Stereoselective Synthesis of Benzo[<i>e</i>][1,4]oxazino[4,3‑<i>a</i>][1,4]diazepine-6,12-diones with Two Diversity Positions

Herein, we report a stereoselective formation of tetrahydro-6<i>H</i>-benzo­[<i>e</i>]­[1,4]­oxazino­[4,3-<i>a</i>]­[1,4]­diazepine-6,12­(11<i>H</i>)-diones. Their preparation consisted in solid-phase synthesis of linear intermediates starting from polymer-supported Ser­(<i>t</i>Bu)-OH. Using various 2-nitrobenzoic acids and bromoketones, the key intermediates were obtained in five steps and subjected to trifluoroacetic acid-mediated cleavage from the resin, followed by stereoselective reduction with triethylsilane. Subsequent catalytic hydrogenation of the nitro group and cyclization yielded the target compounds with full retention of the C^12a stereocenter configuration

Stereoselective Polymer-Supported Synthesis of Morpholine- and Thiomorpholine-3-carboxylic Acid Derivatives

Herein we report the polymer-supported synthesis of 3,4-dihydro-2<i>H</i>-1,4-oxazine-3-carboxylic acid derivatives using immobilized Fmoc-Ser­(<i>t</i>Bu)-OH and Fmoc-Thr­(<i>t</i>Bu)-OH as the starting materials. After the solid-phase-synthesis of <i>N</i>-alkyl-<i>N</i>-sulfonyl/acyl intermediates, the target dihydrooxazines were obtained using trifluoroacetic acid-mediated cleavage from the resin. This approach was also studied for the preparation of dihydrothiazines from immobilized Fmoc-Cys­(Trt)-OH. Inclusion of triethylsilane in the cleavage cocktail resulted in the stereoselective formation of the corresponding morpholine/thiomorpholine-3-carboxylic acids. Stereochemical studies revealed the specific configuration of the newly formed stereocenter and also the formation of stable <i>N</i>-acylmorpholine rotamers