co8b00176_si_001.pdf (1.32 MB)
Polymer-Assisted Synthesis of Single and Fused Diketomorpholines
journal contribution
posted on 2019-01-14, 00:00 authored by Petra Králová, Sandra Benická, Miroslav SouralThe
synthesis of different diketomorpholines via N-acyl-3,4-dihydro-2H-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(tBu)-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-c][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-c][1,4]oxazine-dione with full control of the newly formed stereocenter.