Organocatalysts Derived from Unnatural α-Amino Acids: Scope and Applications.

The organocatalytic properties of unnatural alpha-amino acids are reviewed. Post-translational derivatives of natural alpha-amino acids include 4-hydroxy-l-proline and 4-amino-l-proline scaffolds, and also proline homologues. The activity of synthetic unnatural alpha-amino acid-based organocatalysts, such as beta-alkyl alanines, alanine-based phosphines, and tert-leucine derivatives, are reviewed herein. The organocatalytic properties of unnatural monocyclic, bicyclic, and tricyclic proline derivatives are also reviewed. Several families of these organocatalysts permit the efficient and stereoselective synthesis of complex natural products. Most of the reviewed organocatalysts accelerate the reported reactions through covalent interactions that raise the HOMO (enamine intermediates) or lower the LUMO (iminium intermediates).