Carbopalladation arylation

Very recently, Suarez and Greaney explored a novel sequence of Pd-catalyzed indole C—H activation/alkyne carbopalladation/arylation of alkynyl indoles with dia-ryliodonium salts, furnishing functionalized indole alkenes in good to excellent yield, with the reaction being selective for the Z-alkene [74] (Scheme 6.51). 

The transmetallation of various organometallic compounds (Hg, Tl, Sn, B, Si, etc.) with Pd(II) generates the reactive cr-aryl, alkenyl, and alkyl Pd compounds. These carbopalladation products can be used without isolation for further reactions. Pd(II) and Hg(II) salts have similar reactivity toward alkenes and aromatic compounds, but Hg(II) salts form stable mercuration products with alkenes and aromatic rings. The mercuration products are isolated and handled easily. On the other hand, the corresponding palladation products are too reactive to be isolated. The stable mercuration products can be used for various reactions based on facile transmetallation with Pd(II) salts to generate the very reactive palladation products 399 and 400 in rim[364,365]. 

Termination of cyclic carbopalladation of alkynes via caibonylative lactamization can be achieved more satisfactorily with alkenyl or aryl halides containing an oo-caiboxamido or co-sulfonamido group than with those containing an 0)-amino group. The method appears to be satisfactory for the preparation of certain piperidines (e.g., 102) <96T(52)11529>. 

Recently, Larock and coworkers used a domino Heck/Suzuki process for the synthesis of a multitude of tamoxifen analogues [48] (Scheme 6/1.20). In their approach, these authors used a three-component coupling reaction of readily available aryl iodides, internal alkynes and aryl boronic acids to give the expected tetrasubsti-tuted olefins in good yields. As an example, treatment of a mixture of phenyliodide, the alkyne 6/1-78 and phenylboronic acid with catalytic amounts of PdCl2(PhCN)2 gave 6/1-79 in 90% yield. In this process, substituted aryl iodides and heteroaromatic boronic acids may also be employed. It can be assumed that, after Pd°-cata-lyzed oxidative addition of the aryl iodide, a ds-carbopalladation of the internal alkyne takes place to form a vinylic palladium intermediate. This then reacts with the ate complex of the aryl boronic acid in a transmetalation, followed by a reductive elimination. 

Tietze and coworkers [60] observed a combination of a Heck reaction and a C-H-activation by treatment of the alkyne 6/1-111 with Pd°. These authors aimed at compound 6/1-112, but 6/1-110 was obtained as a single product in high yield (Scheme 6/1.29). It can again be assumed that after oxidative addition a cis-carbopalladation of the triple bond takes place to give an alkenyl Pd intermediate which undergoes the C-H-insertion into the neighboring naphthalene and not into the aryl ether moiety. 

Recently, synthesis of aryl ketones by a combination of palladium-catalyzed C-H activation of arenes and intermolecular carbopalladation of nitriles has been reported (Equation (119)).474... 

An organic halide, RX (R = aryl or vinyl) adds oxidatively to Pd(0) species to form a RPdX species. An allene readily undergoes carbopalladation of the species to generate a jr-allylpalladium intermediate [3] in a highly regioselective manner. Finally, an allylic compound is produced by a nucleophile attack (Scheme 16.1). 

Ma and Zhao reported a highly regio- and diastereoselective synthetic method for 2-amino-3-alken-l-ols and 4-amino-2-( )-alken-l-ols by the palladium-catalyzed reaction of 2,3-allenols, aryl iodides and amines (Scheme 16.24) [29]. Carbopalladation of PhPdl to the allene probably generates a thermodynamically more stable anti-Jt-allylpalladium species for steric reasons. Regioselectivity of the amine attack depends largely on the stereoelectronic effect on the a-substituents. 

A clean twofold Heck coupling of unsubstituted butadiene 46 (R = H) in the 1- and 4-positions has not been reported. However, the initial carbopalladation product from 46 (R = H) and an in situ formed arylpalladium halide, the cr-allylpalladium halide 47 equilibrating with the corresponding 7r-allylpalladium halide, can efficiently be trapped with the anion formed by arylation of malononitrile or cyanoacetate to give 48, a product of reductive 1,4-arylation-alkylation of 1,3-butadiene 46 (R = H)." /3-Hydride elimination from the intermediate 47 (R H) can be accomplished when the reaction is carried out in the presence of silver acetate or thallium acetate, leading to the... 

Termination of cascade carbopalladation sequences by arylation can play a major role in systems that form a reasonably long-lived palladium intermediate and contain a suitably functionalized arene moiety in the vicinity of the organopalladium function. In particular, neopentylpalladium intermediates have been found to intramolecularly attack an adjacent arene moiety. For example, iodoarenes 149 with electron-withdrawing substituents in the... 

With its (9r/ (9-(cu-phenylalkynyl) group, the iodoarene 156 in the presence of a palladium catalyst initiates the cascade process with an intramolecular carbopalladation this is followed by an intermolecular insertion, for example, into the double bond of the 3-azanorborn-5-en-l-one 157 and terminated by ortho-2XX,2Jz of the norbornyl-type cr-palladium intermediate on the previously terminal aryl group to yield the two regioisomeric hexacyclic systems 158 and 159 in a ratio of 1 1 (Scheme 39). ... 

