Pd-Catalyzed Cross-Coupling Reactions

Microwave and fluorous technologies have been combined in the solution phase parallel synthesis of 3-aminoimidazo[l,2-a]pyridines and -pyrazines [63]. The three-component condensation of a perfluorooctane-sulfonyl (Rfs = CgFiy) substituted benzaldehyde by microwave irradiation in a single-mode instrument at 150 °C for 10 min in CH2CI2 - MeOH in the presence of Sc(OTf)3 gave the imidazo-annulated heterocycles that could be purified by fluorous solid phase extraction (Scheme 9). Subsequent Pd-catalyzed cross-coupling reactions of the fluorous sulfonates with arylboronic acids or thiols gave biaryls or aryl sulfides, respectively, albeit it in relatively low yields. 

In contrast to the transition metals, where there is often a change in oxidation level at the metal during the reaction, there is usually no change in oxidation level for boron, silicon, and tin compounds. The synthetically important reactions of these three groups of compounds involve transfer of a carbon substituent with one (radical equivalent) or two (carbanion equivalent) electrons to a reactive carbon center. Here we focus on the nonradical reactions and deal with radical reactions in Chapter 10. We have already introduced one important aspect of boron and tin chemistry in the transmetallation reactions involved in Pd-catalyzed cross-coupling reactions, discussed... 

An unusual Pd-catalyzed cross-coupling reaction of a diindium reagent obtained from 3-bromo-l-iodopropene 6/1-239 was recently described by Hirashita and coworkers [118] to afford homoallylic alcohols 6/1-240 (Scheme 6/1.62). 

In the Pd-catalyzed cross-coupling reactions of acylzirconocene chlorides with allylic halides and/or acetates (Section 5.4.4.4), the isolation of the expected p,y-unsaturated ketone is hampered by the formation of the a, P-un saturated ketone, which arises from isomerization of the p,y-double bond. This undesirable formation of the unsaturated ketone can be avoided by the use of a Cu(I) catalyst instead of a Pd catalyst [35], Most Cu(I) salts, with the exception of CuBr - SMe2, can be used as efficient catalysts Thus the reactions of acylzirconocene chlorides with allyl compounds (Table 5 8 and Scheme 5 30) or propargyl halides (Table 5.9) in the presence of a catalytic amount (10 mol%) of Cu(I) in DMF or THF are completed within 1 h at 0°C to give ffie acyl--allyl or acyl-allenyl coupled products, respectively, in good yields. ill... 

The Pd-catalyzed cross coupling reaction of 3-stannylated pyrroles is also known. Muchowski has thus prepared and utilized 96 to effect Stille couplings leading to 97 [59]. 

An application of Stille couplings to the solid phase using a traceless A-glycerol linker with 2-stannylindoles has been developed [177]. Only a few examples of the use of 3-stannylindoles in Stille reactions have been described. Ortar and co-workers prepared 169 and 170 and effected Pd-catalyzed cross coupling reactions with several aryl, heteroaryl, and vinyl substrates (bromides, iodides, triflates) to give the expected products 171 in high yields [178]. Enol triflates behave exceptionally well under the Ortar conditions, e.g., 172 to 173. 

Doi and Mori made excellent use of dihydroindole triflate 189 in Pd-catalyzed cross-coupling reactions. This compound was discussed earlier in the Suzuki section, and it also undergoes Stille couplings as illustrated below [140]. A final dehydrogenation completes the sequence to indoles. 

The results given above clearly demonstrate the good leaving group ability of the readily introduced benzylsulfanyl moiety in copper-promoted, Pd-catalyzed cross-coupling reactions. Moreover, the use of non-protected polyhydroxylated substrates has proven to be compatible with the cross-coupling conditions. 

Pd-catalyzed cross-coupling reactions of the in situ-generated (cr-allenyl)palladium (II) intermediates with terminal alkynes were also realized in the presence of a catalytic amount of Cul [35-38], The reactions are similar to the well-known Sonoga-... 

As shown in the previous sections, a (cr-allenyl)palladium species, which is formed from a propargyl electrophile and a Pd(0) catalyst, reacts with a hard carbon nucleophile in a manner analogous to the Pd-catalyzed cross-coupling reaction to give a substituted allene. The results indicate that the reactivity of the (cj-allenyl)palladium species is similar to that of an alkenylpalladium intermediate. Indeed, it was found that the (cr-allenyl)palladium species reacted with olefins to give vinylallenes, a reaction process that is similar to that of the Heck reaction of alkenyl halides [54]. 

The molecular weight (M , GPO with polystyrene standard) is in the range of 8-14 kD (P 10-30). The M values for the metal-organic polymers are generally lower compared to that of the metal-free organic polymer (Pq). The authors therefore came to the conclusion that the Re-bipyridine monomer 58 is less reactive in the Pd-catalyzed cross-coupling reaction compared to the biphenyl monomer 59. These polymers have also been characterized by and NMR, as well as by FTIR spectroscopy. 

Cyclic triarylbismuth(III) compounds also undergo the Pd-catalyzed cross-coupling reaction with benzoyl chloride (Scheme 27) [42]. The exocyclic aryl group was selectively transferred to form 4-methylbenzophenone in good yield. Bismuth-containing products could not be isolated except for the cyclic bismuth compound possessing a SO2 moiety, for which cyclic bismuth chloride was isolated in 86% yield. 

The procedure described above is based on a paper reporting the Ni- or Pd-catalyzed reaction of arylzinc derivatives with aryl halides. The Ni- or Pd-catalyzed cross coupling reaction represents one of the most general and satisfactory routes to unsymmetrica1 biaryls. 

TABLE 1. Classification of Pd-catalyzed cross-coupling reactions 3... 

Mn, the highest TONs were observable with Zn as the countercation. Some of the high TONs observed in the Pd-catalyzed cross-coupling reactions of organozincs are shown in Scheme 2563. 

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