Heck reaction conditions

Aryl chlorides are not very reactive under normal Heck reaction conditions but reaction can be achieved by inclusion of tetraphenylphosphonium salts with Pd(OAc)2 or PdCl2 as the catalysts.138... 

Since Heck reactions on metalated substrates are known (e.g., with organomercurials [105]), applications of these transformations to pyrrole chemistry have been reported. For example, mercuration of pyrrole 149 followed by exposure to methyl acrylate under Heck reaction conditions leads to 150 [106]. This Heck variation has been extended by Smith to mercurated porphyrins [107]. Pyrrolylacrylates like 150 have also been made using conventional Heck reactions on 3-iodopyrroles [108,109]. 

Haloarene chromium tricarbonyl complexes are activated to nucleophilic attack by thiolate anions [58, 59]. High yields of the thioethers are obtained under liquiddiquid two-phase conditions, but optimum yields are achieved under soliddiquid conditions. In many cases the thioether is produced directly but, where the reaction mixture contains thioether and its chromium complex, the thioether can be isolated by degradation of the complex with iodine or an excess of the thiol. Both 1,2- and 1,4-dichlorobenzenes yield only monothioethers, even when an excess of thiolate anion is used. In contrast, 1,3-dichlorobenzenes produce a mixture of the mono- and dithioethers [59]. Aryl allyl thioethers have been produced under catalysed Heck reaction conditions from S-allyl thiocarbamates and iodobenzene [60]. 

Palladium-catalysed C-C bond formation under Heck reaction conditions, which normally requires anhydrous conditions and the presence of copper(I) salts, is aided by the addition of quaternary ammonium salts. It has been shown that it is frequently possible to dispense with the copper catalyst and use standard two-phase reactions conditions [e.g. 18, 19]. Tetra-/i-butylammonium salts catalyse the palladium-catalysed reaction of iodoarenes with alkynes to yield the arylethynes in high yield [20, 21], whereas the reaction with 3-methylbut-1 -yn-3-ol (Scheme 6.30) provides a route to diarylethynes [22]. Diarylethynes are also formed from the reaction of an iodoarene with trimethylsilylethyne [23], Iodoalkynes react with a,p-unsaturated ketones and esters to produce the conjugated yne-eneones [19],... 

Coupling of 1 with iodobenzene under Heck reaction conditions gave the phenyl-substituted diene 242-Ph which was isolated in up to 78% yield [146-148]. When heated at 80 °C in DMF or MeCN with various dienophiles 244-R (acrylate, maleate, or fumarate), 242-Ph and its analogs 242-Ar obtained from 1 and other haloarenes cleanly gave the spiro[2.5]octene derivatives 245-Ar (Scheme 57). 

A number of modified reaction conditions have been developed. One involves addition of silver salts, which activate the halide toward displacement.94 Use of sodium bicarbonate or sodium carbonate in the presence of a phase-transfer catalyst permits especially mild conditions to be used for many systems.95 Tetraalkylammonium salts often accelerate reaction.96 Solid-phase catalysts in which the palladium is complexed by polymer-bound phosphine groups have also been developed.97 Aryl chlorides are not very reactive under normal Heck reaction conditions, but reaction can be achieved by inclusion of triphenylphosphonium salts with Pd(OAc)2 or PdCl2 as the catalyst.98... 

As described in Section III.A.l, the silyl group in vinylsilanes is replaced under the Heck reaction conditions. Several procedures are known to enable the carbon-silicon... 

Whilst, not unexpectedly, the secondary amide 38 failed to undergo a 6-exo trig addition with palladium(0) complex, the corresponding tertiary amide 39 did so, when subjected to Heck reaction conditions, to furnish styrene 40 in good yield. 

Aryl and vinyl sulfonate esters are reactive toward oxidative addition, and the perfluoroaUcyl versions are useful substrates in the Heck reaction. Conditions can be mild, comparable to those for vinyl iodide reactions. The enol (vinyl) triflates are particularly attractive, since they are prepared directly from the corresponding ketone (equation 21). ... 

Lewis-acid-sensitive groups, such as the diene and dioxane functionalities in 45, to Heck reaction conditions. 

In 1984, Jeffery discovered that under ligand-free conditions, Pd-catalyzed vinylation of organic halides proceeds at or near room temperature, whereas normal Heck reactions require higher temperatuies [64]. Jeffery s hgand-free conditions have been broadly applied to a variety of Heck arylations that were not feasible using more standard reaction conditions. For example, efforts to use classical Heck-reaction conditions for the conversion of Al-allyl-Al-benzyl(3-bromoquinoxalin-2-yl)amine (64) to l-benzyl-3-methylpyrrolo[2,3-/ ]quinoxaline (65), resulted in slow reactions and low yields [65], which may be attributed to the poisoning of the palladium catalyst via complexation to the aminoquinoxalines. In contrast, the Jeffery conditions afforded the desired product in 83% yield. The enhanced reactivity and yield under Jeffery s ligand-free conditions may be due to the coordination/solvation of the palladium intermediates by bromide ions present in the reaction mixture, which presumably prevents the precipitation of Pd(0). 

