Diamino acids are important structural motifs present in many natural products and medicinal agents, and are implicated in a variety of biological functions. 1 1,2-Diamines derived from these amino acids have also found wide application as chiral auxilaries and as ligands for asymmetric synthesis. 2 Although a number of methods for their preparation exist, catalytic enantioselective variants remain rare. 1 A direct, catalytic, enantioselective Mannich reaction between a glycine equivalent and an imine, involving the creation of a C-C bond and two stereogenic centers in a single operation, represents an attractive and atom-efficient route to these compounds (eq 1). Although a handful of syntheses corresponding to this approach has been described, all lead to the selective formation of syn-configured products. 3 In this communication we detail a new synthesis of protected R,β-diamino acids, which delivers anti-configured products in good yields and with excellent enantioselectivities.

The combination of three reagents—a tridentate pybox ligand (pybox=pyridine bis(oxazoline)), magnesium perchlorate, and Hünig base (iPr2EtN)—allows the catalytic generation of a chiral glycine enolate from 1 that undergoes highly enantioselective addition to a range of aryl aldehydes 2. The protected aryl β‐hydroxy‐α‐amino acid products obtained include a protected version of one of the aryl serine units present in the glycopeptide antibiotic vancomycin.

Aller guten Dinge sind drei Reagentien: Ein katalytisches System aus einem dreizähnigen Pybox‐Liganden (Pybox=Bis(oxazolinyl)pyridin), Magnesiumperchlorat und der Hünig‐Base (iPr2EtN) erzeugt das chirale Glycinenolat von 1, das hoch enantioselektiv an Arencarbaldehyde 2 addiert. Unter den so erhältlichen geschützten Aryl‐β‐hydroxy‐α‐aminosäuren ist auch eine geschützte Version einer der Arylserin‐Einheiten des antibiotischen Glycopeptids Vancomycin.