Combining the [2,3] sigmatropic rearrangement and ring-closing metathesis strategies for the synthesis of spirocyclic alkaloids. A short and efficient route to (±)-perhydrohistrionicotoxin
1999; Elsevier BV; Volume: 55; Issue: 5 Linguagem: Inglês
10.1016/s0040-4020(98)01115-6
ISSN1464-5416
AutoresDavid Tanner, Lars Hagberg, Anders Poulsen,
Tópico(s)Asymmetric Synthesis and Catalysis
ResumoThis 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%).
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