We can explore metathesis catalysts known as “Grubb catalyst” or “Schrock catalyst” to make insect pheromones.
The facile synthesis of a few lepidopteran insect pheromones can be accomplished using ruthenium-based Z-selective olefin metathesis catalyst. Quite a few pheromones are approved by the EPA as pest control pheromone/semiochemical agents.
These metathesis methods can be extended to synthesize other insect pheromone analogs containing cis-olefins in a similar manner and can be applied for EPA approval for pest control.
This metathesis chemistry can provide an economically feasible route to make several pheromones efficiently in good yields with high cis-selectivity in a minimal number of steps from commercially available olefins containing various functional groups such as alcohols, aldehydes, ketones, acetates, epoxides and unconjugated (E,Z) diene.
Terminal alkene can be reacted with seed oil derivatives in the presence of low catalyst loading (about 1 mol %) to yield the desired cross products in good yields with high cis-selectivity as an alternative to conventional methods used to form cis-olefins via cis-hydrogenation of alkynes and the Wittig reaction.
The synthesis of the pheromones can be taken up after understanding the reactivity and selectivity of catalysts shown below.
|Grubb Catalyst||Schrock Catalyst
|Special third generation catalyst
Some examples of shortest synthetic routes to cis-pheromones containing various functionality are shown below.
The reaction of 1-hexene with oleyl alcohol directly produced 3 in 77% yield and with 86% of the Z-olefin. The product (5) made from 11-eicosenol was obtained in 75% yield and with 86% Z-olefin, and can be oxidized using Swern method to yield pheromone 6. This syntheses is the shortest routes to form pheromones 3 and 6.
However, there is a limitation of this metathesis chemistry, for example, cross metathesis of the same seed oil derivatives with 1-butene is less efficient than with 1-hexene.
A little more complex metathesis can be designed and carried such as below. Secondary alcohol 18, can be reacted with 1-heptene in a Z-selective cross metathesis reaction with low catalyst loading (0.5 mol%) to yield 19 in good yield (70%) with high Z-selectivity (88%). This was then Swern oxidized to the desired ketone-containing pheromone 20 in 47% overall yield and 88% of the Z-olefin, in three steps from commercially available starting material.