Palladium acetate intramolecular

Another approach is based on the palladium-catalyzed intramolecular carbocyclization of the allylic acetate moiety with the alkene moiety (Scheme 96). After the formation of a 7t-allylpalladium complex, with the first double bond the intramolecular carbometallation of the second double bond occurs to form a new C-C bond. The fate of the resulting alkylpalladium complex 393 depends on the possiblity of /3-elimination. If /3-elimination is possible, it generates a metallated hydride and furnishes the cycloadduct 394. This cyclization could be viewed as a pallada-ene reaction, in which palladium replaces the hydrogen atom of the allylic moiety.231... 

A twofold intramolecular Heck reaction of the dibromobenzene derivative 19 has been used to construct the heptacyclic skeleton 20 of cephalostatin analogs. This reaction required a precise control of the reaction time and temperature. The conversion proceeded best with a catalytic amount of the palladacycle from tris(< -tolyl)phosphine and palladium acetate, and gave exclusively (in 80% yield) the heptacycle 20 with an unusual m-annelation of the two newly formed rings (Scheme 10). ... 

The intramolecular palladium catalyzed ring closure of the tetrahydro-isoquinoline derivative depicted in 8.41. led to the formation of the aporphine derivative in good yield, which was then converted into racemic aporphine in three steps. In the ring closing step 20 mol% palladium acetate and 40 mol% tricyclohexylphosphine were used as catalyst. The removal of the hydroxyl group was also achieved by palladium catalysis through its conversion to triflate and the subsequent reduction with ammonium formate in the presence of palladium acetate and dppf.53... 

In contrast, the closely related palladium acetate-promoted intramolecular alkylation of alkenes by tri-methylsilyl enol ethers (Scheme 4)6,7 has been used to synthesize a large number of bridged carbocyclic systems (Table 1). In principle, this process should be capable of being made catalytic in palladium(II), since silyl enol ethers are stable to a range of oxidants used to carry the Pd° -> Pd11 redox chemistry required for catalysis. In practice, catalytically efficient conditions have not yet been developed, and the reaction is usually carried out using a full equivalent of palladium(II) acetate. This chemistry has been used in the synthesis of quadrone (equation 2).8 With the more electrophilic palladium(II) trifluoroace-tate, methyl enol ethers underwent this cyclization process (equation 3).9... 

Pd-catalysed chelate-directed acetoxylation of meta -substituted arenes has been studied.61 Many substituted groups are tolerated by this process and the reaction shows a high degree of regioselectivity for the less sterically hindered ortfto-position. For example, 2-(3-nitrophenyl)pyridine forms 2-(2-acetoxy-3-nitrophenyl)pyridine. Finally, density functional calculations62 on the palladium acetate-promoted cyclomet-allation of dimethylbenzylamine suggest that reaction occurs via an agostic C-H complex rather than a Wheland intermediate. An intramolecular H-transfer to a coordinated acetate via a six-membered transition state follows. 

Jt-allyl complex can be generated after cyclization, as suggested by Takacs in a Fe(0)-catalyzed cyclization of polyenes. It also can be preformed if an active functional group is present in the allylic position. The palladium-catalyzed intramolecular cycloisomerization reaction of allylic acetates is an efficient method for constructing five- or six-membered rings [56, 57]. An asymmetric approach to this transformation has been studied and so far only poor enantioselectivity has been achieved (0-20% ee) [58]. Very recently, Zhang et al. also reported a Rh-catalyzed cycloisomerization involving a Jt-allylrhodium intermediate formed from an allylic halide [59]. 

Methylene chromans can be prepared by a palladium-catalyzed intramolecular cyclization of 2-iodophenyl alkynyl ethers 455. Simple modifications to the reaction conditions lead to either (E)- or (Z)-4-methylene chromans (Scheme 103) <2001TL2657>. 2-Iodophenyl alkynyl acetals are also viable substrates for this reaction <2005JOG489>. Addition of tris(2,6-diphenylbenzyl)tin hydride (TDTH) to a triethylborane-mediated intramolecular cyclization of 2-iodophenyl alkynyl ethers ensures complete (A)-selectivity is observed in the resulting 4-methylene chroman <2001AGE411>. 

