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:

Remarkable Configurational Stability of Magnesiated Nitriles, G. Barker, M.R. Alshawish, M.C. Skilbeck, I.Coldham, Angew, Chem. Int. Ed. 2013, 52, 7700-7703.
Synthesis of 1-Substituted Tetrahydroisoquinolines by Lithiation and Electrophilic Quenching Guided by In Situ IR and NMR Spectroscopy and Application to the Synthesis of Salsolidine, Carnegine and Laudanosine, X. Li, D. Leonori, N. S. Sheikh, I. Coldham, Chem-Eur J 2013, 19, 7724-7730.
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, 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, 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, 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, A. Sanderson, J. Am. Chem. Soc. 2010, 132, 7260-7261.
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, R. E. Gawley, Chem. Commun. 2009, 5239-5241.

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 foun ColdhamPicforWeb d 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.
Heterocyclic Chemistry (Year 3)
This segment introduces aromatic and non-aromatic heterocyclic compounds.
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

First Year Demonstrating
Second Year Demonstrating
Third Year Advanced Practical Chemistry Techniques
Fourth Year Research Project