Enantioselective Bioreduction of 5-Hexen-2-one in Directional Synthesis of Insect Pheromones

(2S)-Tridecyl acetate (sex pheromone of Drosophila mulleri) and (S)-1-methylbutyl esters of (2E)-2-methylpent-2-enoic and (2E)-2,4-dimethylpent-2-enoic acids (components of aggregation pheromone of Rhyzopertha dominica lesser grain borer) were synthesized from commercially available 5-hexen-2-one (allylacetone) in overall yields of 31.0, 28.8, and 29.2%, respectively, based on the starting ketone. The key steps of the process were enantioselective bioreduction of 5-hexen-2-one with cells of Rhodococcus erythropolis A-25 actinobacteria to (S)-5-hexen-2-ol in 77% yield (ee 98.4%) and the following chemoselective reactions: ozonolytic cleavage of (S)-5-hexen-2-yl acetate, followed by reduction of the peroxy products with NaBH4 to (S)-5-hydroxypent-2-yl acetate in 88% yield; transformation of (S)-4-acetoxy-1-tosyloxypentane into (2S)-tridecyl acetate in 58% yield by dilithium tetrachlorocuprate catalyzed cross-coupling with the Grignard reagent derived from n-octyl bromide; and reduction of both ester groups in the tosylate with lithium aluminum hydride to (S)-pentan-2-ol (yield 79%), followed by its esterification with (2E)-2-methylpent-2-enoyl or (2E)-2,4-dimethylpent-2-enoyl chloride with 68 and 69% yields, respectively.

Automated summary

This article reports a method for synthesizing (2S)-tridecyl acetate and two (S)-1-methylbutyl esters from the commercially available compound 5-hexen-2-one. In this process, enantioselective bioreduction and chemoselective reactions were used to achieve the desired products.