Studies Directed at the Synthesis of Optically Active Pretazzetine via Intramolecular Nitrone/Alkene Cycloaddition Reactions

Article abstract of DOI:10.1021/jo00023a019

A protocol for the synthesis of optically active pretazzine which focuses on both the control of relative stereochemistry between the angular aryl and C6a hydroxyl groups and absolute stereochemistry has been developed and executed.The synthesis of the 1,3-dithiane ketal of (Z)-ethyl 3-(1,3-benzodioxol-5-yl)-5,7-dioxo-2-heptanoate is described.Treatment of this alkene aldehyde with N-(α-methylbenzyl)hydroxylamine afforded a nitrone, which underwent intramolecular 1,3-dipolar cycloaddition to afford the two diasteromeric isoxazolidine cycloadducts in a 16:1 ratio.Thesense of chirality transfer was determined by a single-crystal X-ray analysis of the major isomer.