Chain-walking chemistry installs new carbon bonds

Chemistry

Wandering catalyst activates carbon atoms to form carbon-carbon bonds

Published online 23 June 2016

Like a tightrope walker on a high wire, a chain-walking catalyst traverses a chain of carbon atoms before activating the middle of the chain toward bond formation.

Like a tightrope walker on a high wire, a chain-walking catalyst traverses a chain of carbon atoms before activating the middle of the chain toward bond formation.

© Giancarlo Banfi/EyeEm/Getty

Inspired by a reaction that has become a mainstay of polymer synthesis, Keio University researchers have discovered a novel way to construct small organic molecules. Their method uses a 'chain-walking' catalyst to activate otherwise unreactive parts of simple molecules, catalyzing the formation of new carbon-carbon bonds1.

The conventional formation of new carbon-carbon bonds -- which turn simple starting molecules into complex structures, such as therapeutic drugs -- is to first install a chemical 'handle'. For example, a chlorine atom might be used to pre-activate a particular carbon atom toward bond formation. Adding and manipulating these handles can make the synthesis of complex molecules slow and inefficient, so there is much interest in finding ways to directly install new bonds at unreactive carbon atoms.

Chain walking could be just such a reaction, realized Takuya Kochi from the Department of Chemistry at Keio University. Chain-walking chemistry was pioneered in the 1990s, when polymer chemists discovered a palladium catalyst that would attach to the end of a chain of carbon atoms, then 'walk' along the polymer chain before adding the next building block to the chain. "It is not a conventional way to form a carbon-carbon bond," says Kochi.

Polymer chemists use bulky substituents around the palladium atom to slow a competing reaction, alkene exchange, in which the palladium drops off the growing polymer chain. "We felt that if we just removed the bulky substituent, we could switch the rates," says Kochi, favoring alkene exchange over polymerization -- the desired pathway when making small molecules rather than polymers.

The researchers tested their slimmed-down catalyst on a variety of starting molecules, each of which contained two parallel 'arms' consisting of carbon atoms. They showed the catalyst would attach to the end of one arm, then walk from atom to atom until it was opposite a carbon-carbon double bond on the other arm. It would join the two arms of the molecule at that point -- activating the otherwise unreactive carbon it had walked to -- to form the new carbon-carbon single bond.

Using their reaction, the team has been able to synthesize a structure called prostane, the underlying carbon framework of a family of natural products. They are now investigating the reaction to identify which molecules are particularly suited to chain walking. "The chemistry is still in its initial phase," says Kochi.

Reference

  1. Hamasaki, T., Aoyama, Y., Kawasaki, J., Kakiuchi, F. and Kochi, T. Chain walking as a strategy for carbon-carbon bond formation at unreactive sites in organic synthesis: Catalytic cycloisomerization of various 1,n-dienes. Journal of the American Chemical Society 137, 16163 (2015). | article

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This article was made for Keio University by Nature Research Custom Media, part of Springer Nature.