Preparative-Scale Synthesis of Vedejs Chiral DMAP Catalysts

Kinens, A.; Balkaitis, S.; Suna, E. J. Org. Chem. 2018, 83, 12449–12459.

DOI: 10.1021/acs.joc.8b01687

Abstract

A scalable synthesis of chiral Vedejs-type DMAP catalysts is reported. The key step of the synthesis is amination of the enantiomerically pure 4-chloropyridine derivative using well-defined ZnCl2(amine)2 complexes. A series of Zn(II)–amine complexes have been synthesized to explore the scope of the ZnCl2-mediated amination of 4-halopyridines. Mechanistic studies support a Zn(II)-facilitated nucleophilic aromatic substitution as a plausible mechanism for the chlorine-to-amine exchange.