Vinylpalladium intermediate

The indole skeleton can also be constructed by Pd-mediated cyclization of A -propargyl-n-haloanilines. The vinylpalladium intermediates formed in the cyclization are sufficiently stable to permit further rcaction[4,5]. For example. 

A related cyclization of 2-(alkynyl)phenylisocyanates with terminal alkynes to oxindoles was also reported by the same group (Equation (115)).472 (E)-exo-olefinic oxoindoles are selectively obtained. It was proposed that a palladium acetylide generated by the C-H activation of terminal alkynes regioselectively inserts to the alkyne moiety and the resulting vinylpalladium intermediate adds to the C=0 part of the isocyanate to give a (Z)-oxindole. This (Z)-isomer is isomerized to the ( )-isomer under the reaction conditions through catalysis of the phosphine. 

The palladium(II)-catalyzed oxidation of allenes with chloride was studied by Hege-dus et al. [3], In this reaction the dimeric products 4 and 6 as shown in Scheme 17.4 were obtained. The (allene)palladium(II) complex formed can react with chloride ions in two different ways (Scheme 17.4) [4]. Attack at the terminal carbon gives a vinylpalladium intermediate 2 whereas attack at the middle carbon produces a 2-chloro(jt-allyl)palladium complex 3. The former complex is the kinetic intermediate (k2 > kj) and is in equilibrium with the (allene)palladium complex. The 2-chloro(jt-allyl)palladium complex is formed more slowly but is more stable and has been isolated [2]. The vinyl complex can undergo further reaction with excess allene to give a new (jt-allyl)palladium complex, which undergoes attack with chloride to give the observed dimer 6 [3]. The dichloride from attack on the 2-chloro-(jT-allyl)palladium complex 3 was not observed. 

An alternative mechanism involving a palladium-hydride as the active species was proposed by Scrivanti et al. following their labeling experiments with CH3OD and detection of a deuterated a-vinylpalladium intermediate (Scheme 19) [118]. 

Scheme 19 Structure of the deuterated <7-vinylpalladium intermediate detected in labeling experiments...

On the other hand, when the oxidative carbonylation of a ,a -disubstituted propynylamines was carried out in the presence of an excess of CO2, the intermediate carbamate species could undergo cyclization with incorporation of CO2 into the five-membered cycle, either by direct nucleophilic attack of the carbamate oxygen to the triple bond coordinated to Pd(II) (Scheme 33, path a) or through the intermediate formation of a palladium carbamate complex followed by triple bond insertion (Scheme 33, path b). Carbon monoxide insertion into the Pd - C bond of the resulting stereoisomeric vinylpalladium intermediates then led to the final oxazolidi-none derivatives. 

The insertion of alkynes into arylpalladium complexes might also be accompanied by the insertion of carbon monoxide into the resulting vinylpalladium intermediate. The carbonylative annulation of TV-protected 2-iodoanilines and internal alkynes under an ambient pressure of carbon monoxide resulted in the formation of 2-quinolones (4.14.), The protection of the nitrogen atom in the aniline is crucial to the success of the reaction. 

N-Tosyl carbamates, such as 325, derived from allylic alcohols, undergo the Pd(II)-catalysed cyclization to furnish oxazolidinones 326 under 1 atm of CO439. Analogous Pd(II)-catalysed N-cyclization of allenic N-tosylcarbamates has generated the corresponding vinylpalladium intermediate that could be further alkylated440. 

On the basis of the reaction of conjugated dienes with unsaturated halides in the presence of external nucleophiles, an elegant intramolecular version leading to a-alkylidene-y-lactams, has been developed (Scheme 8.19). Starting with an aryl halide, the regioselective insertion of an arylpalladium halide to the triple bond of acyclic compound 42 gives the c-vinylpalladium intermediate 43. Subsequent intramolecular carbopalladation of the diene affords a re-allyl palladium intermediate... 

The mechanism of the indenone synthesis (Scheme 3) seems to involve (1) oxidative addition of the aryl iodide to Pd(0) (2) arylpalladium coordination to the alkyne and subsequent insertion of the alkyne to form a vinylpalladium intermediate (8), (3) then either the vinylic palladium intermediate adds to the carbonyl group and subsequently undergoes a /3-hydride elimination (path A) or the alde-hydic C-H bond may oxidatively add to the palladium to produce an organopalla-dium(IV) intermediate (six-membered ring palladacycle) which subsequently undergoes rapid reductive elimination of the indenone and palladium (path B). The actual mode of ring closure of the vinylic palladium intermediate to the inde-... 

Attempted annulation of 3-iodoflavones, for example 428, by internal alkynes catalyzed by Pd(OAc)2 in the presence of NaOAc and LiCl yielded a mixture of two compounds (Scheme 73) <1998JOC2002>. While the expected benzoxanthenes (e.g., 429) were isolated as the minor compound, tetrasubstituted furans (e.g., 430) resulting from the electrophilic attack on the carbonyl oxygen atom by the vinylpalladium intermediate followed by pyrone ring opening were the major product. 

Lu and Xie have reported a three-component coupling for the synthesis of o -alkylidenc-y-lactams 69 (Scheme 22) [62], Treatment of N-(2,4-dienyl)alkynamide 66 with an aryl iodide 67 affords a cr-vinylpalladium intermediate 70 through regioselective insertion of the active ArPdX species into the triple bond. Subsequent intramolecular carbopalladation of the diene affords 7r-allylpalladium complex 71, which undergoes nucleophilic attack by amines 68 at the less hindered terminus to afford the product 69. 

