Factors Controlling Regioselectivity in Deprotonations of Unsymmetrical Ketimines

Article abstract of DOI:10.1021/ja00351a045

The regioselectivity of deprotonation of equilibrium E-Z mixtures of the benzyl, n-butyl, cyclohexyl, phenyl, and tert-butyl imines of 2-butanone by lithium diisopropylamide (LDA) in tetrahydrofuran has been shown to be a function of both the nitrogen substituent and the temperature of the deprotonation reaction.High regioselectivity at either the methyl or methylene substituent could be obtained for all imines except the benzyl and n-butyl imines.Pure (Z)-2-butanone imines (R = n-C4H9, c-C6H11, t-C4H9), prepared by LDA deprotonation of acetone imines followed by methylation, were deprotonated by LDA at the methyl position at -78 deg C and at 0 deg C.Studies of the rates of deprotonation of the E and Z isomers of n-butyl, cyclohexyl, and tert-butyl imines of 2-butanone and of the rates and mechanisms of isomerizations of these isomeric ketimines were performed.Temperature dependent deprotonation regioselectivity was also observed in lithium diethylamide deprotonations of the benzyl, cyclohexyl, phenyl, and tert-butyl imines of 2-butanone.A general scheme accounting for these results and other accounts of variable regioselectivity in ketimine deprotonation is presented.