Margery Cortes Clerget
University of California at Santa Barbara, USA
Margery Cortes-Clerget has completed her PhD in 2015 from the Université Paris 13 (France) under the supervision of Prof. Marc Lecouvey. She is currently doing her Post-doctoral researches in the field of Green Chemistry at the University of California at Santa Barbara under the supervision of Prof. Bruce Lipshutz.
By miming enzymes through H-bonding, hydrophobic effects and in-solvent organization, peptides are great candidates for asymmetric synthesis purpose, acting as multiactivating molecules. Combinatorial screening methods allowed the identification of efficient peptide catalysts for C-X and C-C bonds creation. In 2007, Wennemers introduced the tripeptide H-R-Pro-Pro-Glu-NH2 for Michael addition with great selectivities. Herein we propose an unprecedented combination of aminocatalysis and phosphonic acid activation on a peptide structure. A library of 16 organocatalysts, holding a phosphonic acid was synthesized with a particular emphasis on amino acids modification to install the phosphonic acid on a side chain. These peptides were applied to Michael addition between aldehydes with nitroalkenes with up to 95:5 d.r. and 93:7 e.r at only 1 mol% loading. These catalysts were easily recovered thanks to their aqueous solubility and reused over 10 cycles without any significant loss of selectivity. The impact of the phosphonic acid in place of a carboxylic acid was investigated, as opposite selectivities were observed. Mechanistic investigations were conducted through structural modifications, kinetic studies and modelisation to understand, and, in the future, optimize this library.