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Carboxylation Made Simple

Green Chemistry: Method directly adds CO2 to aromatic C–H bonds

by Stu Borman
July 5, 2010 | A version of this story appeared in Volume 88, Issue 27

Credit: Adapted from J. Am. Chem. Soc.
Credit: Adapted from J. Am. Chem. Soc.

A straightforward and environmentally friendly technique uses carbon dioxide to convert acidic C–H bonds in aromatic compounds into acid and ester groups. The reaction could make aromatic acids and esters more readily available for use in organic synthesis, drug discovery, and other applications.

The reaction uses N-heterocyclic carbene (NHC) gold(I) catalysts, which are stable and recyclable and require no special handling. It was developed by postdoctoral fellow Ine I. F. Boogaerts and chemistry professor Steven P. Nolan of the University of St. Andrews, in the U.K. (J. Am. Chem. Soc., DOI: 10.1021/ja103429q). Unlike existing ways to carboxylate aromatic C–H bonds, the reaction proceeds at room temperature and moderate pressure, and its only by-product is water.

“This is probably the first example of taking an unactivated C–H bond and directly converting it into a carboxylic acid group,” comments Tomislav Rovis of Colorado State University, a specialist in NHC and transition-metal catalysis. “It’s surprising that the reaction conditions are so mild. The scope is limited to acidic aromatics, but it’s neat chemistry that could stimulate other work in this area.”

“It’s a striking transformation, and we’ll see how general it becomes” as its applicability is further investigated, says John F. Hartwig of the University of Illinois, Urbana-Champaign, a C–H bond functionalization specialist. “It’s a breakthrough in using a base as catalyst for carboxylation and therefore has potential for development.”

C–H bonds in oxazoles, chlorinated or fluorinated benzenes, and other aromatic compounds are typically carboxylated with powerful bases like alkyllithiums and Grignard reagents or in transition-metal-catalyzed reactions. The former reactions are stoichiometric, require anaerobic conditions, and produce toxic by-products. The latter use nonrecyclable catalysts, need a C–H bond prefunctionalization step, and require forcing conditions (inert atmospheres, high temperatures and pressures, and large amounts of catalyst).

In the new reaction, the recyclable catalyst activates the most acidic aromatic C–H bond, and CO2 inserts at that position. C–H prefunctionalization is not necessary.

“Nothing of the sort has been so simply done,” Nolan says. “We have hit on something interesting here and are currently exploring how general such functionalizations can be.”



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