A Highly Stereocontrolled Formal Total Synthesis of (±)- and (-)-Grandisol by 1,4-Conjugated Addition of Organocopper Reagents to Cyclobutylidene Derivatives

BERNARD, ANGELA MARIA;FRONGIA, ANGELO;J. OLLIVIER;P. P. PIRAS;SECCI, FRANCESCO;SPIGA, MARCO

2007-01-01

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Abstract

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 alpha,beta-unsaturated cyclobutylidene carbonyl derivative. (c) 2007 Elsevier Ltd. All rights reserved.