Fluorine in pheromones: Synthesis of fluorinated 12-dodecanolides as emerald ash borer pheromone mimetics

Abstract

A series of five 12-dodecanolides have been synthesised containing CF2 groups at C5, C6, C7, C8 and in one case, a double substitution at C5 & C8, as a strategy to bias the conformational space accessed by these macrocycles, and to assess if the analogues may act as mimetics of 13-membered macrolide pheromones associated with the emerald ash borer. Accordingly individual syntheses of 5,5-difluoro- 5, 6,6-difluoro- 6, 7,7-difluoro- 7, 8,8-difluoro- 8 and 5,5,8,8-tetrafluoro- 9, 12-dodecanolides are outlined, and X-ray structural data were obtained for three (5, 8 and 9) of these compounds. The structures show clearly that the CF2 groups occupy ‘corner’ locations in the macrocycle consistent with their ability to bias accessible conformations. The fluorine containing 12-dodecanolides all generated an electro-antennogram response in female beetles.