Lithium diisopropylamide-mediated lithiations of N-alkyl ketimines derived from cyclohexanones reveal that simple substitutions on the N-alkyl side chain and the 2-position of the cyclohexyl moiety afford a 60,000-fold range of rates. Detailed rate studies implicate monosolvated monomers at the rate-limiting transition structures in all instances. Comparisons of experimentally derived regioselectivities and rates, taken in conjunction with density functional theory computational studies, reveal a number of factors that influence reactivities including: (a) axial versus equatorial disposition of the proton on the cyclohexane ring, (b) syn versus anti orientation of the lithiation relative to the N-alkyl group, (c) the presence or absence of a potentially chelating methoxy moiety on the N-alkyl group, (d) the presence of a 2-methyl substituent at the geminal or distal a-carbon, and (e) branching in the N-alkyl group. The isolated contributions are not large, yet they display a strong and predictable additivity leading to a kinetic resolution of imines derived from racemic 2-methylcyclohexanone.