Intramolecular Staudinger Ligation: A Powerful Ring-Closure Method To Form Medium-Sized Lactams

摘要

Medium-sized lactams constitute a very important class of compounds with high potential in drug, materials, and catalysis research. Efficient ring closure to form many medium-sized (7-10-membered) lactams is still a significant synthetic problem. Direct ring closure through the activation of the carboxy group of an ω-amino acid only gives high yields if structural elements that favor the facile approach of the mutually reactive end groups are present within the linear precursor. A class of compounds that are especially resistant to ring closure are dipeptides made up of linear α- and a linear β-amino acid, which represent potential prescursors to the monocyclic seven-membered [1,4]diazepane-2,5-dione (or homodiketopiperazine) skeleton. The main reason for the failure of these dipeptides to undergo cyclization is the predominant trans arrangement of the amide bond, which prevents the required spatial positioning of the terminal amine and activated carboxy groups for cyclization to occur.