Paraskevi Kokkala1, Thayalan Rajeshkumar2, Anastasia Mpakali3, Efstratios Stratikos3,4, Konstantinos D Vogiatzis2, Dimitris Georgiadis1. 1. Department of Chemistry, Laboratory of Organic Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15784, Athens, Greece. 2. Department of Chemistry, University of Tennessee Knoxville, Knoxville, Tennessee 37996, United States. 3. National Centre for Scientific Research Demokritos, Patriarchou Gregoriou and Neapoleos 27, Agia Paraskevi, 15341 Athens, Greece. 4. Department of Chemistry, Laboratory of Biochemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15784, Athens, Greece.
Abstract
The first example of a carbodiimide-mediated P-C bond-forming reaction is described. The reaction involves activation of β-carboxyethylphosphinic acids and subsequent reaction with Boc-aminals using acid-catalysis. Mechanistic experiments using 31P NMR spectroscopy and DFT calculations support the contribution of unusually reactive cyclic phosphinic/carboxylic mixed anhydrides in a reaction pathway involving ion-pair "swapping". The utility of this protocol is highlighted by the direct synthesis of Boc-protected phosphinic dipeptides, as precursors to potent Zn-aminopeptidase inhibitors.
The first example of a carbodiimide-mediated pan class="Chemical">P-C bond-forming reaction is described. The reaction involves activation of β-carboxyethylphosphinic acids and subsequent reaction with Boc-aminals using acid-catalysis. Mechanistic experiments using 31P NMR spectroscopy and DFT calculations support the contribution of unusually reactive cyclic phosphinic/carboxylic mixed anhydrides in a reaction pathway involving ion-pair "swapping". The utility of this protocol is highlighted by the direct synthesis of Boc-protected phosphinicdipeptides, as precursors to potent Zn-aminopeptidase inhibitors.