ChemInform Abstract: Combining the [2,3] Sigmatropic Rearrangement and Ring-Closing Metathesis Strategies for the Synthesis of Spirocyclic Alkaloids. A Short and Efficient Route to (.+-.)-Perhydrohistrionicotoxin

This paper describes the use of selenium-based [2,3] sigmatropic rearrangement in combination with ruthenium-catalyzed ring-closing metathesis (RCM) for the synthesis of azaspiro ring systems, as exemplified by the reactions of model substrates 5 and 6 . The methodology has been applied to a short and efficient formal total synthesis of the alkaloid (±)-perhydrohistrionicotoxin ( 2 ). Thus, (±)-depentylperhydrohistrionicotoxin, 1 , a known key intermediate for the synthesis of 2 , was synthesised from 2,3-epoxycyclohexan-1-one in 10 laboratory operations and ca. 20% overall yield. The synthetic route is potentially enantioselective, and key steps were the [2,3] sigmatropic rearrangement of 11 to 12 via the corresponding allylic selenide (86% yield) and ruthenium-catalyzed RCM of 13 to 14 (80%).