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A general synthetic approach to diterpenoids of the cis-clerodane family has been developed, culminating in the first total synthesis, in racemic form, of usd({\pm})usd-6usd\betausd-acetoxy-2-oxokolavenool (85) and usd({\pm})usd-2-oxo-usd5\alpha ,8\alphausd-13,14,15,16-tetranorclerod-3-en-12-oic acid (86). The key operation involved is the face-selective Diels-Alder reaction of dienone ester 90 and trans-piperylene, giving rise to adduct 87 containing the decalin nucleus and correct stereogenic centers common to many cis-clerodane diterpenoids. Dienophile 90 was readily prepared from 3-ethoxy-6-methyl-2-cyclohexenone (93) according to the synthetic sequence outlined in Scheme 13. Alkylation of 93 with methyl bromoacetate followed by reduction with lithium aluminum hydride gave diol 95 which was subjected to selective benzylation and acid-catalyzed hydrolysis to give enone 96. This compound was subjected to carbomethoxylation using methyl cyanoformate to give enone ester 97. A double bond was then introduced via a phenylselenenylation-oxidative elimination process to afford dienone ester 90. The Diels-Alder adduct 87, produced from 90 and trans-piperylene under zinc chloride catalysis (Scheme 15), served as a common intermediate for the synthesis of 85 and 86. Conjugate addition of lithium dimethylcuprate to 87 followed by lithium aluminum hydride reduction using the ensuing enolate furnished hydroxy ketone 100. The hydroxy group of this compound was subsequently removed by a three-step operation: conversion of 100 to the corresponding mesylate, Zn-NaI reduction of the mesylate, and ring opening of the resulting cyclopropanol 102. The transformation of ketone 104 thus obtained to the natural acid 86 was carried out via the synthetic sequence outlined in Scheme 16. Wolff-Kishner reduction of 104 gave an inseparable mixture of olefins 115 and 116 (3:1), which was subjected to photooxygenation in the presence of acetic anhydride, pyridine and 4-dimethylaminopyridine using 5,10,15,20-tetraphenyl-21H,23H-porphine as a photosensitizer to give enone 117. Debenzylation of 117 with ferric chloride followed by Jones oxidation led to the completion of the total synthesis of ()-2-oxo-usd5 \alpha,8\alphausd-13,14,15,16-tetranorclerod-3-en-12-oic acid (86). For the synthesis usd({\pm})usd-85 (Scheme 19), ketone 104 was reduced with lithium aluminum hydride. Reductive debenzylation of the resulting alcohol 119 gave rise to diol 128, the primary alcohol of which was selectively oxidized with usd\rm (Ph\sb3P)\sb3RuCl\sb2usd to the aldehyde level. Wittig reaction of aldehyde 129 thus formed with usd(\alphausd-methoxyethylidene)triphenylphosphorane followed by acid hydrolysis gave ketone 131. Photooxygenation of this ketone under conditions similar to those used for the preparation of 117 resulted in enone acetate 132. Finally, addition of vinylmagnesium bromide gave usd({\pm})6\betausd-acetoxy-2-oxokolavenool (85).
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