Highly Enantio- and Diastereoselective Synthesis of γ-Amino Alcohols from α,β-Unsaturated Imines through a One-Pot β-Boration/Reduction/Oxidation Sequence

A simple one-pot three-step synthetic route towards chiral gamma-amino alcohols has been established. Considering the overall stereocontrol of the synthetic protocol, the first and key step is the enantioselective beta-boration of alpha,beta-unsaturated imines. By screening a small library of potential chiral auxiliaries, several chiral phosphorus ligands have been identified which induce exceptional enantioselectivities (up to 99% ee). For the stoichiometric reduction of the imino group, it has been found that high levels of 1,3-diastereocontrol can be achieved using achiral reducing agents. A new methodology for the synthesis of both diastereoisomers, syn and anti, has been established. The last step of the reaction sequence, oxidative substitution of the boryl unit with a hydroxy group, proceeds with complete retention of the configuration at the C-beta-atom. Most importantly, the three simple steps can be carried out in one pot without significant change in the overall stereoselectivity.