Experimental and Theoretical Studies on Stereomutation Through gem-Difluorocyclopropanylide Intermediates

A desilylation process of optically active silyl-substituted gem-difluorocyclopropanes with tetrabutylammonium fluoride (TBAF) showed a substantial reduction of enantiopurity of the resultant gem-difluorocyclopropanes even at ambient temperatures. The electron-withdrawing aryl substituent at the 3-position in the 1-silyl-2,2-difluorocyclopropane system accelerated the racemization, indicating a correlation with the stability of the anionic intermediates. The plausible racemization pathway through homolytic cleavage of the distal bond in gem-difluorocyclopropane is inconsistent with the experimental results because the high energy of >34 kcal/mol is required for generating the open-shell 2,2-difluoropropane-1,3-diyl skeleton. The DFT studies using the anionic 2,2-difluoromethyl-3-phenylcyclopropanylide intermediate supported the alternative isomerization pathway through the intramolecular migration of hydrogen and the resultant thermodynamically stable 2,2-difluoromethyl-1-phenylcyclopropanylide anion could facilitate the racemization process at the stereocenter. Although the transition state indicated considerable activation energies, the high frequency of imaginary vibration should correlate with a barrier of a very narrow width enabling quantum tunneling under the H-migration step. The observed isotope effect is compatible with the proposed mechanism through the intramolecular H-migration.