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Synthesis of Macrocyclic Lactams from 2-(ω-Aminoalkyl)-2-benzoylamino-3-phenyl-N,N-dimethylpropanamides via direct Amide Cyclization


Fritschi, S P; Linden, A; Heimgartner, H (2009). Synthesis of Macrocyclic Lactams from 2-(ω-Aminoalkyl)-2-benzoylamino-3-phenyl-N,N-dimethylpropanamides via direct Amide Cyclization. Heterocycles, 79:985-1005.

Abstract

The alkylation of 4-benzyl-2-phenyl-1,3-oxazol-5(4H)-one (11) with
ω-azidoalkyl iodides (12) by deprotonation with LDA in THF/HMPT at –78 °C
yielded mixtures of the 4,4-disubstituted 1,3-oxazol-5(4H)-ones (13) and the O-alkylated 1,3-oxazoles (14) in 65–50%, with 13 as the major product. The reaction of the latter with dimethylamine in acetonitrile at room temperature led to ω-azido-2-benzamido-2-benzylalkane amides (15), which were reduced to give the corresponding ω-amino derivatives (16). On treatment with HCl gas or BF3 in boiling toluene, the macrocyclic 2-benzamido lactams (18) were formed in up to 27% yield via the intermediate formation of 1,3-oxazol-5(4H)-ones (17). The structures of the 14- and 15-membered lactams have been established by X-ray crystallography.

The alkylation of 4-benzyl-2-phenyl-1,3-oxazol-5(4H)-one (11) with
ω-azidoalkyl iodides (12) by deprotonation with LDA in THF/HMPT at –78 °C
yielded mixtures of the 4,4-disubstituted 1,3-oxazol-5(4H)-ones (13) and the O-alkylated 1,3-oxazoles (14) in 65–50%, with 13 as the major product. The reaction of the latter with dimethylamine in acetonitrile at room temperature led to ω-azido-2-benzamido-2-benzylalkane amides (15), which were reduced to give the corresponding ω-amino derivatives (16). On treatment with HCl gas or BF3 in boiling toluene, the macrocyclic 2-benzamido lactams (18) were formed in up to 27% yield via the intermediate formation of 1,3-oxazol-5(4H)-ones (17). The structures of the 14- and 15-membered lactams have been established by X-ray crystallography.

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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:1 April 2009
Deposited On:20 Nov 2009 10:48
Last Modified:05 Apr 2016 13:32
Publisher:The Japan Institute of Heterocyclic Chemistry
ISSN:0385-5414
Funders:Swiss National Science Foundation (SNF), F. Hoffmann-La roche AG, Basel
Publisher DOI:https://doi.org/10.3987/COM-08-S(D)76
Permanent URL: https://doi.org/10.5167/uzh-23869

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