Japanese beetle pheromone, synthesis

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... 

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. 

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... 

Chiral y-iactones (10, 321). Midland3 has extended his synthesis of chiral y-lactones to an efficient synthesis of the sex pheromone (2) of the Japanese beetle. The overall optical yield of (2) from optically pure a-pinene is 97%. 

Asymmetric syntheses directed toward construction of enantiomers of the western and southern corn root-worm pheromones are described. A brief review of the subject of asymmetric synthesis as it is related to the synthesis of insect sex pheromones is presented. The laboratory s previous research with chiral pheromones is summarized (Japanese beetle, white peach scale, and lesser tea tortrix) before detailing synthetic work on the pheromones of the aforementioned rootworm species. Throughout the course of the synthetic effort, cholesteric stationary phases for GLC have found use. Their superior ability to separate crucial diastereomeric intermediates for synthesis is detailed. 

The Japanese beetle (Popillia japonica) sex pheromone (144) is a lactone with an unsaturated side chain (Scheme 27). Optically active (7 )-(-)-glutamic acid (140 a) served as the starting material in the synthesis by Tumlinson et al 73) shown in Scheme 27. After ring closure with retention of configuration and formation of the aldehyde, inverse addition of the Wittig reagent afforded the desired R,Z configuration. 

Most asymmetric syntheses require rather more than one or two steps from chiral pool constituents. Male bark beetles of the genus Ips produce a pheromone that is a mixture of several enantiomerically pure compounds. One is a simple diene alcohol (S)-(-)-ipsenol. Japanese chemists in the 1970s noted the similarity of part of the structure of ipsenol (in black) to the widely available amino acid (S)-leucine and decided to exploit this in a chiral pool synthesis, using the stereogenic centre (green ring) of leucine to provide the stereogenic centre of ipsenol. 

---