Chiral N-Heterocyclic Carbenes (NHC)

Carbene refers to a highly reactive intermediate with only two bonds bonded to a carbon atom and two unbonded electrons. A chiral N-heterocyclic carbene refers to an N-heterocyclic ring containing a carbene in a heterocyclic structure and having a chiral center. The chiral N-heterocyclic carbene generally exists in the form of a single line, and the outer electron orbitals of the central carbon atom exist in the sp² hybrid form, and the two electrons are in the same orbit. The p-electron orbital of the carbene carbon atom is conjugated to the lone pair of electrons in the p-electron orbital of the nitrogen atom at both ends, thus increasing the electron cloud density of the carbene carbon atom and having a strong nucleophilicity. Chiral N-heterocyclic carbenes are one of the most widely studied nucleophilic carbene. Chiral N-heterocyclic carbene is similar in nature to typical sigma electron donor ligands and can replace classical two-electron ligands such as amines, ethers and phosphines in metal coordination chemistry. In addition, chiral N-heterocyclic carbenes have stronger electrons and advantages. Firstly, chiral N-heterocyclic carbene is aromatic and more stable in air. Secondly, chiral N-heterocyclic carbene is a strong σ-electron donor and a weak π-electron acceptor, so it can form complexes with both metallic and non-metallic elements. Finally, the chiral N-heterocyclic carbene has strong nucleophilicity, making the complex formation more stable under severe conditions.

Figure 1. Chiral imidazole carbenes

Figure 2. Chiral triazole carbenes

Applications

Chiral N-heterocyclic carbenes are widely used in the field of organic synthesis. In addition to its own role as a substrate for organic reactions, chiral N-heterocyclic carbene can also be used as a ligand to form complexes with metal or non-metal elements to catalyze many types of reactions.

1. Coupling reaction: The reaction of a halogenated aromatic hydrocarbon with a nucleophilic reagent and coupling to form a C-C bond or a C-N bond has become an important method in organic synthesis. As a nucleophilic carbene, a chiral N-heterocyclic carbene can be directly coupled to a halogenated aromatic hydrocarbon as a substrate. In addition, the chiral N-heterocyclic carbene can also be used as a ligand to form a catalyst with a metal such as Pd, Rh or Cu to catalyze various coupling reactions. Many chiral N-heterocyclic carbene complexes have been successfully used to catalyze C-C coupling reactions and C-N coupling, including Suzuki coupling reaction, Heck coupling reaction, Sonogashira coupling reaction, Ullmann coupling reaction, Kumada coupling reaction, Stilie coupling reaction, Hiyama coupling reaction, and the like.
2. Dilute hydrocarbon metathesis reaction: The chiral N-heterocyclic carbene has strong electron donating ability and high stability, and is used as a ligand to form a ruthenium catalyst with metal Ru. The catalyst can not only catalyze the metathesis reaction of general olefins, but also catalyze the rare metathesis reaction of olefins with large steric hindrance. In addition, the amount of rhodium catalyst is greatly reduced compared to other catalysts, and the selectivity of the product is also improved.
3. Asymmetric catalytic reaction: As a good σ-electron donor, a chiral N-heterocyclic carbene can form a catalyst with a transition metal and thus can be used in the field of asymmetric synthesis. There are many types of asymmetric reactions catalyzed by chiral N-heterocyclic carbene metal catalysts. Including asymmetric conjugate addition reaction, asymmetric hydrogenation reaction, asymmetric alkylation reaction, asymmetric benzoin condensation reaction, asymmetric intermolecular Setter reaction, and the like.
4. Other reactions: In addition to the above-mentioned common types of reactions, there are many chiral N-heterocyclic carbene metal complex catalyzed reactions such as hydrogenation, polymerization, ring opening, transesterification and the like.

References

1. Soeta, Takahiro. (2016). "Chiral NHC Ligands Bearing a Pyridine Moiety in Copper-Catalyzed 1,2-Addition of Dialkylzinc Reagents to β-Aryl-α,β-unsaturated N-Tosylaldimines." Journal of Organic Chemistry 8(7), 2817-2826.
2. Chen, Jiean. (2015). "Highly enantioselective sulfa-Michael addition reactions using N-heterocyclic carbene as a non-covalent organocatalyst." Chemical Science 6(7), 4184-4189.
3. Sanchez, Diez. (2015), "Enantioselective Synthesis of Tertiary Propargylic Alcohols under N-Heterocyclic Carbene Catalysis." Chemistry-A European Journal 21(23), 8384-8388.