Abstract: | Temperature‐dependent selectivity in nucleophilic additions is affected by the solvent. In this context, we investigated the effect on diastereoselectivity of solvent mixtures with respect to pure solvents. Binary systems of THF/hexane and of four different hydrocarbon mixtures were employed in BuLi addition to 2‐phenylpropanal, (2S)‐2‐(tert‐butyl)dimethylsilyloxy]‐2‐phenylethanal, and (2S)‐2‐(tert‐butyl)dimethylsilyloxy]‐N‐(trimethylsilyl)propan‐1‐imine. A 5‐mol‐% of THF in hexane affects the isomer ratio by reducing both ΔΔH≠ and ΔΔS≠ contributions, and suppresses Tinv. On the contrary, in hydrocarbon binary mixtures, the Tinv is still observed and occurs at a higher temperature than in pure solvents. Studying the dependence of Tinv on the hexane/decane mixture composition, we propose the formation of a peculiar solvation cluster that is unaffected by the composition of the bulk reaction solvent. |