Dual Effect of Halides in the Stille Reaction: In Situ Halide Metathesis and Catalyst Stabilization

Abstract

Halide anions can increase or decrease the transmetallation rate of the Stille reaction through in situ halide metathesis. Although the influence of the halogen present in oxidative addition complexes on the transmetallation rate with organostannanes was already known, the application of in situ halide metathesis to accelerate cross-coupling reactions with organometallic reagents is not described in the literature yet. In addition a second unprecedented role of halides was discovered. Halide anions stabilize the [Pd(0)(L)(2)] catalyst in Stille reactions, by means of [Pd(0)X(L)(2)](-) formation (X=Cl, I), hereby preventing its leaching from the catalytic cycle. Both arene (iodobenzene) and azaheteroarene (2-halopyridine, halopyrazine, 2-halopyrimidine) substrates were used.

Mechanism of Palladium‐Catalyzed Suzuki–Miyaura Reactions: Multiple and Antagonistic Roles of Anionic “Bases” and Their Countercations

“…(10)], Ar = p-CN-C 6 H 4 -, X = I, K I = 5, DMF, 27 8C from 31 P NMR spectroscopic data). [28] The isolated trans-[PdF(ptrans-½PdðArÞðLÞ 2 X þ F À ! trans-½PdðArÞFðLÞ 2 þ X À ð10Þ The mechanism of the Suzuki-Miyaura performed in the presence of fluoride ions is given in Scheme 15. As for hydroxide ions, fluoride ions play three kinetically antagonistic roles: 1) formation of trans-[Pd(Ar)F(L) 2 ] reactive in the rds transmetallation with Ar'B(OH) 2 , 2) catalysis of the reductive elimination from trans-[Pd(Ar)A C H T U N G T R E N N U N G (Ar')(L) 2 ], and 3) formation of less or unreactive arylfluoroborates.…”

On the Triple Role of Fluoride Ions in Palladium‐Catalyzed Stille Reactions

“…1e A transfer of the R′ group of R′SnBu 3 to CuI to form a more reactive {R′Cu} species in the transmetallation was also disclosed 3c. 1f We reported a dually beneficial role of chloride ions in the Stille reaction when using the precatalyst [PdCl 2 (PPh 3 ) 2 ],4 namely i) in situ halide metathesis in [ArPdX(PPh 3 ) 2 ] (X=I, Br) leading to [ArPdCl(PPh 3 ) 2 ], which is more reactive in the transmetallation step with organostannane derivatives, and ii) stabilisation of [Pd 0 (PPh 3 ) 2 ] (formed by reduction of [PdCl 2 (PPh 3 ) 2 ] by R′SnBu 3 ) with formation of stable anionic [Pd 0 Cl(PPh 3 ) 2 ] − , which prevents the Pd 0 decomposition that occurs in the absence of Cl − . A high catalyst loading is maintained in the presence of Cl − and the catalytic reactions become faster 4.…”

“…The postulated mechanism involves at least three steps: i) oxidative addition of a [Pd 0 L n ] complex with ArX to generate [ArPdXL n ] ( n =1 or 2), ii) transmetallation of [ArPdXL n ] by R′SnR 3 , and iii) reductive elimination of ArR′ from [ArPdR′L n ] ( n =1 or 2) 1. Stille reactions are known to be more efficient in the presence of additives such as copper,3 chloride4 and fluoride anions,5 or copper with fluorides,6 owing to a synergetic effect. The beneficial role of CuI in Stille reactions was rationalised as a complexation of one ligand L of [ArPdXL 2 ] to CuI 3c.…”

Computationally deciphering palladium‐catalyzed reaction mechanisms

“…Anionic Pd complexes were proposed as an alternative reactive species in Pd‐catalyzed cross‐coupling reactions by Amatore and Jutand . Several computational studies were performed to assess the competitiveness of anionic Pd compared to the neutral Pd(0) textbook mechanism . However, a direct comparison of neutral and anionic pathways by means of computations is problematic due to an inaccurate description of solvation of small anions (as discussed above) and has thus been avoided .…”