Research Guides

Computational Organic Chemistry

The group's research interests focus on solving problems in organic and bio-organic chemistry using computational methods. Predictions and designs of new reactions, reagents, and catalysts are tested through our close collaborations with experimentalists. Please visit our Research Group Website for further information.

Part II and DPhil Studentships 2012

The group accepts on average 3 Part II students each year. Research in the group is focussed on Organic and Bio-organic chemistry, in particular understanding reaction mechanisms and selectivity (e.g. chemo-, regio-, stereoselectivity) with computational methods. Available projects vary from being 100% computational (i.e. no bench work), to collaborative projects combining organic synthesis and computational work – the precise mix can be tailored to the interests and skills of the student. No prior experience with molecular modelling packages is assumed. A keen interest in Organic Chemistry and solid mechanistic knowledge is recommended. Please look at our Research Group Website for further information, or get in touch to arrange a visit.

Accelerated Catalyst Design

The discovery of new synthetic catalysts still depends on trial-and-error experimentation. We hope to combine computation with synthesis and NMR spectroscopy to design and test new small organic catalyst molecules which are able to accelerate reactions which are ordinarily difficult to achieve. These designer molecules will be developed to achieve stereoselective transformations with lower catalytic loadings than the current generation or organocatalysts.

Natural Product Biosynthesis

By simulating the reactions that occur in naturally-occurring enzymes we will investigate the biogenesis of natural products. Of particular interest to us are polyethers and halogenated natural products. Nature often catalyzes transformations selectively, giving products that are not seen in the same reaction in solution. We hope to elucidate these mechanisms of biosynthesis.  

Ab Initio Structural Assignment

Assignment of the gross and stereostructure of newly discovered natural products is a challenging task, and as a consequence may be uncertain or possibly incorrect. We will apply ab initio NMR simulation techniques to this problematic area, to lend credence to proposed structures, or to propose new assignments. 

Understanding Synthetic Control

A full understanding of the catalytic cycles, rate-limiting and selectivity-determining steps in asymmetric synthesis is desirable since it drives the rational discovery of new and improved reagents and catalysts. We use computational chemistry to analyze the aspects of chemo-, regio- and streoselectivity and to derive new models of reactivity that may be used to predict the outcomes in new systems.

Computational Methods Development

In each of the core areas identified above, we are trying to develop new and improved computational methods to obtain increased precision for more accurate agreement with experiment and prediction. Of particular importance are better ways to model reactions in solution and to sample the flexibility of the types of systems that chemists like to study experimentally. We are also actively involved in deriving new models of chemical reactivity to interpret the energetic trends that we observe in our computations. 

Experimental Diels-Alder Reactivities of Cycloalkenones and Cyclic Dienes Explained Through Transition State Distortion Energies
Paton*, R. S.; Kim, S.; Ross, A. G.; Danishefsky, S. J.; Houk, K. N. Angew. Chem. Int. Ed. 2011, article early view.

Unravelling the Mechanism of Cascade Reactions of Zincke Aldehydes
Paton, R. S.; Steinhardt, S. E.; Vanderwal, C. D.; Houk, K. N. J. Am. Chem. Soc. 2011, 133, 3895-3905.

Indolyne Experimental and Computational Studies: Synthetic Applications and Origins of Selectivities of Nucleophilic Additions
Im, G.-Y. J.; Bronner, S. M.; Goetz, A. E.; Paton, R. S.; Cheong, P.-H. Y.; Houk, K. N. Garg, N. K. J. Am. Chem. Soc. 2010, 132, 17933-17944

The [4+2], not [2+2], Mechanism Occurs in the Gold-Catalyzed Intramolecular Oxygen Transfer Reaction of 2-Alkynyl-1,5-Diketones
Liu, L.-P.; Malhotra, D.; Paton, R. S.; Houk, K. N.; Hammond, G. B. Angew. Chem. Int. Ed. 2010, 49, 9318-9321.

Origins of Stereoselectivity in the trans-Diels-Alder Paradigm
Paton, R. S.; Mackey, J. L.; Kim, W. H.; Lee, J. H.; Danishefsky, S. J.; Houk, K. N. J. Am. Chem. Soc. 2010, 132, 9335-9340.

Indolyne and Aryne Distortions and Nucleophilic Regioselectivities
Cheong, P. H. Y.; Paton, R. S.; Bronner, S. M.; Im, G. Y.; Garg, N. K.; Houk, K. N. J. Am. Chem. Soc. 2010, 132, 1267-1269.