Intramolecular reactions carbopalladation

A double intramolecular carbopalladation reaction of the g< -di bromide 250 provides a route to the bicyclic 3,6-dihydropyran 251 in high yield (Equation 112) <1998JOC9156>. 

Presumably, the oxidative cyclization of 1 commences with direct palladation at the orfAo-position, forming o-arylpalladium(II) complex 3 in a fashion analogous to a typical electrophilic aromatic substitution (this notion is useful in predicting the regiochemistry of oxidative cyclizations). The mechanism of the second formal C—H bond functionalization step is not fully elucidated, but may occur either via (a) an intramolecular carbopalladation reaction (migratory insertion) followed by czHft-P-hydride elimination from 4 (Path A) (b) by o-bond metathesis (through a four-centered transition state) followed by reductive elimination (Path B) (c) by electrophilic aromatic substitution followed by C—C bond-forming reductive elimination (PathC) [9]. 

Even in cases where the topology of a given substrate renders cyclization a priori rather unlikely, it is potentially misleading to invoke a template effect without appropriate control experiments. An illustrative example was reported by Negishi and co-workers (Scheme 9-5) [7]. Intramolecular carbopalladation reactions of m-haloallenes provide a... 

The comparison of intramolecular carbopalladation reactions of allenes and alkenes outlined in Schemes 9-5 and 9-6 illustrates that not every transition metal catalyzed ring closure necessarily involves a template effect. Others, however, clearly benefit from it. A prototype example is the palladium catalyzed cycloisomerization of alkenyl epoxides carrying distal pre-nucleophiles [38, 39], representing one variant of the famous Tsuji-Trost allylation [40]. 

The CH-activation can be combined with an intramolecular carbopalladation reaction to yield cyclic aromatic systems. In this case, indoles can be synthesized in an efficient manner (Experimental Procedure below). ... 

The intramolecular carbopalladation (or insertion) of the triple bond in dimethyl 4-pentynylmalonate (215) with Pd—H species and malonate anion as shown by 216 proceeds in the presence of f-BuOK and 18-crown ether, affording the methylenecyclopentane derivatives 217 and 218, the amounts of which depend on the reaction conditions. The Pd—H species may be formed... 

A twofold intramolecular Heck reaction has been employed as a key step for the synthesis of the skeleton of the natural product (—)-chimonanthine 58 (Scheme 19). The synthetically most challenging structural features of this bispyrro-loindoline alkaloid are its two adjacent quaternary centers. They were both built up by intramolecular double-bond carbopalladations, which stereoselectively produced the pentacycle 57 from the f72-symmetrical bis[A-(2-iodophenyl)-cyclohexane-1,2-dicarboxamide 55 via the intermediate 56. The key intermediate 57 was thus obtained as a single enantiomer in 90% yield. 

A different reaction mode was observed in the Pd-catalyzed co-cyclization of the 2-bromo-l-en-6-yne 76 and 4-octyne 77. After an intramolecular carbopalladation of the triple bond in 76, the formed alkenylpalladium bromide carbopalladates 77 and this is followed by another intramolecular carbopalladation or 67r-electrocyclization and dehydropalladation to yield the oligosubstituted indane derivative (Scheme 22). ... 

Five-membered ring closures have been observed when o-halostyrene derivatives such as 113 were coupled with alkenes under palladium catalysis. Apparently, an intramolecular carbopalladation with S-exo-trig ring closure to give 114-R can favorably compete with / -hydride elimination in the first-formed intermediate to yield 115-R This reaction mode for the halostyrene is observed especially under Jeffery conditions, when the alkene is ethene or propene (Scheme 31). Under the same conditions, however, < -dibromobenzene gives very high yields of o-dialkenylbenzene derivatives (see Scheme 2). ... 

The transformations of 136 proceed cleanly upon treatment with a catalytic amount of Pd(PPh3)4, in the presence of triethylamine and molecular sieve (MS) 4 A it apparently is initiated by oxidative addition of the N(sp )-0 bond of 136 to the Pd(0) complex, and this is succeeded by two or even three intramolecular carbopalladations followed by / -hydride elimination. This Heck-type reaction is not affected by the configuration of the oxime derivatives probably due to a facile enough if/Z-isomerization of the alkylideneaminopalladium intermediate. 

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... 

Whereas the intermolecular Heck reaction is limited to unhindered alkenes, the intramolecular version permits the participation of even hindered substituted alkenes, and many cyclic compounds can be prepared by the intramolecular Heck reaction [37]. The stereospecific synthesis of an A ring synthon of la-hydroxyvitamin D has been carried out. Cyclization of the (7T)-alkene 88 gives the (fT)-exo-diene 90, and the (Z)-alkene 91 affords the (Z)-exo-diene 92 [38]. These reactions are stereospecific, and can be understood by cis carbopalladation to form 89 and the. sun-elimination mechanism. 

