Effective and Scalable General Method for the Preparation of Enantiomeric (α‐Aminoalkyl)dimethylphosphine Oxides

Abstract

AbstractThe Ti(OPr‐i)4‐mediated three–component condensation of enantiomeric Ellman's amides, dimethylphosphine oxide, and aliphatic, aromatic or heteroaromatic aldehydes proceeds in high yields and diastereoselectivities enabling the rapid, scalable and general asymmetric synthesis of (α‐amino)dimethylphosphine oxide derived compounds bearing alkyl, cycloalkyl or hetaryl group at the chiral carbon atom. Asymmetric synthesis of α‐amino‐α‐polyfluoroalkyl dimethylphosphine oxides was accomplished through diastereoselective addition of dimethylphosphine oxide to enantiomeric Ellman's aldimines, RFCH=NS(O)tert‐Bu (RF=CF3, CHF2, PhCF2).