Inherent Reactivity of Spiro-Activated Electrophilic Cyclopropanes

The kinetics of the ring-opening reactions of thiophenolates with geminal bis(acceptor)-substituted cyclopropanes in DMSO at 20 °C was monitored by photometric methods. The determined second-order rate constants of the S_N 2 reactions followed linear relationships with Mayr nucleophilicity parameters (N/s_N ) and Brønsted basicities (pK_aH ) of the thiophenolates as well as with Hammett substituent parameters (σ) for groups attached to the thiophenolates. Phenyl-substituted cyclopropanes reacted by up to a factor of 15 faster than their unsubstituted analogues, in accord with the known activating effect of adjacent π-systems in S_N 2 reactions. Variation of the electronic properties of substituents at the phenyl groups of the cyclopropanes gave rise to parabolic Hammett relationships. Thus, the inherent S_N 2 reactivity of electrophilic cyclopropanes is activated by electron-rich π-systems because of the more advanced C1-C2 bond polarization in the transition state. On the other hand, electron-poor π-systems also lower the energetic barriers for the attack of anionic nucleophiles owing to attractive electrostatic interactions.