Asymmetric Reactions

Catalysis has the unique advantage that it is possible to obtain a large amount of optically active products by using a small amount of catalyst, which has been the hot spot and frontier of research for decades. Alfa Chemistry Catalysts provides a wide variety of catalysts for asymmetric synthesis reactions, helping customers to meet many challenges in the field of drug synthesis and total synthesis of natural products.

Classification

Asymmetric reaction types mainly include asymmetric hydrogenation, asymmetric epoxidation, asymmetric isomerization, asymmetric hydrocresolation, asymmetric hydrosilylation, asymmetric cyclopropanation and aziridine, and asymmetric Diels- Alder reaction, asymmetric phase transfer catalytic reaction, etc.

Catalysts for asymmetric reactions can be divided into four categories according to the nature of functional groups: asymmetric organic catalysis, asymmetric hybrid organic/metal catalysis, asymmetric multifunctional multi-metal catalysis, and anionic bifunctional asymmetric catalysis.

Applications and References

• Asymmetric organocatalysis

Asymmetric organocatalysis has been established as a powerful strategy for the stereo-controllable synthesis of optically active compounds, and one of its important advantages is the good compatibility of different types of organocatalysts. Multifunctional organocatalysis is divided into the following types, namely H-bond donor tertiary amine catalysis, H-bond donor-enamine catalysis, H-bond donor phase transfer catalysis, H-bond donor-tertiary phosphine catalysis, chiral phosphoric acid catalysis, Symmetrical bifunctional salt catalysis and miscellaneous.

Studies have shown that hydrogen bond donor-tertiary amine catalysis is a special catalyst scaffold because the tertiary amine moiety can act as a Bronsted or Lewis base to activate a large number of nucleophiles, while the hydrogen bond donor moiety can activate electrophiles reagents and stabilize transition states through hydrogen bonding interactions.

Figure 1. General model of H-bond donor-tertiary amine multifunctional catalysis. [1]

• Asymmetric hybrid organic/metal catalysis

Various types of mixed organic/metallic multifunctional catalysts have been developed for asymmetric reactions, such as Brønsted base/lewis acid bifunctional catalysis. In 1986, researchers reported the highly enantioselective asymmetric aldol reaction of aldehydes with isocyanoacetates, catalyzed by chiral ferrocenylphosphine-derived Au(I) complexes at the sidearm terminal position with tertiary amine

Figure 2. Aldol reaction catalyzed by ferrocenylphosphine/Au(I) catalyst. [2]

• Asymmetric multifunctional multimetallic catalysis

Endo et al. discovered a class of multinuclear complexes, including copper and zinc metal centers, that are more efficient than previous systems in the Cu-catalyzed asymmetric conjugate addition of organozinc reagents to α, β-unsaturated ketones. The excellent performance of the catalyst can be explained by the formation of multinuclear complexes.

Figure 3. Structural catalyzed asymmetric addition reactions of polynuclear complexes. [3]

References

1. Jin-Sheng Yu. (2014). "Multicatalyst System in Asymmetric Catalysis," Chapter 3.
2. Yoshihiko. Ito. (1986). "Catalytic asymmetric aldol reaction: reaction of aldehydes with isocyanoacetate catalyzed by a chiral ferrocenylphosphine-gold(I) complex," Journal of the American Chemical Society 108(20): 6405-6406.
3. Kohei Endo. (2010). "Multinuclear Catalyst for Copper-Catalyzed Asymmetric Conjugate Addition of Organozinc Reagents," Angew. Chem. Int. Ed. 49: 2410-2413.