Solvation-dependent diastereofacial selectivity: addition of lithioacetonitrile to 2-phenyl propanal

Diastereofacial selectivity in the addition of lithioacetonitrile to 2-phenyl propanal is temperature and solvent-dependent. Each solvent studied (benzene, toluene, n-hexane, cyclohexane, methylcyclohexane, THF, and diethyl ether) shows a different Eyring plot of ln(anti/syn) versus 1/T with specific differential activation parameters ΔΔH≠ and ΔΔS≠, and discloses the presence of inversion temperatures (Tinvs). We demonstrated that the opposite temperature behaviour of the diastereomeric ratio (dr) observed for n-hexane and methylcyclohexane does not depend on the base (n-BuLi, LDA and LiHMDS) used to generate the anion, but is exclusively due to the reaction solvent. A 5 mol% of an amine in n-hexane and methylcyclohexane deeply affects the anti/syn ratio, the differential activation parameters, and the Tinv values. For n-hexane we were able to connect the inversion temperature of the pure solvent and of the Bu3N-mixture with dynamic solvation phenomena revealed by VT 13C NMR measurements.