Zn-, Mg-, and Li-TMP Bases for the Successive Regioselective Metalations of the 1,5-Naphthyridine Scaffold (TMP=2,2,6,6-Tetramethylpiperidyl)

Moritz Balkenhohl; Robert Greiner; Ilya S Makarov; Benjamin Heinz; Konstantin Karaghiosoff; Hendrik Zipse; Paul Knochel

doi:10.1002/chem.201703638

Zn-, Mg-, and Li-TMP Bases for the Successive Regioselective Metalations of the 1,5-Naphthyridine Scaffold (TMP=2,2,6,6-Tetramethylpiperidyl)

Chemistry. 2017 Sep 21;23(53):13046-13050. doi: 10.1002/chem.201703638. Epub 2017 Aug 23.

Authors

Moritz Balkenhohl¹, Robert Greiner¹, Ilya S Makarov¹, Benjamin Heinz¹, Konstantin Karaghiosoff¹, Hendrik Zipse¹, Paul Knochel¹

Affiliation

¹ Ludwig-Maximilians-Universität München, Department Chemie, Butenandtstrasse 5-13, Haus F, 81377, München, Germany.

PMID: 28777497
DOI: 10.1002/chem.201703638

Abstract

A set of successive regioselective metalations and functionalizations of the 1,5-naphthyridine scaffold are described. A combination of Zn-, Mg-, and Li-TMP (TMP=2,2,6,6-tetramethylpiperidyl) bases and the presence or absence of a Lewis acid (BF₃ ⋅OEt₂ ) allows the introduction of up to three substituents to the 1,5-naphthyridine core. Also, a novel "halogen dance" reaction was discovered upon metalation of an 8-iodo-2,4-trifunctionalized 1,5-naphthyridine allowing a fourth regioselective functionalization. Additionally, reactions leading to key 1,5-naphthyridines for the preparation of OLED materials and a potential antibacterial agent were performed.

Keywords: TMP bases; halogen dance; metalation; naphthyridine; nitrogen heterocycles.