Vinyl palladation

Having favored pathway (a) for the majority of our reactions involving the formation of heterocyclic products from cyclopalladated complexes, now we need to explain the passage of A to C in Scheme 16, which appears to be the result of a reductive eUmination process between the vinyl palladated group and the heteroatom coordinated to the metal. 

Reaction of the cyclometallated derivative of phenyl-2-pyridylketone 73 leads to indenol-chelated, palladium-containing derivatives 74. Here, incorporating an electrophilic (CO) function in the starting palladacycle signifies that, following alkyne insertion in the Pd-C bond, an intramolecular attack of the vinyl palladated unit on the metal-bound, activated CO function occurs. This is in sharp contrast to the reaction described in Scheme 9 whereby incorporating a nucleophilic, masked, secondary amine function leads to indole derivatives 40 and to the azepinium synthesis from the metallated benzylpyridine complex 34. Therefore, these reactions are rather sensitive to the nature of other potentially reactive functions within the metallacyclic framework. 

The problem with free carbanions was circumvented by the use of masked carbon nucleophiles via vinyl palladation or the use of an allylsilane or allene (see the next three subsections). In another approach, the oxidation system was changed to comply with nonacidic conditions (Section 11.3.1.5.4). 

Strongly suggests that the first step is a di-chloropalladation and the second a cw-vinyl-palladation of the coordinated alkyne. 

Indenols, and ultimately indanones, can be prepared via a nucleophilic vinyl pallad-ation of o-bromobenzaldehyde. Stereoselective addition of a -amino-organometallics to aldehydes have been reviewed (62 references). " Diastereoselective additions of MeMgX and MeLi to an oxo-sugar have been reported. ... 

Pd(II) compounds coordinate to alkenes to form rr-complexes. Roughly, a decrease in the electron density of alkenes by coordination to electrophilic Pd(II) permits attack by various nucleophiles on the coordinated alkenes. In contrast, electrophilic attack is commonly observed with uncomplexed alkenes. The attack of nucleophiles with concomitant formation of a carbon-palladium r-bond 1 is called the palladation of alkenes. This reaction is similar to the mercuration reaction. However, unlike the mercuration products, which are stable and isolable, the product 1 of the palladation is usually unstable and undergoes rapid decomposition. The palladation reaction is followed by two reactions. The elimination of H—Pd—Cl from 1 to form vinyl compounds 2 is one reaction path, resulting in nucleophilic substitution of the olefinic proton. When the displacement of the Pd in 1 with another nucleophile takes place, the nucleophilic addition of alkenes occurs to give 3. Depending on the reactants and conditions, either nucleophilic substitution of alkenes or nucleophilic addition to alkenes takes place. 

Somei and co-workers made extensive use of the Heck reaction with haloindoles in their synthetic approaches to ergot and other alkaloids [26, 40, 41, 240-249]. Thus, 4-bromo-l-carbomethoxyindole (69%) [26], 7-iodoindole (91%) (but not 7-iodoindoline or l-acetyl-7-iodoindoline) [40, 41], and l-acetyl-5-iodoindoline (96%) [41] underwent coupling with methyl acrylate under standard conditions (PdlOAc /PhsP/EtjN/DMF/100 °C) to give the corresponding (E)-indolylacrylates in the yields indicated. The Heck coupling of methyl acrylate with thallated indoles and indolines is productive in some cases [41, 241, 246]. For example, reaction of (3-formylindol-4-yl)thallium bis-trifluoroacetate (186) affords acrylate 219 in excellent yield [241], Similarly, this one-pot thallation-palladation operation from 3-formylindole and methyl vinyl ketone was used to synthesize 4-(3-formylindol-4-yl)-3-buten-2-one (86% yield). 

The allyl propionate exchange (Equation 4) also involves acetoxy-palladation, and thus its kinetic behavior might be expected to parallel that for vinyl propionate exchange. In its general features it is, in fact, very similar to vinyl ester exchange. The rate profile with sodium acetate concentration is of the same form as Figure 1. 

