Methodologies in Amine Synthesis

Scheme 1.36 TM‐free Rubottom oxidation.

Scheme 1.37 TM‐free NH‐aziridination of unactivated olefins.

Source: Modified from Cheng et al. [53].

Two sets of conditions for the synthesis of primary α‐aminoketones from silyl enol ethers were developed. Electron‐rich substrates can be α‐aminated without transition metal catalysis, while substrates bearing electron‐withdrawing substituents can undergo α‐amination with the help of Rh or Cu catalysts.

Further studies in the Kürti group have shown that it is possible to achieve TM‐free NH‐aziridination of unactivated olefins with highly reactive NH‐oxaziridines via the “Butterfly Mechanism” [53]. These unique NH‐oxaziridines bear one or more strongly electron‐withdrawing group(s), which greatly enhance the electrophilicity of the nitrogen atom. With the further enhancement provided via the hydrogen bonding interactions by the HFIP solvent molecules, these highly reactive intermediates are capable of TM‐free transfer of the NH onto the unactivated olefins ( Scheme 1.37).

However, because of their high reactivities, these highly electron‐deficient NH‐oxaziridines cannot be isolated. The Kürti group solved this issue by forming these intermediates in situ from HOSA and ketones bearing electron‐withdrawing groups. Mass spectrometric studies confirmed the existence of the highly reactive oxaziridine intermediates.

By using a chiral nonracemic ketone as the organocatalyst, the reaction can give enantiomerically enriched products.

In the past two decades, a number of C—N bond‐forming reactions have been developed that take advantage of hydroxylamine‐based electrophilic aminating agents as sources of nitrogen. A great deal of structural diversity has been achieved in terms of the products. Olefins, substituted aromatic systems, as well as organometallic compounds have been successfully aminated. Although the vast majority of reported methods utilize transition metal complexes as catalysts, metal‐free and even organocatalytic methods have also emerged during the past decade. The two emerging trends are to incorporate unprotected amino groups directly and to use inexpensive and nontoxic transition metal catalysts such as iron complexes. We are confident that during the next decade, we will see further innovation in electrophilic amination chemistries.

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