Why do you think your paper is highly cited?

Our paper is a review covering "enamine catalysis" as an area of catalysis that has grown considerably during the last nine years. While appreciated as an enzymatic reaction mechanism, chemists hardly made use of this powerful concept over the last century, especially not in asymmetric catalysis. This has changed significantly and, since 2000, there have been literally hundreds of papers on the subject, with new ones coming up on a daily basis.

 Does it describe a new discovery, methodology, or synthesis of knowledge?

Enamine catalysis is new as a general methodology. In enamine catalysis, amines are used as catalysts with a well-defined mode of action, reacting carbonyl compounds with electrophiles. The generalization and conceptualization of enamine catalysis has inspired the design of many new reactions and powerful catalysts.

 Would you summarize the significance of your paper in layman’s terms?

Perhaps its key significance lies in the possibility of "making life-saving drugs with edible catalysts."

 How did you become involved in this research and were any particular problems encountered along the way?

We describe the results reported by hundreds of groups around the world. Our own studies date back to the very beginning of the field in 2000. Inspiration came from reactions developed by industrial chemists in the late 1960s as well as from work done with catalytic antibodies. My idea has been to catalyze the intermolecular aldol reaction, at the time a huge challenge to asymmetric catalysis, with the amino acid proline.

Indeed, this catalyst turned out to be state-of-the-art, comparable only to a complex lanthanum catalyst that was developed by Masakatsu Shibasaki's group at the University of Tokyo. Shortly after our initial observation, we have discovered other reactions that can be catalyzed using the same activation principle, which we have termed "enamine catalysis."

Regarding problems encountered along the way, two big challenges right from the beginning were (a) the skeptical advice by colleagues that organic catalysts should be generally less active and selective compared to transition metal catalysts and enzymes and (b) subsequent competition from the same people after proving them wrong.

 Where do you see your research leading in the future?

It looks like there is a deeper understanding of enamine catalysis now and of the things you can accomplish with it. The concept of enamine catalysis has led to major discoveries of which chemists had not even dreamed until now. However, there are remaining challenges, certain other "dream reactions" we would still like to discover.

 Do you foresee any social or political implications for your research?

It would certainly be nice if our concepts would help in improving life on earth by enabling the environmentally friendly and safe synthesis of drugs for human health.

Prof. Dr. Benjamin List
Max-Planck-Institut für Kohlenforschung
Mülheim an der Ruhr, Germany
The Research Group of Benjamin List:
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KEYWORDS: DIRECT ALDOL REACTION; MANNICH-TYPE REACTIONS; ENANTIOSELECTIVE MICHAEL ADDITION; AMINO-ACID-DERIVATIVES; DE-NOVO SYNTHESIS; CHIRAL BUILDING-BLOCKS; POLY(ETHYLENE GLYCOL)-SUPPORTED PROLINE; ORGANOCATALYTIC ALPHA-FLUORINATION; DYNAMIC KINETIC RESOLUTION; HIGHLY EFFICIENT CATALYST.