Asymmetric total synthesis of all four isomers of 6-acetoxy-5-hexadecanolide: the major component of mosquito oviposition attractant pheromones

An asymmetric total synthesis of (5S,6R)-(+)-erythro-6-acetoxy-5-hexadecanolide 1a has been accomplished from readily available hex-5-yn-1-ol via Shi’s asymmetric epoxidation as the key step, in eight steps with an overall yield of 33.5%. In addition, the stereoselective synthesis of all four isomers of 6-acetoxy-5-hexadecanolide 1a–1d were obtained via Sharpless asymmetric dihydroxylation and Mitsunobu reaction as the key steps with overall yields of 16.5–21.2%, respectively.

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4-((2R,3R)-3-Decyloxiran-2-yl)butan-1-olC16H32O2[α]D25 = +26.7 (c 0.52, CHCl3)Source of chirality: Shi’s asymmetric epoxidation reactionAbsolute configuration: (2R,3R)

(5R,6R)-6-Hydroxy-5-hexadecanolideC16H30O3[α]D25 = −10.5° (c 1.2, CHCl3)Source of chirality: Sharpless AD reactionAbsolute configuration: (5R,6R)

(5S,6S)-6-Hydroxy-5-hexadecanolideC16H30O3[α]D25 = +9.8° (c 0.73, CHCl3)Source of chirality: Sharpless AD reactionAbsolute configuration: (5S,6S)

(5R,6S)-6-Hydroxy-5-hexadecanolideC16H30O3[α]D25 = −12.5° (c 0.75, CHCl3)Source of chirality: Sharpless AD reactionAbsolute configuration: (5R,6S)

(5S,6R)-6-Hydroxy-5-hexadecanolideC16H30O3[α]D25 = +12.0 (c 0.42, CHCl3)Source of chirality: Sharpless AD reactionAbsolute configuration: (5S,6R)

(5R,6S)-6-Hydroxy-5-hexadecanolide-4-nitrobenzoateC23H33NO6ee = 97.9%[α]D25 = +10.8 (c 0.44, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (5R,6S)

(5S,6R)-6-Hydroxy-5-hexadecanolide-4-nitrobenzoateC23H33NO6ee = 98.7%[α]D25 = −11.2 (c 0.23, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (5S,6R)

(5R,6R)-6-Acetoxy-5-hexadecanolideC18H32O4[α]D25 = +14.6 (c 0.12, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (5R,6R)

(5S,6S)-6-Acetoxy-5-hexadecanolideC18H32O4[α]D25 = −13.7 (c 0.10, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (5S,6S)

(5R,6S)-6-Acetoxy-5-hexadecanolideC18H32O4[α]D25 = −37.4 (c 0.65, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (5R,6S)

(5S,6R)-6-Acetoxy-5-hexadecanolideC18H32O4[α]D25 = +38.0 (c 0.60, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (5S,6R)