Oxygen Activated, Palladium Nanoparticle Catalyzed, Ultrafast Cross‐Coupling of Organolithium Reagents

Abstract

The discovery of an ultrafast cross-coupling of alkyl- and aryllithium reagents with a range of aryl bromides is presented. The essential role of molecular oxygen to form the active palladium catalyst was established; palladium nanoparticles that are highly active in cross-coupling reactions with reaction times ranging from 5 s to 5 min are thus generated in situ. High selectivities were observed for a range of heterocycles and functional groups as well as for an expanded scope of organolithium reagents. The applicability of this method was showcased by the synthesis of the [ C]-labeled PET tracer celecoxib.

Murahashi Cross‐Coupling at −78 °C: A One‐Pot Procedure for Sequential C−C/C−C, C−C/C−N, and C−C/C−S Cross‐Coupling of Bromo‐Chloro‐Arenes

“…Recent advancements in the cross‐coupling of hard organometallic nucleophiles have been accelerated by the design of reactive catalysts with very high turnover frequencies . Published work on the coupling of organolithium reagents offers new insights into the active palladium catalyst.…”

“…An interesting article for the biaryl synthesis by homo‐ and hetero‐Kumada couplings in water has also been reported . Feringa and co‐workers have reported the use of Pd‐phosphine catalysts for the coupling of organolithium reagents and found that, despite high turnover frequencies, coupling below −10 °C was not feasible …”

“…[8d] Feringa and co-workersh ave reported the use of Pdphosphine catalysts for the coupling of organolithium reagents and found that, despite high turnover frequencies, coupling below À10 8Cwas not feasible. [2] The Pd-NHC( N-heterocyclic carbene) catalystf amilyh as also showng reat stability and reactivity in the presence of aryland alkyllithium nucleophiles (Scheme 1i)a nd has simultaneously provent ob eap articularly active catalyst system for the cross-coupling of av ariety of functionalized andc hallenging nucleophiles [R-ZnBr, R-B(OR) 2 ,R -SnR 3 ]i nb atch or flow (Scheme 1ii). [9][10][11][12][13][14][15][16][17][18] Compared to simple NHC complexes, the designo fPd-PEPPSI catalysts with increased bulk on the flanking aryl groups increases turnover numbers [16] while decreasing competing side reactions arising from rearrangements, such as is seen in the coupling of secondary alkyl substrates by mitigating migratory insertion.…”

Rapid Access to Bi‐ and Tri‐Functionalized Dibenzofurans and their Application in Selective Suzuki–Miyaura Cross Coupling Reactions

“…Melting points were measured on a Büchi Melting Point B‐540. Compounds 38 , 40 ,[33b] 42 , 48 , 50 and 52 are literature‐known. Therefore, merely GC‐MS measurements were conducted to confirm their formation during the reactions.…”

Recent Advances in Methylation: A Guide for Selecting Methylation Reagents

“…In 2017, Feringa et al. reported an ultrafast cross‐coupling of alkyl‐ and aryllithium reagents with a range of aryl bromides in the presence of both catalytic palladium nanoparticles and O 2 . The cross‐coupling of arylbromides with MeLi gave good to excellent yields with good functional group tolerance (Table ).…”