Chiral Ammonium Salts

Chiral Ammonium Salts

The ammonia molecule is coordinated with a hydrogen ion to form an ammonium ion (ammonia provides a lone pair of electrons), and the ammonium ion can combine with an anion to form an ammonium salt. The chiral ammonium salt means that the nitrogen atom of the ammonium salt is attached to the chiral carbon atom. The most common organic ammonium salt is a quaternary ammonium salt (also known as a quaternary ammonium base) which is an ionic compound composed of four alkyl groups bonded to a nitrogen atom.

Applications

• Catalytic Steglich rearrangement reaction: Some scholars have reported that the quaternary ammonium salt betaine catalyzes the Mannich-type reaction of N-Boc imine with nitrocarboxylate, and has high enantioselectivity. These new zwitterionic quaternary salt catalysts have received extensive attention and have been successfully applied in asymmetric catalytic reactions, which also have provided new ideas for the design and synthesis of new catalysts.
• Catalytic asymmetric Mannich reaction: Lewis acid is usually used as a catalyst in nucleophilic catalysis. However, the chiral zwitterionic quaternary ammonium derived from a single naphthalene skeleton can be successfully used in the Steglich rearrangement reaction as an ionic nucleophilic catalyst. This reaction gives excellent yields and excellent enantioselective products. This betaine as an ionic nucleophilic catalyst provides a new way for the development of asymmetric nucleophilic catalysis.
• Catalytic isomerization reaction: The clementine alkaloid-derived zwitterionic quaternary ammonium salt can catalyze the proton transfer reaction to achieve isomerization of trifluoromethyl ketimine. During the reaction, the π-π interaction between the catalyst and the substrate compensates for the defect that the phenolic anion and the quaternary ammonium salt are far away. The isomerization of trifluoromethyl ketimine is achieved with high enantioselectivity.
• Catalytic addition reaction: By adjusting the rigidity and flexibility of the binaphthyl skeleton by a linking group, the chiral binaphthyl double-spirocyclic quaternary ammonium salt PTC-28 shows good enantioselectivity in the ruthenium addition reaction of 2-nitropropane and chalcone. More importantly, by adjusting the length of the aliphatic chain between the two spirocyclic quaternary ammonium salts, the addition product configuration can be reversed, that is, the same chiral source-derived catalyst realizes the chiral switch in the asymmetric reaction.

  Figure 1. Conjugate addition with bisquaternary ammonium salts derived from chiral binaphthyl

• Catalytic Aldol reaction: Asymmetric aldol reaction of α-substituted nitroacetate with aqueous formaldehyde solution can be achieved by using a bifunctional naphthyl ammonium salt phase transfer catalyst to obtain a highly enantioselective α-alkyl serine derivative. Besides, asymmetric aldol reaction of tert-butyl N-dibenzylidene glycinate with phenylpropanal is catalyzed by a simplified Maruoka catalyst and a symmetric naphthyl ammonium salt phase transfer catalyst. It is possible to obtain cis- and trans-β-hydroxy-α-amino acid derivatives.

  Figure 2. Asymmetric aldol reaction of α-substituted nitro acetate

• Catalytic asymmetric alkylation reaction: Derivatives of cinchonine and cinchonidine (PTC-8 and PTC-9) can be used in the asymmetric alkylation of N-diphenylmethylene glycine tert-butyl ester. Although its enantioselectivity is only moderate, the product can be easily obtained by concentrated recrystallization deprotection or the like.

  Figure 3. Cinchona base phase transfer catalyst and its application in asymmetric alkylation.

References

1. Hua M Q, Cui H F, Wang L. (2010). “Reversal of enantioselectivity by tuning the conformational flexibility of phase-transfer catalysts.” Angewandte Chemie International Edition. 49(15), 2772-2776.
2. Wang L, Shirakawa S, Maruoka K. (2011). “Asymmetric neutral amination of nitroolefms catalyzed by chiral bifunctional ammonium salts in water-rich biphasic solvent.” Angewandte Chemie International Edition. 50(23), 5327-5330.
3. Makosza M.(1975). “Two-phase reactions in the chemistry of carbanions and halocarbons-a useful tool in organic synthesis.” Pure and Applied Chemistry. 43(3-4), 439-462.