The PGA Research Group

Thishana Singh

The field of catalytic asymmetric synthesis has expanded tremendously during the last two decades and is of paramount importance, with many applications in the pharmaceutical and fine chemical industry. However, despite this, many of the asymmetric transition-metal catalyzed reaction mechanisms are not known in detail and most of the research and development of new catalysts and chiral ligands is today carried out on a trial and error basis. As a result of this research strategy (or lack of it), most of the highly stereoselective processes known today are hampered by a very narrow substrate scope and/or strenuous reaction conditions and/or low reaction rates. During the optimization of the catalyst a better understanding of the factors that are responsible for the rate and selectivity of the reaction is imperative. An important tool in this process is theoretical calculations that often can pin down the mechanism and thus also which interactions within the transition states are responsible for the rate and selectivity. Using this methodology, provides an understanding, and more importantly, the ability to design more effective catalysts for a number of asymmetric, catalytic processes. Thus computational calculations are performed in order to reveal the reaction mechanism and to understand the selectivity process of the catalyst in a reaction.

The projects I am currently working on include:

Dehydrogenative decarbonylation reaction:

This is a catalytic system that dehydrogenates primary alcohols and decarbonylates the aldehyde that forms, releasing hydrogen and carbon monoxide.

The catalyst in the reaction being investigated is IrCl(CO)BINAP:

pKa calculations

Ligands complexed to metal centers influence the acidities of transition-metal hydrides and thus can have an influence on catalysis. The following methodology, based on the Born-Haber Cycle, is used for these calculations.

Asymmetric isomerisation of allylic alcohol

 
Alcohol coordinated to the catalyst

The reaction was modelled by coordinating both “faces” of the alcohol to the iridium catalyst.

The “front” face:

And the “reverse” face: