Nitrone cycloaddition: an approach to the cyclophane alkaloid (±)-lythranidine

Abstract

The synthesis of (±)-lythranidine 1, a cyclophane alkaloid from Lythrum anceps Makino, involves three interesting problems. These are the construction of the 17-membered ring, the formation of the trans- 2,6-dialkylpiperidine and the establishment of the correct relative stereochemistry at the four asymmetric centres (C-3, C-5, C-9, C-11). In our approach to the synthesis of this alkaloid, the trans-dialkylpiperidine was formed via a nitrone cycloaddition reaction. Cyclisation to give the 17-membered ring was achieved using tris(triphenylphosphine)nickel(o), prepared in situ from bis(triphenylphosphine) nickel dichloride, and the di-iodide 9. Deprotection of macrocyclic biaryl 10 gave the (C-3, C-11) epimer of (±)-lythranidine.