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Copying Nature’s Assembly Line

Organic Synthesis: Successive homologation reactions let chemists tailor carbon chain’s conformation

by Bethany Halford
September 15, 2014 | A version of this story appeared in Volume 92, Issue 37

Reaction repeatedly inserts organolithium compound into carbon-boron bond, creating chains up to 10 carbons long.
Reaction scheme shows assembly-line style chemistry to produce a final boronic ester product.
Reaction repeatedly inserts organolithium compound into carbon-boron bond, creating chains up to 10 carbons long.

Organic chemists have long admired nature for its ability to perform chemistry in an assembly-line style, wherein the same reaction or sets of reactions are carried out repeatedly to create a target molecule. Polyketide natural products, for example, are biosynthesized via such an assembly-line process.

Now, chemists at England’s University of Bristol report an assembly-line reaction that can be done in a flask (Nature 2014, DOI: 10.1038/nature13711).

Using a boronic ester and an organolithium compound, a team led by Varinder K. Aggarwal, Craig P. Butts, and Jeremy N. Harvey can create carbon chains up to 10 atoms long via repeated homologation of a carbon-boron bond. Each carbon in the chain bears a methyl group, and because the chemists can control the stereochemistry of these methyl groups, they can also control the shape the chain ultimately takes. For example, when the stereochemistry of the methyl groups alternates, the chain curls into a helix.

Nature, Aggarwal points out, often uses methyl groups to determine a molecule’s conformation. But nature can only put methyl groups on every other carbon in a chain. This new chemistry can put methyl groups on every carbon, adding even more control over the shape a molecule takes.

“If we already know what shapes we want, we can make them using the chemistry that we’ve developed,” Aggarwal explains. “You could make L-shaped molecules, U-shaped molecules, V-shaped molecules, any sort of molecules that you wish. This could be very useful for all sorts of applications, such as materials chemistry.”

“One of the contemporary challenges in synthetic organic chemistry is the ability to control configurational stereochemistry and molecular conformation,” notes David O’Hagan, a chemistry professor at the University of St. Andrews, in Scotland, who studies conformational effects. “The elegance here is to show how one follows the other.” He notes that the isomeric structures created by the Bristol chemists have distinctly different conformations. “The ability to adjust the stereochemistry to order by programming the method at each stage is impressive and powerful,” he says. “The next stage now must be to relate stereochemistry to function.”



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