A novel generation of coupling reagents. Enantiodifferentiating coupling reagents prepared in situ from 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and chiral tertiary amines.

Abstract

Coupling of racemic N-protected amino acids with amino components by means of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) in the presence of chiral tertiary amines such as strychnine, brucine, and sparteine proceeds enantioselectively, affording appropriate amides or dipeptides in 69-85% yield. The configuration of the preferred enantiomer and enantiomeric enrichment depend on the structures of the amine and carboxylic acid. Calculated Kagan enantioselectivity parameters (s) are in the range 1.6-195. Chiral triazinylammonium chlorides formed in situ from CDMT and chiral tertiary amines are postulated as reactive intermediates involved in the process of enantioselective activation of N-protected amino acids.