A Chiral Synthesis of (+)-Lineatin, the Aggregation Pheromone of Trypodendron lineatum (Olivier), from D-Ribonolactone

Article abstract of DOI:10.1021/jo00350a045

Lineatin, the aggregation pheromone of Trypodendron lineatum (Olivier), has been shown to be (+)-(1R,4S,5R,7R)-3,3,7-trimethyl-2,9-dioxatricyclo<3.3.1.0^4,7>nonane, (+)-1, by the first stereospecific chiral synthesis.D-Ribonolactone (3) was used to prepare (2S,3R)-2,3-(isopropylidenedioxy)-4-methyl-4-<<2-(trimethylsilyl)ethoxy>methoxy>pentanal (12).Condensation with the cyanophosphonate 7 provided two isomeric α,β-unsaturated nitriles, 13.Catalytic hydrogenation furnished (3RS,5R,6R)-3-cyano-5,6-(ispropylidenedioxy)-7-methyl-7-<<2-(trimethylsilyl)ethoxy>methxoy>-1,1-dimethoxyoctane (14), which, upon acid-catalyzed hydrolysis, produced the diastereoisomeric mixture 17.Blocking of the hemiacetal function of 17 with a tert-butyldimethylsilyl group, followed by reaction with methanesulfonyl chloride, produced the mixture 22.Acid-catalyzed cyclization of the deprotected hemiacetal 23 yielded (1R,4R,5R,7S)-7-cyano-3,3-dimethyl-4-<(methylsulfonyl)oxy>-2,9-dioxabicyclo<3.3.1>nonane (24).Intramolecular nucleophilic ring closure provided (1R,4S,5R,7S)-7-cyano-3,3-dimethyl-2,9-dioxatricyclo<3.3.1.0^4,7>nonane (25).Conversion of the cyano group to a methyl group using diisobutylaluminium hydride, followed by Wolff-Kishner reduction, produced (+)-1.This 16-step synthetic route to (+)-lineatin clearly established the absolute configuration as 1R,4S,5R,7R and produced (+)-lineatin in 2.7percent overall yield.