On the Conjugative Isomerizations of β,γ-Unsaturated Esters. Stereochemical Generalizations and Predictions for 1,3-Prototropic Shifts under Basic Conditions

Article abstract of DOI:10.1021/jo00219a020

An investigation of the base-catalyzed conjugative isomerization of a series of β,γ-unsaturated esters to their corresponding α,β-unsaturated esters was performed.It was found that, withh sodium hydride in THF, methyl 3-butenoate isomerized initially to a 5:1 ratio of (Z)- to (E)-methyl 2-butenoates; the Z:E ratio is time dependent, and after several days, the thermodynamic ratio 1:23 = Z:E was obtained.The isomerization appears to be catalytic in NaH, as it proceeds with less than 1 molar equiv of base, no hydrogen evolution is observed, and the reaction rate is approximately first order in NaH and zero order in ester.Under the same conditions (Z)-methyl 3-hexenoate isomerized stereoselectively to (E)-methyl 2-hexenoate while (E)-methyl 3-hexenoate isomerized to a 2:1 mixture of (Z)- and (E)-methyl 2-hexenoates.These product ratios are far from the isomeric compositions obtained under equilibrating conditions.To investigate further the stereochemical outcome of these isomerizations, three isomeric β,γ-unsaturated methyl esters were studied: (a) methyl 3-ethyl-3-butenoate isomerized exlusively to (E)-methyl 3-methyl-2-pentenoate; (b) (E)-methyl 3-methyl-3-pentenoate isomerized exlusively to (Z)-methyl 3-methyl-2-pentenoate; (c) (Z)-methyl 3-methyl-3-pentenoate isomerized exlusively to (E)-methyl 3-methyl-2-pentenoate.In the latter three cases, dimerization was not observed presumably due to steric effects.Related results were observed for a smaller series of β,γ-unsaturated amide isomerizations.Examination of the literature on olefin isomerizations reveals a general trend that the current results exemplify.Thus, in the absence of severe steric factors or cation-anion complexation, deprotonation at allylic positions kinetically preferentially forms the anion possessing a cisoid crotyl subunit (if available) regardless of initial substrate conformation.The stereochemical consequences of this results in E <*> Z and Z <*> E geometry conversions in kinetic 1,2-transpositions of olefins.This generalization can also be applied to the stereochemical results of ketone, ester, and hydrazone enolate formation, base-catalyzed exchange in polysubstituted aromatics and heteroaromatics, and other reactions involving the formation of allylic or benzylic anions.