Transforming carbon dioxide gas into valuable building block for organic synthesis

Now, Zhaomin Hou and colleagues from the RIKEN Advanced Science Institute in Wako have found a way to insert CO₂ directly into the framework of aromatic molecules, turning them into carboxylic acid derivatives that are widely used as pharmaceuticals, agrichemicals, and dyes¹. Importantly, this transformation can be achieved economically and with negligible environmental impact, thanks to a low cost copper complex bearing an organic ligand.

N-heterocyclic carbenes (NHCs) are molecules with near metal-like reactivity because of an electron-deficient carbon center. For the past two decades, scientists have used NHCs as organic replacements for metal catalysts and as ‘spectator’ ligands that attach to metal centers and influence their catalytic behavior. Hou and colleagues recently discovered that adding NHCs to copper, one of the most abundant metals in nature, created a complex that catalyzed CO₂ addition to boron esters²—a trick the team hoped to repeat with aromatic hydrocarbons.

The most efficient way to incorporate CO₂ into benzene-like molecules is by replacing one of the carbon–hydrogen (C–H) bonds on the outer ring; unfortunately, these bonds are notoriously unreactive. To overcome this problem, the researchers turned to benzoxazole: this double-ringed aromatic compound has a C–H bond situated between nitrogen and oxygen atoms, making it easier to chemically activate this position.

With just a pinch of the NHC–copper catalyst complex, the team found they could convert a mixture of CO₂ and several different benzoxazole-based molecules into solid carboxylic acids and esters in excellent yields (Fig. 1). Carefully characterizing the crystal structures of several intermediate compounds revealed that CO₂ inserted in between a copper–carbon bond formed at the benzoxazole C–H site, followed by a dissociation step that regenerated the catalyst.

According to Hou, the NHC ligand was essential in enabling CO₂ capture. “The electron-donating ability of NHC could make the C–H activation and CO₂ insertion steps easier, while its steric bulk brings stability to the active catalyst species,” he notes. The researchers now hope to extend this technique to less reactive C–H bonds by fine-tuning the catalyst complex and optimizing reaction conditions.

More information: 1. Zhang, L., et al. Copper-catalyzed direct carboxylation of C–H bonds with carbon dioxide. Angewandte Chemie International Edition 49, 8670–8673 (2010).
2. Ohishi, T., et al. Carboxylation of organoboronic esters catalyzed by N-heterocyclic carbene copper(I) complexes. Angewandte Chemie International Edition 47, 5792–5795 (2008).

Provided by RIKEN