Carbocyclizations reductive elimination

Intramolecular arylation of G-H bonds gives cyclic aromatic compounds. In this intramolecular arylation, the carbon-palladium cr-bond is first formed by the oxidative addition of Pd(0) species and then the resulting electrophilic Pd(n) species undergoes the intramolecular G-H bond activation leading to the formation of the palladacycle, which finally affords the cyclic aromatic compounds via reductive elimination.87 For example, the fluoroanthene derivative is formed by the palladium-catalyzed reaction of the binaphthyl triflate, as shown in Scheme 8.88 This type of intramolecular arylation is applied to the construction of five- and six-membered carbocyclic and heterocyclic systems.89 89 89 ... 

The borostannylation of an enyne has also been reported by Tanaka to proceed in a high yield (Scheme 71).273 The mechanism of this cyclization has not been investigated in detail, but the insertion of the alkyne takes place preferentially into the Pd-B bond over the Pd-Sn bond. Then, the addition of the vinylpalladium 279 to the alkene moiety followed by reductive elimination furnished the cycloadduct 278. However, Tanaka does not exclude a palladacycle intermediate. Similarly, a borylsilylative carbocyclization has also been reported by Tanaka.274... 

A proposed mechanism of the bis(allene) cyclization involves the formation of the allyl(stannyl)palladium species 6, which undergoes carbocyclization to give vinyl(stannyl)palladium intermediate 7 (Scheme 36). Reductive elimination and cr-bond metathesis may lead to the formation of the m-pentane derivative and the bicyclic product, respectively. The cyclization of allenic aldehydes catalyzed by a palladium complex was also reported.163... 

Cascade silylcarbocyclization reactions tiave been developed based on the fact that it is possible to realize successive intramolecular carbocyclizations, as long as the competing reductive elimination is slower than the carbometallation. For example, the reaction of dodec-6-ene-l,ll-diyne 67 with PhMe2SiH catalyzed by Rh(acac)(CO)2 at 50°C under 1 atm CO gives bis(exo-methylenecyclopentyl) 68 in 55% yield [44]. The reaction is stereo-specific that is, (6 )- and (6Z)-dodec-6-ene-l,ll-diynes, ( )-67 and (Z)-67, afford R, R )-68 and (S, R -68 respectively. A possible mechanism for this reaction is outlined in Scheme 7.20. It should be noted that none of the tricyclic product is formed even though a third carbocyclization in the intermediate III.2c is conceptually possible. 

The domino carbonylation and Diels-Alder reaction proceed only as an intramolecular version. Attempted carbonylation and intermolecular Diels-Alder reaction of conjugated 2-yne-4-enyl carbonates 101 in the presence of various alkenes as dienophiles give entirely different carbocyclization products without undergoing the intermolecular Diels-Alder reaction. The 5-alkylidene-2-cyclopenten-4-onecarboxy-lates 102 were obtained unexpectedly by the incorporation of two molecules of CO in 82% yield from 101 at 50 °C under 1 atm [25], The use of bidentate ligands such as DPPP or DPPE is important. The following mechanism of the carbocyclization of 103 has been proposed. The formation of palladacyclopentene 105 from 104 (oxidative cyclization) is proposed as an intermediate of 108. Then CO insertion to the palladacycle 105 generates acylpalladium 106. Subsequent reductive elimination affords the cyclopentenone 107, which isomerizes to the cyclopentenone 108 as the final product. 

Whereas 6-membered palladacycles readily undergo reductive elimination to give 5-membered rings as final products, the analogous process to give 4-mem-bered carbocycles from 5-membered palladacycles is less feasible, although not completely ruled out, and restricted to special cases (see, for instance, product 7 in... 

Both alkane reductive elimination and alkali metal reduction reactions have been used to prepare a family of bis(indenyl)zirconium sandwich complexes.104 Crystallographic characterization of the Pr1 304 and the SiMe2But variants establishes an unprecedented 7y9-hapticity of the indenyl ligand where all nine carbons of the carbocycle are engaged in bonding with the zirconium center. Interestingly, this coordination mode was computationally predicted before structural confirmation.183... 

