Heck reaction scope

The scope of the multiphasic system was extended to coupling reactions—like the Heck reaction—using a heterogeneous supported catalyst, such as Pd/C. The rationale here lay in the observation that aryl halides were activated in the multiphasic system (as seen for hydrodehalogenation), and that therefore they should also be activated toward C-C coupling reactions. 

A full discussion of all the issues related to this concept is out of the scope of this preliminary communication. Instead, we present here the basics of the general approach, as well as a specific example illustrating one iteration in the optimization of Pd-catalyzed Heck reactions using bidentate ligands, which demonstrate higher catalytic activities and lifetimes than monodentates (6). The full technical details of the algorithms and the theoretical treatment of the catalyst library diversity will be published elsewhere (7). 

Members of the she same compound class, arylethenylpurines, can also be prepared in a two step sequence. The cross-coupling of a halopurine with vinyl-tributylstannane leads to the formation of a vinylpurine, which in turn can undergo palladium catalyzed Heck reaction with a series of aryl halides (8.20.),28 The two step procedure is of particular interest, since the alternate approach, the Heck reaction of halopurines and arylethenes is of very limited scope. 

Larhed, M. and Hallberg, A. Scope, mechanism, and other fundamental aspects of the intermolecular Heck reaction. In Negishi, E.-i., (Ed.) Handbook ofOrganopalladium Chemistry for Organic Synthesis, Wiley sons Inc., New York, 2002, Vol 1, pp. 1133-1178. 

The term Heck reaction is associated with such a huge variety of transformations that it is impossible to cover them all within the scope of this chapter. We therefore restricted ourselves to giving an outline of the reaction principle and discussing a number of illustrative developments in this exciting field of research. For a more comprehensive overview, we recommend recent review articles [6-8],... 

Almost simultaneously, several groups developed efficient procedures for Heck reactions of deactivated chloroarenes 22 involving sterically crowded monodentate phosphines as activating ligand on the palladium (Scheme 11) [31]. Littke and Fu employed commercially available P(t-Bu)3, Hartwig P(t-Bu)3 or bis-t-butyl-ferroce-nylphosphine, and Beller di(l-adamantyl)-n-butylphosphine. The use of biscyclo-hexylmethylamine as the base instead of alkali metal carbonates or phosphates significantly extends the scope of the Fu procedure in respect of the olefin partner. 

Currently, there seems to be a widespread tendency to call many reactions proceeding via carbopalladation the Heck reaction. However, this practice is clearly incorrect, since the scope of carbopalladation is significantly wider than that of the Heck reaction. The alkyne carbopalladation reaction shown in Scheme 4, which is not accompanied by /J-dchydropalladation may not be viewed as an example of the Heck reaction. In fact, this chapter focuses its attention on various carbopalladation reactions that may not be considered as examples of the Heck reaction. Although some of such processes are combined with the Heck reaction in many cases. 

Another catalytic methodology that is widely used for C-C bond formation is the Heck and related coupling reactions [86, 87]. The Heck reaction [88] involves the palladium-catalysed arylation of olefinic double bonds (Fig. 1.31) and provides an alternative to Friedel-Crafts alkylations or acylations for attaching carbon fragments to aromatic rings. The reaction has broad scope and is currently being widely applied in the pharmaceutical and fine chemical industries. For example, Albemarle has developed a new process for the synthesis of the anti-in-... 

The scope of the Heck and related coupling reactions was substantially broadened by the development, in the last few years, of palladium/ligand combinations which are effective with the cheap and readily available but less reactive aryl chlorides [86, 87] rather than the corresponding bromides or iodides. The process still generates one equivalent of chloride, however. Of interest in this context, therefore, is the report of a halide-free Heck reaction which employs an aromatic carboxylic anhydride as the arylating agent and requires no base or phosphine ligands [89]. 

Over the past 30-1- years, cross-coupling protocols utilizing a wide variety of metals and metalloids have been studied. However, we will cover only those that have been applied the most often in organic synthesis. Furthermore, the related Heck (see Heck Reaction) and Tsuji-Trost reactions, which follow different mechanisms (and hence, do not fall under our more narrow definition), are beyond the scope of this entry. 

The applications of microwave chemistry to organic chemistry are too numerous to mention. A few representative examples will be given to illustrate the scope and utility. Microwave chemistry is widely used in synthesis. Examples include the Heck reaction (reaction 13-10)," the Suzuki reaction (reaction 13-12)," the Sonogashira reaction (reaction 13-13)," Ullman type couplings (reaction... 

