Catalyst Cross-coupling

By utilizing a solid support-based tetradentate A-heterocyclic carbene-palladium catalyst, cross couplings of aryl bromides with phenylboronic acid were achieved in neat water under air.121 A high ratio of substrate to catalyst was also realized. 

Keywords. Organotin compounds. Palladium catalyst. Cross-coupling reaction, Carbonylative coupling... 

N-Heterocyclic carbenes (NHC) are examples of ligands that possess the desired attributes [19]. In 2004, Caddick and Cloke reported that a Pd/NHC-based catalyst cross-couples primary alkyl bromides with alkyl- and vinyl-9-BBN reagents (Eq. 6) [20]. A system composed of Pd(dba)2/IPr HCl/AgOTf (IPr HCl=l,3-bis(2,6-diisopropylphenyl)imidazolium chloride) in the presence of KOt-Bu provides the most efficient catalyst. The yields of the cross-coupling products are modest (Table 3). 

Keywords Aryl haUdes C-N bond formation Copper catalyst Cross-Coupling Heterocycles Heterogeneous Reusable catalysts... 

The ester 870 is prepared by the cross-coupling of the chloroformate 869 with an organotin reagent. Some chloroformates are easily decomposed by a Pd catalyst, and hence the reaction should be carried out by slow addition of the chloroformates. Similarly, the amide 872 is prepared by the reaction of the carbamoyl chloride 871 [742]. The coupling of alkylcopper with ethyl chloroformate catalyzed by Pd affords esters[743]. 

Alkyl- and aryl-pyridazines can be prepared by cross-coupling reactions between chloropyridazines and Grignard reagents in the presence of nickel-phosphine complexes as catalysts. Dichloro[l,2-bis(diphenylphosphino)propane]nickel is used for alkylation and dichloro[l,2-bis(diphenylphosphino)ethane]nickel for arylation (78CPB2550). 3-Alkynyl-pyridazines and their A-oxides are prepared from 3-chloropyridazines and their A-oxides and alkynes using a Pd(PPh3)Cl2-Cu complex and triethylamine (78H(9)1397). 

They have also developed a route to 2-allenylindole derivatives (98T13929). When prop-2-ynyl carbonates (76) are reacted with 73 in the presence of palladium catalyst, a cross-coupling reaction occurs to give 77a (46%) and 77b (45%). Under a pressurized carbon monoxide atmosphere (10 atm), the palladium-catalyzed reaction of 73 with 78 provides 79a (60%) and 79b (60%) (2000H2201). In a similar reaction, when the substrate is changed to aryl halides (80), 2-aryl-1-methoxyindoles such as 81a (70%) and 81b (60%) are prepared (97H2309). 

The postulated steps that constitute the Suzuki coupling process are shown in Scheme 25. After oxidative addition of the organic halide to the palladium(o) catalyst, it is presumed that a metathetical displacement of the halide substituent in the palladium(ii) complex A by ethoxide ion (or hydroxide ion) takes place to give an alkoxo-palladium(ff) complex B. The latter complex then reacts with the alkenylborane, generating the diorganopalladium complex C. Finally, reductive elimination of C furnishes the cross-coupling product (D) and regenerates the palladium(o) catalyst. 

An intramolecular palladium(o)-catalyzed cross-coupling of an aryl iodide with a trans vinylstannane is the penultimate maneuver in the Stille-Hegedus total synthesis of (S)-zearalenone (142) (see Scheme 38).59 In the event, exposure of compound 140 to Pd(PPh3)4 catalyst on a 20% cross-linked polystyrene support in refluxing toluene brings about the desired macrocyclization, affording the 14-membered macrolide 141 in 54% yield. Acid-induced hydrolysis of the two methoxyethoxymethyl (MEM) ethers completes the total synthesis of 142. 

Carbon-carbon bond formation reactions and the CH activation of methane are another example where NHC complexes have been used successfully in catalytic applications. Palladium-catalysed reactions include Heck-type reactions, especially the Mizoroki-Heck reaction itself [171-175], and various cross-coupling reactions [176-182]. They have also been found useful for related reactions like the Sonogashira coupling [183-185] or the Buchwald-Hartwig amination [186-189]. The reactions are similar concerning the first step of the catalytic cycle, the oxidative addition of aryl halides to palladium(O) species. This is facilitated by electron-donating substituents and therefore the development of highly active catalysts has focussed on NHC complexes. 

Polymerization using the Stille coupling, the cross-coupling of aryl-alkenyl halides with organotins in the presence of palladium catalysts (Scheme 9.10),13 appeared in 1989 (Scheme 9.11).14 The low nucleophilicity of organotins makes it possible to use functionalized monomers for the polymerization.15... 

Modem cross coupling chemistry is heavily dominated by the use of palladium and nickel complexes as the catalysts, which show an impressively wide scope and an excellent compatibility with many functional groups.2 This favorable application profile usually overcompensates the disadvantages resulting from the high price of the palladium precursors, the concerns about the toxicity of nickel salts, the need for ancillary ligands to render the complexes sufficiently active and stable, and the extended reaction times that are necessary in certain cases. 

The palladium-catalyzed cross-coupling of alkenylsilanols has been extensively studied with respect to the structure of both the silicon component and the acceptor halide. The preferred catalyst for coupling of aryl iodides is Pd(dba)2 and for aryl bromides it is [allylPdCl]2. The most effective promoter is tetrabutylammonium fluoride used as a 1.0M solution in THF. In general the coupling reactions occur under mild conditions (room temperature, in 10 min to 12 hr) and some are even exothermic. 

The procedure in Section C is representative of the synthesis of non-natural a-amino acids featuring the palladium cross coupling reaction of a (1-alaninc organozinc derivative with aromatic electrophiles. This methodology has been successfully extended with modifications to both the electrophile and the catalyst as shown in the Table. 

---