Aldol reactions between L-erythrulose derivatives and chiral alpha-amino and alpha-fluoro aldehydes: competition between Felkin-Anh and Cornforth transition states

Both matched and mismatched diastereoselection have been observed in aldol reactions of a boron enolate of a protected L-erythrulose derivative with several chiral alpha-fluoro and alpha-amino aldehydes. Strict adherence to the Felkin-Anh model for the respective transition structures does not account satisfactorily for all the observed results, as previously observed in the case of alpha-oxygenated aldehydes. In some cases, only the Cornforth model provides a good explanation. The factors that influence this dichotomy are discussed and a general mechanistic model is proposed for aldol reactions with alpha-heteroatom-substituted aldehydes. Additional support for the model was obtained from density functional calculations.