Total Sintesis Senyawa Nuciferal

Total Sintesis Senyawa Nuciferal

Nuciferal (1) and Nuciferol (2) are constituents of natural volatile woold oil separated  from the wood Torreya nucifera.The structure of nuciferal hass been known to be an aromatic sesquiterpenic aldehyde,2-methyl-6-(p-tolyl)-trans-2-heptenal,which  is similar to that of sinensal(3) that has been isolated from orange oil (citrus sinensis L) and is an important for the creation of orange flavors.

           Several synthetic procedurs for nuciferal (1) have been reported in the literature. Vig et al.synthesized (±)-1 starting  from 4-(p-tolyl)-valeric acid.Buchi and wuest used p-tolylacetophenone and Evands et al .used 3-(p-tolyl)-2-butenoate ester as starting materials, respectively,for the synthesis of this compound. in recent  communication ,yamamoto et al . investigated a synthetic method of α,β-unsaturated aldehyde by the reaction of vinylsilanes with dichloromethyl ether promoted by titanium tetrachloride, and applied this procedure to the synthesis  of (±)-1. In this paper, the authors wish to provide a new synthetic procedure of (±)-1 and (±)-2 starting from p-tolualdehyde, as shown in scheme 1.  

             A simple synthesis of racemic  nuciferal (1) was carried out using inexpensive chemicals. The benzylic choloride 6 was prepared in almost quantitative yield by reacting p-toualdehyde (4) with methylmagnesium iodide to give a benzylic alcohol 5, followed by successive conversion of 5 with thionyl choride into corresponding choride. The bromodioxolane 7 was prepared by condensation of acrolein with ethylene glycol in the presence of anhydrous hydrogen bromide. The cross-coupling of the two halides,6 and 7, was in vestigated in several ways. The reaction of the Grignard reagent. Prepared from 6, with the bromide 7 gave rise to a cross-coupling product, the cyclic acetal 8. It has benn known that the cross-coupling of organometalice reagent with a halide  is sometimes facilitated by cuprous iodide. However, in the presence of cuprous iodide,this reaction did not give the cross-coupling product, but a self-coupling of the benzylic choride (6) was observed, producing symmetrically substituted ethane derivative 12 in excellent yield (about 80%).

           On the other hand,we tried the coupling reaction by exchanging the Girdnard reagent of the halide 6 for that of the halide 7. The Girdnard reagent prepared from 7 was reacted with 6 in the presence and absence of the cuprous salt. Neither cross-coupling nor self-coupling products were produced. We tried also the coupling reaction by substituting the organomagnesium reagent for organolithium reagent. This reaction did not proceed well, and no coupling products were afforded.

           The natural product 11, ar-curcumene, could be obtained quantitatively by the wittig reaction of the pentanal 9 and isopropylide 10. The stereospecific,allylic oxidation of the gem-dimethyl olefin (11) could be accomplished by following the procedure of Rapoport. The oxidation of 11 with selenium dioxide yielded exclussively the tarns aldehyde,racemic nuceferal (1),which was reduced to nuciferol (2).

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https://www.researchgate.net/publicatio/264116257_A_Total_Synthesis_of_Nuciferal_and_Nuciferol