Catalytic 1,3-Difunctionalisation of Organic Backbones through a Highly Stereoselective, One-Pot, Boron Conjugate-Addition/Reduction/Oxidation Process

A simple one-pot, three-step synthetic route to chiral 1,3-amino alcohols and 1,3-diols has been established. Considering the overall stereo-control of the synthetic protocol, the first and key step is an enantioselective beta-boration of alpha,beta-unsaturated imines and ketones, respectively. The enantioselectivity provided by the Cu-I catalyst modified with Josiphos- and Mandyphos-type ligands has been examined. The oxidative substitution of the boryl unit with a hydroxyl group proceeds with complete retention of configuration at the C-beta-atom. In parallel, the stoichiometric reduction of the imino or carbonyl group provides a second stereogenic centre. Depending on the nature of the reducing reagent, exceptionally high diastereoselectivity is achieved, especially for syn-1,3-amino alcohols and 1,3-diols.