Preparative-Scale Synthesis of Vedejs Chiral DMAP Catalysts

Artis Kinens; Simonas Balkaitis; Edgars Suna

doi:10.1021/acs.joc.8b01687

Preparative-Scale Synthesis of Vedejs Chiral DMAP Catalysts

J Org Chem. 2018 Oct 19;83(20):12449-12459. doi: 10.1021/acs.joc.8b01687. Epub 2018 Oct 10.

Authors

Artis Kinens^{1

2}, Simonas Balkaitis^{1

2}, Edgars Suna^{1

2}

Affiliations

¹ Latvian Institute of Organic Synthesis , Aizkraukles 21 , LV-1006 Riga , Latvia.
² Department of Chemistry , University of Latvia , Jelgavas 1 , LV-1004 Riga , Latvia.

PMID: 30256638
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.