Heck and Related Reactions

Selectivity between a- and p-vinylation of enol ethers has been investigated again diphosphines and nitrogen-based ligands promote a-products. Cyclic enol ethers also remain popular substrates for asymmetric Heck reactions (40-96% ee). Use of hindered bases and BINAP facilitates these reactions. Similar strategies may be employed using 2-pyrrolines (up to 83% ee) or intramolecular arylations.446 Two examples of stereodirected Heck reactions and a kinetic resolution have also appeared 

Insertion of palladium vinyls derived from 30 into tethered alkynes leads to 31. In the presence of alkenes, or appropriate pendant unsaturated functions, rearrangemrat to 32 and spontaneous cyclisation take place. These reactions therefore constitute efficient routes to arene or diene containing, or completely saturated - tricyclic systems under PdL2 catalysis. If the geometry of 32 is unfavourable or prevented completely diverse products can arise, including cyclopropanes. 52 

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The vinylmetals are also efficiently prepared by oxidative addition of a metal to a Ct/ 2-halogen bond. However, the Heck and related reactions and their wide applications in organic synthesis, especially cascades, are not... 

As mentioned in the previous section, there are good reasons to search for new reaction conditions for Heck and related reactions, which permit catalyst recovery, the use of less toxic solvents, and simpler product recovery. The use of liquid or supercritical (SC) CO2 addresses all of these issues [171]. Until recently, however, the use of supercritical COj had been limited to organometallic Pd complexes functionalized with perfluorinated ligands [172-174], due to the limited solubility of metal colloids in CO2, and often required the use of water as a co-solvent [175]. The work described here shows that dendrimers can be used to solubilize Pd nanoclusters in liquid and SC CO2. This new finding opens the door to the combined benefits of a catalyst that promotes Heck couplings, but without the need for toxic ligands or solvents. 

In 1995 Herrmann discovered highly efficient palladacyde catalysts in Heck and related reactions of aryl halides with catalyst turnover numbers (TONs) up to 500,000 [ 117]. Later, TONs of the intermolecular Heck reaction reached up to 8,900,000 [ 118]. On the other hand, few syntheses of chiral palladacyde catalysts were envisioned and most of these attempts failed. Recently, the first AHR using a chiral phosphapalladacycle catalyst was reported by Buono et al. [ 119]. The chiral phosphapalladacycle catalyst 129, which was prepared from Pd(OAc)2... 

Very likely, similar effects are responsible for the solvent effects observed in Heck and related reactions [157-159]. For example, Cal6 et al. demonstrated that the butoxycarbonylation of 4-bromoacetophenone proceeded much less efficiently in [C4mim]Br than in [N4444]Br (16 and 76% yield, respectively, under otherwise identical conditions), likely due to the reduced availability of the bromide anion in the former system [159],... 

Heck and related reactions. In < While Et N is used as base in many He< acetate or bicarbonate together with a i tion of alkenes is subject to a remarkaM... 

Mechanistic Aspects of Heck (and Related) Reactions by (Supported) Nanoparticles Homogeneous or Heterogeneous Catalysis ... 

There has been extensive discussion of the possible role of Pd(IV) in Heck and related reactions catalyzed by Pd(II) intramolecular coordination complexes such as... 

Phase-Transfer Catalysis in the Heck and Related Reactions. A... 

For reviews of this and related reactions, see Heck Palladium Reagents in Organic Syntheses Academic Press New York. 1985, pp. 179-321 Ryabov Synthesis 198S, 233-252 Heck Org. React. 1982,27. 345-390. Adv. Catal. 1977. 26, 323-349 Volkova Levitin Vol pin Russ. Chem. Rev. 1975, 44, 552-560 Moritani Fujiwara Synthesis 1973, 524-533 Jira Freieslcben Organomet. React. 1972,3, 1-190, pp. 84-105. 

With such benefits offered by silver salts in these Heck-type reactions, chemists looked for similar improvements in other palladium-catalyzed couplings and related reactions. 

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]. 

As discussed in Sect, ni.2.8.1, the Sonogashira alkyne synthesis f and related Heck-type alkynylation using terminal alkynes as reagents collectively offer widely applicable and generally satisfactory procedures for Pd-catalyzed alkynylation. Even so, various limitations and difficulties associated with the Sonogashira and related reactions have... 

In 1977 Kosugi et reported the Pd-catalyzed aUylation with aUyltins, which most probably is the first Pd-catalyzed aUylation reaction and the first Pd-catalyzed crosscoupling with organotins, whUe Negishi et al. reported what appears to be the first Pd-catalyzed benzylation with benzylzinc halides. So, Pd-catalyzed aUylation and benzyla-tion began in 1977 (Scheme 1). The related propargylation most probably was reported first in 1980. Prior to these developments, the stoichiometric reaction of arylmercuric halides with allyl halides and Pd complexes was reported by Heck. The catalytic version of this and related reactions was later developed as tiie Heck reaction, as discussed in Part IV. 

In 2008, Application of CyclopaUadated Compounds as Catalysts for Heck and Sonogashira Reactions, by Najera and Alonso [110], Palladacyclic Precatalysts for Suzuki Coupling, Buchwald-Hartwig Amination and Related Reactions Bedford [111]... 

Csscade Heck Reaction. Besides cycloisomerization and related reactions, Pd(0) species also catalyzes cascade Heck reactions, which offer attractive routes to a wide variety of polycyclic compounds (99-101). For example, pyra-nosides 107 has been synthesized through 5-exo trig double Heck annulation of bromo-diene 106 in the presence of a catalytic amovmt of Pd(OAc)2 and PPha (Scheme 54) (102). 

Figure 5-9. Some chiral ligands used for asymmetric Heck (and related crosscoupling) reactions. ...

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. 

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