Stereocontrolled Synthesis of (±)-Grandisol

Abstract A synthetic approach to grandisol is described. The route to the cyclobutane core relies on an efficient intramolecular [2+2] cyclo­addition that establishes the required cis-ring fusion at the adjacent side chains of the cyclobutane ring. Using a new two-step lithium/halide homologation procedure, norgrandisol was efficiently converted into grandisol. This new approach enables the synthesis of grandisol in five steps from commercially available starting material in 22% overall yield.