Chiral Arylated Amines via C-N Coupling of Chiral Amines with Aryl Bromides Promoted by Light

The Buchwald-Hartwig C-N coupling reaction has found widespread applications in organic synthesis. Over the past two decades or so, many improved catalysts have been introduced, allowing various amines and aryl electrophiles to be readily used nowadays. However, there lacks a protocol that could be used to couple a wide range of chiral amines and aryl halides, without erosion of the enantiomeric excess (ee). Reported in this article is a method based on molecular Ni catalysis driven by light, which enables stereoretentive C-N coupling of optically active amines, amino alcohols, and amino acid esters with aryl bromides, with no need for any external photosensitizer. The method is effective for a wide variety of coupling partners, including those bearing functional groups sensitive to bases and nucleophiles, thus providing a viable alternative to accessing synthetically important chiral N-aryl amines, amino alcohols, and amino acids esters. Its viability is demonstrated by 92 examples with up to 99 % ee.

Automated summary

The article introduces a method based on molecular Ni catalysis driven by light, allowing stereoretentive C-N coupling of optically active amines, amino alcohols, and amino acid esters with aryl bromides without the need for any external photosensitizer. The method is effective for a wide variety of coupling partners with functional groups sensitive to bases and nucleophiles, providing a viable alternative for accessing synthetically important chiral N-aryl amines, amino alcohols, and amino acids esters, as shown by 92 examples with up to 99% ee.