Fluorinated palladium source

Supercritical carbon dioxide can be a solvent for rapid cross-coupling reaction [314]. Fluorinated palladium sources are reported to be surperior to non-fluorinated ones in such a reaction medium (Scheme 88) [315,316]. 

Shezad, N., Oakes, R.S., Clifford, A.A. and Rayner, C.M. (1999) Use of fluorinated palladium sources for efficient Pd-catalyzed coupling reactions in supercritical carbon dioxide. Tetrahe-... 

An in situ catalyst formed from palladium acetate and the perfluoroalkyl-substituted ligand [F(CF2)6(CH2)2 2PPh resulted in the formation of methylcin-namate in 91 % isolated yield after 64 h at 100 °C and an estimated CO2 density of ca. 0.7 g mL [62]. The ligand 3,5-H°F -tpp gave almost identical yield after 24 h at 90 °C under otherwise very similar conditions [63]. Tris(2-furyl)phos-phine also lead to active catalysts [63], especially when used together with fluorinated Pd-sources like palladium trifluoroacetate [64]. Most of the above systems lost their activity if metallic palladium was formed under non-optimum reaction conditions. However, the use of a commercial heterogeneous Pd/C catalyst was reported to give up to 85% yield of methyl cinnamate in the presence of CO2 at temperatures and pressures beyond the critical data [65]. The CO2 density in the latter experiments can be estimated to ca. 0.22 g mL" and was... 

Additional publications from Sanford et al. describe the full exploration of palladium-catalyzed chelate-directed chlorination, bromination, and iodination of arenes using N-halosuccinimides as the terminal oxidant <06T11483>. Moreover, an electrophilic fluorination of dihalopyridine-4-carboxaldehydes was reported by Shin et al. <06JFC755>. This was accomplished via transmetalation of the bromo derivative, followed by treatment with A-fluorobenzenesulfinimide as the source of electrophilic fluorine. 

By means of nickel-catalyzed couplings of vinyl zirconocenes, Schwaebe et al. succeeded in obtaining fluorinated materials using a-bromo esters as electrophiles (Scheme 4.62) [113]. The yields achieved, albeit modest (24—65%), were far better using Ni(0) than those obtained in experiments based on several palladium(O) sources (no product observed). Isopropyl esters appear to be crucial, as competing 1,2-addition occurs with both ethyl and n-butyl analogues. Curiously, t-butyl esters were found to completely inhibit both modes of reaction of the zirconocene. 

The asymmetric fluorination of 3-ketoesters has been achieved in 62-90% ee using F-TEDA (Selectfluor) as fluorine source in the presence of 0.5 mol% of the chiral nonracemic titanium-based Lewis acid (5.108). ° A greater range of p-ketoesters are fluorinated with higher ee using catalytic quantities of the palladium-BINAP complex (5.109) and N-fluorobenzenesulfonamide (NFSI). ° In both cases the reaction proceeds through the intermediacy of a chiral enolate. 

The coupling reaction of arylsilanes with aryl iodides is also mediated by a palladium catalyst and a fluoride ion.f " Optimized reaction conditions are as follows (i) two fluorine atoms on silicon are required (ii) an ethyl or propyl group as a dummy alkyl ligand is preferred, because a methyl group competitively participates in the crosscoupling reaction and (iii) TBAF, a highly effective fluoride ion source, can be replaced by inexpensive KF. Various unsymmetrical biaryls are synthesized under the conditions (Scheme 10). 

The reaction of 2-arylbenzoxazoles with Al-chlorosuccinimide in the presence of a palladium catalyst yields the chlorinated product (4). However, in the related ace-toxylation process, the reaction occurs at the position ortho to nitrogen in the aryl ring and involves a palladated intermediate. The palladium-catalysed reaction of Al-arylamides with Al-fluoro-2,4,6-trimethylpyridinium triflate, a source of F, results in selective ortho-fluorination and may lead to mono- or di-fluorinated benzoic acids. Here, (5) is a likely intermediate. A review of selectivity in electtophilic Auorinations has been published. ... 

Commercially available palladium complexes like [Pd(OCOCF3)2 containing fluorinated ligands used in conjunction with PCys are superior to nonfluorinated sources for carrying out a variety of palladium-catalyzed coupling reactions, in supercritical carbon dioxide. 4... 

The palladium-catalyzed C—F bond formation could be accelerated in a CsF packed-bed microreactor, which enables the handling of large amounts of the fluorine source [22], Increasing the temperature resulted in an accelerated fluorination process, with 130 °C being identified as the optimal reaction temperature (Figure 11.4). Further increase of the temperature resulted in lower yields probably due to catalyst decomposition or ligand dissociation. It was also found that elevated temperatures could reduce the catalyst loading. 

The fluorination of unfimctionalized C—H bonds is a challenging reaction however, it is a highly valuable transformation. To this end, the palladium-catalyzed fluorination of benzyl C—H bonds was developed (Example 7.1) [12]. The chemistry used a common palladium salt to catalyze the process, and A(-fluoropyridinium tetrafluoroborate served as a source of electrophilic fluorine. While only a few substrates were screened in this work, it provided the proof of concept for the approach. Following this report, a host of benzyl C—H fluorination reactions have been reported. Several of these reactions are summarized in Schemes 7.5 through 7.9 and Examples 7.1 through 7.3. 

Ma and coworkers reported the palladium-catalyzed direct amination of phenylalanine derivatives for the synthesis of dipeptides containing indoline-2-carboxylate via 2-methoxyiminoacyl (MIA) as a directing group and an fluorine source as the oxidant [22]. This method features high efficiency and wide functional group tolerance (Scheme 2.24). 

Again, a wide substrate scope was demonstrated, and with this system it was shown not to be necessary to block the ortho position, as control of mono-versus difluorination of the substrates evaluated could be controlled through the stoichiometry of the pyridinium salt utilised as the fluorinating reagent. The auxiliary can either be purchased from commercial sources or prepared via aminolysis of inexpensive octafluorotoluene. The mechanism of these directed electrophilic fluorinations has not been established, though the intermediacy of palladium(iv) complexes has been proposed. ... 

---