Applications of the Heck reaction in natural-product syntheses were rather limited in the first 20 years, in spite of the great potential of this reaction for a wide scope of arylations... 

Blaser and Spencer used aroyl halides in place of aryl halides, with aroyl chlorides being of specific interest as ubiquitous, relatively cheap compounds ( Blaser reaction ) [24], This latter reaction is normally conducted in aromatic solvents phosphines are not used here as catalyst ligands since they fully inhibit the reaction. In the same way, benzoic acid anhydrides can be used as the aryl source in combination with PdCl2 and catalytic amounts of NaBr [79]. In this reaction, one of the arenes is used in the coupling reaction by elimination of CO, whereas the other benzoate serves as the base. The benzoic acid thus formed can easily be recycled into the anhydride. The use of aryl and vinyl triflates according to Cacchi [25] and Stille [26] extends the scope of the Heck coupling to carbonyl compounds phenol derivatives act via triflate functionalization as synthetic equivalents of the aryl halides. The arylation of cyclic alkenes [27], electron-rich vinyl ethers [28], and allylic alcohols [29] is accessible through Heck reactions. Allylic alcohols yield C-C-saturated carbonyl compounds (aldehydes) for mechanistic reasons (y9-H elimination), as exemplified in eq. (6). 

The Heck reaction has the same scope and limitations as Pd-catalyzed car-bonylation. Pd(II) complexes are often added to the reaction mixture and are reduced in situ. Primarily trans alkenes are obtained due to conformational preferences in the rotamer from which /3-hydride elimination takes place. Sometimes the /3-hydride elimination occurs away from the new C-C bond, and in this case a new stereocenter is formed. If the starting material is prochiral, the reaction can be made asymmetric by the use of chiral phosphine ligands like BINAP (2,2 -bis(diphenylphosphino)-1,1 -binaphthyl). 

The first report of C-C bond formation by C=C insertion, which we now call Heck olefination, was reported by Mizoroki in Japan in 1971 about a year before Heck s first paper appeared. Some refer to the Heck reaction as the Mizoroki-Heck reaction, but Mizoroki unfortunately died shortly after his original work was published. Since Heck and his co-workers vigorously pursued research on the mechanism and scope of this transformation after 1972, Heck s name is the only one usually attached to the process. T. Mizoroki, K. Mori, and A. Ozaki, Bull. Chem. Soc. Jpn., 1971, 44, 581 and R. F. Heck and J. P. Nolley, Jr., J. Org. Chem., 1972, 37, 2320. 

Scope and limitations of the Heck reaction synthesis of dienes The Heck reaction with electron-rich alkenes A synthesis of strychnine Recent developments in the Heck reaction Sp2-sp2 Cross-Coupling Reactions by Transmetallation Stille coupling... 

Scope and limitations of the Heck reaction synthesis of dienes... 

This solution takes the method outside the scope of the Heck reaction which is better realised with vinyl triflates 138 [Triflate = OTf = 0S02CF3]. These can be made into palladium o-complexes but do not function as electrophiles since the P-elimination of Pd and OTf is a poor reaction. The small amount of Pd a-complex 139 formed in solution adds both to the alkene and the remaining vinyl triflate but P-elimination leads rapidly to product, releasing Pd(0) for the next cycle, from only intermediate 141. 

The first successful case was reported by Overman et al. in 1989 [66], a pioneering strategy, which opened the way for the development of AHRs leading to quaternary centers. Furthermore it was outlined that polycyclizations are well within the scope of the Heck reaction. According to Scheme 20 it can be expected that contrary to the case of polycyclizations of carbocations and free radicals, cy-... 

The suitability of the homogeneous aqueous catalysts and thus the scope of application in general will be extended in commercial or pilot-plant operation to other central atoms and reactions such as Heck reactions and other carbonylations (with Pd), hydrogenations (Pd, Pt, Rh, Ir), formation of water-soluble polymers (Pd), vinylations, metathesis conversions (Ru), Suzuki couplings, etc. (cf. Section 6.6). 

Note that palladacycles typified by 2 are poisoned by 1,4-dienes, in contrast to other Pd(0) catalyst systems. Accordingly, the Heck reaction cannot employ these catalysts. On the other hand, 3 has a high thermal stability and broad scope of application (aryl couplings). Complex 4 is also a highly active catalyst for the Heck reaction (3 examples,... 

Coupling reactions. Scopes of many well-established reactions continue to be explored. The Heck reaction of alkenyl(2-pyridyl)dimethylsilanes is benefited by the direction of the heteroaromatic group during carbopalladation and the expediency in product purification and catalyst recovery. ... 

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