Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• groups is accessible for the use as precursors of peptidomimetics. Keywords: amino acid analogous side chains; desilylation; Ellman’s chiral sulfinamide; intramolecular Huisgen reaction; peptidomimetics; propargylamines; rearrangement to α,β-unsaturated imines; Introduction Terminal alkynes display an

• chiral sulfinamide auxiliary to produce diastereomerically pure amines [7]. Ellman’s chiral sulfinamide can be readily synthesized on a laboratory scale [24]. Moreover, sulfinamides can be cleaved easily under acidic conditions [1][25][26] and the produced sulfinic acid can even be recycled [25][27

• with Ellman’s chiral sulfinamide, mediated by KHSO4 [29], Cs2CO3 [30], Ti(OEt)4 [31][32][33], or CuSO4 [34], followed by either reduction [35][36][37][38][39][40] or addition of a nucleophile to the imine [41]. In general, there are two options (Figure 3) for the synthesis of enantiomerically pure