A highly stereocontrolled formal total synthesis of (±)- and of (−)-grandisol by 1,4-conjugated addition of organocopper reagents to cyclobutylidene derivatives

Starting from suitable cyclopropanes, a formal total synthesis of racemic grandisol and of the enantiopure (−)-grandisol is presented. The racemic synthesis of the grandisol precursor was accomplished in five steps. The synthesis of the chiral non-racemic precursor (1S,2S,2′R)-cis of this pheromone was realized in 10 steps, with an overall yield of 45%, using the enantiopure cyclobutanone (R,S), previously obtained by ring expansion of an optically pure oxaspiropentane. The key stereodefining step was the addition of lithium dimethylcuprate to a chiral α,β-unsaturated cyclobutylidene carbonyl derivative.