The first step in the cycle, analogous to the cross-coupling reactions, is the oxidative addition of an aryl (vinyl) halide or sulfonate onto the low oxidation state metal, usually palladium(O). The second step is the coordination of the olefin followed by its insertion into the palladium-carbon bond (carbopalladation). In most cases palladium is preferentially attached to the sterically less hindered end of the carbon-carbon double bond. The product is released from the palladium in a / -hydrogen elimination and the active form of the catalyst is regenerated by the loss of HX in a reductive elimination step. To facilitate the process an equivalent amount of base is usually added to the reaction mixture. 

Keywords Carbopalladation, Asymmetric Heck reaction, Vinylation, Arylation... 

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... 

In their pioneering work on the catalytic carbopalladation reaction of 1,2-heptadiene with phenyl iodide in the presence of a suitable base, Shimizu and Tsuji observed the formation of the corresponding substituted 1,3-dienes 62 via a / -hydride elimination from the 7z>allyl intermediate 61 [61]. Based on these observations, a three-component Heck-Diels-Alder cascade process has been developed by Grigg and co-workers [73]. A wide variety of aryl and heteroaryl iodides were used for the intermolecular reaction with dimethylallene to afford the corresponding 1,3-dienes. These subsequently react in situ with N-methylmaleimide to give the bicyclic adducts 63 (Scheme 8.30). 

When the carbopalladation of the bicyclopropylidene is performed in the presence of methyl acrylate, the reaction takes a different course (Scheme 8.34) [79]. The 1,3-diene intermediate 75 reacts in situ with the dienophile to give the spiro[2.5]octane derivative 76. An extension of this cascade Heck-Diels-Alder reaction involving l,3-dicyclopropyl-l,2-propadiene as the alkene partner, an alkenyl or aryl halide and a dienophile has been reported [80]. 

Over 35 years ago, Richard F. Heck found that olefins can insert into the metal-carbon bond of arylpalladium species generated from organomercury compounds [1], The carbopalladation of olefins, stoichiometric at first, was made catalytic by Tsutomu Mizoroki, who coupled aryl iodides with ethylene under high pressure, in the presence of palladium chloride and sodium carbonate to neutralize the hydroiodic acid formed (Scheme 1) [2], Shortly thereafter, Heck disclosed a more general and practical procedure for this transformation, using palladium acetate as the catalyst and tri-w-butyl amine as the base [3], After investigations on stoichiometric reactions by Fitton et al. [4], it was also Heck who introduced palladium phosphine complexes as catalysts, enabling the decisive extension of the ole-fination reaction to inexpensive aryl bromides [5],... 

A mechanistic rationale for the Pd-catalyzed addition of a C-H bond at nitriles to allenes is outlined in Scheme 3. The oxidative insertion of Pd(0) into the C-H bond of nitrile 1 produces the Pd(II) hydride species 16 (or alternatively a tautomeric structure E E2C=C=N PdH Ln may be more suitable, where E = H, alkyl, aryl and/or EWG). Carbopalladation of the allene 2 would afford the alkenylpalladium complex 17 (carbopalladation mechanism), which would undergo reductive coupling to give the addition product 3 and regenerates Pd(0) species. As an alternative mechanism, it may be considered that the hydropalladation of allenes with the Pd(II) intermediate 16 gives the jr-allylpalladium complex 18 which undergoes reductive coupling to afford the adduct 3 and a Pd(0) species (hydropalladation mechanism). 

A domino Heck carbopalladation/cyclization reaction of (Z)-3-(2-(but-2-ynyloxy)phenyl)prop-2-en-l-ol 453 with aryl iodides furnishes chroman derivatives 454 in good yield (Equation 185) <2004AGE5997>. 

Step 5 of the mechanism shown in Figure 16.35 (part II) is new. It consists of the cw-selec-tive addition of the aryl-Pd complex to the C=C double bond of the acrylic acid methyl ester, i.e., a carbopalladation of this double bond. A related reaction, the cw-selective car-bocupratlon of C=C triple bonds, was mentioned in connection with Figure 16.17. The regioselectivity of the carbopalladation is such that the organic moiety is bonded to the methylene carbon and Pd to the methyne carbon of the reacting C=C double bond. The addition product is an alkyl-Pd(II) complex. 

The same authors also reported on palladium-catalyzed domino cycli-zation-anion capture reactions employing allene (69) as a relay switch (Scheme 10) [52], Such a reaction of the alkynyl-tethered aryl iodide 68 starts with an oxidative addition to the catalytic metal species, and is followed by an intramolecular carbopalladation of the triple bond. An intermolecular car-... 

The same palladium-catalyzed domino cyclization-anion capture sequence involving carbopalladation of allene (69), which was employed by Grigg et al. for the synthesis of diene 70 (Scheme 10) can yield 1,3,5-hexatriene 194, when starting from 2-bromo-l-ene-6-yne 193 instead of the aryl iodide 68 (Scheme 32) [52], Under the conditions of its formation, 194 immediately undergoes thermal 67r-electrocyclization to give the bicyclic product 195. 

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