Professor Willie Motherwell FRS FRSE - Alexander Williamson Professor of Chemistry

Research Overview

Our international group is a relatively small one (10-15 co-workers) but is highly adventurous and productive.

Our research effort in Organic Synthesis is directed towards the invention of new reactions and reagents and their application in processes and syntheses of relevance to the petrochemical and pharmaceutical industries. Within this framework we choose to explore relative intermediates which are less commonly used in traditional organic chemistry and hence some of our current programmes feature themes involving transition metal catalysed reactions, metallocarbenoids, hydride transfer, electron transfer, and free radical chain reactions.

Some recent studies include such diverse areas as the selective introduction of fluorine atoms into pharmaceutically important molecules using hypervalent iodoarene difluorides, a rhodium-catalysed method for controlled generation of enolate anions which does not involve the carbonyl group, the generation and reactivity of organozinc carbenoids for alkoxycyclopropanation without the use of dangerous or toxic diazo or gem-dihalo compounds, a preparative free radical chain reaction for biaryl synthesis, and catalytic photoinduced charge transfer osmylation for cyclitol production. We also have an increasing interest in the biomedical sciences. Programmes on such themes as the chemistry of thionitrite esters, non covalent interactions and the design and synthesis of artificial enzymes are also underway.

The new reactions which we explore are tested in appropriate total synthesis of both natural and unnatural analogues of biologically active materials, as in our recent synthesis of Steganone analogues and Pinitol (Chem. Commun. 1997, 1283 and 1999, 917). Our research philosophy of invention and discovery has remained unchanged over the years and can be found under the title "A Curiosity-Driven Search for New Chemical Reactions" in Aldrichimica Acta, 1992, 25, 71.

Some of the above facets are encapsulated by the reactions shown in the scheme. (Cover feature J. Chem. Soc., Perkin 1, 1999, October Number 20).


Reaction schemes relevant to the Motherwell group

Selected Publications by theme

Free Radical Reactions

  1. E. Bonfand, L. Forslund, W. B. Motherwell, and S. Vazquez. Observations on the Enforced Orthogonality Concept for the Synthesis of Fully Hindered Biaryls by a Tin-Free Intramolecular Radical Ipso Substitution. Synlett, 2000, 4, 475-478.
  2. P. Girard, N. Guillot, W. B. Motherwell, R. S. Hay-Motherwell, and P. Potier. The Reaction of Thionitrites with Barton Esters: a Convenient Free Radical Chain Reaction for Decarboxylative Nitrosation. Tetrahedron , 1999 (Barton Memorial Issue), 55, 3573-3584.
  3. M. Cavero, W.B. Motherwell, P. Potier and J.-M. Weibel,Thioepoxide Formation by Ring Closure of Allylthiyl Radicals – A Novel Rearrangement of Allylic Thionitrites. J. Chem. Soc. Chem. Commun., 2002 (2394)

Fluorination

  1. J.J. Edmunds, M.F. Greaney, W.B. Motherwell and J.W. Steed,Fluorination of Sulfur-containing Amides using Difluoroiodotoluene. J. Chem. Soc. Perkins Trans 1, 2002, 2816-2826.
  2. W.B.Motherwell and L. Storey, Some studies on nucleophilic trifluoromethylation using the shelf-stable trifluoromethylacetophenone-N,N-dimethyltrimethylsilylamine adduct. Journal of Fluor. Chem., 2005, 126,491-498. Special Issue dedicated to Professor R. Chambers.

Transition Metal Catalysed Reactions

  1. L. J. Gazzard, W. B. Motherwell, and D. A. Sandham. Rhodium promoted isomerisation of allylic alkoxides: a new method for enolate anion formation. J. Chem. Soc., Perkin Trans, 1999, 1, 979-993.
  2. P. M. J. Jung, W. B. Motherwell and A.S. Williams. Stereochemical observations on the bromate induced monobromopentahydroxylation of benzene by catalytic photoinduced charge transfer osmylation. A concise synthesis of (±) pinitol. J. Chem. Soc. Chem. Commun., 1997, 1283-1284.
  3. M. Freiria, A.J. Whitehead, D.A. Tocher, W.B. Motherwell, Further observations on the rhodium(I)- catalysed tandem hydrosilylation-intramolecular aldol reaction. Tetrahedron, 2004, 60, 2673-2692

Organozinc Carbenoids

  1. W.B. Motherwell, On the Evolution of Organozinc Carbenoid Chemistry from Carbonyl Compounds. J. Organometal. Chem., 2001, 624, 41-46.
  2. G. Begis, D. Cladingboel and W.B. Motherwell, The Generation and Trapping of Organozinc carbenoids from N-diethoxy-methyl Amides: a new Amidocyclopropanation Reaction. J. Chem. Soc. Chem. Commun. 2003, 2656-2567
  3. W. B. Motherwell, G.Bégis, D. E. Cladingboel, L. Jerome and T. D. Sheppard , Observations on the direct amidocyclopropanation of alkenes using organozinc carbenoids, Tetrahedron, 2007 63 6462-6476

Multicomponent Reactions and Tandem Sequences

  1. L. J. Diorazio, W.B. Motherwell, T. D. Sheppard, R.W. Waller,Observations on the Reaction of N-Alkyloxazolidines, Isocyanides and Carboxylic Acids: A Novel Three-Component Reaction Leading to N-Acyloxyethylamino Acid Amides. Synlett 2006 2281-2283.
  2. W.B.Motherwell and A. J.Whitehead , A Convenient One-Pot Aza-Annulation of Primary Amines, Acryloyl Chloride and Electron – Deficient Allenes,. P. J. Gray, Synlett, 2007, 431- 434.

Artificial Enzymes

  1. A.E. Aliev, C.E. Atkinson and W.B. Motherwell,Binding Site Optimsation for Artificial Enzymes by Diffusion NMR of Small Molecules. Chemistry, A European Journal, 2003, 9, 1714-1723.
  2. C. E. Atkinson, W. B. Motherwell, A.E.Aliev, B. Warrington and S. C. Wong,A Simple Protocol for the Modular Assembly of "Millipede" Artificial Enzymes through Design and Selection. Angew. Chem. Int. Edn., 2004, 43, 1225-1228
  3. W.B.Motherwell, J. Moise, A.E. Aliev , M. Nic, S.J .Coles, P.N .Horton, M.B. Hursthouse, G. Chessari, C.A. Hunter and J.G. Vinter,Some Studies of Noncovalent Functional Group – Arene Interactions.,Angew Chem. Int. Ed n, 2007 46(41) 7823-7826 DOI:10.1002/anie.200701463.