The Predominance and Quantification of Steric Effects in the Solvolysis of Secondary Aliphatic Esters

Article abstract of DOI:10.1021/jo00369a010

The solvolysis rates of 35 tosylates in hexafluoroisopropyl alcohol are measured and compared to MM2 calculated strain energies, ΔSI, between weighted sp³ states and the lowest sp² state.For unhindered (pseudo)equatorially substituted cycloalkyl tosylates a linear correlation, free from ambiguities involved, e.g., with the leaving group simulation, is obtained which shows a sensitivity of m=1.04+/-0.05, indicating an extremely late transition state or limiting behavior.Based on the corresponding equation, it is shown that alkyl substituents in the γ- and in the β-position do not promote significant rate increases, even when there is an antiperiplanar disposition between the leaving group and a migrating β-methyl substituent.Instead, these substituents can lead to substantial ΔG^* increase (by up to 5 kcal/mol in comparison to the ΔSI prediction), which is related to steric hindrance of solvation and/or hindrance for elimination. 17-(Tosyloxy)androstanes show extremely large epimeric rate ratios of>30000; these are not due to anchimeric assistance but only to the exceedingly slow reaction of the hindered 17β isomer, whereas the fast reaction of the 17α tosylate (e.g. 200 times higher than cyclopentyl tosylate) is in line with the ΔSI calculation. endo-Bicyclo<2.2.1>heptane esters show evidence for steric hindrance; exo-norbornyl tosylate has, however, a ΔG^* value lower by 4 kcal/mol than predicted. k_s/k_c values, obtained by rate comparison in 80percent ethanol and 97percent HFIP, vary between 0.5 and 300, mainly as a result of different steric hindrance to rearside nucleophilic subnstitution