N-heterocyclic Compound

Nitrogen heterocyclic carbenes can form stable C-M bonds with transition metals, which are more stable than traditional phosphine ligands, are electron-rich, have strong coordination capabilities to metals, and have better steric and electronic effects.

Classification

• There are four common types of nitrogen heterocyclic carbenes: thiazoles, imidazolidines, imidazoles and triazoles. The most common metal nitrogen heterocyclic carbene catalysts are imidazolidines and imidazoles.
• In the most widely used palladium nitrogen heterocyclic carbene catalyst, in addition to the coordination with the carbene ring, other heterocyclic ligands [(NHC)PdCl2(L)], such as pyridine, quinoline, isoquinoline, and imidazole, will also be added. Pyrazole and morpholine, etc. There are relatively few other Cu, Ag and Au azacarbene catalysts.

Applications

• The traditional palladium, copper and other transition metal coordination catalysts must participate in the reaction under oxygen-free conditions, and the metal nitrogen heterocyclic carbene catalysts can even carry out the Suzuki coupling reaction under aerobic conditions due to their high stability. Heck coupling reaction and Sonogashira coupling reaction and other cross-coupling reactions. Early metal nitrogen heterocyclic carbene catalysts, which were well-known in organic synthesis, were the Grubbs catalysts (second generation) used in olefin metathesis reactions.
• However, the metal nitrogen heterocyclic carbene catalysts used in cross-coupling reactions are mainly Pd, Cu, Ag and Au. Nitrogen heterocyclic carbene palladium and copper catalysts are often used in coupling reactions. Nitrocyclic carbene silver and gold catalysts are rarely used in coupling reactions, and are commonly used to catalyze cycloaddition reactions, hydrolysis reactions, reduction reactions, oxidation reactions, rearrangement reactions, and so on.

Research Cases

• Palladium nitrogen heterocyclic carbene catalyst

Under the catalysis of Pd-PEPPSI-IPr, arylamide undergoes C-N bond activation and boric acid undergoes Suzuki reaction to prepare ketones.

Figure 1. The general PEPPSI type Pd-NHC complex used as a catalyst for amide cross-coupling [1]

• Copper nitrogen heterocyclic carbene catalyst

Under the catalysis of NHC-Cu, allyl phosphate reacts with propadiene borate or propadiene borate for propargylation or propadiene reaction, respectively.

Figure 2. SN2"-Selective and Enantioselective Substitution by a NHC-Cu Complex [2]

• Silver nitrogen heterocyclic carbene catalyst

Silver NHC catalysts have been developed for the selective oxidation of alcohols to aldehydes or carboxylic acids in the presence of BnMe3 NOH or KOH in dry air. The conditions of aerobic oxidation are mild and the yield is excellent. Further tandem catalysis can synthesize imines in a one-pot method with excellent yield.

Figure 3. Alcohols can obtain aldehydes, imines and acids in high yields under various controlled conditions under Ag(NHC) catalysis. [3]

References

1. Peng Lei. (2017). "Pd-PEPPSI: Pd-NHC Precatalyst for Suzuki-Miyaura Cross-Coupling Reactions of Amides," The Journal of Organic Chemistry 82(13): 6638-6646.
2. Yuebiao Zhou. (2018). "SN2"-Selective and Enantioselective Substitution with Unsaturated Organoboron Compounds and Catalyzed by a Sulfonate-Containing NHC-Cu Complex, " Journal of the American Chemical Society 140(48): 16842-16854.
3. Lei Han. (2014). "Selective Aerobic Oxidation of Alcohols to Aldehydes, Carboxylic Acids, and Imines Catalyzed by a Ag-NHC Complex," Organic Letters 16(13): 3428-3431.