title: New avenues in the directed deprotometallation of aromatics: recent advances in directed cupration.
abstract: Recent advances in the selective deprotometallation of aromatic reagents using alkali metal cuprates are reported. The ability of these synergic bases to effect deprotonation under the influence of a directing group is explored in the context of achieving new and more efficient organic transformations whilst encouraging greater ancillary group tolerance by the base. Developments in our understanding of the structural chemistry of alkali metal cuprates are reported, with both Gilman cuprates of the type R2CuLi and Lipshutz and related cuprates of the type R2Cu(X)Li2 (X = inorganic anion) elucidated and rationalised in terms of ligand sterics. The generation of new types of cuprate motif are introduced through the development of adducts between different classes of cuprate. The use of DFT methods to interrogate the mechanistic pathways towards deprotonative metallation is described. Theoretical modelling of in situ rearrangements undergone by the cuprate base are discussed, with a view to understanding the relationship between R2CuLi and R2Cu(X)Li2, their interconversion and the implications of this for cuprate reactivity. The advent of a new class of adduct between different cuprate types is developed and interpreted in terms of the options for expelling LiX from R2Cu(X)Li2. Applications in the field of medicinal chemistry and (hetero)arene derivatization are explored.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. aehw2@cam.ac.uk.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Harford
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. aehw2@cam.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Peel
authors.affiliation: UMR 6226, Institut des Sciences Chimiques de Rennes, Chimie et Photonique Moléculaires, Université de Rennes 1-CNRS, Campus de Beaulieu, Bâtiment 10A, Case 1003, 35042 - Rennes Cedex, France. Florence.Mongin@univ-rennes1.fr.
authors.forename: Floris
authors.initials: F
authors.lastname: Chevallier
authors.affiliation: Advanced Elements Chemistry Research Team, RIKEN Center for Sustainable Resource Science (CSRS), and Elements Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. uchiyama@mol.f.u-tokyo.ac.jp and Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Takita
authors.affiliation: UMR 6226, Institut des Sciences Chimiques de Rennes, Chimie et Photonique Moléculaires, Université de Rennes 1-CNRS, Campus de Beaulieu, Bâtiment 10A, Case 1003, 35042 - Rennes Cedex, France. Florence.Mongin@univ-rennes1.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Mongin
authors.affiliation: Advanced Elements Chemistry Research Team, RIKEN Center for Sustainable Resource Science (CSRS), and Elements Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. uchiyama@mol.f.u-tokyo.ac.jp and Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Uchiyama
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. aehw2@cam.ac.uk.
authors.forename: Andrew E H
authors.initials: AEH
authors.lastname: Wheatley
mesh_terms: D003300:Copper / Q000737:chemistry*; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D008672:Metals, Alkali / Q000737:chemistry*; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry*
chemical_list: D006841:Hydrocarbons, Aromatic; D008672:Metals, Alkali; D009942:Organometallic Compounds; D003300:Copper