Cross pheromone synthesis

Interesting results have been obtained in the synthesis of biologically active compounds such as insect pheromones. Conventional synthetic routes to these pheromones are often multistep sequences, which make many pheromones too expensive for widespread use [23]. Metathesis offers a shorter, alternative route to pheromone synthesis, generating these compounds in a few steps only. The use of insect sex pheromones is an environmentally friendly, effective, and selective method of pest control. Kiipper and Streck [24] synthesized insect sex pheromones by cross-metathesis reactions between linear olefins. In the presence of the catalyst Re207/Al203, 9-tricosene was synthesized by cross-metathesis of the readily available aUcenes 2-hexadecene and 9-octadecene (Eq. 8). 

The utility of the Suzuki reaction in the challenging arena of natural product total synthesis has been explored. The constitution of bombykol (106) (see Scheme 26), a well-known pheromone, lends itself to a Suzuki coupling. Indeed, in a short stereospecific synthesis of 106, Suginome et al. demonstrated that ( )-vinylboronic acid ( )-104 can be smoothly cross-coupled with (Z)-l-pentenyl bromide [(Z)-105] 44 the configurations of both coupling partners are preserved in the C-C bond forming process. 

Recent trend in the synthesis of olefinic pheromones is the use of transition metal-catalyzed cross coupling reaction for carbon-carbon bond formation. Scheme 8 summarizes a synthesis of the termite trail marker pheromone, (3Z,6Z)-3,6-dodecadien- l-ol (2) by Oehlschlager [19]. The key-step is the palladium-catalyzed cross-coupling of allylic chloride A and alkenylalane B. 

The use of menthol in the synthesis of important synthons for optically active methyl branched insect pheromones is discussed briefly. Applications of olefin cross metathesis in production of commercial products, including insect pheromones has been discussed. ... 

Together with the organoboron procedures mentioned above, the Pd-catalyzed cross coupling procedures have been applied to the synthesis of a wide variety of insect pheromones, terpenoids, and carotenoids. 

Another very important aspect of these transition metal-catalysed cross-coupling reactions stems from the high selectivity observed with stereo-defined vinyl sulfides. Applications to the stereoselective syntheses of pheromones were straightforward (see [321] and references therein), as shown in the two-step synthesis of muscalure from (Z)-l-bromo-2-phenylthioethylene [322] involving its sequential coupling through the bromo and phenylthio substituents with the appropriate derivatives. 

Recently, Rossi et al. have applied the cross-coupling of 1-alkenylboranes with 1-alkynyl halides for the synthesis of natural products. Thus, (7 , 9Z)-7,9-dodecadien-1-yl acetate (32), the sex pheromone of Lobesia botrana, has been synthesized by the following sequence involving ... 

Since a number of insect pheromones are nonfiinctionalized alkenes, they are potential target molecules for synthesis from petrochemicals by the metathesis reaction. Cross metathesis between unsymme-trical internal alkenes can lead to a complex mixture of products however, in some cases, this reaction provides the easiest method for production of such alkenes. For example, the pheromone for Musca do-mestica, tricosene, has been prepared from 2-hexadecene and 9-octadecene (equation 6). Both of these alkenes are readily available. 

The synthesis of the ant alarm pheromone mannicone 117 is a good example. Enone disconnection reveals that we need a crossed aldol condensation between the symmetrical ketone 118, acting as the enol component, and the enolisable aldehyde 119. 

Via stereoselective ethenolysis of 1,5-cyclooctadiene (COD), Bykov et al. [25] prepared l,d5-5,9-decatriene, a precursor for the synthesis of many ds-isomeric insect sex pheromone compounds. In the presence of the MoCl5/Si02/Me4Sn catalyst system, at 20 °C and an ethene pressure of 25 bar, a 80 % conversion of COD was obtained with a selectivity of 68.4% for l,ds-5,9-decatriene. From this triene, many long-chain (CiQ-Cig) unsaturated acetates, alcohols and aldehydes can be obtained with the required biologically active cis conformation. Cross-metathesis of cyclooctene with a-olefins in the presence of the same catalyst gave... 

Synthesis of Pheromones and other Products via Cross-metathesis... 

The decisive step in the stereoselective synthesis of ( )-l-bromo-and (Z)-l-iodo-l-alkenes, which were required for the preparation of various pheromones, consists in the hydroboration of different 1-bromo- and 1-iodoacetylenes [107-109] conjugated alkenynes could be readily prepared by metal-catalyzed cross-coupling of 1-alkenylboranes with 1-bromoalkynes [110]. 

