title: Enolate Stabilization by Anion-π Interactions: Deuterium Exchange in Malonate Dilactones on π-Acidic Surfaces.
abstract: Of central importance in chemistry and biology, enolate chemistry is an attractive topic to elaborate on possible contributions of anion-π interactions to catalysis. To demonstrate the existence of such contributions, experimental evidence for the stabilization of not only anions but also anionic intermediates and transition states on π-acidic aromatic surfaces is decisive. To tackle this challenge for enolate chemistry with maximal precision and minimal uncertainty, malonate dilactones are covalently positioned on the π-acidic surface of naphthalenediimides (NDIs). Their presence is directly visible in the upfield shifts of the α-protons in the (1) H NMR spectra. The reactivity of these protons on π-acidic surfaces is measured by hydrogen-deuterium (H-D) exchange for 11 different examples, excluding controls. The velocity of H-D exchange increases with π acidity (NDI core substituents: SO2 R>SOR>H>OR>OR/NR2 >SR>NR2 ). The H-D exchange kinetics vary with the structure of the enolate (malonates>methylmalonates, dilactones>dithiolactones). Moreover, they depend on the distance to the π surface (bridge length: 11-13 atoms). Most importantly, H-D exchange depends strongly on the chirality of the π surface (chiral sulfoxides as core substituents; the crystal structure of the enantiopure (R,R,P)-macrocycle is reported). For maximal π acidity, transition-state stabilizations up to -18.8 kJ mol(-1) are obtained for H-D exchange. The Brønsted acidity of the enols increases strongly with π acidity of the aromatic surface, the lowest measured pKa =10.9 calculates to a ΔpKa =-5.5. Corresponding to the deprotonation of arginine residues in neutral water, considered as "impossible" in biology, the found enolate-π interactions are very important. The strong dependence of enolate stabilization on the unprecedented seven-component π-acidity gradient over almost 1 eV demonstrates quantitatively that such important anion-π activities can be expected only from strong enough π acids.
authors.affiliation: Department of Organic Chemistry, University of Geneva, Geneva, Switzerland), Fax.
authors.forename: François N
authors.initials: FN
authors.lastname: Miros
authors.affiliation: Department of Organic Chemistry, University of Geneva, Geneva, Switzerland), Fax.|Institute of Polymers, ETH Zurich, Zurich, Switzerland.|Qingdao University of Science and Technology, P. R. China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Organic Chemistry, University of Geneva, Geneva, Switzerland), Fax.|South Texas College, McAllen, Texas, USA.
authors.forename: Gevorg
authors.initials: G
authors.lastname: Sargsyan
authors.affiliation: Department of Organic Chemistry, University of Geneva, Geneva, Switzerland), Fax.
authors.forename: Marion
authors.initials: M
authors.lastname: Pupier
authors.affiliation: Department of Organic Chemistry, University of Geneva, Geneva, Switzerland), Fax.
authors.forename: Céline
authors.initials: C
authors.lastname: Besnard
authors.affiliation: Department of Organic Chemistry, University of Geneva, Geneva, Switzerland), Fax.|AKYADO, Remaufens, Switzerland.
authors.forename: César
authors.initials: C
authors.lastname: Beuchat
authors.affiliation: Department of Organic Chemistry, University of Geneva, Geneva, Switzerland), Fax.
authors.forename: Jiri
authors.initials: J
authors.lastname: Mareda
authors.affiliation: Department of Organic Chemistry, University of Geneva, Geneva, Switzerland), Fax.
authors.forename: Naomi
authors.initials: N
authors.lastname: Sakai
authors.affiliation: Department of Organic Chemistry, University of Geneva, Geneva, Switzerland), Fax. stefan.matile@unige.ch.
authors.forename: Stefan
authors.initials: S
authors.lastname: Matile
keywords: acidity; anion-π interactions; deuterium exchange; enolates; macrocycles; stereoselectivity