Petschen, I., Parrilla, A., Bosch, M.P, Amela, C., & Botar, A.A. 1999 First total synthesis of the sex pheromone of the oleander scale Aspidiotus nerii: An unusual sesquiterpenic functionalized cyclobutane.. Chemistry - A European Journal 5(11): 3299-3309.

Notes: The first total synthesis of the sex pheromone of the oleander scale Aspidiotus nerii (5), an economically important polyphagous pest, is described. The synthesis is based on a stereocontrolled and completely regioselective intramolecular exo-cyclization of cis-epoxynitrile 9 to afford cyclobutane alcohol t-10 stereoselectively. Introduction of the unusual 4-methylpent-4-enyl group onto the cyclobutane skeleton was effected through Wittig reaction of aldehyde 17b with the bulky ylide 3,3(ethylenedioxy)butylidenetriphenyl-phosphorane. This process requires protection of the primary hydroxy group of 10 with a nonbulky protecting agent, like methoxymethyl (MQM) but not tetrahydropyranyl (THP), as confirmed by molecular modelling studies. After selective transformations to manipulate the three acid-sensitive protecting functionalities present, that is, the tert-butyl-dimethylsilyl (TBDMS), ethylene acetal, and MOM groups, compound 5 was obtained in 26.4% overall yield from t-10b. In a different approach, complete cleavage of these protecting groups in 19b furnished keto diol 31, which after regioselective acetylation of the primary alcohol and Wittig reaction afforded acetate 5 in 21.4% overall yield from t-10b. The synthetic material exhibited spectroscopic features identical to those of the natural material and showed remarkable biological activity in field tests.