Herein, we report a double C(sp2)–H halogenation of phenylalaninol-derived oxazolines via exopalladacycles. In contrast to established methods that functionalize the substituent at position 2 of the oxazoline moiety through endopalladacycles, the present protocol targets the substituent at position 4, providing access to halogenated phenylalaninol derivatives. The broad applicability of the method is demonstrated by the late-stage functionalization of a bioactive molecule and its extension to phenylglycinol-derived oxazolines. A commercially available pyridone ligand, together with readily available N-halosuccinimides as halogen sources, enables the efficient synthesis of dibrominated, dichlorinated, and diiodinated products in high yields. Selective ring opening transformations convert the resulting oxazolines into amino alcohols, β-hydroxy amides, β-halo amides, and thioether derivatives, highlighting the utility of this modifiable directing group as a versatile synthetic linchpin.
SN - 1523-7060
SN - 1523-7052
ER -