title: Bifunctional Tripeptide with a Phosphonic Acid as a Brønsted Acid for Michael Addition: Mechanistic Insights.
abstract: 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-NH2, 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.
authors.affiliation: Sorbonne Paris Cité-Laboratoire CSPBAT-CNRS UMR 7244, Université Paris 13, 1 Rue de Chablis, 93000, Bobigny, France.
authors.forename: Margery
authors.initials: M
authors.lastname: Cortes-Clerget
authors.affiliation: Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology, Avgda. Països Catalans, 16, 43007, Tarragona, Spain.|Departament de Química Inorgànica i Orgànica, Secció de Química Inorgànica, Universitat de Barcelona, Martí i Franquès 1-11, 08028, Barcelona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Jover
authors.affiliation: Sorbonne Paris Cité-Laboratoire CSPBAT-CNRS UMR 7244, Université Paris 13, 1 Rue de Chablis, 93000, Bobigny, France.
authors.forename: Jade
authors.initials: J
authors.lastname: Dussart
authors.affiliation: Université Paris Sud, ICMMO, UMR 8182, 15 Rue Georges Clemenceau, 91405, Orsay Cedex, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Kolodziej
authors.affiliation: Sorbonne Paris Cité-Laboratoire CSPBAT-CNRS UMR 7244, Université Paris 13, 1 Rue de Chablis, 93000, Bobigny, France.
authors.forename: Maelle
authors.initials: M
authors.lastname: Monteil
authors.affiliation: Sorbonne Paris Cité-Laboratoire CSPBAT-CNRS UMR 7244, Université Paris 13, 1 Rue de Chablis, 93000, Bobigny, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Migianu-Griffoni
authors.affiliation: Sorbonne Paris Cité-Laboratoire CSPBAT-CNRS UMR 7244, Université Paris 13, 1 Rue de Chablis, 93000, Bobigny, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gager
authors.affiliation: Sorbonne Paris Cité-Laboratoire CSPBAT-CNRS UMR 7244, Université Paris 13, 1 Rue de Chablis, 93000, Bobigny, France.
authors.forename: Julia
authors.identifier: http://orcid.org/0000-0002-1979-6913
authors.initials: J
authors.lastname: Deschamp
authors.affiliation: Sorbonne Paris Cité-Laboratoire CSPBAT-CNRS UMR 7244, Université Paris 13, 1 Rue de Chablis, 93000, Bobigny, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lecouvey
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry; D000595:Amino Acid Sequence; D002384:Catalysis; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009574:Nitro Compounds / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry*; D010757:Phosphorous Acids / Q000737:chemistry*; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D000447:Aldehydes; D000475:Alkenes; D009574:Nitro Compounds; D009842:Oligopeptides; D010757:Phosphorous Acids; C570063:phosphonic acid
keywords: Michael addition; density functional calculations; mechanism studies; organocatalysis; phosphonopeptide