Synthesis of Racemic δ,δ‐Dimethylproline Derivatives

A versatile methodology for the preparation of racemic δ,δ‐dimethylproline derivatives has been developed. Methyl N ‐Boc‐δ,δ‐dimethylprolinate was synthesized from a β‐amino acid in six steps and 55 % overall yield. The route is amenable to the preparation of a broad range of δ,δ‐disubstituted prolines by starting with the adequate β‐amino acids. In addition, one of the intermediate compounds in the synthetic route has been used for the preparation of a δ,δ‐dimethylproline derivative that is substituted at the β‐position with a phenyl group. This has been achieved by coupling phenylboronic acid with a regioselectively generated vinyl triflate followed by a stereoselective hydrogenation.