Submitted to: Tetrahedron Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/14/2017
Publication Date: 4/24/2017
Citation: Shirali, S., Guzman, F., Weber, D.C., Khrimian, A. 2017. Expedient synthesis of bisabolenol stink bug pheromones via stereodefined cyclohex-2-enones. Tetrahedron Letters. 58:2066-2068.
Interpretive Summary: Insect pests cause a significant damage to crops and forest, and monitoring their populations aids greatly to reducing the pesticide use and biological control. Pheromones, or chemicals that trigger a natural behavioral response in another member of the same species, are commonly used as baits for sampling inset populations. We recently identified and synthesized pheromones of important agricultural pests, brown marmorated stink bug and harlequin bug. However, the existing synthesis used expensive reagents and provided low yield of an important component necessary for field attractiveness. Now we report on the new syntheses that circumvents these deficiencies. A field bioassay with harlequin bugs showed no statistically significant difference between the batch of pheromone synthesized with current method and the pheromone prepared using previously described procedure. The results of this study are of interest to other chemists and entomologist involved in the research of potential pest control compounds, and to state and federal agencies involved in monitoring and controlling insect pests of agriculture and forest.
Technical Abstract: We recently synthesized all stereoisomers of 1,10-bisaboladien-3-ol and 10,11-epoxy-1-bisabolen-3-ol, including three stink bugs pheromones, via a rhodium-catalyzed asymmetric addition of trimethylaluminum to diastereomeric mixtures of cyclohex-2-enones. However, yields of trans isomers were low and scaling reactions using expensive catalysts were cumbersome. Now we describe a new synthesis of bisabolenol stink bug pheromones via (S)- and (R)-4-((R)-6-methylhept-5-en-2-yl)cyclohex-2-enones prepared by enantioselective Michael additions of methyl vinyl ketone to (S)- and (R)-citronellals and lithium hydroxide monohydrate-catalyzed stereoselective cyclizations of intermediate ketoaldehydes. Addition of methyllithium to these enones provided cis- and trans-1,10-bisaboladien-3-ols, separated by chromatography on silica and further converted to 10,11-epoxy-1-bisabolen-3-ols. Thus, more convenient syntheses of pheromones of the rice stink bug, the harlequin bug, and brown marmorated stink bug were developed.