Derivatives of oleic acid that imdergo cross-metathesis with simple olefins are listed in Table 9.4, while Table 9.5 gives some examples of cross-metathesis reactions of simple olefins with other functional olefins. Such cross-metathesis reactions may provide useful routes to speciality chemicals such as synthetic perfumes, insect pheromones (Crisp 1988), prostaglandin intermediates (Dalcanale 1985), etc. (see Mol 1982, 1991). Of special interest are ethenolysis reactions, which allow the synthesis of compoimds with terminal double bonds. Ethenolysis (and cross-metathesis with lower olefins) has been investigated extensively for... 

The fact that the unsymmetrical product dominates in the cross-metathesis of a cyclic olefin and a terminal olefin is an advantage for the efficient synthesis of the brown algae pheromones multifidene (yield 31%) and viridiene (yield 30%) via the cross-metathesis between bicyclo[3.2.0]hepta-2,6-diene and but-l-ene or butadiene, respectively (molar ratio 1/2), in the presence of lmol% of Ru(=CHCH=CPh2)(Cl)2(PCy3)2 Scheme 15.1 (Randall 1995). 

Perhaps the most basic form of the olefin metathesis reaction is the cross metathesis (CM) of acyclic olefins to yield new acyclic olefins (Fig. 4.11). The ratio of CM products may be controlled by steric and electronic factors to provide one product preferentially, rather than a statistical mixture, which is key to the synthetic utility of this reaction. For example, various functionalized olefins, dimers with bioactive substituents, and trisubstituted olefins have all been made by CM [33], and one of the industrial applications is the synthesis of insect pheromones [34]. 

Another example of organic synthesis via cross-metathesis is the synthesis of biologically active compounds such as insect pheromones. Use of such pheromones offers an effective and selective pest control method. Thus, cross-metathesis of ethyl oleate with 5-decene results in a cis-trans mixture of ethyl 9-tetradecenoate, an insect pheromone precursor [15]. Cross-metathesis of methyl d.y-5-eicosenoate (obtained from meadowfoam oil) with excess 5-decene gives methyl tm 5-decenoate, which can be transformed into a 83 17 mixture of trani -5-decenylacetate and tran.y-5-decenol (in total 90% trans), the sex pheromone of the Peach Twig Borer moth, a major pest in Northern Hemisphere fruit orchards. The isomeric mixture was active in mating disruption [16]. Other examples of organic synthesis via cross-metathesis are summarised elsewhere [17 18]. 

Dicarboxylic esters are used to prepare polyesters and polyamides. The residual double bonds permit cross-linking of the polymer chains. Cross metathesis of methyl oleate with excess ethene affords methyl 9-decenoate, a key intermediate in the synthesis of queen bee substance , a honey bee pheromone. 

In this chapter, you will be asked to design a synthesis for bombykol, the sex pheromone of the silk moth (bombyx mori) see page 191. Molecules of bombykol diffuse through open pores in the male moth s antenna. When bombykol binds to its receptor, an electrical charge is produced that causes a nerve impulse to be sent to the brain. Bombykol, however, is a nonpolar molecule (page 555) and has to cross an aqueous solution to get to its receptor. This problem is solved by the pheromone binding protein. The protein binds bombykol in a hydrophobic pocket and then carries it to the receptor. The area around the receptor is relatively acidic, and the decrease in pH causes the pheromone binding protein to unfold and release bombykol to the receptor. 

At the time these relatively modest results represented the state-of-the-art in direct catalytic asymmetric aldolizations with a-unbranched aldehyde acceptors. Neither Shibasaki s nor Trost s bimetallic catalysts, the only alternative catalysts available, gave superior results. Moreover, even non-asymmetric amine-catalyzed cross aldolizations with a-unbranched acceptors are still unknown. That the practicality of the process can compensate for the modest yield and enantioselectivity was illustrated by a straightforward synthesis of the natural pheromone (S)-ipsenol (139) from aldol 136d, featuring a high-yielding Stille coupling (Scheme 4.27). 

Rossi, R. Simple synthesis of sex pheromones of the housefly and tiger moths by transition metal-catalyzed olefin cross-metathesis reactions. Chim. Ind. Milan 57, 242—243 (1975). 

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