Internal alkynes will also readily undergo palladium-catalyzed annulation by functionally substituted aromatic or vinylic halides to afford a wide range of heterocycles and carbocycles. However, the mechanism here appears to be quite different from the mechanism for the annulation of terminal alkynes. In this case, it appears that the reaction usually involves (1) oxidative addition of the organic halide to Pd(0) to produce an organopalladium(II) intermediate, (2) subsequent insertion of the alkyne to produce a vinylic palladium intermediate, (3) cyclization to afford a palladacycle, and (4) reductive elimination to produce the cyclic product and regenerate the Pd(0) catalyst (Eq. 28). 

Intermolecular arylation of carbocyclic arenes are rare. Exceptionally, phenols are easily arylated. As treated in Chapter 3.7.4, the aryl ether 48 is formed by reaction of aryl halides with hydroquinone monomethyl ether when bulky and electron-rich phosphines are used, which accelerate reductive elimination. Miura and co-workers found new completely different reactions of phenol with bromobenzene by using Pd(OAc)2, PPhs and CS2CO3 to give the unexpected pentaphenylated product 49 in 58% yield [lb, 15]. 

The proposed mechanism for this reaction is illustrated in (Scheme 46) (i) Regioselective insertion of one of the olefin moiety of 1,6-diene 33 to the Si-[Pd] complex E-I to form /3-silylalkyl-[Pd] complex E-III via E-II, (ii) exo-carbocyclization to give trans-intermediate E-V, and (iii) reductive elimination, probably by a-bond metathesis with a hydrosilane, to yield 34 and regenerate the active catalyst species E-I (Scheme 18). 

A proposed mechanism for this reaction is shown in (Scheme 24). Insertion of the less hindered olefin moiety of a diene into the [Y]-H bond forms G-I. Car-bocyclization of G-I gives G-II, and the subsequent cr-bond metathesis with a hydrosilane yields the product and regenerates Cp 2YH THF. The observed high catalyst activity of the Cp 2YMe and Cp 2LuMe complexes relative to Ni(0) and Rh(I) complexes for this carbocyclization is ascribed to the Lewis acidity of the metal center and the presence of an open coordination site. These features favor both /3-migratory insertion and a-bond metathesis over oxidative addition and reductive elimination processes that are preferred in the Ni(0) and Rh(I) catalyst systems. 

VCPs have served as valuable five-carbon components in various cycloaddition reactions. Usually, they form six-membered metallacycles upon oxidative cycliza-tion with transition metals. Then, migratory insertion of unsaturated molecules, followed by reductive elimination, furnishes the carbocycles. In particular, intermolecular [5-1-2] annulation of VCPs with alkynes, alkenes, and allenes has been studied extensively (Scheme 2.39) [57]. In addition, VCP-cyclopentene rearrangement has been well documented [56 ]. 

The coupling between alkynes and alkenes can also afford cycUzation reactions and leads to strained carbocycles. Most of these reactions are performed via a constrained ruthenacyclopentene intermediate which cannot undergo p-hydride elimination and leads to cyclobutenes via a reductive elimination as in the following example [68] [Eq. (30)]. 

In 2001, Larock and Tian reported a palladium-catalyzed cascade reaction of aryl halides and 1-aryl-l-aIkynes to synthesize 9-aIkylidene-9/f-fluorenes 167 [66] (Scheme 6.44). Based on the active role of Pd(IV) in organopalladium chemistry, the authors proposed a mechanism involving the formation, transformation, and reductive elimination of Pd(IV) intermediates and aryl C—H bond activation. It is noteworthy that both carbocyclic and heterocyclic aryl iodides, such as pyridine and thiophene, could be introduced in this reaction. Later, Zhao and Larock reported an efficient palladium-catalyzed cascade reaction for the synthesis of substituted carbazoles 169 from A/-(3-iodophenyl)anilines 168 and alkynes [67] (Scheme 6.45). 

The reaction was extended to other 5-vinyl pyranoses and the major product has always a cM-configuration between the newly formed stereocenters and a trani-configuration between the vinyl and the adjacent substituent. Considering these results, the proposed mechanism for the CpZr -mediated carbocyclization is depicted in Scheme 3.37. Ligand exchange with the vinyl followed by reductive elimination of the alkoxy group produces aZ-allylic zirconacycle, which immediately cyclizes to the cyclopentane 92 (Scheme 3.37). 

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