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Synthesis of Macrocyclic Lactones via Ring Transformation of 4-(w-Hydroxyalkyl)-1,3-oxazol-5(4H)-ones


Fritschi, Stephan P; Linden, Anthony; Heimgartner, Heinz (2016). Synthesis of Macrocyclic Lactones via Ring Transformation of 4-(w-Hydroxyalkyl)-1,3-oxazol-5(4H)-ones. Helvetica Chimica Acta, 99(7):523-538.

Abstract

The synthesis of alpha-benzamido-alpha-benzyl lactones 23 of various ring size was achieved either via ‘direct amide cyclization’ by treatment of 2-benzamido-2-benzyl-omega-hydroxy-N,N-dimethylalkanamides 21 in toluene at 90 – 110° with HCl gas or by ‘ring transformation’ of 4-benzyl-4-(omega-hydroxyalkyl)-2-phenyl-1,3-oxazol-5(4H)-ones under the same conditions. The precursors were obtained by C-alkylations of 4-benzyl-2-phenyl-1,3-oxazol-5(4H)-one (15) with THP- or TBDMS-protected omega-hydroxyalkyl iodides. Ring opening of the THP-protected oxazolones by treatment with Me2NH followed by deprotection of the OH group gave the diamides 21, whereas deprotection of the TBDMS series of oxazolones 25 with TBAF followed by treatment with HCl gas led to the corresponding lactones 23 in a one-pot reaction.

Abstract

The synthesis of alpha-benzamido-alpha-benzyl lactones 23 of various ring size was achieved either via ‘direct amide cyclization’ by treatment of 2-benzamido-2-benzyl-omega-hydroxy-N,N-dimethylalkanamides 21 in toluene at 90 – 110° with HCl gas or by ‘ring transformation’ of 4-benzyl-4-(omega-hydroxyalkyl)-2-phenyl-1,3-oxazol-5(4H)-ones under the same conditions. The precursors were obtained by C-alkylations of 4-benzyl-2-phenyl-1,3-oxazol-5(4H)-one (15) with THP- or TBDMS-protected omega-hydroxyalkyl iodides. Ring opening of the THP-protected oxazolones by treatment with Me2NH followed by deprotection of the OH group gave the diamides 21, whereas deprotection of the TBDMS series of oxazolones 25 with TBAF followed by treatment with HCl gas led to the corresponding lactones 23 in a one-pot reaction.

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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
Scopus Subject Areas:Physical Sciences > Catalysis
Life Sciences > Biochemistry
Life Sciences > Drug Discovery
Physical Sciences > Physical and Theoretical Chemistry
Physical Sciences > Organic Chemistry
Physical Sciences > Inorganic Chemistry
Uncontrolled Keywords:Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Biochemistry, Drug Discovery, Catalysis
Language:English
Date:June 2016
Deposited On:17 Jun 2016 10:51
Last Modified:30 Jul 2020 22:02
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0018-019X
Funders:F. Hoffmann-La Roche AG, Basel
OA Status:Green
Publisher DOI:https://doi.org/10.1002/hlca.201600023

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