Japanese beetle pheromone

Asymmetric reduction of Myny ketones. The (Reform of the complex (1) reduces alkynyl ketones to optically active propargylic alcohols (usually R) in 65-85% chemical yield and in 85-95% optical yield use of the (S)-form of 1, as expected, results in the epimeric alcohol. This reduction was used in a synthesis of the natural Japanese beetle pheromone (2, equation I).1... 

Noyori et al. demonstrated the effectiveness of the BINAL-H reduction method by synthesizing the Japanese beetle pheromone (R)-167 (Scheme 4.3f). The alkynyl ketone 17 was treated with 3 equivalents of (Wj-IJINAL-H at —100 C for 1 hour and then held at —78 C for 2 hours. The propargylic alcohol 18 was obtained in good yield and with moderate enantioselectivity of 84% ee. Exposure... 

This is not, however, the method used to make Japanese beetle pheromone industrially. Resolution, as you have probably realized, is highly wasteful—if you want just one enantiomer, the other ends up being thrown away. In industrial synthesis, this is not an option unless recycling is possible, since chemical plants cannot afford the expense of disposing of such quantities of high-quality waste. So we need alternative methods of making single enantiomers. 

There are two other factors worth noting in regard to the Japanese beetle pheromone. A single compound apparently possesses all the activity of the pheromone. This is even more surprising when we note that the material obtained from females contained about 15% of the (E) Isomer and 3% of the analog with a saturated side chain. However, these other two compounds had no effect on the activity of the (R)(Z)-isomer when added in the appropriate ratios whether the racemic or the pure enantiomeric forms were used. 

When we first introduced the concept of enantiomers and chirality in Chapter 16, we stressed that any imbalance in enantiomers always derives ultimately from nature. A laboratory synthesis, unless it involves an enantiomerically pure starting material or reagent, will always give a mixture of enantiomers. Here is just such a synthesis of the Japanese beetle pheromone you have just met. You can see the Z-selective Lindlar reduction in use—only one geometrical isomer of the double bond is formed— but, of course, the product is necessarily racemic and therefore useless as beetle bait, because in the original addition of the lithiated alkyne to the aldehyde there can be no control over stereochemistry. If all the starting materials and reagents are achiral, the product must be... 

Figure 7. Faster degradation of the Japanese beetle pheromone, (Rfjaponilure, than the behavioral antagonist, (S)faponilure, by esterase(s) isolated from the Japanese beetle antennae.

Semireduction of internal alkynes with Lindlar catalysts invariably gives cw-olefins. Analysis by NMR of the Japanese beetle pheromone 52 prepared from the corresponding... 

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