The controversy about nonclassical ions: Finished too early?

Abstract

AbstractThe debate on nonclassical ions centered almost exclusively on the behavior of 2‐norbornyl esters. The hallmark of a nonclassical charge distribution in solvolysis reactions was always seen in the seemingly exceptional fast reaction of the 2‐exo‐derivatives, with slow rates of the endo‐esters. While the nonclassical bridged structure of the free norbornyl ion has been unequivocally established, possible steric contributions to the rate differences in solution remained a matter of debate. Many formerly used solvents were less suited to exhibit uniform reaction mechanisms; the most appropriate solvent hexafluorisopropanol was introduced rather late. Solvolysis rates of many cyclic esters including medium rings can be predicted by force field calculated strain energy differences ΔSIsp3/sp2 between sp3 and sp2 states. Large deviations from the correlation are observed for 2‐tosyloxy norbornane‐ and for 17‐tosyloxy steroids; they indicate that both nonclassical charge delocalization and steric hindrance play a major role for the reactivity differences. These reach an unprecedented rate constant ratio of >30.000 between, eg, the 17‐steroid epimers, much larger than the ratio of 1.550 in 2‐norbornyl reactions. The presence of alkyl groups or hydrogen antiperiplanar to the leaving group can lead to extreme reactivities by 1,2‐shifts or Wagner‐Meerwein rearrangement if asymmetric bridged transition states can occur which approach the stability of tertiary cations. The long controversy about nonclassical ions illustrates how progress in science can deviate significantly from the ideal pathways lined out by Karl Popper.