The total synthesis of virol C 1 was accomplished using a diastereoselective carbonyl reduction induced by a chiral sulfoxide, a Pummerer rearrangement to give the corresponding aldehyde fragment, and coupling reactions using Wittig and Cadiot-Chodkiewicz protocols.Water Hemlock, Cicuta Virosa (Umbeliferae) is a wellknown toxic plant widely distributed in temperate regions. The main basic component is cicutoxin, which was isolated in 1915 1 and its planar structure reported in 1953 2 without specification of the absolute configuration.Virol A, B and C are C-17 polyacetylenic alcohol analogs of cicutoxin, recently isolated and synthesized by Oshima and coworkers. 3,4 These interesting compounds are chemically more stable than cicutoxin, making possible the study of their precise mode of pharmacological action. 4As a part of our program on the synthesis of natural polyacetylenes 5 we report in this paper our synthetic efforts toward virol C, 1.Our approach utilized the diastereoselective reduction of a enantiopure b-keto-sulfoxide and an improved procedure for Pummerer rearrangement to give the key fragment of the synthesis, and therefore differs significantly from the route used by the Japanese authors. As shown on Scheme 1, our retrosynthetic analysis utilizes the disconnection of the triple and double bond, affording three basic fragments.The synthesis of 1 started with the preparation of TBSprotected (2S)-2-hydroxy-nonanal, 2. Reaction of methyl octanoate (5) with (R)-methyl p-tolyl sulfoxide anion 6 gave the b-keto-sulfoxide 6. Subsequent reduction using DIBAL in THF at -78 °C 7 yielded (2S)-b-hydroxy sulfoxide 7 in 85% de. The diastereomeric excess was determined by NMR integration of carbinolic hydrogen which were identified as two multiplets with different chemical shifts and by integration of system ABX of a-sulfoxide hydrogens. These results were confirmed by Mosher analysis.
In this paper is described an unreported method employing α‐alkenyl β‐ketoamides as starting material to give 2,3‐dihydrofurans, precursors of substituted furans.
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