Aryl-alkenyl cross-coupling, palladium-catalyzed reactions

The reaction of heterocyclic lithium derivatives with organic halides to form a C-C bond has been discussed in Section 3.3.3.8.2. This cannot, however, be extended to aryl, alkenyl or heteroaryl halides in which the halogen is attached to an sp2 carbon. Such cross-coupling can be successfully achieved by nickel or palladium-catalyzed reaction of the unsaturated organohalide with a suitable heterocyclic metal derivative. The metal is usually zinc, magnesium, boron or tin occasionally lithium, mercury, copper, and silicon derivatives of thiophene have also found application in such reactions. In addition to this type, the Pd-catalyzed reaction of halogenated heterocycles with suitable alkenes and alkynes, usually referred to as the Heck reaction, is also discussed in this section. 

Alkenylsilanols or isopropoxysilanes have been recently used for cross-coupling reactions of aryl or alkenyl halides under mild conditions. The palladium-catalyzed reaction of silanols has been optimized in the presence of Pd(dba)2, but in some cases the use of dimer (1) gave better results.The reaction of (Z)-vinylsilanols with vinyl iodides led to (Z,Z)-diene derivatives in 68% yield (eq 84). The stereoselectivity of the reaction was found to he 92.4% in favor of the (Z,Z)-isomer. 

The palladium-catalyzed reaction of alkenyl-, aryl-, alkynyl- and alkylsiloxanes with aryl, alkyl, and alkenyl halides and triflates in the presence of activators is known as the Hiyama cross-coupling reaction and several reviews have been published. This chapter will present major developments and examples of recent carbon-carbon bond formation methodology and improvements as well as their use in natural products synthesis in the last few years. 

Heck reaction, palladium-catalyzed cross-coupling reactions between organohalides or triflates with olefins (72JOC2320), can take place inter- or intra-molecularly. It is a powerful carbon-carbon bond forming reaction for the preparation of alkenyl- and aryl-substituted alkenes in which only a catalytic amount of a palladium(O) complex is required. 

Tributylstannyl)-3-cyclobutene-1,2-diones and 4-methyl-3-(tributylstan-nyl)-3-cyclobutene-l,2-dione 2-ethylene acetals undergo the palladium/copper-catalyzed cross coupling with acyl halides, and palladium-catalyzed carbon-ylative cross coupling with aryl/heteroaryl iodides [45]. The coupling reaction of alkenyl (phenyl )iodonium triflates is also performed by a palladium/copper catalyst [46],... 

A rapid MW-assisted palladium-catalyzed coupling of heteroaryl and aryl boronic acids with iodo- and bromo-substituted benzoic acids, anchored on TentaGel has been achieved [174]. An environmentally friendly Suzuki cross-coupling reaction has been developed that uses polyethylene glycol (PEG) as the reaction medium and palladium chloride as a catalyst [175]. A solventless Suzuki coupling has also been reported on palladium-doped alumina in the presence of potassium fluoride as a base [176], This approach has been extended to Sonogashira coupling reaction wherein terminal alkynes couple readily with aryl or alkenyl iodides on palladium-doped alumina in the presence of triphenylphosphine and cuprous iodide (Scheme 6.52) [177]. 

The palladium-catalyzed coupling of boronic acids with aryl and alkenyl halides, the Suzuki reaction, is one of the most efficient C-C cross-coupling processes used in reactions on polymeric supports. These coupling reactions requires only gentle heating to 60-80 °C and the boronic acids used are nontoxic and stable towards air and water. The mild reaction conditions have made this reaction a powerful and widely used tool in the organic synthesis. When the Suzuki reaction is transferred to a solid support, the boronic add can be immobilized or used as a liquid reactant Carboni and Carreaux recently reported the preparation of the macroporous support that can be employed to efficiently immobilize and transform functionalized arylboronic adds (Scheme 3.12) [107, 246, 247]. 

The palladium-catalyzed arylation and alkenylation of terminal alkynes with aryl or alkenyl hahdes in presence of a copper(l) co-catalyst is called Sonogashira reaction. In the same way as in the other cross-coupling reactions described before, it is possible to immobihze the alkyne or the aromatic bromides, iodides or triflates on sohd supports (Scheme 3.15). 

When the first electrophile was not a ketone or an aldehyde, as illustrated for the reaction of 276 with crotonyl chloride, the intermediate chelated alkenylmetal 278 could also be subjected to iodinolysis or palladium-catalyzed cross-coupling reactions with aryl and alkenyl iodides in the presence of a stoichiometric amount of CuBr as a promotor as well as a polar cosolvent such as IV, IV-di methyl acetamide (DMA) (equation 131)165 166. 

The palladium-catalyzed cross-coupling of an aryl, alkenyl, or benzylzinc bromide 11 with aryl iodide 12 succeeds with 0.15 mol-% [Pd P(C6H4C6Fi3)3 4] in toluene/1-bromoperfluorooctane, taking advantage of variable miscibility through thermoregulation [20], In this case the electron-deficiency of the phosphanes, due to the perfluorinated side chains, appears to influence the reductive elimination step in the cross-coupling reactions. 

A second important palladium-catalyzed process is cross coupling of an aryl or alkenyl tiaUcyltin reagent with an aUcyl or aryl halide. In this reaction, one carbon-palladimn bond is generated by transmetalation of Pd -X with BU3 Sn-R, while the other carbon-palladium bond is formed by oxidative addition of an organic halide with a Pd°L species. This reaction, which is tolerant of many organic functional groups, is normally known as the Stille Reaction (Scheme 4). ... 

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