Cortes-Clerget Margery, Jover Jesús, Dussart Jade, Kolodziej Emilie, Monteil Maelle, Migianu-Griffoni Evelyne, Gager Olivier, Deschamp Julia, Lecouvey Marc
Sorbonne Paris Cité-Laboratoire CSPBAT-CNRS UMR 7244, Université Paris 13, 1 Rue de Chablis, 93000, Bobigny, France.
Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology, Avgda. Països Catalans, 16, 43007, Tarragona, Spain.
Chemistry. 2017 May 11;23(27):6654-6662. doi: 10.1002/chem.201700604. Epub 2017 Apr 20.
Enamine catalysis is a widespread activation mode in the field of organocatalysis and is often encountered in bifunctional organocatalysts. We previously described H-Pro-Pro-pAla-OMe as a bifunctional catalyst for Michael addition between aldehydes and aromatic nitroalkenes. Considering that opposite selectivities were observed when compared to H-Pro-Pro-Glu-NH , an analogue described by Wennemers, the activation mode of H-Pro-Pro-pAla-OMe was investigated through kinetic, linear effect studies, NMR analyses, and structural modifications. It appeared that only one bifunctional catalyst was involved in the catalytic cycle, by activating aldehyde through an (E)-enamine and nitroalkene through an acidic interaction. A restrained tripeptide structure was optimal in terms of distance and rigidity for better selectivities and fast reaction rates. Transition-state modeling unveiled the particular selectivity of this phosphonopeptide.
