Iminophosphorane-mediated Synthesis of Oxazole Alkaloids: One-Step Preparation of O-Methylhalfordinol and Annuloline

The three-component reaction between triphenylphosphine, 4-methoxyphenacyl azide and nicotinoyl chloride or 3,4-dimethoxycinnamoyl chloride leads directly in good yields to 0-methylhalfordinol or annuloline respectively.Only five naturally occurring bases withanoxazolering have been isolated to date,' allof them are 2.5-disubstituted oxazoles.Worthy of note among these are halfordinol (l)(R=H), the mother compound of oxazole alkaloids of Halfordia screroxylaZ and Aegle mar me lo^;^ annuloline (2), a brilliant blue fluorescent pigment isolated from the roots of the annual rye grass Lolium muItij70nun;~ and pimprinine, a mold metabolite isolated from Streptomices Annuloline (2): yield 0.24 g (54%); mp 108-109°C (lit.,6107-108°C).