title: Synthesis of 2-Oxazolines by in Situ Desilylation and Cyclodehydration of β-Hydroxyamides.
abstract: A powerful method for the synthesis of 2-oxazolines from silyl-protected β-hydroxyamides is reported. Using diethylaminosulfur trifluoride (DAST) or its tetrafluoroborate salt (XtalFluor-E), silyl-protected β-amidoalcohols can be in situ deprotected and dehydrated to give 2-oxazolines in good yields. The utility of this approach was demonstrated by preparing the first reported oligomer of [2,4']-coupled 2-oxazoline units. By tuning the stability of the silyl protecting groups (ex. IPDMS < TES < TBS, etc.), the deprotection rate can be optimized so that all reaction intermediates remain soluble, allowing cyclodehydration to occur at all potential sites of ring closure. N-Terminal Ser residues containing an Fmoc carbamate are converted into 2-(9'-fluorenylmethyloxy)-2-oxazoline in high yield, thereby providing a new pathway for the synthesis of peptides capped with an N-terminal 2-alkoxy-2-oxazoline or 2-oxazolidinone unit.
authors.affiliation: Department of Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Brandstätter
authors.affiliation: Department of Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Roth
authors.affiliation: Department of Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Luedtke
mesh_terms: D000577:Amides / Q000737:chemistry*; D003500:Cyclization; D003681:Dehydration; D008968:Molecular Conformation; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000577:Amides; D010080:Oxazoles