title: Mechanistic Studies on Covalent Assemblies of Metal-Mediated Hemi-Aminal Ethers.
abstract: The use of reversible covalent-bonding in a four-component assembly incorporating chiral alcohols was recently reported to give a method for determining the enantiomeric excess of the alcohols via CD spectroscopy. Experiments that probe the mechanism of this assembly, which consists of 2-formylpyridine (2-PA), dipicolylamine (DPA), Zn(II), and alcohols, to yield zinc-complexes of tren-like ligands, are presented. The studies focus upon the mechanism of conversion of a hemi-aminal (1) to a hemi-aminal ether (3), thereby incorporating the fourth component. It was found that molecular sieves along with 3 to 4 equivalents of alcohol are required to drive the conversion of1to3. Attempts to isolate an intermediate in this reaction via addition of strong Lewis-acids led to the discovery of a five-membered ring pyridinium salt (5), but upon exposure to Zn(II) and alcohols gave different products than the assembly. This was interpreted to support the intermediacy of an iminium species. Kinetic studies reveal that the conversion of1to3is zero-order in alcohol in large excesses of alcohol, supporting rate-determining formation of an intermediate prior to reaction with alcohol. Further, the magnitude of the rate constant for interconversion of1and3are similar, supporting the notion that there are similar rate-determining steps (rds's) for the forward and reverse reactions. Hammett plots show that the rds involves creation of a negative charge (interpreted as the loss of positive charge), supporting the notion that decomplexation of Zn(II) from the assemblies to generate apo-forms of1and3is rate-determining. The individual mechanistic conclusions are combined to create a qualitative reaction coordinate diagram for the interconversion of1and3.
authors.affiliation: Department of Chemistry, The University of Texas at Austin, Austin, Texas, 78712, USA.
authors.forename: Hyun Hwa
authors.initials: HH
authors.lastname: Jo
authors.affiliation: Department of Chemistry, The University of Texas at Austin, Austin, Texas, 78712, USA. ; Division of Medicinal Chemistry, The University of Texas at Austin, Austin, Texas, 78712, USA.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Edupuganti
authors.affiliation: Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, P.R.China. lyou@fjirsm.ac.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: You
authors.affiliation: Division of Medicinal Chemistry, The University of Texas at Austin, Austin, Texas, 78712, USA.
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Dalby
authors.affiliation: Department of Chemistry, The University of Texas at Austin, Austin, Texas, 78712, USA.
authors.forename: Eric V
authors.initials: EV
authors.lastname: Anslyn