Heterocyclic lithium amides as chiral ligands for an enantioselective hydroxyalkylation with n-BuLi

Article abstract of DOI:10.1021/jo8005396

(Chemical Equation Presented) Chiral heterocyclic structures based on 3-aminopyrrolidines (3APs), 3-aminotetrahydrothiophens (3ATTs), and 3-aminotetrahydrofurans (3ATFs) have been synthesized. The corresponding lithium amides have been evaluated as chiral ligands in the condensation of n-BuLi on o-tolualdehyde. The returned levels of induction were in the 46-80% ee range. The cheap and easily prepared 3ATFLi's turned out to be also the best ligands, giving access to the expected R or S alcohols in a same 80% level of induction at -78°C in THF. In all cases, the sense of induction depends on the absolute configuration of C⁸ on the 3-amino appendage. A general concept is proposed to rationalize the process of induction in the presence of organolithium species.