Stereoselective\nSynthesis of (±)-Tetraponerine‑2\nand -4 via the Gold(I)-Catalyzed Intramolecular Dehydrative Amination\nof Allylic Alcohols

The\nconcise and efficient total synthesis of (±)-tetraponerine-2\n(<b>T2</b>) and (±)-tetraponerine-4 (<b>T4</b>) was\nachieved in 9% and 14% overall yield, respectively. The key step included\nthe diastereoselective gold(I)-catalyzed intramolecular dehydrative\namination of an allylic alcohol-tethered sulfamide to produce the <i>cis-</i>1,3-diamine moiety. The resulting olefinic side chain\nwas then elaborated by cross-metathesis and cyclized to a five-membered\npyrrolidine or a six-membered piperidine ring by intramolecular Mitsunobu <i>N</i>-alkylation. The unique tricyclic core of the (±)-tetraponerines\nwas completed through cyclic sulfamide cleavage followed by aminal\nformation using 4-bromobutanal. This flexible synthetic strategy allows\nfor the variation of the ring size, C-5 alkyl side chain length, and\nstereochemistry, which enables the preparation of diverse tetraponerine\nanalogs for biological study.