Decelerating Effect of Alkynes in the Oxidative Addition of Phenyl Iodide to Palladium(0) Complexes in Palladium‐Catalyzed Multicomponent Reactions and Sonogashira Reactions

Abstract

The oxidative addition of PhI to [Pd0(PPh3)4] in DMF is slower when performed in the presence of the terminal alkynes (PhC≡CH, EtO2C−C≡CH) that are reagents in palladiumcatalyzed Sonogashira or multicomponent reactions. The concentration of the reactive [Pd0(PPh3)2] complex decreases because of its partial coordination to the alkyne to form [(η2‐RC≡CH)Pd0(PPh3)2] (R = Ph, EtCO2), which is in equilibrium with [Pd0(PPh3)2]. The complex [(η2‐PhC≡CH)Pd0(PPh3)2] was found to be unreactive whereas [(η2‐EtO2C− C≡CH)Pd0(PPh3)2] was found to be the unique reactive complex at high concentrations of EtO2C−C≡CH. As has been reported for alkenes, terminal alkynes play an unexpected role because they interfere in the oxidative addition before their usual reactions in the carbopalladation and transmetallation steps that follow it. Decreasing the rate of the fast oxidative addition with PhI may promote the efficiency of the catalytic cycle by bringing its rate closer to that of the slower carbopalladation or transmetallation steps. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Aqueous Sonogashira coupling of aryl halides with 1-alkynes under mild conditions: use of surfactants in cross-coupling reactions

“…This alkyne inhibition is consistent with coordination to Pd 0 L 2 (A), forming a (h 2 -RC^CR 0 )Pd 0 L 2 complex that is less electron rich, further decreasing the extent of oxidative addition of the aryl halide to the Pd center. 19 In support of this alkyne inhibition, 1,4-diphenylbuta-1,3-diyne, 4b, was added to the coupling of 1-bromonapthalene and 1-octyne. For the reactions with 20 mmol (25 mol%) diyne, the yield of product 3r was reduced to 51% and 53% for CTAB and SDS respectively (Table 7, entries 6 and 8).…”

Mechanism of the carbopalladation of alkynes by aryl-palladium complexes

“…In a previous work, we reported kinetic data on the oxidative addition of phenyl iodide to Pd 0 (PPh 3 ) 4 (2 mM in DMF) and established that the oxidative addition was slower in the presence of alkynes (PhC"CH or EtO 2 C-C"CH) by complexation of the active Pd 0 (PPh 3 ) 2 complex by the alkyne which generate the unreactive complex (g 2 -PhC"CH)Pd 0 (PPh 3 ) 2 or the less reactive complex (g 2 -EtO 2 C-C"CH)Pd 0 (PPh 3 ) 2 [3]. When PhI (10 equiv.)…”

“…(4) and (5)) [1]. This step, usually named carbopalladation, is often considered as being rate-determining in reactions performed with aryl iodides or activated aryl bromides [1,3]. …”

Insights into Sonogashira Cross‐Coupling by High‐Throughput Kinetics and Descriptor Modeling

“…[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] Despite these numerous applications, our mechanistic understanding of the Sonogashira reaction is limited. [39,40] This is because the Sonogashira reaction, like other coupling reactions, has a complex catalytic cycle that involves several steps. [41][42][43][44][45][46][47] One approach for unravelling the reaction mechanism is to study the kinetics of the (rate-limiting) elementary steps, such as, oxidative addition, [48] reductive elimination, [49] or transmetalation [50] in detail, all of which, however, need to be known (see Figure 1).…”