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(+)-Aromadendrene as chiral starting material for the synthesis of fragrances and pheromones

  • Lamers, Y.M.A.W.
Publication Date
Jan 01, 2003
Wageningen University and Researchcenter Publications
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<p> (+)-Aromadendrene ( <strong>1</strong> ) is a sesquiterpene present in the distillation tail of the oil of <em>Eucalyptus globulus</em> . This distillation tail is commercially available in large quantities at low price and is an interesting starting material for the synthesis of other chiral products. A fair amount of research has already been carried out on aromadendrene (Chapter 1). This research was mainly focussed on transformation and isomerization of the double bond, opening of the cyclopropane ring, oxidations of derivatives of aromadendrene, and rearrangement of the aromadendrene skeleton.</p><p> In this thesis, the possibilities to use aromadendrene for other synthetic strategies were explored and the first interest was the development of an economically feasible route toward the fragrance compound <strong>167</strong> (Chapter 2). Ledene epoxide ( <strong>154</strong> ), easily available from aromadendrene, was selected as the starting material for this route, and rearrangements of thisb-epoxide were investigated. The formation of products with the cubebane ( <strong>159</strong> ) and cadinane skeleton ( <strong>160</strong> ) indicates that bridgehead carbocations are the prefered intermediates in these rearrangements. From these experiments it was concluded that the synthetic route toward <strong>167</strong> as published by Gijsen is the most efficient route known so far.</p><strong/><p><strong>Scheme 1</strong></p><strong/><p/><p/><p> Synthesis of guaiane-type compounds by opening the cyclopropane ring in aromadendrene has proven to be difficult. In Chapter 3 it was shown that the conversion of isoledene ( <strong>107</strong> ), a double bond isomer of aromadendrene, to compounds with the guaiane skeleton can be performed in a fairly easy way. The synthesis of the blue colorant guaiazulene ( <strong>35</strong> ) in 22% isolated yield over two steps from isoledene is an improvement of the existing methods for the dehydrogenation with sulfur of aromadendrane or guaiane type sesquiterpenes.</p><strong/><p><strong> </strong></p><strong/><p><strong>Figure 1</strong></p><strong/><p/><p/><p> A number of guaianes, for example the cyclic ethers <strong>198</strong> and <strong>200</strong> , were synthesized from isoledene epoxide ( <strong>193</strong> ). Isoledene epoxide can be converted by (Lewis) acid to a stabilized cyclopropylcarbinyl cation, which undergoes opening of the cyclopropane ring to a guaiane skeleton. When no water is present during the reaction, ether <strong>198</strong> is obtained and the presence of water leads to formation of ether <strong>200</strong> . Several functionalized derivatives of <strong>198</strong> have been prepared. These compounds were tested for their use as fragrances, but unfortunately they were not suitable as such.</p><strong/><p><strong>Scheme 2</strong></p><strong/><p/><p> A relatively new method for crop protection is the use of pheromone traps for monitoring or mass trapping of insects. By using these pheromone traps, the amount of insecticides often can be reduced considerably, which is more environmentally friendly and more selective. In Chapter 4 a method is described for the conversion of aromadendrene to methyl-branched linear pheromones. These pheromones <strong>( <em>R</em> )-224</strong> , <strong>( <em>S</em> )-298</strong> , and <strong><em>meso</em> -306</strong> were all synthesized from the common linear intermediate <strong>290</strong> . One of the key steps in the synthesis of <strong>290</strong> is the Baeyer-Villiger reaction of bromide <strong>284</strong> , and opening of the lactone ring in a one-pot reaction to give the hydroxy ester <strong>286</strong> . Via a Grob fragmentation using NaOEt in the presence of NaBH <sub>4</sub> and catalytic hydrogenation, <strong>286</strong> was then converted to compound <strong>290</strong> .</p><p> In Chapter 5 investigations towards the synthesis of dimethyl-branched linear pheromones have been described. It was shown that it is possible to convert aromadendrene to the dimethyl-branched linear intermediate <strong>308</strong> , following a route similar to the one described in Chapter 4.</p><strong/><p><strong>Scheme 3</strong></p><strong/><p/><p/><p/><p> </p><p> </p>

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