Functionalization of pyridine via direct metallation

Abstract

The isolation of mixtures of 2-, 3-, and 4-deuteriopyridine, 2-, 3-, and 4-trimethylsilylpyridine, or 2-, 3-, and 4-methylthiopyridine indicates successful metallation of pyridine with a 1 : 1 mixture of BuLi-ButOK in tetrahydrofuran-hexane at -100°C.

Symmetric and Asymmetric Coupling of Pyridylpyrimidine for the Synthesis of Polynucleating Ligands

“…However, there are a few reported cases of direct lithiation of unsubstituted electron-deficient heterocycles. [10,11] Pyrimidine can be lithiated directly in the 4-position using lithium 2,2,6,6-tetramethylpiperidide (LTMP), and its addition to pyrimidine gives 4,4Ј-bipyrimidine (bpym) in modest yield. [11] This suggested that lithiation of 4-(2-pyridyl)pyrimidine (3) [12] in the 6-position, followed by addition to another ligand 3, would give 2a.…”

On the deprotonation of 3,5-dichloropyridine using lithium bases: in situ infrared spectroscopic studies

“…A similar observation was described by Brandsma, when deprotonating quinoline or isoquinoline with equimolar quantities of potassium tert-butoxide and LDA in THF-hexane with HMPA as a co-solvent. 12 A H-bonded complex between the lithio derivative and 2,2,6,6-tetramethylpiperidine (Scheme 2) could be envisaged as responsible for the partial deuteration observed, analogous to that observed several years ago by Seebach between lithium enolates and secondary amines. 13 Nevertheless, chelation between the aryllithium and 2,2,6,6-tetramethylpiperidine is unlikely and a more plausible explanation can be claimed.…”

Lateral Metallation and Redistribution Reactions of Sodium Ferrates Containing Bulky 2,6‐Diisopropyl‐N‐(trimethylsilyl)anilide Ligands

“…Pentafluorobenzene (C 6 F 5 H) and pyridine (py) were chosen as model substrates. The former is highly activated in terms of p K a value of its sole H centre; [41] whereas the latter is a sensitive electron‐deficient substrate for which metallation using conventional polar organometallics can be particularly challenging due to the fragility of their metallated intermediates as well as the difficulty in controlling the regioselectivity of the metal‐H exchange [42–44] …”

“…The former is highly activated in terms of pK a value of its sole H centre; [41] whereas the latter is a sensitive electron-deficient substrate for which metallation using conventional polar organometallics can be particularly challenging due to the fragility of their metallated intermediates as well as the difficulty in controlling the regioselectivity of the metal-H exchange. [42][43][44] Focusing first on C 6 F 5 H, addition of 1 equivalent of this substrate to a toluene solution of 1 produced an instant colour change in the solution from bright orange to pale yellow and the emergence of a light coloured precipitate. Gentle heating to obtain a solution followed by slow cooling to 5 °C furnished large pale pink crystals of [Na{N(SiMe 3 )Dipp}(HMDS)Fe(C 6 F 5 )] 1 (4) in a 57 % crystalline yield (Scheme 4 and Figure 3, RHS).…”