<i>Syn</i>-Selective Synthesis of β‑Branched α‑Amino Acids by Alkylation of Glycine-Derived Imines with Secondary Sulfonates

A <i>syn</i>-selective synthesis of β-branched α-amino acids has been developed based on the alkylation of glycine imine esters with secondary sulfonates. The potassium counterion for the enolate, the solvent, and the leaving group on the electrophile were key levers to maximize the diasteroselectivity of the alkylation. The optimized conditions enabled a straightforward preparation of a number of β-branched α-amino acids that can be challenging to obtain

Scale-up of Azide Chemistry: A Case Study

We report research and development conducted to enable the safe implementation of a highly enantioselective palladium-catalyzed desymmetrization of a <i>meso</i>–<i>bis</i>-ester using trimethylsilylazide (TMSN₃) as the nucleophile. This work is used as a case example to discuss safe practices when considering the use of azide reagents or intermediates, with a focus on the thermodynamic and quantitative analysis of the hazards associated with hydrazoic acid (HN₃)