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


Brandstätter, Marco; Roth, Fabian; Luedtke, Nathan W (2015). Synthesis of 2-Oxazolines by in Situ Desilylation and Cyclodehydration of β-Hydroxyamides. Journal of Organic Chemistry, 80(1):40-51.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:2015
Deposited On:06 Mar 2015 07:55
Last Modified:05 Apr 2016 18:52
Publisher:American Chemical Society
ISSN:0022-3263
Additional Information:This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Organic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher.
Publisher DOI:https://doi.org/10.1021/jo5016695

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