Palladium‐Catalyzed Zinc‐Amide‐Mediated CH Arylation of Fluoroarenes and Heteroarenes with Aryl Sulfides

Abstract

C-H arylation of polyfluoroarenes and heteroarenes with aryl sulfides proceeds smoothly with the aid of a palladium-N-heterocyclic carbene catalyst. A bulky zinc amide, TMPZnCl⋅LiCl, plays a key role as an effective base to generate the corresponding arylzinc species in situ. This arylation protocol is practically much easier to perform than our previous method, which necessitates preparation of the arylzinc reagents in advance from the corresponding aryl halides. Aryl sulfides that are prepared through sulfur-specific reactions, such as SN Ar sulfanylation and extended Pummerer reactions, undergo this direct arylation, offering interesting transformations that are otherwise difficult to achieve with conventional halogen-based organic synthesis.

C–S Bond Activation

“…Not only the electron-rich nature of NHC-ligated palladium center accelerates oxidative addition, but also the strongly coordinating NHC ligand would keep the palladium catalyst molecular and highly active by preventing the formation of Pd nanoparticles. This catalysis was applied to deprotonative arylation of polyfluoroarenes and heteroarenes with aryl sulfides [45]. Deprotonative zincation with a 2,2,6,6-tetramethylpiperidinylzinc base followed by palladium-NHC-catalyzed cross-coupling with aryl sulfides afforded the corresponding arylated products with high efficiency.…”

Cross-coupling of Aryl Sulfides Powered by <i><b>N</b></i>-Heterocyclic Carbene Ligands

“…We then turned our attention to direct C H arylation of arenes via deprotonative zincation with 2,2,6,6 tetramethylpiperidylzinc chloride lithium chloride complex (TMPZnCl LiCl) as base. 15 Pd PEPPSI SIPr was again the best catalyst for this transformation, and the desired product was obtained quantitatively from 3 and penta uorobenzene (12a) ( Table 2).…”

A Predictive Model Towards Site‐Selective Metalations of Functionalized Heterocycles, Arenes, Olefins, and Alkanes using TMPZnCl⋅LiCl

“…were present, a metalation could be performed using the mild base TMPZnCl⋅LiCl (6 out of 23 structures are depicted in Figure ) . Thus, p K a values for electron‐poor arenes 7 a – e were calculated (p K a (H1)=22.6–32.9) and deprotonation occurred at the most acidic sites at 25–160 °C within 1–7 h, producing the expected arylzinc reagents 8 a – e in 65–80 % yield . A reliable prediction for the tropolone scaffold was difficult ( 7 f ), similarly as with chromone 5 c due to the carbonyl group, which has proven to strongly coordinate to zinc amide bases, inducing a deprotonation in α‐position (Figure ) …”