Synthesis of Guaipyridine Alkaloids Rupestine M and L by Cycloaddition/Cycloreversion of an Intermediate 1,4-Oxazinone.

A new method to prepare 1,4-oxazinone intermediates was developed based on aza-conjugate addition of ß-amino alcohols to electron-deficient alkyne precursors. A tandem intramolecular cycloaddition/cycloreversion reaction sequence was evaluated, leading to the synthesis of the guaipyridine alkaloid natural products rupestine M and L. Starting from (-)-citronellal and thus a known configuration of the C5 stereocenter, a revised absolute configuration of natural rupestine L is suggested based on optical rotation.