Prof. Iain Coldham
Professor of Synthetic Organic Chemistry
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.
Organic synthesis, new methodology in organic chemistry, asymmetric organolithium chemistry, heterocyclic chemistry
- An Experimental and In Situ IR Spectroscopic Study of the Lithiation-Substitution of N-Boc 2-phenylpyrrolidine and piperidine: Controlling the Formation of Quaternary Stereocenters, N. S. Sheikh, D. Leonori, G. Barker, J. D. Firth, K. R. Campos, A. J. H. M. Meijer, P. O’Brien, I. Coldham, J. Am. Chem. Soc. 2012, 134, 5300-5308.
- Synthesis and Evaluation of 1-Amino-6-halo-beta-carbolines as Antimalarial and Antiprion Agents, M. J. Thompson, J. C. Louth, S. M. Little, M. P. Jackson, Y. Boursereau, B. Chen, I. Coldham, Chem. Med. Chem. 2012, 7, 578-586
- 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.
- 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.
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 found 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).
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).
- First Year Demonstrating
- Second Year Demonstrating
- Third Year Advanced Practical Chemistry Techniques
- Fourth Year Research Project