Direct, Asymmetric, and Stereodivergent Reactions of <i>N</i>-Azidoacetyl Thioimides with Aromatic Acetals Catalyzed by Chiral Nickel(II) Complexes. An Approach to the Synthesis of <i>syn</i>- and <i>anti-</i>β-Alkoxy-α-amino Acids

A new approach to the synthesis of all 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 <i>N</i>-azidoacetyl thioimides with dialkyl acetals from aromatic aldehydes catalyzed by chiral nickel(II) complexes. This produces at will both the corresponding <i>syn</i> and <i>anti</i> adducts, which can be smoothly converted into enantiomerically pure intermediates such as dipeptide fragments. In turn, computational calculations have unveiled clues for a better understanding of such a stereocontrolled carbon-carbon bond-forming transformation.