title: Gaining Insight Into Reactivity Differences Between Malonic Acid Half Thioesters (MAHT) and Malonic Acid Half Oxyesters (MAHO).
abstract: An efficient two-step synthesis of structurally and functionally diverse thiophenol- and (cyclo)alkyl-derived malonic acid half thioesters (MAHTs) and phenol-derived malonic acid half oxyesters (MAHOs) has been achieved using cheap, readily available and easily handled starting materials. The synthesis of the MAHTs and MAHOs (the majority of which have not been previously reported) is readily scalable to afford gram quantities of product. In a hydrogen→deuterium exchange, an interesting stereoelectronic effect was observed when different aryl groups were incorporated. Significant changes in the rates of hydrogen→deuterium exchange and levels of isotope incorporation were observed. By way of example, using [2H]methanol and 4-bromophenol-derived MAHO afforded only 14 % [2H]-incorporation (9 min, k=31) whereas the corresponding 4-bromothiophenol-derived MAHT afforded 97 % [2H]-incorporation (9 min, k=208). In a benchmark procedure and comprehensive DFT study, 54 ester and thioester configurations and conformations were characterized. In the MAHT series, a sulfur-containing molecular orbital provides a path for increased delocalisation of electron density into the enol that is unavailable in MAHOs. This facilitates keto-enol tautomerisation and consequently enhances the rate and percentage of hydrogen→deuterium exchange.
authors.affiliation: School of Chemistry, Norwich Research Park, University of East Anglia, NR4 7TJ, UK.
authors.forename: Sean P
authors.identifier: http://orcid.org/0000-0002-9087-9463
authors.initials: SP
authors.lastname: Bew
authors.affiliation: School of Chemistry, Norwich Research Park, University of East Anglia, NR4 7TJ, UK.
authors.forename: G Richard
authors.initials: GR
authors.lastname: Stephenson
authors.affiliation: Laboratoire de Chimie Moleculaire et thio-organique (LCMT), UMR CNRS 6507, Ensicaen, 6 Boulevard du Marechal Juin, 14050, Caen, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Rouden
authors.affiliation: School of Chemistry, Norwich Research Park, University of East Anglia, NR4 7TJ, UK.
authors.forename: Jeremey
authors.initials: J
authors.lastname: Godemert
authors.affiliation: School of Chemistry, Norwich Research Park, University of East Anglia, NR4 7TJ, UK.
authors.forename: Haseena
authors.initials: H
authors.lastname: Seylani
authors.affiliation: School of Chemistry, Norwich Research Park, University of East Anglia, NR4 7TJ, UK.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Martinez-Lozano
keywords: density functional calculations; hydrogen bonding; isotope exchange; reaction rates; thioesters