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

Preparation of 4-Halobenzoate-Containing Phosphane-Based Building Blocks for Labeling Reactions Using the Traceless Staudinger Ligation

“…[7][8][9] Due to the mild reaction conditions and the formation of an amide (peptide) bond, 10 this Staudinger approach has found various applications, e.g. the labeling of bioactive molecules with fluorescence dyes 11 as well as radionuclides, [12][13][14] the chemoselective modification of peptides 5,15,16 and proteins, 17,18 the modification of polymers, 19 the preparation of special lactams, 20,21 or the synthesis of glycosyl amides. 22,23 The absence of cytotoxic copper salts makes the Staudinger approach interesting for potential in vitro and in vivo applications in contrast to other ligation reactions like the 1,3-dipolar Huisgen cycloaddition.…”

6.11 N-Acylation Reactions of Amines

“…However, the problem of carrying out medium-ring lactamization cyclization reactions has been addressed indirectly by van Maarseveen and coworkers using an intramolecular Staudinger reaction to facilitate ring closure ( Figure 50). 336 First, the amino group of an amino acid is converted into its corresponding azide derivative, before a thio-phosphane auxiliary is introduced as its borane complex to prevent unwanted side reactions and premature cyclization from occurring. Removal of the borane of the resultant intermediate with 1,4-diazabicyclo[2.2.2]octane (DABCO) liberates a phosphane, which then undergoes facile Staudinger ligation to afford carbocyclic and heterocyclic medium-ring lactams in acceptable yields.…”

Total chemical synthesis of polypeptides and proteins: chemistry of ligation techniques and beyond

“…In another interesting report, traceless Staudinger ligation was employed to prepare medium-sized lactams from peptides made of a-and b-amino acids. 125 …”