10.1021/acscombsci.8b00176.s001
Petra Králová
Petra
Králová
Sandra Benická
Sandra
Benická
Miroslav Soural
Miroslav
Soural
Polymer-Assisted Synthesis of Single and Fused Diketomorpholines
American Chemical Society
2019
crude purities
α- halocarboxylic acids
reaction conditions
oxazine-dione
oxazino
dihydrooxazine -3-carboxylic acids
α- bromoketone
Polymer-Assisted Synthesis
triethylsilane-trifluoroacetic acid
4- Nos group
olefin reduction
acid-mediated cleavage
TES
solid-phase synthesis
Fused Diketomorpholines
2019-01-14 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Polymer-Assisted_Synthesis_of_Single_and_Fused_Diketomorpholines/7603325
The
synthesis of different diketomorpholines via <i>N</i>-acyl-3,4-dihydro-2<i>H</i>-1,4-oxazine-3-carboxylic acids
is reported in this article. The key intermediates were prepared using
a convenient solid-phase synthesis starting from polymer-supported
Ser(<i>t</i>Bu)-OH. After subsequent sulfonylation with
4-nitrobenzenesulfonyl chloride (4-Nos-Cl), alkylation with an α-bromoketone,
cleavage of the 4-Nos group and acylation with an α-halocarboxylic
acids, acid-mediated cleavage from the resin yielded dihydrooxazine-3-carboxylic
acids in high crude purities. Depending on the reaction conditions,
exposure to base resulted in cyclization to either oxazino[3,4-<i>c</i>][1,4]oxazine-diones or 3-methylidenemorpholine-2,5-diones.
Further reaction with triethylsilane-trifluoroacetic acid (TES/TFA)
led to olefin reduction, in the case of oxazino[3,4-<i>c</i>][1,4]oxazine-dione with full control of the newly formed stereocenter.