A conjugate addition/dipolar-cycloaddition cascade sequence for the synthesis of (+/-)-cylindricine C

作者：Flick Andrew C; Arevalo Caballero Maria Jose; Padwa Albert^*

来源：Tetrahedron, 2010, 66(21): 3643-3650.

DOI：10.1016/j.tet.2010.03.088

• Alkaloid
• Cylindricine C
• 2,3-Bis(phenylsulfonyl)-1,3-butadiene
• Oxime
• Nitrone
• Intramolecular dipolar cycloaddition

An efficient stereocontrolled route to (+/-)-cylindricine C is described. Reaction of 9-hydroxynon-1-en-5-one oxime with 2,3-bis(phenylsulfonyl)-1,3-butadiene affords a 7-oxa-1-azanorbornane cycloadduct in high yield. The formation of the bicyclic isoxazolidine arises from conjugate addition of the oxime onto the diene to give a transient nitrone that spontaneously undergoes an intramolecular dipolar cycloaddition. The resulting cycloadduct derived from the cascade sequence was converted into (+/-)-cylindricine C by: (1) a reductive-cyclization to set the BC-ring skeleton, (2) a base-induced cyclization to construct the tricyclic core, and (3) an oxidation-conjugate addition of the n-hexyl side chain to complete the synthesis.

• 出版日期2010-5-22