Two additional syntheses of indole alkaloids which utilize the Heck reaction are ( )-c j-trikentrin A (185) and infractin (187). As outlined in Scheme 32,7-bromoindole 183 was coupled with an excess of methyl crotonate to give 184 under the Heck reaction conditions (86). 184 was... 

An indole alkaloid synthesis employing a bona fide intramolecular Heck reaction was documented in Sundberg s preparation of 5,6-homoiboga derivatives [90]. Several attempts to construct S,6-homoiboga derivative 191 using inter- or intramolecular Heck reaction conditions with phosphine ligands led to poor yields. Application of Jeffery s ligand-free" phase-transfer... 

Under modified Heck reaction conditions, coupling diethyl (Z)-2-iodovinylphosphonate with acrolein in MeCN at room temperature produces the diethyl (lZ,3 )-dienylphosphonate in 92% yield with high stereoselectivity (Scheme 5.47). ... 

The palladium-catalysed Heck reaction of aryl or vinyl halides with olefins has been widely used in synthetic chemistry. The reaction works impressively well with a wide range of electron-deficient and neutral olefins, generally affording (1-arylatcd products. In the case of electron-rich olefins, however, a mixture of regioisomers is usually obtained under standard Heck reaction conditions (Figure 5.1).[1] This... 

Alkenylation of benzoxazole and benzothiazole occurs at C-2 under Heck reaction conditions.Cross-coupling of ArX and Ar Si(Me)20K is improved by PhsPO, which serves as a stabilizing ligand for the Pd catalyst. ... 

One of the silyl groups in A-bis(trimethylsilyl)methylcarhoxamides is activated by coordination to the carbonyl and under the Heck reaction conditions it can submit a methyl group. Among A-directed reactions methyl group transfer from dicumyl peroxide, involving Pd insertion into the O—O bond and ehmination of acetophenone to afford the transfer reagent, is also a relatively new discovery. ... 

The different Pd dispersion, catalyst preparation or pre-treatment conditions, respectively, explain well the differences in the catalytic activity of the various catalysts reported in the literature (15) in comparison to the high activity of catalyst 3W. The influence of the Pd oxidation state (0 or II) can be interpreted in the context of Pd dispersion as well each thermal treatment under reducing conditions to produce Pd(0), which is generally accepted as the active state (2), is connected vdth a decrease in Pd dispersion (Table 2.) Obviously, the in situ reduction of Pd(II) under Heck reaction conditions leads to the best catalysts with the highest dispersion. 

Heck reaction conditions have been applied to introduction of the dehydroalanine side-chain on to indoles. Under catalytic conditions, 4-bromo-l-tosylindole is converted to the 4-isomer of dehydrotryptophan in 90% yield. However, with a stoichiometric amount of PdClj in acetic acid the 3 position was substituted, albeit in only 17% yield. A much better yield of the 3-substitution product was obtained by changing from acetyl to an N-ethoxycarbonyl protecting group in the dehydroalanine. <94CPB832> Both of these reactions presumably involve indolylpalladium species. Under the Heck conditions the 4-indolylpalladium(II) species is formed by oxidative addition. With the stoichiometric amount of PdClj, the dominant reaction is electrophilic palladation at the 3-position. 

As is the case with most reactions of aryl halides, iodides are the most reactive, followed by aryl bromides. When bromides are used a triaryl- or trialkyIphosphine (Ar3P or R3P) is included in the reaction mixture. Phosphines coordinate with Pd(0) to give a more active catalyst of the type (Ar3P)4Pd or (R3P)4Pd. Typical Heck reaction conditions for aryl iodides and bromides are ... 

Even though aminophosphine- and phosphite-based pincer complexes, as well as other systems such as SCS-based pincer-type Heck catalysts, were shown to serve as stable and clean sources of palladium nanoparticles in Heck reactions [24a, 25], and also xylene-derived phosphine-based systems were found to decompose under Heck reaction conditions in the presence of organic bases and hence palladium nanoparticles generally are considered to be the catalytically active form of palladium pincer Heck catalysts [27], catalytic cycles with the involvement of Pd intermediates could not have been excluded to be operative in pincer-catalyzed versions of the Heck reaction. In contrast, experimental observations, such as halide exchange reactions... 

These computational investigations showed for the first time that catalytic cycles with the involvement of Pd intermediates are indeed thermally accessible for palladium pincer complexes under Heck reaction conditions and hence are a true alternative to palladium nanoparticle-catalyzed versions of the Heck reaction. This, however, does not imply that Pd /Pd mechanisms are operative in any case for palladium pincer complexes in the Heck reaction. In contrast, palladium nanoparticles have been often shown to be the catalyticaUy active form of pincer-type Heck catalysts, as it is, for example, the case for the aminophosphine-based palladium pincer Heck catalyst [2,6-CgH3(NHP(piperidinyl)2)2Pd(Cl)] (10) (under the reaction conditions applied) - the pincer complex with the highest electron density on the metal center and thus where the lowest energy path was calculated. Therefore, it is reasonable to anticipate that palladium pincer Heck catalysts exist that operate via Pd /Pd mechanisms whereas others serve as sources of palladium nanoparticles. This hypothesis got strong experimental support from... 

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