Remote Functionalization

Nature Communications reports a paradigm shift in functionalizing molecules by Technion researchers

Researchers at the Technion’s Schulich Faculty of Chemistry have reported a paradigm shift by functionalizing organic molecules at a very distant position of the most reactive site. The article, published in the journal Nature Communications, is co-authored by Prof. Ilan Marek, head of The Mallat Family Laboratory of Organic Chemistry, Dr. Sukhdev Singh (a postdoctoral student from India), Jeffrey Bruffaerts (a doctoral student from Belgium) and Dr. Alexandre Vasseur (a postdoctoral student from France).

The practice of constructing molecules of carbon is called organic synthesis and it is at once an exact science and a fine art. Synthetic chemists have perfected this science to the point where not only can genes and proteins can be synthesized, but also an array of complex and fascinating molecular structures can be assembled on demand and tested for various applications. Such useful compounds range from biological tools and medicines to high-value materials, computers, sophisticated machines, and useful devices.

Prof. Ilan Marek

Organic synthesis derives its power from chemical reactions, reagents, and conditions, and synthetic strategies – a field in which several leading researchers have already won the Nobel Prizes. “You could see us are molecular architects,” explains Prof. Marek, “and as any architects that have to plan constructions, we as synthetic organic chemists, are planning the construction of important molecular framework following well-established rules”. However, continues Prof. Marek “in my research group, we are building molecules in a non-classical way and our approaches are always meant to solve the most acute synthetic problems in our field coupled with efficiency and elegance.” Classically organic chemists functionalize molecules at the most reactive sites but in the present study, the research group of Prof. Marek was interested to functionalize molecules at the less reactive position by using a transfer of chemical information along the molecular backbone of the molecule. This concept of “remote functionalization” could formally open the door to synthetic transformations that were not available before to the synthetic community.

“The idea of remote functionalization was proposed several decades ago,” explains Professor Marek, “but the field was in its complete infancy due to the major synthetic problems that it generated”. Now, as stated, the group has managed to transfer chemical information from the original location of the functional group to a very remote point in the molecule, in a single process (one-pot operation) and independently of the molecular distance between the two points. Moreover, by using a strained structure in the molecular backbone, the migration of the information releases the strain and allows the creation of several chiral carbon centers (a carbon atom with four different substituents can exist in two distinct stereochemical orientations, which are related to one another as any object is to its mirror image, is called chiral carbon center), that might have far-reaching applications in the academic world, but also for chemical industries and in particular for pharmaceutical companies.  

Sukhdev Singh (Left) and Jeffrey Bruffaerts

Prof. Ilan Marek was born in Israel and moved with his family to France at the age of 18 months. In 1988 he completed his doctorate at the University Pierre and Marie Curie in Paris, and after a short postdoctoral stay in Belgium, he returned to the same university as an independent researcher. In 1997, after 34 years in France, he returned to Israel and joined the Schulich Faculty of Chemistry at the Technion-Israel Institute of Technology. He now heads the Mallat Family Laboratory of Organic Chemistry and holds the Sir Michael and Lady Sobell Academic Chair. Prof. Marek has won numerous awards, including the Weizmann Prize for Exact Sciences, the Israel Chemical Society Award for Excellence, the Janssen Pharmaceutica Prize for Academic Excellence, the Royal Society Chemistry organometallic Award, the Yigal Alon Fellowship, the Michael Bruno Memorial Award, the Taub Award for Academic Excellence, the ERC advanced research grant and awards for excellence in teaching, including the Yanai Prize awarded by the Technion. He is also member of the scientific advisory boards of many journals in organic chemistry.

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