As discussed in conjunction with the intermolecular cascade carbopalladation reaction shown in Scheme 4, it has been very difficult to satisfactorily control both queuing or pair -selectivity and regioselectivity of intermolecular cascade carbopalladation processes. Consequently, essentially all of the cascade carbopalladation reactions discussed here are at least partially intramolecular. The currently known cyclic cascade carbopalladation processes can be classified into a few to several types shown in Scheme 6. 

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-... 

While the syntheses of the acyclic precursors in the examples above each require a couple of steps, symmetrical dienynes with a central triple bond and heteroatoms in the tethers are more easily accessible. They can yield heterotricyclic compounds by the same reaction mode, for example, the diaza- and dioxatricycles 121 are obtained starting from dienynes 119 (Scheme 18) [73]. Yields were best (90%) with N-tosyl linkers, with N-Boc groups the reaction was slower (41% yield), and with N-benzyl linkers only decomposition occurred. This may be due to coordination and blocking of the catalyst by the more Lewis-basic amines. The cis- and frans-diastereomers of 121 were formed in a ratio of 1.8 1, and this ratio did not change in other solvents, at different temperatures, with other catalyst precursors or under high pressure (10 kbar). In view of the apparent influence of the tether, the unsymmetrical oxazaprecursor 122 gave a 7 3 mixture of tricycles 123 and 124. Obviously, the hydridopalladation of the triple bond occurred with some regioselectivity such that intramolecular carbopalladation of the allyl-amine predominated. It is noteworthy that in these cases the intramolecular Diels-Alder reactions of the intermediate trienes 120 already occur under the employed conditions, i.e. at 80 °C. 

Based upon the studies on the mechanism of the Cl sequence we rationalized that the elusive allenol intermediate 19 (Chap. 2.2) could participate in intramolecular trapping reactions as an allenyl ether. Furthermore, vinyl allenes are perfectly suited as dienes in Diels-Alder reactions. Considering both reactive functionalities, allenyl ethers and vinyl allenes, which are perfectly suited for domino processes, we designed an insertion sequence based upon cyclizing carbopalladation [76], where the vinyl aUene results from an isomerization of an alkynylation of a vinyl... 

In more complex reaction cascades an additional alkyne-insertion step can occur. Thus starting with intramolecular carbopalladation of a vinyl iodide to a carbon-carbon triple bond, followed by two intramolecular alkene-insertion steps and termination with dehydropalladation, a palladium-catalyzed synthesis of l-(5 -methylbicyclo[3.1.0]hex-T-yl)-5,5-bis(carboethoxy)cyclo-hexadiene (52) starting from l-iodo-4,4-bis(carboethoxy)-ll-methyldodeca-l,ll-dien-6-yne (51) is achieved. ... 

Stereoselective intramolecular carbopalladation of ( )-4-halo-2-butenyl 2-propynoates 17 with bis(benzonitrile)dihalopalladium catalysts gives (Z)-3-(halomethylene)dihydro-4-vinyl-2(3//)-furanones 18 in excellent yields and high stereoselectivities44,45,56,57. Although resembling metallo-ene reactions (see Section 1.5.8.3.7.), this conversion is interpreted as proceeding via a primary tram- halopalladation of the triple bond. 

Due to the higher reactivity of the allene moiety toward hydropalladation in 1,6-allenynes, the reaction may proceed via a hydropalladation of the allene moiety of 146 affording a vinylic palladium intermediate 147. Subsequent intramolecular carbopalladation of the C-C triple bond moiety would lead to the 1,3-dienyl palladium formate 148. Releasing of CO2 and reductive elimination afford the final product 149 and Pd(0). Pd(0) would react with HCO2H to afford HC02PdH, which is the catalytically active species (Scheme 61) [36]. 

Reaction of the o-iodoaniline derivative 431 with 1,2-decadiene in the presence of the chiral bisoxazoline 433 as a ligand and Ag salt provided the indoline 432 with 80 % ee [164], Construction of indole skeletons was carried out by intramolecular carbopalladation of allenes followed by amination. The 7r-allylpalladium intermediate 435 was formed from o-iodoaniline derivative 434, and intramolecular amination afforded the indole 436 in 89 % yield [165]. 

These nucleophilic attacks proceed in an intermolecular fashion and give the anti or exo addition products. This has been clearly demonstrated in the reaction of Pd(l,5-cod)Cl2 with sodium methoxide, which has yielded a complex analyzed by NMR spectroscopy. On the contrary, syn or endo addition takes place when Grignard reagents are used. In these cases, transmetallation leading to the formation of a o- C—Pd bond takes place first (Scheme 11). As a result, the nucleophile is delivered intramolecularly in a syn or endo fashion, via a carbopalladation reaction (Scheme 11). ... 

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