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Breaking bonds in unstrained rings

Catalyst system activates carbon-carbon bonds in cyclopentanones

by Bethany Halford
November 3, 2016 | A version of this story appeared in Volume 94, Issue 44

Bond Breaker

Catalyst system activates carbon-carbon bonds in cyclopentanones.
Catalyst system transforms aryl-substituted cyclopentanones into α-tetralones.

Although synthetic chemists typically regard carbon-carbon single bonds as inert, they have used metal catalysts to spring open C–C bonds in strained rings, such as cyclopropanes and cyclobutanes. Performing a similar transformation with less strained but more common five- and six-membered rings, however, has proven more difficult.

Now, chemists report a way of opening up C–C bonds in aryl substituted cyclopentanones to produce α-tetralones—a common structural motif and versatile building block in organic synthesis. The reaction makes use of a rhodium pre-catalyst, an N-heterocyclic carbene ligand, and an amino-pyridine co-catalyst (Nature 2016, DOI: 10.1038/nature19849). The chemists also used this strategy to turn aryl substituted cyclohexanones into α-indanones.

The reaction, developed by University of Chicago’s Guangbin Dong and Ying Xia along with University of Pittsburgh’s Peng Liu and Gang Lu, was discovered by accident, Dong tells C&EN. While exploring a different reaction with an aryl-substituted cyclopentanone, the chemists noticed a small amount of α-tetralone by-product and decided to figure out how to shift their reaction conditions in favor of that product.

It turns out that when an aryl group is present on the third carbon of a cyclopentanone, the chemists’ catalytic system activates the bond between the ring’s first and second carbons, inserting a metal between the carbons. Subsequent activation of a C–H bond on the aromatic ring followed by reductive elimination knits the rings together into an α-tetralone.

“This incredible transformation makes an elegant addition to the synthetic toolbox,” comments Masahiro Murakami, an expert in organic chemistry at Kyoto University. “Carbon-carbon and carbon-hydrogen bonds are robust sigma bonds,” he notes. In this new reaction such bonds “are not only both broken but also swapped, making a totally different framework,” he says.

Next, Dong says, the group is working to make the intramolecular transformation into an intermolecular one. And he hopes it will inspire others to find novel methods for activating C–C bonds.



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