Amination

Catalytic C-H amination reactions enable direct functionalization of unactivated C(sp3)-H bonds with high levels of regioselectivity, chemoselectivity, and stereoselectivity. Catalytic C-H amination technology is one of the powerful tools to unlock the potential of inert C-H bonds. Alfa Chemistry Catalysts offers a wide range of catalysts for amination reactions.

Background

Amines occupy a very special place in organic chemistry because they are present in many natural biologically important molecules such as amino acids, nucleic acids, alkaloids, etc. Various chemical methods have been developed to prepare compounds with amines as key structures. Among them, reductive amination, in which mixtures of aldehydes or ketones and amines are treated with reducing agents in a one-pot manner, is one of the most useful and versatile methods for the preparation of amines and related functional compounds in organic synthesis and biological systems.

The amines thus obtained are very useful in industry and have found widespread use as intermediates in pharmaceuticals, dyes, resins, fine chemicals, solvents, textile additives, disinfectants, rubber stabilizers, corrosion inhibitors, and in the manufacture of detergents agents and plastics.

Research Applications

• Intramolecular C-H amination

Several catalytic systems and nitro nitrogen sources have been investigated for intramolecular C(sp3)-H amination. A popular system is based on in situ generation of metal nitrene from carbamate and sulfamate in the presence of a rhodium catalyst and an oxidant. For example, since the pioneering work of Du Bois, catalytic systems using dirhodium species have indeed proven to be very successful for intramolecular C-H aminations.

Figure 1. Typical features of intramolecular C-H amination [1]

• Intermolecular C-H amination

While intramolecular delivery of nitrones can ensure a high degree of chemical and regioselectivity, designing a similar process for intermolecular C-H bond differentiation is more challenging. In transformations based on C-H activation, exploiting the chelation effect yields efficient solutions. It has been found to catalyze the intramolecular C-H amination of carbamate and sulfamate, and the binuclear silver(I) complex has also been shown to be active for the intermolecular amination of various hydrocarbons.

Figure 2. Silver-catalyzed intermolecular C-H amination [2]

• Amination via C-H activation

The development of numerous C-H activation-based methods for the selective functionalization of C-H bonds has received considerable attention. Thu et al. found potassium persulfate K₂S₂O₈ to be a more suitable oxidant, allowing Pd(OAc)₂-catalyzed amination using sulfonamides, carbamates, and even formamides. The catalytic reaction is initiated by chelation-assisted cyclopalladation and involves C-H bond activation.

Figure 3. Palladium-catalyzed C-H amination [3]

References

1. Damien Hazelard. (2017). "Catalytic C-H amination at its limits: challenges and solutions," Organic Chemistry Frontiers 4: 2500-2521.
2. Florence Collet. (2009). "Catalytic C-H amination: recent progress and future directions," Chemical Communications 34: 5061-5074.
3. Hung-Yat Thu. (2006). "Intermolecular Amidation of Unactivated sp2 and sp3 C-H Bonds via Palladium-Catalyzed Cascade C-H Activation/Nitrene Insertion," Journal of the American Chemical Society 128(28): 9048-9049.