Synthesis of 2-Oxazolines by in Situ Desilylation and Cyclodehydration of β-Hydroxyamides

Marco Brandstätter, Fabian Roth, Nathan W Luedtke
2015
A powerful method for the synthesis of 2-oxazolines from silyl-protected -hydroxyamides is reported. Using diethylaminosulfur trifluoride (DAST) or its tetrafluoroborate salt (XtalFluor-E), silylprotected -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 <
more » ... . 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.
doi:10.5167/uzh-105836 fatcat:gszuqyz7kbakle44iiszd72kqu