Synthesis of racemic brevioxime and related model compounds

The synthesis, in racemic form, of the insect juvenile hormone inhibitor brevioxime (1) is described, as well as exploratory studies that led to the related model compounds 14 and 15a. The route to 1 involves Ag(+)-mediated coupling of the amine derived from 20 with the beta-keto thioester 32. Acid treatment of the coupled product 33 led by acetal hydrolysis, cyclization, and desilylation to 34a,b, from which 1 was reached by oxidation and conversion into the oxime. In the synthesis of the amino component 20, a known, but unusual, reduction was used for converting a nitrile into an amine hydrochloride.