Another interesting example of the acetal formation is the synthesis of brevicomin (2), a cyclic acetal, by the palladium-catalyzed intramolecular oxidation and acetal formation of 6,7-dihydroxy-1-nonene (equation 3). ... 

Polycyclic indoles. The treatment of the 3-benzoylindoles 1 and 3 with palladium acetate (0.5 equiv.) in acetic acid leads to 2 and 4, respectively, by intramolecular oxidative ring closure. ... 

In this case, the modified Heck reaction of amide 220 bearing fully protected functional groups, which was prepared from 5S,6S-bis(methoxy-methoxy)-4-(4f )-azidocyclohex-2-enone, is a key step. The protected amide 220 underwent intramolecular cyclization with palladium acetate in the presence of thallium(I) acetate and l,2-bis(diphenylphosphono)ethane... 

The final paragraph in this section details carbazole syntheses that involve the formation of C-C bonds. Intramolecular Diels-Alder cycloaddition of ynamides provided a new route to [b -fused carbazoles <05OL2213>. An electrocyclization of 2,3-divinylindole intermediates produced functionalized carbazoles <05TL4045>. A domino alkynylation/palladium migration/C-H activation approach to 4-vinylcarbazoles was reported <050L701>. For example, treatment of A-arylaniline 134 with diphenylacetylene in the presence of palladium acetate, cesium pivalate (CsPv), and bis(diphenylphosphino)methane (dppm) gave carbazole 136 via post-palladium migration intermediate 135. 

More than three decades ago, Itanani and coworkers reported that the intramolecular oxidative coupling of diphenyl ether in the presence of Pd(OAc)2, acetyl-acetone, and oxygen afforded dibenzofurans along with dimers of diphenyl ether [72, 73]. The yield of dibenzofuran obtained was up to 10,400% based on the reacted palladium acetate (104 TON). In 1975, Akermark and coworkers reported that the corresponding intramolecular oxidative coupling products were obtained in high yields when diphenyl ether, diphenylamine, benzophenone, and benzanilide were heated in acetic acid with a stoichiometric amount of Pd(OAc)2 [74]. However, diphenyl sulfide failed to yield the cyclized product. 

Since then, a series of intramolecular oxidative coupling reactions between two arenes have been reported. This method was extensively used to synthesize many naturally occurring carbazoles (for reviews see [75, 76]), as shown in Table 2. However, most of these transformations are carried out in the presence of stoichiometric or substoichiometric amounts of palladium acetate. 

Other oxidants like thallium(III) oxide, vanadium(V) oxyfluoride, palladium ) acetate, and ruthenium(IV) tetrakis(trifluoracetate) have been developed as powerful tools for the intramolecular biaryl coupling reaction [7,93,113]. Nevertheless, DDQ is still one of the most versatile reagents in oxidative coupling reactions (see Scheme 14 and 29 [82,114]). The highly strained dioxa[8](2,7)pyrenophane (65), portraying an overall curvature of nearly 90° for the pyrene subunit, was finally obtained from the mefa-cyclophanediene (66) by dehydrogenation with DDQ in refluxing benzene in 67% yield [114]. 

A series of Pd-catalyzed intramolecular Heck reactions of N-(2-halophenyl)-substituted enaminones was performed by Pombo-Villar et al. [114]. The reactions were performed in the presence of palladium acetate with a phosphonium ligand as catalyst, sodium acetate, and tetrabutylammonium chloride (TBACl) as the PTC catalyst in DMF solution to afford desired coupling product in 25 to 99% yields (Eq. 79). 

Aryl coupling can also be effected by palladium complexes and can be illustrated by the intramolecular coupling of the iV-acylindole (147) to the tetracyclic compound (148) (Equation (40)) <9iTL33i7>. Unbrominated aryl rings can also be coupled using palladium acetate in a stoichiometric process and can also be considered within the current context. Relevant indole examples include the conversion of A,iV -carbonylbis-4,6-dimethoxyindole (149) into the biindolyl (150) <85CC1174>... 

Intramolecular Heck reactions are particularly efficient and have been used considerably in organic synthesis.In situ reduction of palladium acetate and oxidative addition of the resulting palladium(O) into the aryl iodide 210 gave an... 

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