Solvent and Temperature Effects on Diastereofacial Selectivity: Amines as Co‐Solvents in n‐ Butyllithium Addition to α‐Chiral Aldehydes

Temperature‐dependent selectivity in nucleophilic additions to α‐chiral aldehydes is affected by solvent mixtures. In this context, we investigated the effect on diastereoselectivity of tertiary amines as co‐solvents. Addition of 5 mol% of an amine to hexane strongly influences the anti / syn ratio in the additions of n BuLi to 2‐phenylpropanal and to (2 S )‐2‐[( tert ‐butyl)dimethylsilyloxy]‐2‐propanal. In these hexane/amine mixtures as reaction solvents, we observed diastereoselectivities higher than those obtained in hexane. In the corresponding Eyring plots of ln( anti / syn ) against the reciprocal temperature, we observed inversion temperatures ( T inv ), these generally occurring at higher temperatures in the hexane/amine mixtures than in pure hexane. The presence of the inversion temperatures confirms that these tertiary amines take part in the solvation of the starting aldehyde, thus contributing to a solvent effect on facial selectivity. In some cases, the differential entropy of activation is the predominant factor in differentiating the diastereoselectivity among these hexane/amine mixtures. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)