Other Cross-Coupling Reactions

A variety of less common cross-coupling reactions are discussed in this section, including borylations, silastannylations, and even cross-coupling with diindium compounds. 

For the domino transition metal-catalyzed synthesis of macrocycles, conditions must be found for two distinct cross-coupling reactions, of which one is inter- and the other intramolecular. For this purpose, Zhu s group [115] has developed a process of a Miyura arylboronic ester formation followed by an intramolecular Suzuki reaction to give model compounds of the biphenomycin structure 6/1-232 containing an endo-aryl-aryl bond. 

A regio- and diastereoselective Pd-catalyzed domino silastannylation/allyl addition of allenes 6/1-236 containing a carbonyl moiety with Bu3Sn-SiMe3 6/1-237 is described by Kang and coworkers [117]. The reaction allows the synthesis of hetero-and carbocyclic compounds with a ring size of five and six. It can be assumed that 

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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). 

The use of expensive catalysts, sometimes difficult to prepare and recover, is a concern, especially when working in large scale. Also, as previously mentioned, the very common use of phosphine-based catalysts oftentimes brings along undesired oxidation side-reactions and formation of difficult-to-remove phosphine oxides. To overcome these problems, ligandless systems are of interest for this and other cross-coupling reactions. 

For reviews of the Pd-catalyzed acylation and other cross-coupling reactions with a-hetero-substituted organic electrophiles, see ... 

A plethora of copolymers have been synthesized using many of the other cross-coupling reactions used in earlier sections [310]. Some of the more prominent structure types are shown above in Scheme 65 [315-320]. The possibilities for new Jt-conjugated copolymers seem endless as a huge combination of monomers can be coupled, being restricted only by polymerization-compatible functional groups. 

Two problems had to be solved for these reactions to be made usefiil. First, reductive elimination to form C N and bonds was not a well-known reaction with classical ligands such as PPh3. Second, jS-hydride elimination is very facile for primary and secondary heteroatom substrates. As with other cross-coupling reactions, the use of hindered, basic phosphines turned out to be cmcial. Amination reactions tend to give better yields, since reductive elimination is faster for more basic groups. For example, the base used in catalytic aminations is Na-O-t-Bu, but the product is the aryl amine. 

Unlike other cross-coupling reactions, for which the scope has rapidly expanded in recent years, the range of electrophilic substrates that can be used successfully in the Sonogashira protocol is still rather limited. Vinylic substrates (iodides, bromides, chlorides, triflates, and more recently tosylates) typically yield the best results. For aromatic substrates, iodides and triflates are preferred over bromides, which in turn give far better yields than aryl chlorides. This latter aspect of the reaction is particularly frustrating when one considers the recent advances in the activation of aryl chloride substrates for reactivity in other cross-coupling protocols. ... 

As with other cross-coupling reactions, it is possible to intercept the palladium intermediates when the reaction is conducted under carbon monoxide pressure [143]. For the example of iodopyiidine 152, pyridyl ketone 409 could be isolated during the reaction with (Z)- l-ethoxy-2-(tributylstannyl)ethane. 

Palladium-catalyzed amination and alkoxylation of aryl halides have been developed only since the mid-1990s. The catalytic cycle is similar to other cross-coupling reactions (Scheme 20). 

Heck reactions catalyzed by 10, performed with phenyl bromide and n-butyl acrylate in NMP at 140 °C with 0.01 mol% of catalyst and K2CO3 as base. Whereas dramatically retarded conversion rates were observed with the phosphine-based pincer complex 21 in the presence of l-methyl-l,4-cydohexadiene [42], only a marginal effect was noticed under identical reaction conditions with catalyst 10 (as well as with 3). These results exclude the possibihty that the catalyticaUy active species derived from 10 (or 3) and from 21 are of the same type, and in turn imply that different reaction mechanisms can indeed be operative with different pincer complexes in Heck reactions (and most probably also in other cross-coupling reactions). Therefore, its reasonable to anticipate that palladium pincer Heck catalysts can operate via homogeneous (Pd /Pd ) mechanisms and serve as sources of palladium nanopartides, depending on the reaction conditions applied. 

Having seen steps such as oxidative addition, insertion, and reductive elimination in the context of transition metal-catalyzed hydrogenation using Wilkinsons catalyst, we can now see how these same types of mechanistic steps are involved in a mechanism proposed for the Heck-Mizoroki reaction. Aspects of the Heck-Mizoroki mechanism are similar to steps proposed for other cross-coupling reactions as well, although there are variations and certain steps that are specific to each, and not all of the steps below are involved or serve the same purpose in other cross-coupling reactions. 

This mechanistic interpretation of the StiUe reaction has been the base for the formulation of the mechanisms of other cross-coupling reactions. Model studies on the couphng of alkynes with vinyl triflates with [Pt(PPhj)4] were in overall agreement with that proposal [54], although involvement of cationic complexes in the transmetallation step was strongly suggested by this work. Farina [55] and Brown [56] also found that the intermediates formed upon oxidative addition of organic triflates to Pd(0) are cationic complexes such as [PdR (S)L2] nd [PdR L3]+. 

Transmetallation of alkenylsilanes takes place with retention of the double bond configuration, as in other cross-coupling reactions [295]. Owing to the lower transmetallation rate, competing 1,2-insertion of the alkene in the intermediate organopalladium complex (as a Heck type reaction) may take place, which affects the regioselectivity of the Hiyama reaction in some cases (Scheme 1.38) [296]. This... 

As in all C-C cross-coupling reactions, the Negishi reaction mechanism consists in three steps (Fig.4.1) oxidative addition, transmetalation, and reductive elimination. The former and the latter are common to all the other cross-coupling reactions, whereas the transmetalation step is particular of this reaction. Unfortunately, this transmetalation has been less studied compared to the ones in the Stille [12-17] or Suzuki reactions, [18-21] in spite of the fact that the transmetalation between organozinc and palladium complexes is also involved in other relevant processes, such as the hydroalkylation of styrenes, [22] the asymmetric allylation of aryl aldehydes, [23] the coupling propargylic benzoates and aldehydes, [24] or the double-transmetalation oxidative cross-coupling reaction [25, 26]. 

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