Amination is the process by which an amine group is introduced into an organic molecule. This type of reaction is important because organonitrogen compounds are pervasive. The ability to form new C−N bonds in a direct and efficient manner is crucially important due to their ubiquity in organic molecules. In particular Cinchona Alkaloid derivatives serve as a versatile tool to perform enantioselective aminations.

Enantioselective Amination

The catalytic construction of nitrogen-substituted quaternary stereocenters is an important and challenging task in asymmetric synthesis. As a chiral organocatalyst Cinchona alkaloid derivatives such as Cupreine or Cupreidine can be used for enantioselective amination of α,α-disubstituted carbonyl compounds that are suitable for the creation of nitrogen-substituted quaternary stereocenters in either the R or S configuration.

For the α-amination of oxindoles the well-known (DHQD)₂PHAL catalyst can be used. The reaction is highly enantioselective, operationally simple, and affords the desired products in high yields with good to excellent enantioselectivity.

A further example for enantioselective aminations is the electrophilic amination of benzoyl butyrolactones with azodicarboxylates. Quaternary carbon stereocenter bearing α-amino-γ-butyrolactones can be prepared efficiently, a key framework in numerous bioactive compounds.

(DHQD)₂AQN enables the enantioselective allylic amination of Morita–Baylis–Hillman carbamates in the presence of a Brønsted acid efficiently. Chiral allylic amines can be produced in high yields and high enantioselectivities. This method provides an efficient and easily performed route to prepare α-methylene-β-lactams, and other optically active β-lactams, such as the cholesterol-lowering drug Ezetimibe.

A wide variety of α-amino esters containing various functional groups can be synthesized in high yield and enantioselectivity from α-keto esters by transamination using easily accessible Cinchona alkaloid derivatives.

Please find further examples of enantioselective aminations promoted by Cinchona Alkaloids in our Buchler Chiral Catalyst Search.

Example from literature

Highly enantioselective amination of α-substituted α-cyanoacetates with chiral catalysts accessible from both quinine and quinidine. (Liu et al; Org. Lett. 2005, 7(2), 167-169.)