Abstract
Conformationally restrained exo-isomers of N-Boc-protected spiro[2′,2′-difluorocyclopropane-3′,2′-tropanes] were synthesized in 62–83% yield via absolutely diastereoselective cycloaddition of CF2, generated in situ from Me3SiCF3/NaI in refluxing THF, to double bonds of 3-alkylidenetropanes. Standard removal of Boc protecting groups afforded corresponding exo-spiro[2′,2′-difluorocyclopropane-3′,2′-tropane] hydrochlorides in 82–94% yields. DFT and CCSD(T) calculations revealed that the observed exo-selectivity of difluorocarbene addition is likely to be caused by a lower activation barrier of the exo-difluorocyclopropanation compared to the endo-reaction.
Key words
tropane - difluorocarbene - diastereoselective difluorocyclopropanation - DFT - CCSD(T)