Catalytic oxy-palladation is an extremely useful method for the synthesis of functionalized THF and tetrahydropyran moieties. This reaction is brought about simply by treating a 1,4- or 1,5-hydroxy alkene with 0.1 mol-eq of Pd(II) salts and copper(I) chloride in DMF, with oxygen (equation 181)655. If this reaction is carried out in the presence of carbon monoxide in methanol, then an ester moiety is introduced into the product molecule (equation 182)656-658. If an alkene is introduced in place of the CO, then a tandem vinylation reaction also takes place (equation 183)659. 

Allenols undergo a palladium(0)-catalyzed cyclization process to yield highly functionalized vinyl oxiranes in a diastereoselective manner (Equation 77) <1999JA7943>. Initial carbon palladation forms a palladium allyl intermediate that suffers subsequent attack by the internal oxygen nucleophile to generate the oxirane fragment. 

Pd (II) in acetic acid oxidizes ethylene mainly to vinyl acetate. This is the product expected from Pd( II)-hydride elimination from an oxy-palladation adduct. However, 1,1-diacetoxyethane has been reported to be a primary product under some conditions (33). Thus, as discussed above, decomposition of the adduct may not occur by simple Pd(II)-hydride elimination. 

The palladation products exhibit reactivity similar to that of the arylpalladium complexes formed by oxidative addition of aryl halides to Pd(0) species, although the reactions are stoichiometric with respect to palladium. Representative examples include vinylation via an olefin insertion process (eq (88)) [119], double and single carbonylation (eq (89) and (90)) [120,121], and alkylation via a transmetallation process (eq (91)) [122]. 

Palladous acetate has been widely studied in connection with vinyl acetate synthesis (page 798). It acts to some extent like Hg11 and Pblv acetates in attacking benzene and other aromatic hydrocarbons in acid media.11 Thus, in acetic acid, it specifically attacks the side chain of toluene. 

A Stille-related paper reported different regioselectivities in a q clocarbo-palladation in which the multistep reaction described terminated in a Stille cross-coupling. Mechanistic studies with deuterium provided a background for a discussion of the different outcomes when alkynyl or vinyl stannanes were used. Microwave heating was found to increase the rate of the reaction with two vinyl stannanes and one heteroaromatic stannane as substrates [80]. 

Abstract Palladium readily catalyzes the cross-coupling of functionally substituted aryl or vinylic halides and alkynes to afford a wide variety of heterocycles and carbocycles in one efficient step. Terminal alkynes presumably initially generate aryl (vinylic) alkynes, which under the reaction conditions are rapidly cyclized by the palladium or copper salts employed in the first step to produce the final product. Internal alkynes apparently react by carbo-palladation of the alkyne and subsequent intramolecular nucleophilic substitution of the palladium moiety to generate the observed products. A variety of other closely related processes have also been reported, including the simultaneous annulation of alkynes and car-... 

Vinylation can be carried out directly at the 3-position on indoles without a halogen or sulfonate substituent <84H(22)1493>. This reaction presumably involves an electrophilic palladation at C3 followed by a Heck reaction (Equation (116)). These reactions can also be carried out in the presence of a cooxidant such as Cu(OAc)2 or AgOAc which serves to reoxidize palladium. Similar reactions have been carried out on 1-benzenesulfonylindole <84S236> and 1-acylindoles <83JCS(Pl)l36l>. 

Palladous chloride sodium chloride carbon Vinyl esters by transacylation... 

The Pd(II)-mediated reaction of benzene with alkenes affords styrene derivatives 164. The reaction can be vmderstood by palladation, insertion of olefin to give 163, and y3-H elimination [67,68]. In addition to benzene and naphthalene derivatives, electron-rich heteroaromatic compounds such as ferrocene, furan and thiophene react with alkenes to give vinyl heterocycles. The effect of substituents in this reaction is similar to that observed in the electrophilic aromatic substitution [69]. 

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