Arenes, especially electron-rich ones, have been found to react with alkynes in the presence of Pd(ll) or Pt(ll) species in a mixed solvent containing CF3COOH (Eq. 81) [158-160]. The intramolecular reaction is also possible (Eq. 82). The mechanism proposed for the reaction involves aromatic pallada-tion to form arylpalladium species as in Fujiwara-Moritani reaction, insertion of an alkyne, and protonolysis of the resulted vinylpalladium intermediate. 

In an imaginative construction of the angular triquinane ( )-hirsutene (158), Oppolzer and Robyr reported the carbonylative closure of allylic carbonate 155 to yield bicyclooctanes 156 and 157 (Scheme 6-27) [57]. In this multistep transformation, a alJylpalladium intermediate arising from the allylic carbonate 155 undergoes intramolecular Heck insertion of the pendant alkyne. Carbonylation of the resulting vinylpalladium intermediate, another Heck cyclization, and a second carbonylation then provide a mixture of acids, which after esterification yield esters 156 and 157 in good yield. 

Pd(O)-catalyzed hydrogermylcarbonylation of alkynes has been reported quite recently by Oshima (Scheme 11.58) [85]. a,/ -Unsaturated acylgermanes were prepared starting from terminal alkynes. The reaction is considered to proceed by way of a vinylpalladium intermediate followed by CO insertion and subsequent reductive ehmination. 

Treatment of 112b with 0.2 equiv of Pd(PPh3)4 and 1.5 equiv of KO-fBu in refluxing THF gave 113b in 48% yield as a nearly equimolecular mixture of diastereoisomers. It became clear from this result that the substituent at C(3) does not influence the regiocontrol in the formation of the enolate that reacts with the vinylpalladium intermediate species. 

The cyclization can be extended to the cross-annulation of aryl halides with unsaturated compounds [95, 96]. For example, 2-iodobiphenyl reacts with diphenylacetylene via a vinylpalladium intermediate to give a phenanthrene derivative (Eq. 36) [97,98]. It is of particular interest that the same compound can be formed by the reaction with iodobenzene through a domino sequence (Eq.37) [99,100]. 

Excellent yields of fulvenes can now be obtained [142]. This process no doubt involves two consecutive cis insertions of the two molecules of alkyne into the carbon-palladium bond of the initial vinylpalladium intermediate, and then intramolecular addition of the resulting 1,3,5-alkatrienylpalladium species to... 

In contrast to the diverse chemistry of allylpalladium complexes, vinylpalladium intermediates have been involved mainly in the vinylpalladation of carbon-carbon unsaturated systems and in the insertion into carbon-hydrogen and heteroatom-hydrogen bonds (Scheme 10). It is found that a vinylpalladium species reacts with carbon electrophiles such as aldehydes, ketones, and nitriles (Scheme 11, type a). Oxidative addition of vinyl-halogen and -pseudohalogen bonds to Pd(0) is the common way to generate the vinylpalladium species. Vinyl-... 

The key intermediate should be a deuterated vinylpalladium species (H) generated via syn addition of D-Pd species (Scheme 9). This vinylpalladium intermediate H is similar in its structure to the Negishi intermediate in the Mizoroki-Heck-type cyclization of 2-iodo-1,6-dienes to six-membered carbo-cycles, which proceeds with olefmic geometry inversion[53-56]. Thus, the plausible mechanism follows a D-Pd syn addition, p-carbon elimination, and P H elimination mechanism effective in controlling olefin inversion via cyclopropane intermediate (E and then I). 

The intramolecular version of the Heck reaction leads to the formation of cyclic compounds (Scheme 6.40) [130], In this case the C-C bond is generally formed at the most substituted position of the alkene (exo mode), in contrast with the intermolecular case where the opposite regiochemistry holds. The Baldwing rules for cyclization are usually operative. The Scheme 6.40 (a) depicts the general cyclization reaction of an enyne, where the vinylpalladium intermediate is formed by insertion of the alkyne fragment into a Pd-H bond formed by protonation of Pd(0) species the first M-C bond can also be formed by oxidative addition of a... 

Trost and Toste explain their Pd(0)-catalyzed reaction by the following mechanism. First, reaction of Pd(0) and HCO2H generates hydridopalladium 38, and the vinylpalladium intermediate 39 is formed by insertion of alkyne, and either the... 

In contrast to the diverse insertion chemistry of vinylpalladium intermediates discussed in Sects. IV.3 and IV.5, the reactions of vinylpalladium complexes with electrophiles had not been reported until recently. Although a single report on the annulation of the o-mer-curio benzaldehyde with diphenylacetylene into the corresponding indenols and inde-nones catalytic in palladium and stoichiometric in copper had been communicated in 1992, the more synthetically useful protocol for the catalytic version of this type of transformation remained unknown until 1999. In this section the intermolecular carbopalladation of alkynes with aryl halides followed by the intramolecular trapping of the formed vinylpalladium species with ketones, aldehydes, and nitriles will be discussed. 

Cascade intermolecular carbopalladations of alkynes followed by intramolecular trapping with electrophiles represent not only a novel type of organic transformation involving vinylpalladium intermediates, but also provide synthetically useful routes toward differently substituted indenols, indanones, indenones, and naphthy-lamines." Although these protocols are restricted to the intramolecular trapping with electrophiles, a wide application of this methodology toward the synthesis of various types of complex carbocychc compounds may be anticipated in the near future. 

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