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.