Diastereoselective Nucleophilic Addition to Aldehydes with Polar α- and α,β-Substituents

The stereoselectivities obtained in Lewis acid-promoted Mukaiyama aldol additions and Sakurai allylations of mono-, and syn- and anti-disubstituted aldehydes possessing various polar α- and β-substituents under non-chelating conditions are presented. The stereochemical outcome in the nucleophilic addition to α-substituted aldehydes containing an α-benzyloxy, α-fluoro or α-sulfonamide substituent are accurately predicted by current stereoinduction models. In contrast, the selectivitites obtained from addition of sterically demanding nucleophiles to α-chloro-substituted aldehydes cannot be rationalized by the same models and an alternative is discussed. The stereochemichal outcome in the additions to α,β-disubstituted aldehydes is more complex and cannot be predicted using current models.