Isoxazole Strategy for the Synthesis of 2,2′-Bipyridine Ligands: Symmetrical and Unsymmetrical 6,6′-Binicotinates, 2,2′-Bipyridine-5-carboxylates, and Their Metal Complexes

• Published in: Journal of organic chemistry 2019-03, Vol.84 (6), p.3524-3536
• Main Authors: Galenko, Ekaterina E, Novikov, Mikhail S, Shakirova, Firuza M, Shakirova, Julia R, Kornyakov, Ilya V, Bodunov, Vladimir A, Khlebnikov, Alexander F
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.9b00115

An effective strategy was developed for the synthesis of new 2,2′-bipyridine ligands, symmetrical and unsymmetrical 6,6′-binicotinates, and 2,2′-bipyridine-5-carboxylates, from 4-propargylisoxazoles. The synthesis of symmetrical 2,2′-disubstituted 6,6′-binicotinates was achieved using the Eglinton reaction of 5-methoxy-4-(prop-2-yn-1-yl)­isoxazoles with Cu­(OAc)2, followed by Fe­(NTf2)2/Au­(NTf2)tBuXPhos-catalyzed isomerization of the so-formed mixture of isoxazole/azirine-substituted biacetylenic intermediates. Unsymmetrical 2,2′-disubstituted 6,6′-binicotinates were prepared via a copper-free Sonogashira coupling of 5-methoxy-4-(prop-2-yn-1-yl)­isoxazoles with 6-bromonicotinates to give methyl 6-(3-(5-methoxyisoxazol-4-yl)­prop-1-ynyl)­pyridine-3-carboxylates, followed by a transformation of the propargylisoxazole moiety of the adduct into the pyridine fragment under Fe­(II)/Au­(I) relay catalysis conditions. 6-(Pyrid-2-yl)­nicotinates were synthesized by a Stille-type coupling of 2-(tributylstannyl)­pyridine with 6-bromonicotinates. Several cyclopalladated complexes of a new series of 6,6′-binicotinates and 2,2′-bipyridine-5-carboxylates and the homoleptic Cu­(I) complex were synthesized in high yields.