Bulky monophosphines

The Mizoroki-Heck reaction is a subtle and complex reaction which involves a great variety of intermediate palladium complexes. The four main steps proposed by Heck (oxidative addition, alkene insertion, )3-hydride elimination and reductive elimination) have been confirmed. However, they involved a considerable number of different Pd(0) and Pd(Il) intermediates whose structure and reactivity depend on the experimental conditions, namely the catalytic precursor (Pd(0) complexes, Pd(OAc)2, palladacycles), the Ugand (mono- or bis-phosphines, carbenes, bulky monophosphines), the additives (hahdes, acetates), the aryl derivatives (ArX, ArOTf), the alkenes (electron-rich versus electron-deficient ones), which may also be ligands for Pd(0) complexes, and at least the base, which can play a... 

A new Pd(0) -catalyzed carboiodination reaction of alkenes with aryl iodides, which generates a C-C and a C-I bond, involves a rate-determining reductive elimination step to form the C(sp ) - I bond, which is facilitated by bulky monophosphine ligands by preventing the formation of tetracoordinated intermediates [365]. 

For the C-N bond formation in the presence of bulky monophosphines, the catalytic cycle is expanded by an additional amine-binding step to the monophosphine-Pd complex. The major difference of this process is the deprotonation of the amine bound to the Pd complex, which is acidified due to the coordination to the metal... 

The main steps of the mechanism proposed by Heck have been further on confirmed. New ligands (diphosphines, carbenes, bulky monophosphines, polyphosphines) and new precatalysts (P,C-palladacycles) were introduced all along the last 50 years. Mechanistic investigations revealed that depending on the experimental conditions, the catalytic cycle may involve intermediate palladium complexes whose structure differs from the original ones proposed by Heck. 

All ligands that make Pd complexes able to activate aryl bromides and chlorides in oxidative additions, such as palladacycles, NHC carbenes, bulky monophosphines, or polyphosphines, have also been successfully used for most cross-coupling reactions reported in the following that aU involve oxidative addition as the first step of the catalytic cycle [3h, k, 9,12d, 15e]. 

In 1983, Migita and coworkers reported the first palladium-catalyzed C—N coupling of organotin derivatives as nitrogen nucleophile using P(o-tol)j as ligand (Scheme 20.6) [6]. The limitation of this method is the formation of low amount of desired anilines over the (3-hydride-eliminated byproduct arene. This could be attributed to the labile nature of the bulky monophosphine ligand. 

Intermolecular C—O bond formation has been less well investigated in the synthesis of benzofurans. However, Anderson et al. reported a route involving such a step using o-chloroalkyne substrates such as 58 (Scheme 24.29, disconnection D-3) [118]. These substrates have been used in the synthesis of indoles (Scheme 24.5), and indazoles (Scheme 24.19), and in this case a combination of potassium hydroxide and a palladium catalyst derived from the bulky monophosphine ligand t-butyl XPhos 59 led to benzofuran derivatives (Scheme 24.32). Zhao et al. went on to develop a copper-catalyzed version of this process utilizing o-iodoalkynes such as 60 [119]. 

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