Highly Regioselective Addition of Allylic Zinc Halides and Various Zinc Enolates to [1.1.1]Propellane

We report a range of highly regioselective openings of [1.1.1]propellane with various allylic zinc halides, as well as zinc enolates of ketones, esters and nitriles. The resulting zincated bicyclopentanes (BCPs) were trapped with a range of electrophiles including acyl chlorides, sulfonothioates, hydroxylamino benzoates, tosyl cyanide as well as aryl and allyl halides, generating highly functionalized BCP‐derivatives. The unusually high regioselectivity of these reactions has been rationalized using DFT calculations. A bioisostere of the synthetic opioid pethidine was prepared in 95 % yield in one step using this method.
A wide range of allylic zinc reagents as well as zinc enolates open [1.1.1]propellane to generate zincated bicyclopentanes (BCPs) in a highly regioselective manner. These intermediate zinc reagents are trapped with various electrophiles, giving access to fully functionalized BCPs including a BCP‐analogue of the synthetic opioid pethidine.