Disparlure synthesis

The method has been applied in asymmetric and regioselective syntheses of several natural compounds. Two simple examples are the commercial syntheses of the gipsy moth hydrophobic sex attractant, disparlure (RE. Rossiter, 1981, 1985) and < mono-epoxidation of a diene in a leukotriene B4 synthesis (L.S. Mills, 1983). 

Scheme 4. The Sharpless asymmetric epoxidation in the J.T. Baker Company s commercial synthesis of (7/ ,8S)-disparlure (15).

When n-BuLi is used instead of t-BuLi, the byproduct after desulfinylation (n-BuS(O)Ph) possesses an acidic proton, which is abstracted by the metalated epoxide. Hence, overall, a stereoselective protodesulfmylation is achieved. This can be used for the asymmetric synthesis of epoxides, such as that of (-)-disparlure from enantiopure sulfoxide 222 (Scheme 5.53) [78]. 

R,8S)-(+)-Disparlure (12) is the female sex pheromone of the gypsy moth (Lymantria dispar). Advent of Sharpless asymmetric dihydroxylation (AD) allowed several new syntheses of 12 possible. Sharpless synthesized 12 as shown in Scheme 17 [27]. Scheme 18 summarizes Ko s synthesis of 12 employing AD-mix-a [28]. He extended the carbon chain of A by Payne rearrangement followed by alkylation of an alkynide anion with the resulting epoxide to give B. Keinan developed another AD-based synthesis of 12 as shown in Scheme 19 [29]. Mit-sunobu inversion of A to give B was the key step, and the diol C could be purified by recrystallization. 

It should be added that many other groups have contributed to the predevelopments of these inventions and also to later developments. All four reactions find wide application in organic synthesis. The Sharpless epoxidation of allylic alcohols finds industrial application in Arco s synthesis of glycidol, the epoxidation product of allyl alcohol, and Upjohn s synthesis of disparlure (Figure 14.4), a sex pheromone for the gypsy moth. The synthesis of disparlure starts with a Ci3 allylic alcohol in which, after asymmetric epoxidation, the alcohol is replaced by the other carbon chain. Perhaps today the Jacobsen method can be used directly on a suitable Ci9 alkene, although the steric differences between both ends of the molecules are extremely small ... 

Of interest is the fact that one of the coupling partners in the looplure synthesis was the half acid-half ester (59). Since the ester was untouched in the coelectrolysis, it could potentially function as a site for a second Kolbe oxidation and subsequent coupling. This strategy was utilized in the synthesis of disparlure (67 Scheme 16) [36]. A mixed coupling between the half-acid ester (62) and nonanoic acid (63) (1 10 ratio) proceeded smoothly to afford (64). Saponification... 

Scheme 14. Resolution of a czs-2,3-disubstituted epoxide and synthesis of (+)-disparlure...

This transformation has been applied to several chiral production processes, the first being the synthesis of a pheromone (Disparlure) intermediate (S) albeit with low turnover numbers and only 91 % ee. Another industrial product is the epoxide of allyl alcohol as developed by PPG-Sipsy, to give a process where catalyst loading was decreased by molecular sieve addition and the safety factors involving peroxide contamination were overcome. These examples are shown in Figure 1.46. 

Asymmetric epoxidation is a key step in a synthesis of (+ )-disparlure (I), the sex utlructunt of the gypsy moth, as outlined in equation (I). ... 

This catalytic epoxidation method has been applied to the synthesis of a variety of natural products, particularly polyhydioxylated compounds, including carbohydrates (54) and macrolides. In addition, this reaction has been used for commercial synthesis of disparlure, a gypsy moth pheromone [J. T. Baker Co. (55) and the Shanghai Institute for Organic Chemistry (56)], and more importantly, glycidol, a versatile intermediate for synthesis of /3-blockers and other functionalized chiral molecules (Arco Co.) (Scheme 23) (57). 

Sharpless epoxidation of (E)-(l,2-dialkyl)vinylsilanols 13, prepared from hydrolysis of ( )-( 1,2-dialkyl )vinyldimethylbutoxysilanes 12, gave silylepoxides 14, which were treated with Et4NF in MeCN to afford epoxides 15 in 62-70% overall yield and 44-70% ee (Scheme 6AA.6).7 The overall transformation can be considered as asymmetric epoxidation of simple internal alkenes. This approach was applied to the synthesis of a naturally occurring insect sex pheromone (+)-disparlure.7... 

Mori, K. and Ebata, T. (1981). Synthesis of optically active pheromones with an epoxy ring, (+)-disparlure and the saltmarsh caterpillar moth pheromone (Z,Z)-3,6-d.s-... 

The sex attractant pheromone of the gypsy moth [Lymantrla dispar (L.)] is disparlure (cis-7,8-epoxy-2-methyloctadecane). The natural attractant is the (+) enantiomer it is a powerful attractant for male moths and is used throughout the United States as a bait in traps to detect infestations. A convenient and economic synthesis, recently reported, involves oxidation of an inactive unsaturated precursor with an optically active complex to yield an epoxide of high enantiomeric purity. 

The Intermediate In this synthesis of disparlure, (Z)-2-tridecenol, Is obtained by hydrogenation of 2-trldecynol In the presence of a palladium catalyst poisoned with barium sulfate and quinoline. Oxidation of (Z)-2-tridecenol with tert-butyl hydroperoxlde/tItanium tetralsopropoxlde/D (-)-diethyl tartrate gives (2R, 3S)-epoxytrldecanol In enantiomeric excess reported to be as much as 98 percent after recrystalllzatlon. 

The synthesis Is completed by oxidation of the alcohol to an aldehyde with a pyrldine-chromlc oxide complex. The reaction of the alcohol with a Wlttig reagent, 4-methylpentylidene trlphenylphosphorane, gives an olefin which can be hydrogenated to (+)-disparlure, (7 R,8S)-epoxy-2-methyloctadecane. 

Figure la. Asymmetric synthesis of (- -)-disparlure. (Reproduced from J. Amer. 

Figure 12.9 Part[l] Formation of two C-C bonds using acetyiide anions The synthesis of disparlure h "...

Figure 12.9 illustrates the synthesis of disparlure beginning with acetylene. The synthesis is conceptually divided into three parts ... 

Identify the lettered reagents in the synthesis of optically active disparlure. 

---