The cross-coupling of organometallic reagents and its application in pharmaceutical products, is a widely investigated field, and its use in the formation of functionalized heterocycles has proven especially useful. Our group reported several examples of cross-coupling of organolithium reagents, and here is presented the first mechanistic investigation of organolithium cross-couplings. Activation of the catalyst by means of molecular oxygen is discovered and investigated. Optimization of the reaction has lead to the fastest cross-coupling of alkyl- and aryllithium reagents with a range of aromatic bromides. <i>In situ</i> generation of palladium nanoparticles couples lithium nucleophiles in reaction times ranging from 5 seconds to 5 minutes with good to excellent yields. New reactivity is found for a range of heterocycles and functional groups, and the catalyst loading can be lowered to 0.025%mol. The utility of this methodology has been showcased in the synthesis of <sup>11</sup>C-labelled Celecoxib.

Oxygen activated ultra-fast palladium nanoparticle catalyzed cross-coupling of organolithium reagents: A mechanistic insight

253rd National Meeting (2017)

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