Functionalization of diazines and benzo derivatives through deprotonated intermediates

Abstract

This critical review targets as a readership researchers generally oriented toward organic synthesis and in particular those active in heterocyclic chemistry. Diazines and benzo derivatives can undergo deprotonative metalation provided that the base is properly chosen. Metalation reactions of a large range of substrates can be performed using hindered lithium dialkylamides such as lithium 2,2,6,6-tetramethylpiperidide. Subsequent reactions with electrophiles open an entry to a great variety of building blocks, notably for the synthesis of biologically active compounds. (83 references).

Transforming LiTMP Lithiation of Challenging Diazines through Gallium Alkyl Trans‐Metal‐Trapping

“…Lithium alkyls and amides remain front‐runners for base candidates in routine C−H to C−metal transformations, but for non‐routine, more formidable substrates, base selection is generally far from straightforward 2. One of nature's most important class of heterocycles utilized widely in agrochemicals, foodstuffs, pharmaceuticals, and many other commercial commodities, diazines are firmly in the formidable category, especially parent naked diazines devoid of substituents capable of assisting the direction of the metalation 3. To avoid competition from nucleophilic addition caused by a low‐lying LUMO in the heteroaromatic ring, bulky LiTMP (TMP is 2,2,6,6‐tetramethylpiperidide) is preferred to more basic alkyllithium reagents as the base for these π‐deficient diazines, as first noted by Quéguiner 4.…”

Regio‐ und chemoselektive Metallierung von Arenen und Heteroarenen mit gehinderten Metallamidbasen

“…Während solche Metallierungen mit Lithiumreagentien in der chemischen Literatur wohlbekannt sind, [5][6][7][8][9] schließt die hohe Reaktivität von Lithiumbasen die Anwendbarkeit auf viele funktionalisierte Substrate aus. Die aus der Metallierung resultierenden, hoch reaktiven Aryllithiumverbindungen sind im Allgemeinen lediglich bei tiefen Temperaturen stabil und reagieren bereits unter milden Bedingungen mit wichtigen funktionellen Gruppen wie Esteroder ungehinderten Amidfunktionen.…”

Reactions of organolithium reagents with quinazoline derivatives

“…1,2 A number of alternative approaches have therefore been developed for regioselective ortho-disubstitution, and lithiation followed by electrophilic substitution is one of the most recognized and efficient. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] Directed lithiation of aromatic compounds 1 comprises deprotonation of a site ortho to a substituent that possesses a heteroatom (e.g. oxygen, nitrogen or sulfur) by use of a base.…”