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3) The cyclization of (R)-(+)-citronellal (XVIII) with ZnBr2 followed by reaction with diborane and H2O2 gives the diol (XI), which is selectively benzylated with benzyl chloride and NaH to the monobenzyl ether (XX). The oxidation of (XX) with the Jones reagent yields the cyclohexanone (XXI), which is condensed with 3-(trimethylsilyl)-3-buten-2-one (XXII) by means of lithium diisopropylamide to the dione (XXIII). The cyclization of (XXIII) by means of Ba(OH)2 and oxalic acid affords the benzylated octahydronaphthalenone (XXIV), which by reduction with NaBH4 followed by reoxidation with the Jones reagent gives the decalinone (XXV). The Grignard methylation of (XXV) with methylmagnesium iodide yields the tertiary alcohol (XXVI), which is dehydrated with p-toluenesulfonic acid to the octahydronaphthalene (XXVII). The debenzylation of (XXVII) with sodamide, followed by oxidation with the Jones reagent and methylation with diazomethane affords the ester (XXVIII), which is ozonolyzed with O3 to the formyl ketone (XXIX). Selective protection of the ketone group with propane-1,3-dithiol (XXX) and p-toluenesulfonic acid gives the substituted 1,3-dithiane (XXXI), which is treated with methyl orthoformate and p-toluenesulfonic acid to yield the methoxymethylene derivative (XXXII). The elimination of the dithiane group with HgCl2 in aqueous acetonitrile affords the ketoester (XXXIII), which is submitted to a photochemical oxidation using rose bengal as catalyst in methanol, giving the peroxide (XXXIV). Finally, this compound is cyclized by means of HClO4 and OsO4. 4) The benzylated octahydronaphthalenone (XXIV) can also be obtained by benzylation of the ketone (VIII) with benzyl bromide by means of NaH in DMF.

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The (+)-isolimonene (I) was submitted to a regioselective hydroboration with dicyclohexylborane to give the alcohol (II), which was oxidized with CrO3 to the corresponding carboxylic acid (III). The iodolactonization of (III) by means of KI, I2 and NaHCO3 yielded a separable, diastereomeric mixture of iodolactones (IV) + (V). The suitable isomer (IV) was condensed with methyl vinyl ketone (VI) by means of tris(trimethylsilyl)silane and AIBN in refluxing toluene to afford the alkylated lactone (VII) as an inseparable diastereomeric mixture. The ketonic group of (VII) was treated with ethanedithiol (VIII) and BF3/Et2O in dichloromethane to provide a separable mixture of thioketal lactones (IX)+(X). The suitable isomer (X) was hydrolyzed with NaOH in refluxing methanol to give the hydroxyacid (XI), which was treated with diazomethane to yield the corresponding methyl ester (XII). The oxidation of the OH group of (XII) by means of PCC affords the ketoester (XIII), which is submitted to a Wittig condensation with methoxymethyltriphenylphosphonium chloride (XIV) by means of KHMDS in THF/HMPA to provide the methoxymethylene derivative (XV). The cleavage of the dithioketal group of (XV) by means of HgCl2 and CaCO3 in acetonitrile regenerates the keto group giving compound (XVI), which is finally transformed into the target (+)-artemisinin by photooxidation with O2 in methanol in the presence of Rose Bengal, followed by a treatment with 70 % HClO4.

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