Iain ColdhamProf. Iain Coldham

Professor of Synthetic Organic Chemistry

Room: C99

Tel: +44-(0)114-22-29428

Fax: +44-(0)114-22-29346

email:

 


 

Biographical Sketch

Professor Coldham obtained a BA in Chemistry from the University of Cambridge in 1986, followed by a PhD in 1989. After a postdoctoral research fellowship at the University of Texas at Austin (1989-1991), he was a member of staff at the University of Exeter as a Lecturer/Senior Lecturer from 1991 to 2003. In 2003 he became a Reader at the University of Sheffield, where he was promoted to Professor of Synthetic Organic Chemistry in 2008.

Research Keywords

Organic synthesis, new methodology in organic chemistry, asymmetric organolithium chemistry, heterocyclic chemistry

Teaching Keywords

Organic Chemistry

Selected Publications:

Research Interests

New methodology in organic chemistry. Synthetic chemistry depends on reliable, high-yielding and selective reactions that access a wide variety of different structures. The discovery of new methods in synthesis is crucial to expand the range of novel compounds that can be made easily. Especially important is the development of new carbon-carbon bond-forming reactions. Our research group is studying the use of organometallic compounds in asymmetric synthesis, especially for carbon-carbon bond formation of nitrogen-containing compounds, prevalent in many biologically active molecules. We have founColdhamPicforWebd that 2-lithiopyrrolidines, piperidines and other cyclic amines undergo dynamic resolution in the presence of a chiral ligand (L*), leading to highly enantioenriched 2-substituted cyclic amine products. We have determined the kinetics of enantiomerization of several chiral organolithium compounds.

Synthesis of biologically active compounds.
We are using dipolar cycloaddition chemistry to access a variety of alkaloid structures. Intramolecular cycloadditions provide an efficient means to build up bicyclic and polycyclic ring systems in a rapid and stereocontrolled way. We have shown that this chemistry is applicable to the synthesis of the core ring system of the alkaloid manzamine A, which has significant biological activity (anti-cancer, anti-malarial, and other activity). One dipole that we use is an azomethine ylide, that we make by condensation of a secondary amine with an aldehyde. Intramolecular cycloaddition sets up two new rings and up to four new stereocentres in a single step. We have prepared simpler analogues of manzamine A and other heteroaromatic compounds to probe their biological activity.
Recently, we have found that primary amines (such as amino-acids, amino-esters, hydroxylamine) can be used to condense with an aldehyde and promote a cascade process involving imine formation, cyclization, ylide formation and cycloaddition all in one pot. This chemistry provides an efficient method to prepare three rings directly from an acyclic aldehyde in a stereocontrolled way and has been applied to the total syntheses of several alkaloids (such as aspidospermidine, aspidospermine, quebrachamine and myrioxazine A).

Teaching Section

Organic Chemistry

Undergraduate Courses Taught

  • Organic reaction mechanisms (Year 2)
    This segment introduces substitution and elimination reactions.
  • Frontier Molecular Orbital Theory (Year 3 & 4)
    This segment introduces the applications of frontier molecular orbital theory in organic chemistry to understand conformation and reactivity.
  • Organic Chemistry of the Main Group Elements (Year 4)
    This segment surveys the synthetic and mechanistic features of a range of organoelement reagents in the context of modern organic synthesis.

Tutorial & Workshop Support

  • First Year General Tutorials.
  • Second Year Organic Chemistry Tutorials.
  • Third Year Workshops (Heterocyclic Chemistry).
  • Third Year Literature Review.
  • Fourth Year Workshops (Organic Chemistry of Main Group Elements).

Laboratory Teaching

  • Third Year Advanced Practical Chemistry Techniques
  • Fourth Year Research Project

Journal articles

Chapters

Conference proceedings papers

  • Coldham I, Burrell AJM & Oram N (2008) ORGN 422-Highly efficient synthesis of tricyclic amines by a cyclization/cycloaddition cascade: Total syntheses of aspidospermidine, aspidospermine and quebrachamine. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 235
  • Pih SM & Coldham I (2005) Towards the total synthesis of manzamine a using 1,3 dipolar cycloaddition of azomethine ylides.. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 229 (pp U370-U370)
  • Klein R, Gawley RE, Ashweek NJ, Brandt P, Coldham I, Dufour S & Haeffner F (2003) Enantiomerization of unstabilized and dipole-stabilized 2-lithiopyrrolidines: (Absolute) barrier to inversion. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 226 (pp U149-U149)
  • Coldham I & Dufour S (2003) Dynamic resolution of alpha-amino-organolithium species.. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 226 (pp U169-U169)
  • Coldham I, Fernandez JC, Rabot R & Crapnell KM (2001) Synthesis of the core ring system of manzamine A using azomethine ylide cycloaddition chemistry.. ABSTR PAP AM CHEM S, Vol. 221 (pp U100-U100)