Prof. Iain Coldham - Profiles - Staff - Chemistry

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:

Cascade Cyclization, Dipolar Cycloaddition to Bridged Tricyclic Amines Related to the Daphniphyllum Alkaloids, I. Coldham, A. J. M. Burrell, H. D. S. Guerrand and N. Oram, Org. Lett. 2011, 13, 1267-1269.
Synthesis of the Core Ring System of the Yuzurimine Type Daphniphyllum Alkaloids by Cascade Condensation, Cyclization, Cycloaddition Chemistry, I. Coldham, L. Watson, H. Adams and N. G. Martin, J. Org. Chem. 2011, 76, 2360-2366.
Asymmetric Substitutions of 2-Lithiated N-Boc-piperidine and N-Boc-azepine by Dynamic Resolution, I. Coldham, S. Raimbault, D. T. E. Whittaker, P. T. Chovatia, D. Leonori, J. J. Patel and N. S. Sheikh, Chem-Eur J 2010, 16, 4082-4090.
Asymmetric Deprotonation of N-Boc Piperidine: React IR Monitoring and Mechanistic Aspects, D. Stead, G. Carbone, P. O'Brien, K. R. Campos, I. Coldham and A. Sanderson, J. Am. Chem. Soc. 2010, 132, 7260-7261.
Dynamic thermodynamic resolution of lithiated N-Boc-N '-alkylpiperazines, S. P. Robinson, N. S. Sheikh, C. A. Baxter and I. Coldham, Tetrahedron Lett. 2010, 51, 3642-3644.
Regioselective and Stereoselective Copper(I)-Promoted Allylation and Conjugate Addition of N-Boc-2-lithiopyrrolidine and N-Boc-2-lithiopiperidine, I. Coldham and D. Leonori, J. Org. Chem. 2010, 75, 4069-4077.
The barrier to enantiomerization and dynamic resolution of N-Boc-2-lithiopiperidine and the effect of TMEDA, I. Coldham, D. Leonori, T. K. Beng and R. E. Gawley, Chem. Commun. 2009, 5239-5241.
Synthesis of Fused Tricyclic Amines from Enolizable Acyclic Aldehydes by Cyclization then Dipolar Cycloaddition Cascade: Synthesis of Myrioxazine A, A. J. M. Burrell, I. Coldham and N. Oram, Org. Lett. 2009, 11, 1515-1518.
Cascade condensation, cyclization, intermolecular dipolar cycloaddition by multi-component coupling and application to a synthesis of (+/-)-crispine A, I. Coldham, S. Jana, L. Watson and N. G. Martin, Organic & Biomolecular Chemistry 2009, 7, 1674-1679.
Stereoselective Formation of Fused Tricyclic Amines from Acyclic Aldehydes by a Cascade Process Involving Condensation, Cyclization, and Dipolar Cycloaddition, A. J. M. Burrell, I. Coldham, L. Watson, N. Oram, C. D. Pilgram and N. G. Martin, J. Org. Chem. 2009, 74, 2290-2300.

Research Interests

New methodology in organic chemistry. Synthetic organic 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 organic 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 organolithium compounds in asymmetric synthesis, especially for carbon-carbon bond formation of nitrogen-containing compounds, prevalent in many biologically active molecules. Recently, we have found that 2-lithio-pyrrolidines undergo efficient dynamic thermodynamic resolution in the presence of chiral ligands, leading to highly enantioenriched 2-substituted pyrrolidine products. We are currently studying further examples of this asymmetric chemistry and determining the kinetics of enantiomerization of different chiral organolithium compounds.

Synthesis of biologically active compounds.
We are using dipolar cycloaddition chemistry of azomethine ylides 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 alkaloid manzamine A, which has significant anti-cancer activity. It has also been shown to be a potent anti-malarial, an anti-inflammatory agent and to have insecticidal and fungicidal activity. Our chemistry makes use of a simple method to prepare azomethine ylides 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 are currently exploring this chemistry further with the aim to complete the total synthesis of the natural product. In addition, we are preparing simpler analogues of manzamine A, to gain an understanding of which functional groups are important for its activity and to probe its mechanism of action. Alongside this work we are investigating the use of primary amines (such as amino-acids) for a cascade process involving imine formation, cyclization, azomethine 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 recently been applied to the total syntheses of several Aspidosperma alkaloids.

Teaching Section

Organic Chemistry

Undergraduate Courses Taught

CHM2204.2: "Organic reaction mechanisms"
This segment introduces substitution and elimination reactions.
CHM3201.3: "Heterocyclic Chemistry"
This segment introduces aromatic and non-aromatic heterocyclic compounds.
CHM4005.4/CHM4006.4: "Organic Chemistry of the Main Group Elements"
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

First Year Demonstrating
Second Year Demonstrating
Third Year Demonstrating
Fourth Year Research Project