Direct, asymmetric, and stereodivergent reactions of N-azidoacetyl thioimides with aromatic acetals catalyzed by chiral nickel(II) complexes. A new approach to the synthesis of syn- and anti-β-alkoxy-α-amino acids

A new approach to the synthesis of any of the potential stereoisomers of β-alkoxy-α-amino acids derived from phenylalanine, tyrosine, tryptophan, and other β-aryl counterparts is reported. Such a method hinges on direct and asymmetric Lewis acid–mediated aldol-like reactions of N-azidoacetyl thioimides with dialkyl acetals from aromatic aldehydes catalyzed by chiral nickel(II) complexes. This produces at will both the corresponding syn and anti adducts, which can be smoothly converted into enantiomerically pure intermediates, such as dipeptide fragments. In turn, computational calculations have unveiled the clues for a better understanding of such a stereocontrolled carbon–carbon bond–forming transformation.