Trialkylphosphines, cross-couplings

The cross-coupling of aryl or alkenylsilanes with aryl chlorides bearing electron-withdrawing substituents has been reported to require trialkylphosphine (P Pr3) ligands.407... 

The other use of the bulky trialkylphosphines is in the cases where PPh3 or similar ligands can interfere with the cross-coupling reaction by forming by-products (115).412... 

Although some bulky trialkylphosphines have been known for a long time, their usefulness in many previously difficult cases of the Pd- or Ni-catalyzed cross-coupling, such as those involving organic bromides and chlorides, especially alkyl bromides and chlorides, and alkylmetals, has been demonstrated mainly within the past several years. Some representative examples of alkyl-containing phosphines are shown in Figure 1. 

Pioneering studies with trialkylphosphines by Fu and coworkers88 and with dialkylarylphosphines by Buchwald and coworkers89 have provided solutions to many pending problems of the Pd-catalyzed cross-coupling, such as those shown in Scheme 26. Applications of bulky alkyl-containing phosphines are further discussed also in later sections. 

Hydroboration of allenes 65 with pinacolborane in the presence of Pt(DBA)2 and a trialkylphosphine provides either the allyl boronate 66 or the vinyl boronate 67 regioselectively, depending on the stereoelectronic factors of the phosphine employed (Equation 2) <1999CL1069>. Allyl and vinyl boronates are synthetically important because of their ability to undergo nucleophilic addition to carbonyl compounds as well as transition metal-catalyzed cross-coupling. 

Unfortunately, attempts to extend the use of Pd/PCy3 to Suzuki reactions of alkyl tosylates were unsuccessful. However, by modifying the conditions, it was possible to develop a catalyst system that is effective for cross-couplings of a range of primary tosylates (Eq. 4) [16]. Scheme 1 illustrates the remarkable sensitivity of the coupling reaction to the structure of the trialkylphosphine... 

The Suzuki cross-coupling methods described in Sect. 2.1 establish that palladium complexes that bear electron-rich trialkylphosphines of the appropriate size can serve as effective catalysts for reactions of alkyl electrophiles. Naturally, it was of interest to determine if non-phosphine ligands that are bulky and electron-rich can also furnish active catalysts. 

Finally, the dependence of the rate of oxidative addition on the choice of tri-alkylphosphine has been quantified (Table 11). Consistent with the reactivity patterns that have been observed in Pd/trialkylphosphine-catalyzed cross-coupling processes of alkyl electrophiles (e.g.. Scheme 1), Pdl2 complexes derived from P(t-Bu)2Me and PCy3 undergo relatively facile oxidative addition (entries 1 and 2), whereas those based on P(t-Bu)2Et and P(f-Bu)3 are essentially unreactive (entries 3 and 4). 

On the other hand, true ligand acceleration (type 3 processes) shows preference for solvents of low polarity and lower Lewis basicity (toluene, dioxane and THF) with soluble tertiary amines as bases. In this respect, these Mizoroki-Heck reactions resemble cross-coupling processes, which also display strong preference for these solvents. Reactions in nonpolar solvents (toluene or xylene) have been known since Heck s seminal articles [8]. The halide remains a crucial subject of concern in reactions catalysed by phosphine complexes of palladium, aryl iodides prefer triarylphosphines and polar solvents, whereas reactions of aryl bromides and chlorides indeed prefer electron-rich trialkylphosphines and nonpolar solvents [63-65]. 

Palladium-catalyzed cross-coupling reactions of alkyl bromides with arylboron reagents represent another breakthrough for the development of a general method for arylation of alkyl halides. Fu found that the palladiumprimary alkyl bromides with various arylboronic acids (Equation 5.6) [10]. An air-stable commercially available preligand, [HP(t-Bu)2Me]BF4 5, also worked well with a variety of arylboronic acids and gave the same products in comparable yields, as shown in the parentheses in Equation 5.6. 

Triphenylphosphine appears to be by far the least expensive phosphine at present. For a combination of reasons, it is also one of the most effective ligands. For example, the effects of phosphines on the ease of reductive elimination from R Pd(PR3)2 are summarized in Table 4. The results indicate that the efficiency of phosphines decreases in this order PPhj > PPhjMe > PPhMea > PEts. Although not fully clarified, the order may be inversely proportional to their basicity and/or proportional to their stale requirements. The comparative significance of basicity may be indicated by a higher level of efficiency observed with P(2-furyl)3t in some cross-coupling reactions.f" Probably for the same reason, trialkylphosphines are much less effective in Pd-catalyzed cross-coupling. 

Nickel-catalyzed olefmation of unactivated aliphatic dithioacetals gives the corresponding alkenes in good yields [106]. The use of trialkylphosphine is essential for this cross-coupling reaction. 

Fleckenstein CA, Plenio H (2010) Sterically demanding trialkylphosphines for palladium-catalyzed cross-coupling reactions- alternatives to Pt-Bus. Chem Soc Rev 39 694-711... 

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