Aryl azole scaffolds are present in a wide range of pharmaceutically relevant molecules. Their ortho-selective metalation at the aryl ring is challenging, due to the competitive metalation of the more acidic heterocycle. Seeking a practical access to a key Active Pharmaceutical Ingredient (API) intermediate currently in development, we investigated the metalation of 1-aryl-1H-1,2,3-triazoles and other related heterocycles with sterically hindered metal-amide bases. We report here a room temperature and highly regioselective ortho-magnesiation of several aryl azoles using a tailored magnesium amide, TMPMgBu (TMP = 2,2,6,6-tetramethylpiperidyl) in hydrocarbon solvents followed by an efficient Pd-catalyzed arylation. This scalable and selective reaction allows variation of the initial substitution pattern of the aryl ring, the nature of the azole moiety, as well as the nature of the electrophile. This versatile method can be applied to the synthesis of bioactive azole derivatives and complements existing metal-mediated ortho-functionalizations.

A practical nickel-catalyzed cross-coupling of (hetero)­aryl or alkynylzinc pivalates with various unsaturated nonaflates or triflates is described. Organozinc pivalates allow these cross-couplings to take place with high yields and a low catalyst loading (0.5 mol %). Couplings with (E)- and (Z)-alkenyl triflates proceed with retention of configuration.

A mild cobalt-catalyzed Negishi-type cross-coupling of various functionalized dialkylzinc reagents with primary and secondary alkyl iodides in acetonitrile is reported using a combination of 20% CoCl 2 and chelating nitrogen ligands. The method allows the construction of molecules with alkyl chains bearing sensitive functional groups at room temperature.

A cobalt-catalyzed acylation reaction of (hetero)arylzinc pivalates using primary, secondary and tertiary alkyl, benzyl and (hetero)aryl S-pyridyl thioesters has been developed.

Transition metal catalyzed cross‐couplings are essential methods in organic synthesis. Due to their comparable low toxicity and price, cobalt‐salts offer a useful alternative to other common metal‐catalysts (e. g. palladium‐complexes). In this review, we report that cobalt‐catalysts are especially well suited for cross‐coupling reactions with organozinc pivalates, a class of organozinc reagents with enhanced stability towards air and moisture. Furthermore, we discuss applications of cobalt‐catalysis in Negishi cross‐coupling reactions (sp2‐sp2, sp‐sp2, sp‐sp3) as well as electrophilic aminations using organozinc reagents.