title: NMR analysis of t-butyl-catalyzed deuterium exchange at unactivated arene localities.
abstract: Regioselective labelling of arene rings via electrophilic exchange is often dictated by the electronic environment caused by substituents present on the aromatic system. Previously, we observed the presence of a t-butyl group, either covalently bond or added as an external reagent, could impart deuterium exchange to the unactivated, C1-position of estrone. Here, we provide nuclear magnetic resonance analysis of this exchange in a solvent system composed of 50:50 trifluoroacetic acid and D2O with either 2-t-butylestrone or estrone in the presence of t-butyl alcohol has shed insights into the mechanism of this t-butyl-catalyzed exchange. Fast exchange of the t-butyl group concurrent with the gradual reduction of the H1 proton signal in both systems suggest a mechanism involving ipso attack of the t-butyl position by deuterium. The reversible addition/elimination of the t-butyl group activates the H1 proton towards exchange by a mechanism of t-butyl incorporation, H1 activation and exchange, followed by eventual t-butyl elimination. Density functional calculations are consistent with the observation of fast t-butyl exchange concurrent with slower H1 exchange. The σ-complex resulting from ipso attack of deuterium at the t-butyl carbon was 6.6 kcal/mol lower in energy than that of the σ-complex resulting from deuterium attack at C1. A better understanding of the t-butyl-catalyzed exchange could help in the design of labelling recipes for other phenolic metabolites.
authors.affiliation: University of Nebraska at Omaha Chemistry, 6001 Dodge Street, Omaha, NE, 68182, USA. dstack@unomaha.edu.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Stack
authors.affiliation: University of Nebraska at Omaha Chemistry, 6001 Dodge Street, Omaha, NE, 68182, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Eastman
mesh_terms: D002384:Catalysis; D003903:Deuterium / Q000737:chemistry*; D004970:Estrone / Q000737:chemistry; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation
chemical_list: D006841:Hydrocarbons, Aromatic; D004970:Estrone; D003903:Deuterium
keywords: NMR analysis; arene; estrone; reversible; t-butyl catalyzed