N-Heteroarylation of Chiral α-Aminoesters by Means of Palladium-Catalyzed Buchwald–Hartwig Reaction

N-Heteroaryl-α-amino acid derivatives are valuable pharmacological agents as peptidomimetics.

 

 

Classical S_NAr methods using acid catalysis and elevated temperatures could not be extended to various α-amino acids and fairly electrophilic heterocyclic partners.

 

 

Here, we report a mild and versatile method of N-heteroarylation of chiral α-aminoesters without racemization, involving Buchwald–Hartwig conditions.

 

 

It could be extended to various α-amino acids and azines.

 

This efficient N-heteroarylation leads to (i) a chemical library of putative peptidomimetics combining diverse azaheterocycles with the chiral α-aminoesters and their corresponding derivatives (amides, alcohols, etc.) and (ii) arginine derivatives designed as NPFF receptor ligands.

http://pubs.acs.org/doi/pdfplus/10.1021/jo4011427